A receptor required for chitin perception facilitates arbuscular mycorrhizal associations and distinguishes root symbiosis from immunity.

Plants establish symbiotic associations with arbuscular mycorrhizal fungi (AMF) to facilitate nutrient uptake, particularly in nutrient-limited conditions. This partnership is rooted in the plant's ability to recognize fungal signaling molecules, such as chitooligosaccharides (chitin) and lipo-chitooligosaccharides. In the legume Medicago truncatula, chitooligosaccharides trigger both symbiotic and immune responses via the same lysin-motif-receptor-like kinases (LysM-RLKs), notably CERK1 and LYR4. The nature of plant-fungal engagement is opposite according to the outcomes of immunity or symbiosis signaling, and as such, discrimination is necessary, which is challenged by the dual roles of CERK1/LYR4 in both processes. Here, we describe a LysM-RLK, LYK8, that is functionally redundant with CERK1 for mycorrhizal colonization but is not involved in chitooligosaccharides-induced immunity. Genetic mutation of both LYK8 and CERK1 blocks chitooligosaccharides-triggered symbiosis signaling, as well as mycorrhizal colonization, but shows no further impact on immunity signaling triggered by chitooligosaccharides, compared with the mutation of CERK1 alone. LYK8 interacts with CERK1 and forms a receptor complex that appears essential for chitooligosaccharides activation of symbiosis signaling, with the lyk8/cerk1 double mutant recapitulating the impact of mutations in the symbiosis signaling pathway. We conclude that this novel receptor complex allows chitooligosaccharides activation specifically of symbiosis signaling and helps the plant to differentiate between activation of these opposing signaling processes.

Neural mechanisms of different types of envy: a meta-analysis of activation likelihood estimation methods for brain imaging.

Previous studies have a lack of meta-analytic studies comparing the trait (personality) envy, social comparison envy, and love-envy, and the understanding of the similarities and differences in the neural mechanisms behind them is relatively unclear. A meta-analysis of activation likelihood estimates was conducted using 13 functional magnetic resonance imaging studies. Studies first used single meta-analyses to identify brain activation areas for the three envy types. Further, joint and comparative analyses were followed to assess the common and unique neural activities among the three envy types. A single meta-analysis showed that the critical brain regions activated by trait (personality) envy included the inferior frontal gyrus, cingulate gyrus, middle frontal gyrus, lentiform nucleus and so on. The critical brain regions activated by social comparison envy included the middle frontal gyrus, inferior frontal gyrus, medial frontal gyrus, precuneus and so on. The critical brain regions activated by love-envy included the inferior frontal gyrus, superior frontal gyrus, cingulate gyrus, insula and so on. In terms of the mechanisms that generate the three types of envy, each of them is unique when it comes to the perception of stimuli in a context; in terms of the emotion regulation mechanisms of envy, the three types of envy share very similar neural mechanisms. Both their generation and regulation mechanisms are largely consistent with the cognitive control model of emotion regulation. The results of the joint analysis showed that the brain areas co-activated by trait (personality) envy and social comparison envy were frontal sub-Gyral, inferior parietal lobule, inferior frontal gyrus, precuneus and so on; the brain areas co-activated by trait (personality) envy and love-envy were extra-nuclear lobule, lentiform nucleus, paracentral lobule, cingulate gyrus and so on; the brain regions that are co-activated by social comparison envy and love-envy are anterior cingulate gyrus, insula, supramarginal gyrus, inferior frontal gyrus and so on. The results of the comparative analysis showed no activation clusters in the comparisons of the three types of envy.

Hybrid chiral nanocellulose-cyanidin composite with pH and humidity response for visual inspection and real-time tracking of shrimp quality and freshness.

Biobased multi-stimulation materials have received considerable attention for intelligent packaging and anti-counterfeiting applications. Cellulose nanocrystals (CNCs) and cyanidins are good material candidates for monitoring food freshness as they are eco-friendly natural substances. This work incorporated cyanidin with a CNC-hosting substrate to develop a simple, environment-friendly colorimetric device to visualize food freshness. Across the pH range of 2-13, the indicator exhibited noticeable color changes ranging from red to gray and eventually to orange. The CNC-cyanidin (CC) film exhibited a dramatic color change from blue to dark red and high sensitivity at a relative humidity of 30 %-100 %. In corresponding to the total volatile elemental nitrogen (TVB-N) level of shrimp, the indicator showed distinguishable colors at different stages of shrimp. The findings imply that the samples have substantial potential for use as an intelligent indicator for tracking shrimp freshness.

