The transmembrane and cytosolic domains of equine herpesvirus type 1 glycoprotein D determine Golgi retention by regulating vesicle formation.

Accumulating evidence underscores the pivotal role of envelope proteins in viral secondary envelopment. However, the intricate molecular mechanisms governing this phenomenon remain elusive. To shed light on these mechanisms, we investigated a Golgi-retained gD of EHV-1 (gDEHV-1), distinguishing it from its counterparts in Herpes Simplex Virus-1 (HSV-1) and Pseudorabies Virus (PRV). To unravel the specific sequences responsible for the Golgi retention phenotype, we employed a gene truncation and replacement strategy. The results suggested that Golgi retention signals in gDEHV-1 exhibiting a multi-domain character. The extracellular domain of gDEHV-1 was identified as an endoplasmic reticulum (ER)-resident domain, the transmembrane domain and cytoplasmic tail (TM-CT) of gDEHV-1 were integral in facilitating the protein's residence within the Golgi complex. Deletion or replacement of either of these dual domains consistently resulted in the mutant gDEHV-1 being retained in an ER-like structure. Moreover, (TM-CT)EHV-1 demonstrated a preference for binding to endomembranes, inducing the generation of a substantial number of vesicles, potentially originate from the Golgi complex or the ER-Golgi intermediate compartment. In conclusion, our findings provide insights into the intricate molecular mechanisms governing the Golgi retention of gDEHV-1, facilitating the comprehension of the processes underlying viral secondary envelopment.

In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway.

Four new series of curcumin derivatives bearing NO-donating moiety were synthesized via etherification, nucleophilic substitution, and Knoevenagel condensation etc. The cytotoxicity activity of curcumin derivatives against five human tumor cell lines (A549, Hela, HepG2, MCF-7 and HT-29) and two normal cell lines (LO-2 and HK-2) has been studied. The results showed that compound 6a could inhibit the proliferation of MCF-7 cells remarkably and exhibit low toxicity to normal cells. Also, the underlying mechanism in vitro of compound 6a on MCF-7 was investigated. It has been found that compound 6a induced G2/M arrest and apoptosis of MCF-7 in a dose-dependent manner. Compound 6a-induced the fluorescence changes of ROS in MCF-7 cells confirmed the occurrence of apoptosis. Western Blot suggested that compound 6a decreased the expression of PI3K, as well as increased the expression of p53, cleaved caspase-9 and cleaved caspase-3. Furthermore, molecular docking revealed that compound 6a could bind well at active site of PI3K (3zim) with total score 9.59. Together, compound 6a, a potential PI3K inhibitor, may inhibit the survival of MCF-7 cells via interfering with PI3K/Akt/p53 pathway.

Influences of Early Rehabilitation Nursing on Motor Function, Swallowing Function as Well as Quality of Life in Stroke Patients.

Background: Stroke is a major cause of long-term disability in adults. Routine nursing mainly meets the life needs of patients through the intervention of patients' general life but only provides the most basic services for patients, which makes it difficult to meet the requirements of patients' physical exercise and other aspects, affecting the prognosis. Early rehabilitation after a stroke is important for the recovery of bodily functions in stroke patients. However, the impacts of early rehabilitation nursing on motor function, swallowing function as well as quality of life in stroke patients remain to be further explored. Objective: To investigate the effects of early rehabilitation nursing on motor function, swallowing function as well as quality of life in stroke patients. Design: This was a randomized, single-blind, controlled experiment. Setting: This study was carried out in the neurology department at Xuzhou Central Hospital. Participants: A total of 116 acute stroke patients validated by craniocerebral computed tomography (CT) and magnetic resonance imaging (MRI) from January 2021 to December 2022 were chosen and separated into the control group (n=58) and research group (n=58) following the random number method. Interventions: The control group was given routine nursing. The research group implemented early rehabilitation nursing 24 hours after admission on the basis of the control group. Primary Outcome Measures: (1) recovery of swallowing dysfunction (2) recovery of limb function (3) self-care ability (4) sleep quality (5) quality of life and (6) total satisfaction of patients. Results: The research group had an elevated total effective rate of swallowing dysfunction recovery in contrast to the control group after nursing (P < .05). The recovery of limb function, self-care ability, sleep quality, and quality of life were promoted in both groups, followed by nursing (P < .05), and those in the research group were higher relative to the control group (P < .05). The total satisfaction of patients in the research group presented higher relative to the control group (P < .05). Conclusion: The application effect of early rehabilitation nursing in acute stroke patients is outstanding, and the swallowing dysfunction and limb dysfunction of patients can be effectively improved, which has a high nursing value and is worth promoting and applying. Therefore, an early physical rehabilitation program for acute stroke inpatients should be considered for implementation in clinical settings.

