Rapid detection of colored and colorless macro- and micro-plastics in complex environment via near-infrared spectroscopy and machine learning.

To better understand the migration behavior of plastic fragments in the environment, development of rapid non-destructive methods for in-situ identification and characterization of plastic fragments is necessary. However, most of the studies had focused only on colored plastic fragments, ignoring colorless plastic fragments and the effects of different environmental media (backgrounds), thus underestimating their abundance. To address this issue, the present study used near-infrared spectroscopy to compare the identification of colored and colorless plastic fragments based on partial least squares-discriminant analysis (PLS-DA), extreme gradient boost, support vector machine and random forest classifier. The effects of polymer color, type, thickness, and background on the plastic fragments classification were evaluated. PLS-DA presented the best and most stable outcome, with higher robustness and lower misclassification rate. All models frequently misinterpreted colorless plastic fragments and its background when the fragment thickness was less than 0.1mm. A two-stage modeling method, which first distinguishes the plastic types and then identifies colorless plastic fragments that had been misclassified as background, was proposed. The method presented an accuracy higher than 99% in different backgrounds. In summary, this study developed a novel method for rapid and synchronous identification of colored and colorless plastic fragments under complex environmental backgrounds.

Impairments of insulin and glucagon sensitivity in Chinese women with gestational diabetes mellitus.

AIM: To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM). METHODS: In total, 81 women with GDM and 81 age-matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24-28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post-OGTT. Fasting plasma insulin, glucagon and amino acids were also measured. Insulin and glucagon sensitivity were assessed by the homeostatic model assessment of insulin resistance (HOMA-IR) and glucagon-alanine index, respectively. RESULTS: As expected, plasma glucose concentrations were higher at fasting and 1 h and 2 h post-OGTT in GDM participants (p < .001 each). Both the HOMA-IR and the glucagon-alanine index were higher in GDM participants. There was a weak positive correlation between HOMA-IR and glucagon-alanine index (r = 0.24, p = .0024). Combining the HOMA-IR and the glucagon-alanine index yielded better capacity (area under the curve = 0.878) than either alone (area under the curve = 0.828 for HOMA-IR and 0.751 for glucagon-alanine index, respectively) in differentiating GDM from healthy participants. While the majority of GDM participants (64%) exhibited both reduced insulin and glucagon sensitivity, a third of them presented either reduced insulin (20%) or glucagon (14%) sensitivity alone. HOMA-IR and glucagon-alanine index correlated differentially with fasting glucose, triglycerides, low-density lipoprotein cholesterol, sum of amino acids and hepatic steatosis index. CONCLUSIONS: Impairments of both insulin and glucagon sensitivity occur frequently in Chinese women with GDM, which may, individually or together, drive metabolic derangements in GDM. These observations provide new insights into the pathophysiology of GDM and support the need to target insulin or glucagon resistance, or both, in the management of GDM.

Multidimensional analysis of TMEM132A in pan-cancer: unveiling its potential as a biomarker for treatment response prediction.

Background: TMEM132A is a transmembrane protein that regulates gastric cancer cell malignancy and overall survival in bladder cancer patients. However, while some studies have investigated the involvement of TMEM132A in specific cancers, further systematic studies are required to elucidate its specific mechanisms of action in different cancer types. Methods: We investigated the pan-cancer role of TMEM132A using several databases. We analyzed TMEM132A expression and its correlation with clinical survival, immune checkpoints, tumor stemness score, prognostic value, immunomodulators, genomic profiles, immunological characteristics, immunotherapy and functional enrichment. Results: First, it was observed that TMEM132A expression levels were higher in the majority of tumors compared to non-tumor tissues. In addition, high TMEM132A expression may have a higher prognostic value in some cancers. Furthermore, TMEM132A was significantly associated with immune checkpoints, immunomodulators, prognosis, immunomodulatory genes, tumor stemness score, cell function status and immune infiltration in most tumors. Further analysis of TMEM132A-related gene enrichment, mutation sites and types, RNA modification and genomic heterogeneity showed that the major mutations of TMEM132A were missense mutations and that TMEM132A plays a very important role in UCEC, LUAD and LIHC. Finally, these results suggest that high TMEM132A expression may be associated with a better response to specific immunotherapies. Conclusion: This comprehensive study uncovers an important function for TMEM132A in different types of cancer. It also has the potential to identify TMEM132A as a potential biomarker for predicting treatment response. This may help us to better understand how TMEM132A plays a role in cancer and provide valuable insights for developing personalised treatments.

