Analysis of alterations in serum vitamins and correlations with gut microbiome, microbial metabolomics in patients with sepsis.

BACKGROUND: Vitamins are essential micronutrients that play key roles in many biological pathways associated with sepsis. The gut microbiome plays a pivotal role in the progression of sepsis and may contribute to the onset of multi-organ dysfunction syndrome (MODS). The aim of this study was to investigate the changes in serum vitamins, and their correlation with intestinal flora and metabolomic profiles in patients with sepsis. METHODS: The serum levels of vitamins were determined by Ultra Performance Liquid Chromatography (UPLC). 16S rRNA gene sequencing and Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS) targeted metabolomics were used for microbiome and metabolome analysis. RESULTS: In the training cohort: After univariate, multivariate (OPLS-DA) and Spearman analyses, it was concluded that vitamin levels of 25 (OH) VD3 and (VD2 + VD3), as well as vitamins A and B9, differed significantly among healthy controls (HC), non-septic critical patients (NS), and sepsis patients (SS) (P < 0.05). The validation cohort confirmed the differential vitamin findings from the training cohort. Moreover, analyses of gut flora and metabolites in septic patients and healthy individuals revealed differential flora, metabolites, and metabolic pathways that were linked to alterations in serum vitamin levels. We found for the first time that vitamin B9 was negatively correlated with g_Sellimonas. CONCLUSION: Sepsis patients exhibited significantly lower levels of 25 (OH) VD3 and (VD2 + VD3), vitamins A and B9, which hold potential as predictive markers for sepsis prognosis. The changes in these vitamins may be associated with inflammatory factors, oxidative stress, and changes in gut flora.

Long Non-coding RNA DLEU1 Promotes Progression of Osteoarthritis via miR-492/TLR8 Axis.

BACKGROUND: Long non-coding RNAs (LncRNAs) are generally reported to participate in the development of Osteoarthritis (OA) by acting as competing endogenous RNAs (ceRNAs). However, the molecular mechanism is largely unknown. This study aimed to investigate the possible mechanisms contributing to osteoarthritis (OA). METHODS: Four gene expression profiles from patients with OA were downloaded from a public database and integrated to screen important RNAs associated with OA. Differentially expressed (DE) lncRNAs, microRNAs (miRNAs), and mRNAs were filtered, and a ceRNA network was constructed. An in vitro OA model was established by treating chondrocytes with IL-1ß. The expression levels of MMP-13, COL2A1, aggrecan, and RUNX2 were detected by qRT-PCR and western blot. Cell proliferation ability was detected by CCK-8 assay. Flow cytometry was used for apoptosis assay. A dual luciferase reporter gene was used to confirm the relationship between DLEU1, miR-492, and TLR8. RESULTS: An OA-related ceRNA network, including 11 pathways, 3 miRNAs, 7 lncRNAs, and 16 mRNAs, was constructed. DLEU1 and TLR8 were upregulated, and miR-492 was downregulated in IL-1ß-induced chondrocytes. Overexpression of DLEU1 suppressed viability and promoted apoptosis and extracellular matrix (ECM) degradation in IL-1ß induced chondrocytes. Luciferase reporter assay validated the regulatory relations among DLEU1, miR-492, and TLR8. Further study revealed that the effects of DLEU1 on chondrocytes could be reversed by miR-492. CONCLUSION: DLEU1 may be responsible for the viability, apoptosis, and ECM degradation in OA via miR-492/TLR8 axis.

Lineage-specific multifunctional double-layer scaffold accelerates the integrated regeneration of cartilage and subchondral bone.

Repairing cartilage/subchondral bone defects that involve subchondral bone is a major challenge in clinical practice. Overall, the integrated repair of the structure and function of the osteochondral (OC) unit is very important. Some studies have demonstrated that the differentiation of cartilage is significantly enhanced by reducing the intake of nutrients such as lipids. This study demonstrates that using starvation can effectively optimize the therapeutic effect of bone marrow mesenchymal stem cells (BMSCs)-derived extracellular vesicles (EVs). A hyaluronic acid (HA)-based hydrogel containing starved BMSCs-EVs displayed continuous release for more than 3 weeks and significantly promoted the proliferation and biosynthesis of chondrocytes around the defect regulated by the forkhead-box class O (FOXO) pathway. When combined with vascular inhibitors, the hydrogel inhibited cartilage hypertrophy and facilitated the regeneration of hyaline cartilage. A porous methacrylate gelatine (GelMA)-based hydrogel containing calcium salt loaded with thrombin rapidly promoted haematoma formation upon contact with the bone marrow cavity to quickly block the pores and prevent the blood vessels in the bone marrow cavity from invading the cartilage layer. Furthermore, the haematoma could be used as nutrients to accelerate bone survival. The in vivo experiments demonstrated that the multifunctional lineage-specific hydrogel promoted the integrated regeneration of cartilage/subchondral bone. Thus, this hydrogel may represent a new strategy for osteochondral regeneration and repair.