Profiling CCR3 target pathways for discovering novel antagonists from natural products using label-free cell phenotypic assays.

CC chemokine receptor 3 (CCR3) plays important roles in atopic dermatitis (AD) and other related allergic diseases. Activation of CCR3 receptor signaling pathways regulates the recruitment of eosinophils to related tissues, releasing inflammatory mediators and causing inflammatory responses. However, none of the known CCR3 antagonists exhibit promising efficacy in clinical trials. In this work, we sought new natural CCR3 antagonists for drug development. To construct a high-throughput screening model, we established a stably transfected CHO-K1-Gα15-CCR3 cell line, and receptor expression was demonstrated by real-time quantitative PCR, confocal detection and flow cytometry analysis. Then, we applied a label-free cell phenotyping technique to profile and deconvolute CCR3 target pathways in CHO-K1-Gα15-CCR3 cells and found that activation of CCR3 triggered the Gq-PLC-Ca2+ and MAPK-P38-ERK pathways. By in vitro and in silico experiments, we discovered a novel CCR3 antagonist emodin, with an IC50 value of 27.28 ± 1.71 µM out of 266 compounds that were identified in 15 traditional Chinese medicines used in the clinical treatment of skin diseases. Molecular docking graphically presented the binding mode of emodin on CCR3. This work reports a new approach for CCR3 antagonist screening and pathway detection and identifies a new antagonist that would benefit future drug development.

Osteocytes Exposed to Titanium Particles Inhibit Osteoblastic Cell Differentiation via Connexin 43.

Periprosthetic osteolysis (PPO) induced by wear particles is the most severe complication of total joint replacement; however, the mechanism behind PPO remains elusive. Previous studies have shown that osteocytes play important roles in wear-particle-induced osteolysis. In this study, we investigated the effects of connexin 43 (Cx43) on the regulation of osteocyte-to-osteoblast differentiation. We established an in vivo murine model of calvarial osteolysis induced by titanium (Ti) particles. The osteolysis characteristic and osteogenesis markers in the osteocyte-selective Cx43 (CKO)-deficient and wild-type (WT) mice were observed. The calvarial osteolysis induced by Ti particles was partially attenuated in CKO mice. The expression of ß-catenin and osteogenesis markers increased significantly in CKO mice. In vitro, the osteocytic cell line MLO-Y4 was treated with Ti particles. The co-culturing of MLO-Y4 cells with MC3T3-E1 osteoblastic cells was used to observe the effects of Ti-treated osteocytes on osteoblast differentiation. When Cx43 of MLO-Y4 cells was silenced or overexpressed, ß-catenin was detected. Additionally, co-immunoprecipitation detection of Cx43 and ß-catenin binding in MLO-Y4 cells and MC3T3-E1 cells was performed. Finally, ß-catenin expression in MC3T3-E1 cells and osteoblast differentiation were evaluated after 18α-glycyrrhetinic acid (18α-GA) was used to block the intercellular communication of Cx43 between MLO-Y4 and MC3T3-E1 cells. Ti particles increased Cx43 expression and decreased ß-catenin expression in MLO-Y4 cells. The silencing of Cx43 increased the ß-catenin expression, and the over-expression of Cx43 decreased the ß-catenin expression. In the co-culture model, Ti treatment of MLO-Y4 cells inhibited the osteoblastic differentiation of MC3T3-E1 cells and Cx43 silencing in MLO-Y4 cells attenuated the inhibitory effects on osteoblastic differentiation. With Cx43 silencing in the MLO-Y4 cells, the MC3T3-E1 cells, co-cultured alongside MLO-Y4, displayed decreased Cx43 expression, increased ß-catenin expression, activation of Runx2, and promotion of osteoblastic differentiation in vitro co-culture. Finally, Cx43 expression was found to be negatively correlated to the activity of the Wnt signaling pathway, mostly through the Cx43 binding of ß-catenin from its translocation to the nucleus. The results of our study suggest that Ti particles increased Cx43 expression in osteocytes and that osteocytes may participate in the regulation of osteoblast function via the Cx43 during PPO.

