GWAShug: a comprehensive platform for decoding the shared genetic basis between complex traits based on summary statistics.

The shared genetic basis offers very valuable insights into the etiology, diagnosis and therapy of complex traits. However, a comprehensive resource providing shared genetic basis using the accessible summary statistics is currently lacking. It is challenging to analyze the shared genetic basis due to the difficulty in selecting parameters and the complexity of pipeline implementation. To address these issues, we introduce GWAShug, a platform featuring a standardized best-practice pipeline with four trait level methods and three molecular level methods. Based on stringent quality control, the GWAShug resource module includes 539 high-quality GWAS summary statistics for European and East Asian populations, covering 54 945 pairs between a measurement-based and a disease-based trait and 43 902 pairs between two disease-based traits. Users can easily search for shared genetic basis information by trait name, MeSH term and category, and access detailed gene information across different trait pairs. The platform facilitates interactive visualization and analysis of shared genetic basic results, allowing users to explore data dynamically. Results can be conveniently downloaded via FTP links. Additionally, we offer an online analysis module that allows users to analyze their own summary statistics, providing comprehensive tables, figures and interactive visualization and analysis. GWAShug is freely accessible at http://www.gwashug.com.

Factor H binding protein (FHbp): An evaluation of genotypic diversity across Neisseria meningitidis serogroups.

Neisseria meningitidis serogroups A, B, C, W, X, and Y cause invasive meningococcal disease (IMD) worldwide. Factor H binding protein (FHbp), a key meningococcal virulence factor, is an antigen included in both licensed meningococcal serogroup B (MenB) vaccines. This review examines the biology and epidemiology of FHbp and assesses the ability and potential of FHbp vaccine antigens to protect against IMD. Using evidence from the literature and the contemporary PubMLST database, we discuss analyses of MenB genotypes on the representation of the most prevalent multilocus sequence typing (MLST)/clonal complexes, FHbp subfamily distribution, and FHbp and porin A (PorA) variants. We further discuss that the similar genotypes, distribution, and diversity of FHbp variant types have remained stable over long time periods, supporting the potential for FHbp-containing, protein-based vaccines to protect against IMD, including MenB-FHbp (Trumenba®), which contains two lipidated FHbp antigens (one each from both FHbp subfamilies: A and B).

Interpretable machine learning models for the prediction of all-cause mortality and time to death in hemodialysis patients.

INTRODUCTION: The elevated mortality and hospitalization rates among hemodialysis (HD) patients underscore the necessity for the development of accurate predictive tools. This study developed two models for predicting all-cause mortality and time to death-one using a comprehensive database and another simpler model based on demographic and clinical data without laboratory tests. METHOD: A retrospective cohort study was conducted from January 2017 to June 2023. Two models were created: Model A with 85 variables and Model B with 22 variables. We assessed the models using random forest (RF), support vector machine, and logistic regression, comparing their performance via the AU-ROC. The RF regression model was used to predict time to death. To identify the most relevant factors for prediction, the Shapley value method was used. RESULTS: Among 359 HD patients, the RF model provided the most reliable prediction. The optimized Model A showed an AU-ROC of 0.86 ± 0.07, a sensitivity of 0.86, and a specificity of 0.75 for predicting all-cause mortality. It also had an R2 of 0.59 for predicting time to death. The optimized Model B had an AU-ROC of 0.80 ± 0.06, a sensitivity of 0.81, and a specificity of 0.70 for predicting all-cause mortality. In addition, it had an R2 of 0.81 for predicting time to death. CONCLUSION: Two new interpretable clinical tools have been proposed to predict all-cause mortality and time to death in HD patients using machine learning models. The minimal and readily accessible data on which Model B is based makes it a valuable tool for integrating into clinical decision-making processes.

Leveraging Random Effects in Cistrome-Wide Association Studies for Decoding the Genetic Determinants of Prostate Cancer.

Cistrome-wide association studies (CWAS) are pivotal for identifying genetic determinants of diseases by correlating genetically regulated cistrome states with phenotypes. Traditional CWAS typically develops a model based on cistrome and genotype data to associate predicted cistrome states with phenotypes. The random effect cistrome-wide association study (RECWAS), reevaluates the necessity of cistrome state prediction in CWAS. RECWAS utilizes either a linear model or marginal effect for initial feature selection, followed by kernel-based feature aggregation for association testing is introduced. Through simulations and analysis of prostate cancer data, a thorough evaluation of CWAS and RECWAS is conducted. The results suggest that RECWAS offers improved power compared to traditional CWAS, identifying additional genomic regions associated with prostate cancer. CWAS identified 102 significant regions, while RECWAS found 50 additional significant regions compared to CWAS, many of which are validated. Validation encompassed a range of biological evidence, including risk signals from the GWAS catalog, susceptibility genes from the DisGeNET database, and enhancer-domain scores. RECWAS consistently demonstrated improved performance over traditional CWAS in identifying genomic regions associated with prostate cancer. These findings demonstrate the benefits of incorporating kernel methods into CWAS and provide new insights for genetic discovery in complex diseases.