Gas-Sensitive Cellulosic Triboelectric Materials for Self-Powered Ammonia Sensing.

Gas-sensitive materials are capable of dynamic identification and content monitoring of specific gases in the environment, and their applications in the field of gas sensing are promising. However, weak adsorption properties are the main challenge limiting the application of gas-sensitive materials. A highly adsorbent gas-sensitive cellulose nanofibril (CNF)-based triboelectric material with a layered structure is prepared here and it is applied to self-powered gas sensing. The layered structure of the triethoxy-1H,1H,2H,2H-tridecafluoro-n-octylsilane cellulose nanofiber (PFOTES-CNF)-based gas-sensitive material further enhances the adsorption of the material due to electrostatic adsorption in the electrostatic field induced by triboelectricity. It is found that the ammonia-sensitive material obtained by loading Ti3 C2 Tx in PFOTES-CNF has a fast response/recovery (12/14 s), high sensitivity response (Vair /Vgas  = 2.1), high selectivity response (37.6%), and low detection limit (10 ppm) for 100 ppm of ammonia gas. In addition, the ammonia-sensitive CNF-based triboelectric material can accurately identify NH3 concentration changes in the range of 10-120 ppm and transmit the signal wirelessly to the user interface, facilitating real-time online monitoring of NH3 in the environment. A novel strategy is provided here for designing and preparing high-performance gas-sensitive composites and the analysis of self-powered gas sensing is guided.

Hierarchical Porous Cellulosic Triboelectric Materials for Extreme Environmental Conditions.

Synthetic polymer materials such as paraformaldehyde and polyamides are widely used in the field of energy engineering. However, they pose a challenge to environmental sustainability because they are derived from petrochemicals that are non-renewable and difficult to degrade in the natural environment. The development of high-performance natural alternatives is clearly emerging as a promising mitigation option. Inspired by natural bamboo, this research reports a "three-step" strategy for the large-scale production of triboelectric materials with special nanostructures from natural bamboo. Benefiting from the special hierarchical porous structure of the material, Bamboo/polyaniline triboelectric materials can reach short-circuit current of 2.9 µA and output power of 1.1 W m-2 at a working area of only 1 cm2 , which exceeds most wood fiber-based triboelectric materials. More importantly, it maintains 85% energy harvesting after an extreme environment of high temperature (200 °C), low temperature (-196 °C), combustion environment, and multiple thermal shocks (ΔT = 396 °C). This is unmatched by current synthetic polymer materials. This work provides new research ideas for the construction and application of biomass structural materials under extreme environmental conditions.

Spheres Multiple Physical Network-Based Triboelectric Materials for Self-Powered Contactless Sensing.

Non-contact mode triboelectric nanogenerators effectively avoid physical contact between two triboelectric materials and achieve long-term reliable operation, providing broad application prospects in the field of self-powered sensing. However, the low surface charge density of triboelectric materials restricts application of contactless sensing. Herein, by controlling Rayleigh Instability deformation of the spinning jet and vapor-induced phase separation during electrostatic spinning, a polyvinylidene fluoride@Mxene (Ti3 C2 Tx ) composite film with spheres multiple physical network structures is prepared and utilized as the triboelectric material of a self-powered contactless sensor. The structure of the composite film and high conductivity of Ti3 C2 Tx provide triboelectric materials with high output performance (charge output and power output up to 128 µC m-2 and 200 µW cm-2 at 2 Hz) and high output stability. The self-powered contactless sensor shows excellent speed sensitivity (1.175 Vs m-1 ). Additionally, it could accurately identify the motion states such as running (55 mV), jumping (105 mV), and walking (40 mV) within the range of 70 cm, and present the signals in different pop forms. This work lays a solid foundation for the development and application of high-performance triboelectric materials, and has guiding significance for the research of self-powered contactless sensing.

Risk factors for ankle valgus in children with hereditary multiple exostoses: a retrospective cross-sectional study.

PURPOSE: The aim of this study was to identify risk factors for ankle valgus in children with hereditary multiple exostoses (HME). METHODS: We retrospectively reviewed the medical records of patients with HME who were examined at our hospital between 2010 and 2020. Patients' age and sex were recorded along with radiographic variables including mechanical axis deviation (MAD), mechanical lateral distal tibia angle (LDTA), fibula/tibia length ratio (F/T); distal fibula station according to Malhotra's classification, location of exostoses at the ankle joint and fibular neck/physis width (N/P) ratio, which were measured from radiographs. Binary logistic regression analysis was performed to identify significant independent risk factors for ankle valgus. RESULTS: There were 61 children (20 girls and 41 boys; 122 ankles) who met the inclusion criteria. The mean age was 10.4 years (sd 3.4) and mean LDTA was 83° (sd 7°). Ankle valgus was found in 64 ankles (52%). In addition to younger age, exostoses involving the lateral aspects of the distal tibial and the medial aspect of the distal fibula (odds ratio (OR) = 4.091; 95% confidence interval (CI) 1.065 to 15.712; p = 0.040), F/T ratio < 0.96 (OR = 4.457; 95% CI 1.498 to 13.261; p = 0.007) and N/P ratio > 1.6 (OR = 2.855; 95% CI 1.031 to 7.907; p = 0.043) were associated with an increased risk of developing ankle valgus, while sex and MAD were unrelated to its occurrence. CONCLUSION: Young age, exostoses involving both the distal tibia and fibula, the F/T ratio < 0.96 and fibular N/P width ratio > 1.6 seemed to be risk factors of developing ankle valgus. LEVELS OF EVIDENCE: Prognostic studies, IV.