Co-administration of GnRH-agonist and hCG (double trigger) for final oocyte maturation increases the number of top-quality embryos in patients undergoing IVF/ICSI cycles.

BACKGROUND: The utilization of a double trigger, involving the co-administration of gonadotropin-releasing hormone agonist (GnRH-a) and human chorionic gonadotropin (hCG) for final oocyte maturation, is emerging as a novel approach in gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during controlled ovarian hyperstimulation (COH). This protocol involves administering GnRH-a and hCG 40 and 34 h prior to ovum pick-up (OPU), respectively. This treatment modality has been implemented in patients with low/poor oocytes yield. This study aimed to determine whether the double trigger could improve the number of top-quality embryos (TQEs) in patients with fewer than three TQEs. METHODS: The stimulation characteristics of 35 in vitro fertilization (IVF) cycles were analyzed. These cycles were triggered by the combination of hCG and GnRHa (double trigger cycles) and compared to the same patients' previous IVF attempt, which utilized the hCG trigger (hCG trigger control cycles). The analysis involved cases who were admitted to our reproductive center between January 2018 and December 2022. In the hCG trigger control cycles, all 35 patients had fewer than three TQEs. RESULTS: Patients who received the double trigger cycles yielded a significantly higher number of 2PN cleavage embryos (3.54 ± 3.37 vs. 2.11 ± 2.15, P = 0.025), TQEs ( 2.23 ± 2.05 vs. 0.89 ± 0.99, P < 0.001), and a simultaneously higher proportion of the number of cleavage stage embryos (53.87% ± 31.38% vs. 39.80% ± 29.60%, P = 0.043), 2PN cleavage stage embryos (43.89% ± 33.01% vs. 27.22% ± 27.13%, P = 0.014), and TQEs (27.05% ± 26.26% vs. 14.19% ± 19.76%, P = 0.019) to the number of oocytes retrieved compared with the hCG trigger control cycles, respectively. The double trigger cycles achieved higher rates of cumulative clinical pregnancy (20.00% vs. 2.86%, P = 0.031), cumulative persistent pregnancy (14.29% vs. 0%, P < 0.001), and cumulative live birth (14.29% vs. 0%, P < 0.001) per stimulation cycle compared with the hCG trigger control cycles. CONCLUSION: Co-administration of GnRH-agonist and hCG for final oocyte maturation, 40 and 34 h prior to OPU, respectively (double trigger) may be suggested as a valuable new regimen for treating patients with low TQE yield in previous hCG trigger IVF/intracytoplasmic sperm injection (ICSI) cycles.

Late Paleocene paleoclimate recorded in fluid inclusion of halite in Subei basin, East China.

Salt deposits are indicative of relatively extreme climate events. However, due to insufficient independent temperature proxies, paleotemperature records obtained from salt deposition are still lack. The Paleocene evaporite sequence deposited in the Hongze Depression of Subei Basin of eastern China provides an important terrestrial sediment record during this period. In this study we present total of 488 homogenization temperature (Th) data of halite fluid inclusions from drilling core with different stratigraphic depth after detailed petrological observation. The obtained Th ranged from 17.7 °C to 52.3 °C, with the mean Th value of 34.1 °C that in good agreement with the previous studies of climatic proxies. Our study shows that primary fluid inclusions of halite can serve as a robust tool to construct the ancient earth surface temperature.

Relationship between soil and species diversity in typical forest stands in Xianrendong, Liaoning Province based on plant-soil feedback.