The Characteristics and Inheriting Pattern of Skin Aging in Chinese Women: An Intergenerational Study of Mothers and Daughters.

Introduction: The aging of the skin, which is affected by both external and internal causes, can reflect the external age and the internal health status. While the aging characteristics differ across ethnic groups, the specific changes in skin aging within the Chinese population have been underexplored. Moreover, investigating the similarity of aging skin characteristics between parent-offspring pairs remains uncharted territory. This study aims to fill these gaps by examining the skin aging features of Chinese women and assessing the similarity in aging skin characteristics between mother-daughter pairs. Methods: A total of 40 mother-daughter pairs were recruited and analyzed. The perceived ages of the participants were evaluated, and their aging skin traits were systematically graded. Statistical methods were employed to discern the trends of the aging skin characteristics. By introducing a novel similarity parameter, we compared whether various skin aging characteristics have similar patterns between mothers and daughters. Results: Our findings indicate that age 50 represents a pivotal point in skin aging. Beyond this age, the increase in rhytides and laxity scores accelerated noticeably, whereas the escalation in dyschromia scores became less marked. By introducing similar parameters between mother-daughter pairs and the radar map, we discovered that the skin aging characteristics are remarkably consistent between mother-daughter pairs. Conclusion: Understanding the main aging skin characteristics of different age groups can allow caregivers to devise treatments for preventing skin aging in women of various ages. The mother's skin aging trend is also significant for the daughter's skin aging prevention.

Skin aging, a complex process influenced by both internal and external factors, exhibits distinct patterns across ethnic groups. Despite this, the specific aging characteristics within the Chinese population and the hereditary similarities between parents and offspring have not been thoroughly investigated. To address this gap, our study focused on the skin aging features of Chinese women and explored the resemblance in these features between mother-daughter pairs. Eighty-seven women from the same community, including 40 mother-daughter pairs, participated in our study. We assessed how old each participant appeared to be and methodically evaluated their skin aging signs by a modified scale. With the introduction of a new similarity parameter, we further examined the extent to which skin aging traits showed parallel trends between mothers and their daughters. Our findings pinpoint age 50 as a pivotal moment in the skin aging trajectory, where the increase in wrinkles and skin laxity becomes more pronounced, contrasting with a deceleration in skin discoloration. Remarkably, a consistent pattern of aging characteristics was observed between mother-daughter pairs, suggesting a potential genetic influence. This study not only sheds light on the specific skin aging patterns among Chinese women but also underscores the significance of genetic factors in shaping these patterns. The insights gained pave the way for developing targeted interventions for skin aging prevention and treatment, emphasizing the importance of considering familial aging trends.

Cellular and molecular landscape of primary dermatofibrosarcoma protuberans: Insights from single-cell RNA sequencing analysis.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1-PDGFB fusion gene. This study utilized single-cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast-like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF-ß signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets.

In vitro selection and analysis of SARS-CoV-2 nirmatrelvir resistance mutations contributing to clinical virus resistance surveillance.

To facilitate the detection and management of potential clinical antiviral resistance, in vitro selection of drug-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) against the virus Mpro inhibitor nirmatrelvir (Paxlovid active component) was conducted. Six Mpro mutation patterns containing T304I alone or in combination with T21I, L50F, T135I, S144A, or A173V emerged, with A173V+T304I and T21I+S144A+T304I mutations showing >20-fold resistance each. Biochemical analyses indicated inhibition constant shifts aligned to antiviral results, with S144A and A173V each markedly reducing nirmatrelvir inhibition and Mpro activity. SARS-CoV-2 surveillance revealed that in vitro resistance-associated mutations from our studies and those reported in the literature were rarely detected in the Global Initiative on Sharing All Influenza Data database. In the Paxlovid Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients trial, E166V was the only emergent resistance mutation, observed in three Paxlovid-treated patients, none of whom experienced COVID-19-related hospitalization or death.