In vivo and in vitro characteristic of HIF-1α and relative genes in ischemic femoral head necrosis.

BACKGROUND: Legg-Calvé-Perthes Disease (Perthes' disease) is a childhood hip disorder initiated by ischemic necrosis of the growing femoral head. So far, the etiology and pathogenesis of Perthes' disease is poorly understood. MATERIALS AND METHODS: Avascular osteonecrosis rat model was established to mimic the pathophysiological changes of femoral head necrosis. The chondrocytes of newborn Sprague-Dawley rats were isolated and cultured in hypoxic and normoxic condition. The expression characteristic of the hypoxia-inducible factor-1 alpha (HIF-1α) was evaluated both in vivo and in vitro models. Vascular endothelial growth factor (VEGF) and apoptotic genes in chondrocytes treated with normoxia and hypoxia were also studied. RESULTS: HIF-1α expression increased greatly after ischemic operation and kept at relative high level in the arthromeningitis stage and declined in the stages of osteonecrosis and reconstruction. The HIF-1α mRNA levels of chondrocytes incubated at hypoxia were significantly higher than the cells treated with normoxia at 24 and 72 hours. Hypoxia inhibited VEGF expression; chondrocytes could oppose this inhibition manifested by the increasing of VEGF mRNA level after 72 hours hypoxia. The expression of apoptotic genes, Casp3, Casp8 and Casp9, elevated in chondrocytes after hypoxia with time differences. CONCLUSION: Hypoxia might be an etiological factor for femoral head necrosis, HIF-1α, VEGF as well as apoptotic genes participated the pathophysiological process of ischemic osteonecrosis.

Initial severity rating of idiopathic clubfeet is an outcome predictor at age two years.

This study was performed to determine if rating the severity of clubfeet before Ponseti treatment was predictive of the outcomes at age two years. Four hundred and seventy-nine idiopathic clubfeet (323 patients) were numerically rated for severity using Dimeglio classification. Eighty-six feet rated moderate, 305 feet rated severe, and 88 feet rated very severe. Outcomes were classified as Good (plantigrade foot with or without a tendoachilles lengthening), Fair (limited surgery), or Poor (posteromedial release). Significant correlation existed between initial severity of the foot and outcomes, with moderate better than severe and very severe, and severe better than very severe. Initial numerical severity rating strongly correlated with the probability of a good outcome (P<0.0001). Evaluating the severity of clubfeet before Ponseti treatment provides prognostic information for parents.

Dual function of ß-catenin in articular cartilage growth and degeneration at different stages of postnatal cartilage development.

PURPOSE: The objective of this study was to determine the role of ß-catenin in normal postnatal articular cartilage growth and degeneration. METHODS: We investigated ß-catenin gene and protein expression in hip cartilage cells of normal Wistar rats at two, four, six and eight weeks of age by using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Primary articular chondrocytes from eight week old rats were cultured and treated with LiCl for activation of ß-catenin. Collagen X and matrix metalloproteinase 13 (MMP-13) were detected by quantitative RT-PCR and immunofluorescence. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and 5 were detected by quantitative RT-PCR, and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) was used for detecting cell apoptosis. RESULTS: The highest levels of ß-catenin expressions were detected in two week old rats, after which a steady decline was observed over the remaining period of observation (p < 0.05). When primary articular chondrocytes from eight week old rats were treated with LiCl, ß-catenin mRNA and protein were induced (p < 0.05). Moreover, LiCl-activated ß-catenin in chondrocytes was associated with significant concomitant increases in mRNA expression of collagen X and the MMP-13 encoding collagenase 3. Significantly increased mRNA expression of ADAMTS-5 was also seen in primary chondrocytes from eight week old rats after LiCl treatment (p < 0.05). The effect was specific to ADAMTS-5 since ADAMTS-4, which has similar proteolytic activity but different aggrecanase activity, was unaffected. Finally, TUNEL staining revealed that LiCl-activated ß-catenin signalling led to increased cell apoptotic events in chondrocytes (p < 0.05). CONCLUSIONS: Our findings suggest that normal spatiotemporal patterns and degrees of Wnt/ß-catenin signalling are needed to maintain postnatal articular cartilage growth and function. In the early stages of cartilage development, activation of ß-catenin signalling is necessary for articular cartilage growth, while in adult cartilage it leads to degeneration and osteoarthritic-like chondrocytes.