Comparisons of gene expression between peripheral blood mononuclear cells and bone tissue in osteoporosis.

Osteoporosis (OP) is one of the major public health problems in the world. However, the biomarkers between the peripheral blood mononuclear cells (PBMs) and bone tissue for prognosis of OP have not been well characterized. This study aimed to explore the similarities and differences of the gene expression profiles between the PBMs and bone tissue and identify potential genes, transcription factors (TFs) and hub proteins involved in OP. The patients were enrolled as an experimental group, and healthy subjects served as normal controls. Human whole-genome expression chips were used to analyze gene expression profiles from PBMs and bone tissue. And the differentially expressed genes (DEGs) were subsequently studied using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. The above DEGs were constructed into protein-protein interaction network. Finally, TF-DEGs regulation networks were constructed. Microarray analysis revealed that 226 DEGs were identified between OP and normal controls in the PBMs, while 2295 DEGs were identified in the bone tissue. And 13 common DEGs were obtained by comparing the 2 tissues. The Gene Ontology analysis indicated that DEGs in the PBMs were more involved in immune response, while DEGs in bone were more involved in renal response and urea transmembrane transport. And the Kyoto Encyclopedia of Genes and Genomes analysis indicated almost all of the pathways in the PBMs were overlapped with those in the bone tissue. Furthermore, protein-protein interaction network presented 6 hub proteins: PI3K1, APP, GNB5, FPR2, GNG13, and PLCG1. APP has been found to be associated with OP. Finally, 5 key TFs were identified by TF-DEGs regulation networks analysis (CREB1, RUNX1, STAT3, CREBBP, and GLI1) and were supposed to be associated with OP. This study enhanced our understanding of the pathogenesis of OP. PI3K1, GNB5, FPR2, GNG13, and PLCG1 might be the potential targets of OP.

CARMA3 Deficiency Aggravates Angiotensin II-Induced Abdominal Aortic Aneurysm Development Interacting Between Endoplasmic Reticulum and Mitochondria.

BACKGROUND: Abdominal aortic aneurysm (AAA) is life threatening and associated with vascular walls' chronic inflammation. However, a detailed understanding of the underlying mechanisms is yet to be elucidated. CARMA3 assembles the CARMA3-BCL10-MALT1 (CBM) complex in inflammatory diseases and is proven to mediate angiotensin II (Ang II) response to inflammatory signals by modulating DNA damage-induced cell pyroptosis. In addition, interaction between endoplasmic reticulum (ER) stress and mitochondrial damage is one of the main causes of cell pyroptosis. METHODS: Male wild type (WT) or CARMA3-/- mice aged 8 to 10 weeks were subcutaneously implanted with osmotic minipumps, delivering saline or Ang II at the rate of 1 µg/kg/min for 1, 2, and 4 weeks. RESULTS: We discovered that CARMA3 knockout promoted formation of AAA and prominently increased diameter and severity of the mice abdominal aorta infused with Ang II. Moreover, a significant increase in the excretion of inflammatory cytokines, expression levels of matrix metalloproteinases (MMPs) and cell death was found in the aneurysmal aortic wall of CARMA3-/- mice infused with Ang II compared with WT mice. Further studies found that the degree of ER stress and mitochondrial damage in the abdominal aorta of CARMA3-/- mice was more severe than that in WT mice. Mechanistically, CARMA3 deficiency exacerbates the interaction between ER stress and mitochondrial damage by activating the p38MAPK pathway, ultimately contributing to the pyroptosis of vascular smooth muscle cells (VSMCs). CONCLUSIONS: CARMA3 appears to play a key role in AAA formation and might be a potential target for therapeutic interventions of AAA.

SOST gene suppression stimulates osteocyte Wnt/ß-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis.