Soft sensing of NOx emission from waste incineration process based on data de-noising and bidirectional long short-term memory neural networks.

Continuous emission monitoring system is commonly employed to monitor NOx emissions in municipal solid waste incineration (MSWI) processes. However, it still encounters the challenges of regular maintenance and measurement lag. These issues significantly impact the accurate and stable control of NOx emissions. Therefore, developing a soft NOx emission sensor to complement hardware monitoring becomes imperative. Considering data noise, dynamic nonlinearity, time series characteristics and volatility in the MSWI process, this article introduces a soft sensor model for NOx emission prediction utilizing the complete ensemble empirical mode decomposition adaptive noise (CEEMDAN)-wavelet threshold (WT) method and bidirectional long short-term memory (Bi-LSTM). Firstly, the original data signal is decomposed into a group of intrinsic mode functions (IMFs) using the CEEMDAN. Subsequently, the WT processes the high-frequency IMFs that are noise-dominant. Then, all IMFs are reconstructed to obtain the denoized signal. Finally, the Bi-LSTM model is employed to predict NOx emissions. Compared to conventional modelling approaches, the model proposed in this article demonstrates the best predictive performance. The mean absolute percentage error, root-mean-squared error and average absolute error on the test set of the proposed model are 3.75%, 5.34 mg m-3 and 4.34 mg m-3, respectively. The proposed model provides a new method to soft sensing NOx emissions. It holds significant practical value for precise and stable monitoring of NOx emissions in MSWI processes and provides a reference for research on modelling key process parameters.

Dynamics of synaptic damage in severe traumatic brain injury revealed by cerebrospinal fluid SNAP-25 and VILIP-1.

BACKGROUND: Biomarkers of neuronal, glial cells and inflammation in traumatic brain injury (TBI) are available but they do not specifically reflect the damage to synapses, which represent the bulk volume of the brain. Experimental models have demonstrated extensive involvement of synapses in acute TBI, but biomarkers of synaptic damage in human patients have not been explored. METHODS: Single-molecule array assays were used to measure synaptosomal-associated protein-25 (SNAP-25) and visinin-like protein 1 (VILIP-1) (along with neurofilament light chain (NFL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), glial fibrillar acidic protein (GFAP), interleukin-6 (IL-6) and interleukin-8 (IL-8)) in ventricular cerebrospinal fluid (CSF) samples longitudinally acquired during the intensive care unit (ICU) stay of 42 patients with severe TBI or 22 uninjured controls. RESULTS: CSF levels of SNAP-25 and VILIP-1 are strongly elevated early after severe TBI and decline in the first few days. SNAP-25 and VILIP-1 correlate with inflammatory markers at two distinct timepoints (around D1 and then again at D5) in follow-up. SNAP-25 and VILIP-1 on the day-of-injury have better sensitivity and specificity for unfavourable outcome at 6 months than NFL, UCH-L1 or GFAP. Later elevation of SNAP-25 was associated with poorer outcome. CONCLUSION: Synaptic damage markers are acutely elevated in severe TBI and predict long-term outcomes, as well as, or better than, markers of neuroaxonal injury. Synaptic damage correlates with initial injury and with a later phase of secondary inflammatory injury.

Glucoconjugated monoterpene indole alkaloids with xanthine oxidase inhibitory activity from Ophiorrhiza japonica.

Continued interest in the bioactive alkaloids led to the isolation of five undescribed alkaloids (1-5), ophiorglucidines A-E, and seven known analogues (6-12) from the water-soluble fraction of Ophiorrhiza japonica. The structures were elucidated based on spectroscopic data and quantum calculations as well as X-ray crystallographic analysis. The structure of 1 was characterized as a hexacyclic skeleton including a double bridge linking the indole and the monoterpene moieties, which is the first report of a single crystal with this type of structure. Moreover, the inhibitory effect of zwitterionic indole alkaloid glycosides on xanthine oxidase was found for the first time. The alkaloids 2 and 3, both of which have a pentacyclic zwitterionic system, were more active than the reference inhibitor, allopurinol (IC50 = 11.1 µM) with IC50 values of 1.0 µM, and 2.5 µM, respectively. Structure-activity relationships analyses confirmed that the carbonyl group at C-14 was a key functional group responsible for the inhibitory effects of these alkaloids.

Development of a sequence-based in silico OspA typing method for Borrelia burgdorferi sensu lato.