Exploring the relationship between soil properties and species diversity in typical forest stands in Liaoning Xianrendong National Nature Reserve will help maintain the stability of forest communities in the transition zone between flora in Changbai and North China. Based on the plant-soil feedback theory, community sample data from nine typical forest stands in the study area and experimental test data from 54 soil samples, we selected indexes of soil physical and chemical properties based on the minimum data set (temperature, compactness, capillary pore space, bulk weight, capillary water holding capacity, drainage capacity, soil water storage, conductivity, pH, organic matter, Ca, Fe, K, N and P). We adopt the research method of classical statistical analysis. The soil properties of nine typical stands in Xianrendong National Nature Reserve of Liaoning Province were systematically analyzed. The relationship between soil properties and forest stands' species diversity was quantified using correlation and redundancy analyses. The Pearson correlation analysis results showed significant positive correlations between the Gleason abundance index (arbors) with conductivity, pH, organic matter, Ca, N and P; Pielou's evenness index (arbors) with bulk weight and Fe. Significant negative correlations between the Gleason abundance index (arbors) with capillary pore space, bulk weight, drainage capacity, soil water storage and capillary water holding capacity; Simpson dominance index and Shannon-Wiener diversity index with capillary water holding capacity, drainage capacity and soil water storage; Pielou's evenness index (arbors) with Ca and N. The natural moisture content and clay particles are neutral feedback. The results showed that the feedback mechanism of soil physicochemical properties on stand species diversity was complex, which was conducive to species coexistence and community stability.

Crystal-Phase-Selective Etching of Heterophase Au Nanostructures.

Selective oxidative etching is one of the most effective ways to prepare hollow nanostructures and nanocrystals with specific exposed facets. The mechanism of selective etching in noble metal nanostructures mainly relies on the different reactivity of metal components and the distinct surface energy of multimetallic nanostructures. Recently, phase engineering of nanomaterials (PEN) offers new opportunities for the preparation of unique heterostructures, including heterophase nanostructures. However, the synthesis of hollow multimetallic nanostructures based on crystal-phase-selective etching has been rarely studied. Here, a crystal-phase-selective etching method is reported to selectively etch the unconventional 4H and 2H phases in the heterophase Au nanostructures. Due to the coating of Pt-based alloy and the crystal-phase-selective etching of 4H-Au in 4H/face-centered cubic (fcc) Au nanowires, the well-defined ladder-like Au@PtAg nanoframes are prepared. In addition, the 2H-Au in the fcc-2H-fcc Au nanorods and 2H/fcc Au nanosheets can also be selectively etched using the same method. As a proof-of-concept application, the ladder-like Au@PtAg nanoframes are used for the electrocatalytic hydrogen evolution reaction (HER) in acidic media, showing excellent performance that is comparable to the commercial Pt/C catalyst.

Nicotinamide riboside restores nicotinamide adenine dinucleotide levels and alleviates brain injury by inhibiting oxidative stress and neuroinflammation in a mouse model of intracerebral hemorrhage.

Hemorrhagic stroke is a global health problem owing to its high morbidity and mortality rates. Nicotinamide riboside is an important precursor of nicotinamide adenine dinucleotide characterized by a high bioavailability, safety profile, and robust effects on many cellular signaling processes. This study aimed to investigate the protective effects of nicotinamide riboside against collagenase-induced hemorrhagic stroke and its underlying mechanisms of action. An intracerebral hemorrhage model was constructed by stereotactically injecting collagenase into the right striatum of adult male Institute for Cancer Research mice. After 30 minutes, nicotinamide riboside was administered via the tail vein. The mice were sacrificed at different time points for assessments. Nicotinamide riboside reduced collagenase-induced hemorrhagic area, significantly reduced cerebral water content and histopathological damage, promoted neurological function recovery, and suppressed reactive oxygen species production and neuroinflammation. Nicotinamide riboside exerts neuroprotective effects against collagenase-induced intracerebral hemorrhage by inhibiting neuroinflammation and oxidative stress.

The impact of parenting style on malevolent creativity based on Chinese university students: a latent profile analysis.