The most common cause for prosthetic revision surgery is wear particle-induced periprosthetic osteolysis, which leads to aseptic loosening of the prosthesis. Both SOST gene and its synthetic protein, sclerostin, are hallmarks of osteocytes. According to our previous findings, blocking SOST induces bone formation and protects against bone loss and deformation caused by titanium (Ti) particles by activating the Wnt/ß-catenin cascade. Although SOST has been shown to influence osteoblasts, its ability to control wear-particle-induced osteolysis via targeting osteoclasts remains unclear. Mice were subjected to development of a cranial osteolysis model. Micro CT, HE staining, and TRAP staining were performed to evaluate bone loss in the mouse model. Bone marrow-derived monocyte-macrophages (BMMs) made from the C57BL/6 mice were exposed to the medium of MLO-Y4 (co-cultured with Ti particles) to transform them into osteoclasts. Bioinformatics methods were used to predict and validate the interaction among SOST, Wnt/ß-catenin, RANKL/OPG, TNF-α, and IL-6. Local bone density and bone volume improved after SOST inhibition, both the number of lysis pores and the rate of skull erosion decreased. Histological research showed that ß-catenin and OPG expression were markedly increased after SOST inhibition, whereas TRAP and RANKL levels were markedly decreased. In-vitro, Ti particle treatment elevated the expression of sclerostin, suppressed the expression of ß-catenin, and increased the RANKL/OPG ratio in the MLO-Y4 cell line. TNF-α and IL-6 also elevated after treatment with Ti particles. The expression levels of NFATc1, CTSK, and TRAP in osteoclasts were significantly increased, and the number of positive cells for TRAP staining was increased. Additionally, the volume of bone resorption increased at the same time. In contrast, when SOST expression was inhibited in the MLO-Y4 cell line, these effects produced by Ti particles were reversed. All the results strongly show that SOST inhibition triggered the osteocyte Wnt/ß-catenin signaling cascade and prevented wear particle-induced osteoclastogenesis, which might reduce periprosthetic osteolysis. KEY MESSAGES: SOST is a molecular regulator in maintaining bone homeostasis. SOST plays in regulating bone homeostasis through the Wnt/ß-catenin signaling pathway. SOST gene suppression stimulates osteocyte Wnt/ß-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis.

miR-449a ameliorates acute rejection after liver transplantation via targeting procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 in macrophages.

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.

Quantitative resilience assessment of the network-level metro rail service's responses to the COVID-19 pandemic.

The metro rail system has proven to be the most efficient high-capacity carriers. During the unprecedented coronavirus disease 2019 (COVID-19) challenge, non-pharmaceutical interventions become a widely adopted strategy to limit physical movements and interactions. For situational awareness and decision support, data-driven analytics about serviceability are invaluable to metro agencies and decision-makers of cities. This paper presents a data-driven analytical framework that quantitatively evaluates COVID-19-caused resilience performance of metro rails. Several characteristics (e.g., vulnerability, robustness, rapidity, and degree to return) of the metro system's responses to the disturbance were identified and modeled with multivariate multiple regression. The applicability and rationality of the resilience evaluation model were validated by the metro transit data of the United States. The preliminary results disclosed that metro rail transit encountered more vulnerability (90.6%) in passenger trips than motorbus and light rail (around 70%). A set of statistical models were employed to disentangle the effect of socio-demographic variables and COVID-19-related factors on the metro transit. The disclosed emerging knowledge of resilience provides an in-depth understanding of mobility trends for the public and time-sensitive decision support for the policy effects, to further improve the service and management of the metro system under the spread of the epidemic.

A quantitative traffic performance comparison study of bicycles and E-bikes at the non-signalized intersections: Evidence from survey data.

As common transportation modes at non-signalized intersections, bicycles and e-bikes have been involved in most traffic crashes. Although a large number of studies have been dedicated to studying the safety problems caused by bicycles and e-bikes, there is still limited attention paid to the differences between them, especially at non-signalized intersections. This paper compares the differences between bicycles and e-bikes based on a self-administered questionnaire. This questionnaire was distributed to bicycle users (N = 453) and e-bike users (N = 439). The personal characteristics, decision-making capacity, the feeling of infrastructure, perceived level of service, and perceived level of risk were adopted as the performance indicators to depict the difference in the study area. Using statistical methodologies and the Structural Equation Model (SEM), key findings indicate that perceived level of service was found to be significantly different between bicycles and e-bikes at most non-signalized intersections. 43.4 % of e-bike riders often or always choose to avoid riding under extreme weather, while 58.7 % of bicycle riders avoid riding under extreme weather. Moreover, compared with bicycles, e-bikes' decision-making capacity is affected more by infrastructure quality. The difference between bicycles and e-bikes highlights the need for differentiated development of cycling safety education and law enforcement.