Lyme disease (LD), caused by spirochete bacteria of the genus Borrelia burgdorferi sensu lato, remains the most common vector-borne disease in the northern hemisphere. Borrelia outer surface protein A (OspA) is an integral surface protein expressed during the tick cycle, and a validated vaccine target. There are at least 20 recognized Borrelia genospecies, that vary in OspA serotype. This study presents a new in silico sequence-based method for OspA typing using next-generation sequence data. Using a compiled database of over 400 Borrelia genomes encompassing the 4 most common disease-causing genospecies, we characterized OspA diversity in a manner that can accommodate existing and new OspA types and then defined boundaries for classification and assignment of OspA types based on the sequence similarity. To accommodate potential novel OspA types, we have developed a new nomenclature: OspA in silico type (IST). Beyond the ISTs that corresponded to existing OspA serotypes 1-8, we identified nine additional ISTs that cover new OspA variants in B. bavariensis (IST9-10), B. garinii (IST11-12), and other Borrelia genospecies (IST13-17). The IST typing scheme and associated OspA variants are available as part of the PubMLST Borrelia spp. database. Compared to traditional OspA serotyping methods, this new computational pipeline provides a more comprehensive and broadly applicable approach for characterization of OspA type and Borrelia genospecies to support vaccine development.

Preclinical validation of an Escherichia coli O-antigen glycoconjugate for the prevention of serotype O1 invasive disease.

A US collection of invasive Escherichia coli serotype O1 bloodstream infection (BSI) isolates were assessed for genotypic and phenotypic diversity as the basis for designing a broadly protective O-antigen vaccine. Eighty percent of the BSI isolate serotype O1 strains were genotypically ST95 O1:K1:H7. The carbohydrate repeat unit structure of the O1a subtype was conserved in the three strains tested representing core genome multi-locus sequence types (MLST) sequence types ST95, ST38, and ST59. A long-chain O1a CRM197 lattice glycoconjugate antigen was generated using oxidized polysaccharide and reductive amination chemistry. Two ST95 strains were investigated for use in opsonophagocytic assays (OPA) with immune sera from vaccinated animals and in murine lethal challenge models. Both strains were susceptible to OPA killing with O1a glycoconjugate post-immune sera. One of these, a neonatal sepsis strain, was found to be highly lethal in the murine challenge model for which virulence was shown to be dependent on the presence of the K1 capsule. Mice immunized with the O1a glycoconjugate were protected from challenges with this strain or a second, genotypically related, and similarly virulent neonatal isolate. This long-chain O1a CRM197 lattice glycoconjugate shows promise as a component of a multi-valent vaccine to prevent invasive E. coli infections. IMPORTANCE: The Escherichia coli serotype O1 O-antigen serogroup is a common cause of invasive bloodstream infections (BSI) in populations at risk such as newborns and the elderly. Sequencing of US BSI isolates and structural analysis of O polysaccharide antigens purified from strains that are representative of genotypic sub-groups confirmed the relevance of the O1a subtype as a vaccine antigen. O polysaccharide was purified from a strain engineered to produce long-chain O1a O-antigen and was chemically conjugated to CRM197 carrier protein. The resulting glycoconjugate elicited functional antibodies and was protective in mice against lethal challenges with virulent K1-encapsulated O1a isolates.

A new pregnane glycoside from Marsdenia tenacissima and its cytotoxic and NO inhibitory activities.

The Marsdenia tenacissima, has been used as traditional Chinese medicine for six hundred years. Our chemical investigation on the stem of Marsdenia tenacissima led to the isolation of one new pregnane glycoside, namely, marsdeoside J (compound 1) and twelve known compounds. The structure of the new compound was elucidated by spectroscopic analysis including 1D and 2D NMR, HRESIMS, IR, and UV. The absolute configurations of the sugar moiety were identified by comparing the specific optical rotations and Rf values with those of the commercially available standards and the data reported in the literature. Compound 1 showed cytotoxicities against five human cancer cell lines, with IC50 values ranging from 6.5 to 18.1 µM and certain inhibitory activities on NO production.

Autotrophic denitrification by sulfur-based immobilized electron donor for enhanced nitrogen removal: Denitrification performance, microbial interspecific interaction and functional traits.