Introduction: This study investigated the association between parenting styles and malevolent creativity. Methods: It used latent profile analysis to compare the differences in malevolent creativity between different combinations of parenting styles with an online sample (N = 620). Results: The results of the study suggest that a three-profile solution best fits the data, and the three profiles were labelled positive open parenting, undifferentiated parenting and negative limited parenting. Subsequent analyses revealed that there were significant differences in malevolent creativity performance among the three parenting styles, with participants in the positive open parenting having more malevolent creativity. Those with undifferentiated parenting had the lowest scores. Discussion: The findings provide theoretical guidance for parenting strategies. Future intervention studies on malevolent creativity should also consider the potential impact of parenting style to obtain better results.

Self-assembled Abietic acid encapsulated nanoparticles to improve the stability of Proanthocyanin B2.

Procyanidin B2 (Pac B2) has attracted much attention due to its strong antioxidant activity, but poor in vivo stability limits its wide application in food and medicine. In this paper, composite nanoparticles (NPs) were constructed using abietic acid (AA) as a carrier, which significantly enhanced Pac B2 stability. A spherical morphology and average diameter of 396.05 nm were observed in AA-Pac B2 NPs synthesized by solvent co-precipitation. Pac B2 encapsulation was 11.28 %, and thermal stability is improved. Infrared, Ultraviolet spectrum, and MD (molecular dynamics) spectroscopy revealed hydrogen bonding and hydrophobic interaction between AA and Pac B2. For up to 2 h at 37 °C, Pac B2 can be sustainably released in simulated gastric and intestinal fluids. In vitro, AA-Pac B2 NPs at the same concentration exhibited higher bioavailability and uptake efficiency than free Pac B2. The data demonstrate the potential of AA NPs for improving polyphenol thermal stability and bioavailability.

Self-Internal Standard Fluorescence for Ultrasensitive Detecting of mtDNA to Evaluate Matrilineal Genetic Defect Levels.

Mitochondrial DNA (mtDNA) is a unique genetic material characterized by maternal inheritance. It possesses a circular structure devoid of histone protection and exhibits low cellular abundance, which poses great challenges for its sensitive and selective detection at the living cell level. Herein, we have designed three bis-naphthylimide probes with varying linker lengths (NANn-OH, n = 0, 2, 6), facilitating the formation of distinct twisted or folded molecular conformations in the free state. These probes emit the red fluorescence around 627 nm with different fluorescence quantum yields (ΦNAN0-OH = 0.0016, ΦNAN2-OH = 0.0136, and ΦNAN6-OH = 0.0125). When encountering mtDNA (0.4-3.4 µg/mL), these probes undergo conformational changes depending on the length of the attached C-strand and exhibit a gradually increasing fluorescence signal around 453 nm. The fluorescence intensity increased to 13.5-fold, 1.9-fold, and 8.2-fold, respectively. Notably, the red fluorescence intensities around 627 nm remain constant throughout this process, thus serving as an inherent correction mechanism for proportional fluorescence signal enhancement to improve selectivity and sensitivity. NAN0-OH, NAN2-OH, and NAN6-OH showed good linearity for mtDNA in the range of 0.4-3.4 µg/mL with detection limits of LODNAN0-OH = 1.04 µg/mL, LODNAN2-OH = 1.10 µg/mL, and LODNAN6-OH = 1.15 µg/mL. Cellular experiments reveal that NAN6-OH effectively monitors curcumin-induced mtDNA damage in HepG-2 cells while enabling monitoring of genetic mtDNA damage. We anticipate that this tool holds significant potential for the precise evaluation of maternal genetic defects, thereby enhancing hypersensitive assessment in clinical medicine.

Delivery of rapamycin by biomimetic peptide nanoparticles targeting oxidized low-density lipoprotein in atherosclerotic plaques.