Nutrient regulation of lipochitooligosaccharide recognition in plants via NSP1 and NSP2.

Many plants associate with arbuscular mycorrhizal fungi for nutrient acquisition, while legumes also associate with nitrogen-fixing rhizobial bacteria. Both associations rely on symbiosis signaling and here we show that cereals can perceive lipochitooligosaccharides (LCOs) for activation of symbiosis signaling, surprisingly including Nod factors produced by nitrogen-fixing bacteria. However, legumes show stringent perception of specifically decorated LCOs, that is absent in cereals. LCO perception in plants is activated by nutrient starvation, through transcriptional regulation of Nodulation Signaling Pathway (NSP)1 and NSP2. These transcription factors induce expression of an LCO receptor and act through the control of strigolactone biosynthesis and the karrikin-like receptor DWARF14-LIKE. We conclude that LCO production and perception is coordinately regulated by nutrient starvation to promote engagement with mycorrhizal fungi. Our work has implications for the use of both mycorrhizal and rhizobial associations for sustainable productivity in cereals.

Overexpressed DDX3x promotes abdominal aortic aneurysm formation and activates AKT in ApoE knockout mice.

In recent years, abdominal aortic aneurysm (AAA) lesions have become one of the important diseases that threaten public health. Related studies have confirmed that the occurrence of abdominal aortic aneurysms is related to inflammatory stress, cell apoptosis, and elastic fiber degradation. DDX3x is thought to interact with inflammasomes such as NLRP3 to aggravate the process of the inflammatory response, but its role in the occurrence of AAA remains unclear. Since DDX3x is indispensable in animal embryonic growth, we used an adeno-associated virus to construct gene-overexpressing mice to induce aneurysm development through AngII infusion. The results indicated that the incidence of aneurysms, inflammatory cell infiltration, vascular smooth muscle cell transformation, and oxidative stress levels were significantly increased under the condition of DDX3x overexpression. At the signaling level, activation of the AKT pathway exacerbates aneurysm formation. Taken together, we believe that DDX3x plays a key role in the development of aneurysms and may be a new target for the treatment of aneurysm progression.

Arbuscular mycorrhizal fungi induce lateral root development in angiosperms via a conserved set of MAMP receptors.

Root systems regulate their branching patterns in response to environmental stimuli. Lateral root development in both monocotyledons and dicotyledons is enhanced in response to inoculation with arbuscular mycorrhizal (AM) fungi, which has been interpreted as a developmental response to specific, symbiosis-activating chitinaceous signals. Here, we report that generic instead of symbiosis-specific, chitin-derived molecules trigger lateral root formation. We demonstrate that this developmental response requires the well-known microbe-associated molecular pattern (MAMP) receptor, Chitin Elicitor Receptor Kinase 1 (CERK1), in rice, Medicago truncatula, and Lotus japonicus, as well as the non-host of AM fungi, Arabidopsis thaliana, lending further support for a broadly conserved signal transduction mechanism across angiosperms. Using rice mutants impaired in strigolactone biosynthesis and signaling, we show that strigolactone signaling is necessary to regulate this developmental response. Rice CERK1 operates together with either Chitin Elicitor Binding Protein (CEBiP) or Nod Factor Receptor 5 (NFR5) in immunity and symbiosis signaling, respectively; for the lateral root response, however, all three LysM receptors are required. Our work, therefore, reveals an overlooked but a conserved role of LysM receptors integrating MAMP perception with developmental responses in plants, an ability that might influence the interaction between roots and the rhizosphere biota.

The allosteric gating mechanism of the MthK channel.

Allostery is a fundamental element during channel gating in response to an appropriate stimulus by which events occurring at one site are transmitted to distal sites to regulate activity. To address how binding of the first Ca2+ ion at one of the eight chemically identical subunits facilitates the other Ca2+-binding events in MthK, a Ca2+-gated K+ channel containing a conserved ligand-binding RCK domain, we analysed a large collection of MthK structures and performed the corresponding thermodynamic and electrophysiological measurements. These structural and functional studies led us to conclude that the conformations of the Ca2+-binding sites alternate between two quaternary states and exhibit significant differences in Ca2+ affinity. We further propose an allosteric model of the MthK-gating mechanism by which a cascade of structural events connect the initial Ca2+-binding to the final changes of the ring structure that open the ion-conduction pore. This mechanical model reveals the exquisite design that achieves the allosteric gating and could be of general relevance for the action of other ligand-gated ion channels containing the RCK domain.

miR-505-5p alleviates acute rejection of liver transplantation by inhibiting Myd88 and inducing M2 polarizationof Kupffer cells.