Sulfur-driven autotrophic denitrification (SdAD) is a promising nitrogen removing process, but its applications were generally constrained by conventional electron donors (i.e., thiosulfate (Na2S2O3)) with high valence and limited bioavailability. Herein, an immobilized electron donor by loading elemental sulfur on the surface of polyurethane foam (PFSF) was developed, and its feasibility for SdAD was investigated. The denitrification efficiency of PFSF was 97.3%, higher than that of Na2S2O3 (91.1%). Functional microorganisms (i.e., Thiobacillus and Sulfurimonas) and their metabolic activities (i.e., nir and nor) were substantially enhanced by PFSF. PFSF resulted in the enrichment of sulfate-reducing bacteria, which can reduce sulfate (SO42-). It attenuated the inhibitory effect of SO42-, whereas the generated product (hydrogen sulfide) also served as an electron donor for SdAD. According to the economic evaluation, PFSF exhibited strong market potential. This study proposes an efficient and low-cost immobilized electron donor for SdAD and provides theoretical support to its practical applications.

A colorimetric and fluorescent probe of lignocellulose nanofiber composite modified with Rhodamine 6G derivative for reversible, selective and sensitive detection of metal ions in wastewater.

Heavy metal ions have extremely high toxicity. As the top of food chain, human beings certainly will accumulate them by ingesting food and participating other activities, which eventually result in the damage to our health. Therefore, it is very meaningful and necessary to design a simple, portable, stable and efficient material for heavy metal ions detection. Based on the spirolactam Rhodamine 6G (SRh6G) fluorescent probe, we prepared two types of nanocomposite materials (membrane and aerogel) by vacuum filtration and freeze-drying methods with lignocellulose nanofiber (CNF) as a carrier, polyvinyl alcohol (PVA) and glutaraldehyde (GA) as the cross-linkers. Then the microstructure, chemical composition, wetting property, fluorescence intensity and selectivity of as-prepared SRh6G/PVA/CNF would be characterized and analyzed. Results showed that SRh6G/PVA/CNF nanocomposites would turn red in color under strong acidic environment and produced orange fluorescence under ultraviolet light. Besides, they were also to detect Al3+, Cu2+, Hg2+, Fe3+ and Ag+ through color and fluorescence variations. We had further tested its sensitivity, selectivity, adsorption, fluorescence limits of detection (LOD) to Fe3+ and Cu2+. The test towards real water samples (hospital wastewater, Songhua River and tap water) proved that SRh6G/PVA/CNF nanocomposites could detect the polluted water with low concentrations of Fe3+ and Cu2+. In addition, SRh6G/PVA/CNF nanocomposites have excellent mechanical property, repeatability, superhydrophilicity and underwater superoleophobicity, which may offer a theoretical reference for the assembly strategy and detection application of cellulose-based fluorescent probe.

Termites can learn.

It is generally believed that termites can't learn and are not "intelligent". This study aimed to test whether termites could have any form of memory. A Y-shaped test device with one release chamber and two identical test chambers was designed and constructed by 3D printing. A colony of damp wood termites was harvested from the wild. Worker termites were randomly selected for experiment. Repellent odors that could mimic the alarm pheromone for termites were first identified. Among all substances tested, a tea tree oil and lemon juice were found to contain repellent odors for the tested termites, as they significantly reduced the time that termites spent in the chamber treated with these substances. As control, a trail pheromone was found to be attractive. Subsequently, a second cohort of termites were operant conditioned by punishment using both tea tree oil and lemon juice, and then tested for their ability to remember the path that could lead to the repellant odors. The test device was thoroughly cleaned between trials. It was found that conditioned termites displayed a reduced tendency to choose the path that led to expectant punishment as compared with naïve termites. Thus, it is concluded that damp wood termites are capable of learning and forming "fear memory", indicative of "intelligence" in termites. This result challenges established presumption about termites' intelligence.

Tibial cortex transverse transport promotes ischemic diabetic foot ulcer healing via enhanced angiogenesis and inflammation modulation in a novel rat model.

BACKGROUND: Tibial Cortex Transverse Transport (TTT) represents an innovative surgical method for treating lower extremity diabetic foot ulcers (DFUs), yet its underlying mechanisms remain elusive. Establishing an animal model that closely mirrors clinical scenarios is both critical and novel for elucidating the mechanisms of TTT. METHODS: We established a diabetic rat model with induced hindlimb ischemia to mimic the clinical manifestation of DFUs. TTT was applied using an external fixator for regulated bone movement. Treatment efficacy was evaluated through wound healing assessments, histological analyses, and immunohistochemical techniques to elucidate biological processes. RESULTS: The TTT group demonstrated expedited wound healing, improved skin tissue regeneration, and diminished inflammation relative to controls. Marked neovascularization and upregulation of angiogenic factors were observed, with the HIF-1α/SDF-1/CXCR4 pathway and an increase in EPCs being pivotal in these processes. A transition toward anti-inflammatory M2 macrophages indicated TTT's immunomodulatory capacity. CONCLUSION: Our innovative rat model effectively demonstrates the therapeutic potential of TTT in treating DFUs. We identified TTT's roles in promoting angiogenesis and modulating the immune system. This paves the way for further in-depth research and potential clinical applications to improve DFU management strategies.