Drug delivery systems based on biomimetic peptide nanoparticles are steadily gaining prominence in the treatment of diverse medical conditions. This study focused on the development of peptides that depend on ligand-receptor interactions to load rapamycin (RAPA). Furthermore, a multifunctional peptide was engineered to target oxidized low-density lipoprotein (oxLDL) within atherosclerotic plaques, facilitating the localized delivery of RAPA. The interactions between peptides and RAPA/oxLDL were analyzed by simulations and experimental approaches. Results show that the main amino acid residues on the mammalian target of rapamycin that bind to RAPA are constructed as peptides (P1 and P2), which have specific interactions with RAPA and can effectively improve the loading efficiency of RAPA. The encapsulation and drug loading efficiencies of P1/P2 were 68.0/47.9% and 48.3/36.5%, respectively. In addition, the interaction force of the multifunctional peptide (P3) and oxLDL surpassed that of their interaction with human umbilical vein endothelial cells by a factor of 3.6, conclusively establishing the specific targeting of oxLDL by these nanoparticles. The encapsulation and drug loading efficiencies of P3 for RAPA were determined to be 60.2% and 41.5%. P3 can effectively load RAPA and target oxLDL within the plaque, suggesting that P3 has potential as a therapeutic agent for atherosclerotic disease.

PuERF008-PuFAD2 module regulates aroma formation via the fatty acid pathway in response to calcium signaling in 'Nanguo' pear.

Calcium acts as a secondary messenger in plants and is essential for plant growth and development. However, studies on the pathway of aroma synthesis in 'Nanguo' pear (Pyrus ussriensis Maxim.) are scarce. In this study, a bioinformatics analysis of transcriptomic data from calcium-treated 'Nanguo' pear was performed, which identified two fatty acid desaturases, PuFAD2 and PuFAD3, and eight AP2/ERF transcription factors, all exhibiting the same expression patterns. Transient expression experiments showed overexpression of PuFAD2 and PuFAD3 significantly increased the levels of aromatic substrates linoleic acid, hexanal, linolenic acid, and (E)-2-hexenal, but RNAi (RNA interference) had the opposite expression. Promoter sequences analysis revealed that PuFAD2 and PuFAD3 have ERE (estrogen response element) motifs on their promoters. The strongest activation of PuFAD2 by PuERF008 was verified using a dual-luciferase reporting system. Additionally, yeast one-hybrid and electrophoretic mobility shift assays revealed PuERF008 could active PuFAD2. Transient overexpression and RNAi analyses of PuERF008 showed a strong correlation with the expression of PuFAD2. This study provides insights into the process of aroma biosynthesis in 'Nanguo' pear and offers a theoretical basis for elucidating the role of calcium signaling in aroma synthesis.

Quantitative assessment and driving factors analysis of surface urban heat island of urban agglomerations in China based on GEE.

The urban heat island (UHI) effect generated by the development of high-speed urbanization has become one of the major problems affecting the urban ecological environment. As the main body of urbanization in China, China's urban agglomerations are the core areas of urban heat island effect. The purpose of this study is to study the spatial-temporal characteristics and driving factors of surface urban heat island in 19 urban agglomerations in China, with a view to providing theoretical references for the prevention of urban thermal environmental risks. Based on Google Earth Engine (GEE), this paper estimated the surface urban heat island intensity (SUHII) of 19 urban agglomerations in China from 2003 to 2019 using MODIS land surface temperature (LST) data. Correlation analysis and regression analysis were used to explore the correlation between the change of SUHII and driving factors. Finally, the driving factors of SUHII were detected by the geo-detector model. Results showed that (1) the SUHII of 19 urban agglomerations in arid and semi-arid areas of northwestern China is higher than that in humid areas of eastern and southeastern China. (2) The SUHII of 19 urban agglomerations in China generally shows a decreasing trend, and the spatial variation of the change trend is significant. (3) There are positive correlations between SUHII and reference evapotranspiration (ET0), population density (POP), gross domestic product (GDP), nitrogen dioxide (NO2), ozone (O3), and ultraviolet aerosol index (UVAI); negative correlations with normalized difference vegetation index (NDVI), DEM, sulfur dioxide (SO2), carbon monoxide (CO), and formaldehyde (HCHO); the correlations all pass the significance test of P < 0.05 and are statistically significant. (4) The factor detection results showed that NDVI, land cover type (LC), and UVAI were the main driving factors of SUHII. The interaction detection results showed that the interaction between O3 and UVAI had the most significant impact on SUHII.