The occurrence of acute rejection after liver transplantation seriously impairs the prognosis of patients. miRNA is involved in many physiological and pathological processes of the body, but the mechanism of miRNA action in liver transplantation is not completely clear. In this study, we discuss the role of miR-505-5p in acute rejection after liver transplantation and its putative regulating mechanism. We construct an allogeneic rat liver transplantation model, observe the morphological and pathological changes in liver tissue, detect the expression levels of Myd88, miR-505-5p, IL-10 and TNF-α, and confirm that Myd88 is one of the direct targets of miR-505. The effects of miR-505-5p on the Myd88/TRAF6/NF-κB and MAPK pathways are detected both in vitro and in vivo, and the standard markers of Kupffer cell M1/M2 polarization are also detected. The results of qRT-PCR experiments show that miR-505-5p has a downward trend in rats with acute rejection. Western blot analysis reveals that over-expression of miR-505-5p induces the reduction of NF-κB and MAPK pathways both in vitro and in vivo. The role of miR-505-5p in alleviating acute rejection after transplantation may be accomplished by inducing M2-type polarization of Kupffer cells. In conclusion, we find that miR-505-5p alleviates acute rejection of liver transplantation by inducing M2 polarization of macrophages via the Myd88/TRAF6 axis, which suggests a potential strategy based on miRNAs in the follow-up treatment of liver transplantation.

Salidroside alleviates hepatic ischemia-reperfusion injury during liver transplant in rat through regulating TLR-4/NF-κB/NLRP3 inflammatory pathway.

Salidroside has anti-inflammatory, antioxidant and hepatoprotective properties. However, its effect on hepatic ischemia-reperfusion injury (IRI), an unavoidable side effect associated with liver transplantation, remains undefined. Here, we aimed to determine whether salidroside alleviates hepatic IRI and elucidate its potential mechanisms. We used both in vivo and in vitro assays to assess the effect and mechanisms of salidroside on hepatic IRI. Hepatic IRI rat models were pretreated with salidroside (5, 10 or 20 mg/kg/day) for 7 days following liver transplantation while hypoxia/reoxygenation (H/R) model of RAW 264.7 macrophages were pretreated with salidroside (1, 10 or 50 µM). The effect of salidroside on hepatic IRI was assessed using hematoxylin-eosin staining, terminal deoxynucleotidyl transferase dUTP nick-end labeling staining, qRT-PCR, immunosorbent assay and western blotting. Our in vivo assays showed that salidroside significantly reduced pathological liver damage, serum aminotransferase levels and serum levels of IL-1, IL-18 and TNF-α. Besides, salidroside reduced the expression of TLR-4/NF-κB/NLRP3 inflammatory pathway associated proteins (TLR-4, MyD88, p-IKKα, p-IKKß, p-IKK, p-IκBα, p-P65, NLRP3, ASC, Cleaved caspase-1, IL-1ß, IL-18, TNF-α and IL-6) in rats after liver transplantation. On the other hand, data from the in vitro analysis demonstrated that salidroside blocks expression of TLR-4/NF-κB/NLRP3 inflammatory pathway related proteins in the RAW264.7 cells treated with H/R. The salidroside-specific anti-inflammatory effects were partially inhibited by the TLR-4 agonist lipopolysaccharide. Taken together, our study showed that salidroside inhibits hepatic IRI following liver transplantation by modulating the TLR-4/NF-κB/NLRP3 inflammatory pathway.

Osteocytic cells exposed to titanium particles increase sclerostin expression and inhibit osteoblastic cell differentiation mostly via direct cell-to-cell contact.