Neuronal BST2: A Pruritic Mediator alongside Protease-Activated Receptor 2 in the IL-27-Driven Itch Pathway.

Chronic itch is a common and complex symptom often associated with skin diseases such as atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undefined. We sought to investigate IL-27 function in itch using tissue-specific transgenic mice, various itch models, behavior scoring, RNA sequencing, and cytokine/kinase array. Our findings show that IL-27 receptors were overexpressed in human AD skin. Intradermal IL-27 injection failed to directly induce itch in mice but upregulated skin protease-activated receptor 2 (PAR2) transcripts, a key factor in itch and AD. IL-27 activated human keratinocytes, increasing PAR2 transcription and activity. Coinjection of SLIGRL (PAR2 agonist) and IL-27 in mice heightened PAR2-mediated itch. In addition, IL-27 boosted BST2 transcription in sensory neurons and keratinocytes. BST2 was upregulated in AD skin, and its injection in mice induced itch-like response. BST2 colocalized with sensory nerve branches in AD skin from both human and murine models. Sensory neurons released BST2, and mice with sensory neuron-specific BST2 knockout displayed reduced itch responses. Overall, this study provides evidence that skin IL-27/PAR2 and neuronal IL-27/BST2 axes are implicated in cutaneous inflammation and pruritus. The discovery of neuronal BST2 in pruritus shed light on BST2 in the itch cascade.

Injectable Self-Healing Oxidized Starch/Gelatin Hybrid Hydrogel for Preventing Aseptic Loosening of Bone Tissue Engineering.

Aseptic loosening presents a formidable challenge within the realm of bone tissue engineering, playing a pivotal role in the occurrence of joint replacement failures. The development of therapeutic materials characterized by an optimal combination of mechanical properties and biocompatibility is imperative to ensure the enduring functionality of bone implants over extended periods. In this context, this study introduced an injectable, temperature-sensitive irisin/oxidized starch/gelatin hybrid hydrogel (I-OG) system. The hierarchical cross-linked structure endows the I-OG hydrogel with controlled and adjustable physical and chemical properties, making it easy to adapt to different clinical environments. This hydrogel exhibits satisfactory injectable properties, excellent biocompatibility, and good temperature sensitivity. The sol-gel point of the I-OG hydrogel, close to the body temperature, allows it to cushion the shaking of the implant and maintain an intact state during compression of bone tissue. Significantly, the I-OG hydrogel effectively filled the gap between the implant and bone tissue, successfully inhibiting aseptic loosening induced by titanium particles, a result that confirmed the slow release of the irisin protein from the gel. Collectively, the findings from this study strongly support the proposition that functional hydrogels, typified by the I-OG system, hold substantial promise as an accessible and efficient treatment strategy for mitigating aseptic loosening.

High-resolution mass spectrometry-based non-targeted metabolomics reveals toxicity of naphthalene on tall fescue and intrinsic molecular mechanisms.

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous at relatively high concentrations by atmospheric deposition, and they are threatening to the environment. In this study, the toxicity of naphthalene on tall fescue and its potential responding mechanism was first studied by integrating approaches. Tall fescue seedlings were exposed to 0, 20, and 100 mg L-1 naphthalene in a hydroponic environment for 9 days, and toxic effects were observed by the studies of general physiological studies, chlorophyll fluorescence, and root morphology. Additionally, Ultra Performance Liquid Chromatography - Electrospray Ionization - High-Resolution Mass Spectrometry (UPLC-ESI-HRMS) was used to depict metabolic profiles of tall fescue under different exposure durations of naphthalene, and the intrinsic molecular mechanism of tall fescue resistance to abiotic stresses. Tall fescue shoots were more sensitive to the toxicity of naphthalene than roots. Low-level exposure to naphthalene inhibited the electron transport from the oxygen-evolving complex (OEC) to D1 protein in tall fescue shoots but induced the growth of roots. Naphthalene induced metabolic change of tall fescue roots in 12 h, and tall fescue roots maintained the level of sphingolipids after long-term exposure to naphthalene, which may play important roles in plant resistance to abiotic stresses.