Post-Quantum Secure Identity-Based Signature Scheme with Lattice Assumption for Internet of Things Networks.

The Internet of Things (IoT) plays an essential role in people's daily lives, such as healthcare, home, traffic, industry, and so on. With the increase in IoT devices, there emerge many security issues of data loss, privacy leakage, and information temper in IoT network applications. Even with the development of quantum computing, most current information systems are weak to quantum attacks with traditional cryptographic algorithms. This paper first establishes a general security model for these IoT network applications, which comprises the blockchain and a post-quantum secure identity-based signature (PQ-IDS) scheme. This model divides these IoT networks into three layers: perceptual, network, and application, which can protect data security and user privacy in the whole data-sharing process. The proposed PQ-IDS scheme is based on lattice cryptography. Bimodal Gaussian distribution and the discrete Gaussian sample algorithm are applied to construct the fundamental difficulty problem of lattice assumption. This assumption can help resist the quantum attack for information exchange among IoT devices. Meanwhile, the signature mechanism with IoT devices' identity can guarantee non-repudiation of information signatures. Then, the security proof shows that the proposed PQ-IDS can obtain the security properties of unforgeability, non-repudiation, and non-transferability. The efficiency comparisons and performance evaluations show that the proposed PQ-IDS has good efficiency and practice in IoT network applications.

Conductive/Insulating Bioinks with Multitechnology Compatibility and Adjustable Performance.

Conducting/insulating inks have received significant attention for the fabrication of a wide range of additive manufacturing technology. However, current inks often demonstrate poor biocompatibility and face trade-offs between conductivity and mechanical stiffness under physiological conditions. Here, conductive/insulating bioinks based on two-dimensional materials are proposed. The conductive bioink, graphene (GR)-poly(lactic-co-glycolic acid) (PLGA), is prepared by introducing conductive GR into a degradable polymer matrix, PLGA, while the insulating bioink, boron nitride (BN)-PLGA, is synthesized by adding insulating BN. By optimizing the material ratios, this work achieves precise control of the electromechanical properties of the bioinks, thereby enabling the flexible construction of conductive networks according to specific requirements. Furthermore, these bioinks are compatible with a variety of manufacturing technologies such as 3D printing, electrospinning, spin coating, and injection molding, expanding their application range in the biomedical field. Overall, the results suggest that these conducting/insulating bioinks offer improved mechanical, electronic, and biological properties for various emerging biomedical applications.

Mass spectrometry imaging for spatially resolved multi-omics molecular mapping.

The recent upswing in the integration of spatial multi-omics for conducting multidimensional information measurements is opening a new chapter in biological research. Mapping the landscape of various biomolecules including metabolites, proteins, nucleic acids, etc., and even deciphering their functional interactions and pathways is believed to provide a more holistic and nuanced exploration of the molecular intricacies within living systems. Mass spectrometry imaging (MSI) stands as a forefront technique for spatially mapping the metabolome, lipidome, and proteome within diverse tissue and cell samples. In this review, we offer a systematic survey delineating different MSI techniques for spatially resolved multi-omics analysis, elucidating their principles, capabilities, and limitations. Particularly, we focus on the advancements in methodologies aimed at augmenting the molecular sensitivity and specificity of MSI; and depict the burgeoning integration of MSI-based spatial metabolomics, lipidomics, and proteomics, encompassing the synergy with other imaging modalities. Furthermore, we offer speculative insights into the potential trajectory of MSI technology in the future.

In situ Raman reveals the critical role of Pd in electrocatalytic CO2 reduction to CH4 on Cu-based catalysts.