The mechanism underlying induction of periprosthetic osteolysis by wear particles remains unclear. In this study, cultured MLO-Y4 osteocytic cells were exposed to different concentrations of titanium (Ti) particles. The results showed that Ti particles increased expression of the osteocytic marker SOST/sclerostin in a dose-dependent manner, accelerated apoptosis of MLO-Y4 cells, increased the expression of IL-6, TNF-α and connexin 43. SOST silence alleviated the increase of MLO-Y4 cells apoptosis, decreased the expression of IL-6, TNF-α and connexin 43 caused by Ti particles. The different co-culture systems of MLO-Y4 cells with MC3T3-E1 osteoblastic cells were further used to observe the effects of osteocytic cells' changes induced by Ti particles on osteoblastic cells. MLO-Y4 cells treated with Ti particles inhibited dramatically differentiation of MC3T3-E1 cells mostly through direct cell-to-cell contact. SOST silence attenuated the inhibition effects of Ti-induced MLO-Y4 on MC3T3-E1 osteoblastic differentiation, which ALP level and mineralization of MC3T3-E1 cells increased and the expression of ALP, OCN and Runx2 increased compared to the Ti-treated group. Taken together, Ti particles had negative effects on MLO-Y4 cells and the impact of Ti particles on osteocytic cells was extensive, which may further inhibit osteoblastic differentiation mostly through intercellular contact directly. SOST/sclerostin plays an important role in the process of mutual cell interaction. These findings may help to understand the effect of osteocytes in wear particle-induced osteolysis.

Hemodynamic analysis of intermittent pneumatic compression combined with hyperthermia after total hip arthroplasty: an experiment on male rabbits.

OBJECTIVE: To investigate the effect of intermittent pneumatic compression combined with hyperthermia (IPCH) on the hemodynamic changes in lower limbs of male rabbits and to clarify whether its efficacy is superior to that of intermittent pneumatic compression (IPC) or hyperthermia (HT) alone. METHODS: Thirty male adult New Zealand white rabbits with a body mass of 2.6±0.3 kg were obtained to establish a model of postoperative hypercoagulable state by simulating left hip surgery. Then they were randomly divided into HT group, IPC group, and IPCH group. Relevant hemodynamic parameters were examined by color Doppler ultrasound before and after treatment. A femoral vein finite element model was established according to fluid mechanics to analyze the blood flow velocity distribution vector, total deformation, equivalent stress of the femoral vein and venous valve. RESULTS: The heart rate, blood flow per minute, and mean and peak blood velocity of the femoral vein in IPCH group were significantly higher than those in HT and IPC groups (P<0.05). There was no significant difference in venous diameter (P>0.05). The blood flow velocity distribution vector, the total deformation of femoral vein, and the equivalent stress between femoral vein and venous valve in the IPCH group were higher than those in HT and IPC groups, but the total deformation of venous valve was smaller in IPCH group. CONCLUSIONS: IPCH superimposes the effects of IPC and HT, and can more effectively promote changes in local blood circulation to prevent deep vein thrombosis.

Decreased preoperative urinary uromodulin as a predictor of acute kidney injury and perioperative kidney dysfunction in patients undergoing cardiac surgery: A prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a major complication following cardiac surgery that substantially increases mortality. We explored the clinical utility of urinary uromodulin (uUMOD), a marker of renal tubular reserve, for preoperative identification of patients at risk for AKI and perioperative kidney dysfunction. METHODS: This prospective observational study included patients who underwent cardiac surgery between December 2019 and January 2021. AKI was defined according to the Kidney Disease Improving Global Outcomes criteria; perioperative kidney dysfunction was accessed using a longitudinal estimated glomerular filtration rate. RESULTS: A total of 409 participants were enrolled. Patients with uUMOD ≤ 20.7 µg/mL were associated with a higher risk for AKI (odds ratio, 3.24; 95% confidence interval: 1.87-5.63, P < 0.001), independent of baseline kidney function. The uUMOD exhibits adequate discrimination for predicting AKI, with an area under the receiver operating characteristic curve of 0.713 (95% confidence interval: 0.652-0.773), and has well-fitted calibration (Hosmer-Lemeshow goodness-of-fit test, P = 0.163). The trajectory analysis revealed that decreased uUMOD levels were linked to a higher risk of patients being assigned to a worse perioperative kidney function cluster. CONCLUSIONS: Decreased preoperative uUMOD is independently associated with an increased risk of AKI and perioperative kidney dysfunction after cardiac surgery.