Electrocatalytic CO2 reduction reaction (CO2RR) for CH4 production presents a promising strategy to address carbon neutrality, and the incorporation of a second metal has been proven effective in enhancing catalyst performance. Nevertheless, there remains limited comprehension regarding the fundamental factors responsible for the improved performance. Herein, the critical role of Pd in electrocatalytic CO2 reduction to CH4 on Cu-based catalysts has been revealed at a molecular level using in situ surface-enhanced Raman spectroscopy (SERS). A "borrowing" SERS strategy has been developed by depositing Cu-Pd overlayers on plasmonic Au nanoparticles to achieve the in situ monitoring of the dynamic change of the intermediate during CO2RR. Electrochemical tests demonstrate that Pd incorporation significantly enhances selectivity toward CH4 production, and the Faradaic efficiency (FE) of CH4 is more than two times higher than that for the catalysts without Pd. The key intermediates, including *CO2-, *CO, and *OH, have been directly identified under CO2RR conditions, and their evolution with the electrochemical environments has been determined. It is found that Pd incorporation promotes the activation of both CO2 and H2O molecules and accelerates the formation of abundant active *CO and hydrogen species, thus enhancing the CH4 selectivity. This work offers fundamental insights into the understanding of the molecular mechanism of CO2RR and opens up possibilities for designing more efficient electrocatalysts.

IL-27 disturbs lipid metabolism and restrains mitochondrial activity to inhibit γδ T17 cell-mediated skin inflammation.

IL-17+ γδ T cells (γδ T17) are kick-starters of inflammation due to their strict immunosurveillance of xenobiotics or cellular damages and rapid response to pro-inflammatory stimulators. IL-27 is a well-recognized pleiotropic immune regulator with potent inhibitory effects on type 17 immune responses. However, its actions on γδ T17 mediated inflammation and the underlying mechanisms are less well understood. Here we find that IL-27 inhibits the production of IL-17 from γδ T cells. Mechanistically, IL-27 promotes lipolysis while inhibits lipogenesis, thus reduces the accumulation of lipids and subsequent membrane phospholipids, which leads to mitochondrial deactivation and ensuing reduction of IL-17. More importantly, Il27ra deficient γδ T cells are more pathogenic in an imiquimod-induced murine psoriasis model, while intracutaneous injection of rmIL-27 ameliorates psoriatic inflammation. In summary, this work uncovered the metabolic basis for the immune regulatory activity of IL-27 in restraining γδ T17 mediated inflammation, which provides novel insights into IL-27/IL-27Ra signaling, γδ T17 biology and the pathogenesis of psoriasis.

Employing antagonistic C-X-C motif chemokine receptor 4 antagonistic peptide functionalized NaGdF4 nanodots for magnetic resonance imaging-guided biotherapy of breast cancer.

C-X-C motif chemokine receptor 4 (CXCR4) is a promising therapeutic target of breast cancer because it is overexpressed on cell surface of all molecular subtypes of breast cancer including triplenegative breast cancer (TNBC). Herein, CXCR4 antagonistic peptide-NaGdF4 nanodot conjugates (termed as anti-CXCR4-NaGdF4 NDs) have been constructed for magnetic resonance imaging (MRI)-guided biotherapy of TNBC through conjugation of the C-X-C Motif Chemokine 12 (CXCL12)-derived cyclic peptide with tryptone coated NaGdF4 nanodots (5 ± 0.5 nm in diameter, termed as Try-NaGdF4 NDs). The as-prepared anti-CXCR4-NaGdF4 NDs exhibits high longitudinal relaxivity (r1) value (21.87 mM-1S-1), reasonable biocompatibility and good tumor accumulation ability. The features of anti-CXCR4-NaGdF4 NDs improve the tumor-MRI sensitivity and facilitate tumor biotherapy after injection in mouse-bearing MDA-MB-231 tumor model in vivo. MRI-guided biotherapy using anti-CXCR4-NaGdF4 NDs enables to suppress 46% tumor growth. In addition, about 47% injection dose of anti-CXCR4-NaGdF4 NDs is found in the mouse urine at 24 h post-injection. These findings demonstrate that anti-CXCR4-NaGdF4 NDs enable to be used as renal clearable nanomedicine for biotherapy and MRI of breast cancer.