Lycium barbarum polysaccharides regulate the gut microbiota to modulate metabolites in high-fat diet-induced obese rats.

Lycium Barbarum Polysaccharides (LBP) can benefit lipid parameters such as total cholesterol, triglyceride, and high-density lipoprotein levels and upregulate the level of Firmicutes, increase the diversity of gut microbiota and reduce metabolic disorders, finally relieving weight gain of obese rats. But it cannot reverse the outcome of obesity. Over 30 differential metabolites and four pathways are altered by LBP.

Preventative effect of TSPO ligands on mixed antibody-mediated rejection through a Mitochondria-mediated metabolic disorder.

BACKGROUND: Immune-mediated rejection was the major cause of graft dysfunction. Although the advances in immunosuppressive agents have markedly reduced the incidence of T-cell-mediated rejection after transplantation. However, the incidence of antibody-mediated rejection (AMR) remains high. Donor-specific antibodies (DSAs) were considered the major mediators of allograft loss. Previously, we showed that treatment with 18-kDa translocator protein (TSPO) ligands inhibited the differentiation and effector functions of T cells and reduced the rejection observed after allogeneic skin transplantation in mice. This study we further investigate the effect of TSPO ligands on B cells and DSAs production in the recipients of mixed-AMR model. METHODS: In vitro, we explored the effect of treatment with TSPO ligands on the activation, proliferation, and antibody production of B cells. Further, we established a heart-transplantation mixed-AMR model in rats. This model was treated with the TSPO ligands, FGIN1-27 or Ro5-4864, to investigate the role of ligands in preventing transplant rejection and DSAs production in vivo. As TSPO was the mitochondrial membrane transporters, we then investigated the TSPO ligands effect on mitochondrial-related metabolic ability of B cells as well as expression of downstream proteins. RESULTS: In vitro studies, treatment with TSPO ligands inhibited the differentiation of B cells into CD138+CD27+ plasma cells; reduced antibodies, IgG and IgM, secretion of B cells; and suppressed the B cell activation and proliferation. In the mixed-AMR rat model, treatment with FGIN1-27 or Ro5-4864 attenuated DSA-mediated cardiac-allograft injury, prolonged graft survival, and reduced the numbers of B cells, including IgG+ secreting B cells, T cells and macrophages infiltrating in grafts. For the further mechanism exploration, treatment with TSPO ligands inhibited the metabolic ability of B cells by downregulating expression of pyruvate dehydrogenase kinase 1 and proteins in complexes I, II, and IV of the electron transport chain. CONCLUSIONS: We clarified the mechanism of action of TSPO ligands on B-cell functions and provided new ideas and drug targets for the clinical treatment of postoperative AMR.

MiR-155-5p Aggravated Astrocyte Activation and Glial Scarring in a Spinal Cord Injury Model by Inhibiting Ndfip1 Expression and PTEN Nuclear Translocation.

Central nervous injury and regeneration repair have always been a hot and difficult scientific questions in neuroscience, such as spinal cord injury (SCI) caused by a traffic accident, fall injury, and war. After SCI, astrocytes further migrate to the injured area and form dense glial scar through proliferation, which not only limits the infiltration of inflammatory cells but also affects axon regeneration. We aim to explore the effect and underlying mechanism of miR-155-5p overexpression promoted astrocyte activation and glial scarring in an SCI model. MiR-155-5p mimic (50 or 100 nm) was used to transfect CTX-TNA2 rat brain primary astrocyte cell line. MiR-155-5p antagonist and miR-155-5p agomir were performed to treat SCI rats. MiR-155-5p mimic dose-dependently promoted astrocyte proliferation, and inhibited cell apoptosis. MiR-155-5p overexpression inhibited nuclear PTEN expression by targeting Nedd4 family interacting protein 1 (Ndfip1). Ndfip1 overexpression reversed astrocyte activation which was induced by miR-155-5p mimic. Meanwhile, Ndfip1 overexpression abolished the inhibition effect of miR-155-5p mimic on PTEN nuclear translocation. In vivo, miR-155-5p silencing improved SCI rat locomotor function and promoted astrocyte activation and glial scar formation. And miR-155-5p overexpression showed the opposite results. MiR-155-5p aggravated astrocyte activation and glial scarring in a SCI model by targeting Ndfip1 expression and inhibiting PTEN nuclear translocation. These findings have ramifications for the development of miRNAs as SCI therapeutics.

Surface/interfacial transport through pores control desalination mechanisms in 2D carbon-based membranes.

The shortage of freshwater is a critical concern for contemporary society, and reverse osmosis desalination technology has gathered considerable attention as a potential solution to this problem. It has been recognized that the desalination process involving water flow through angstrom-sized pores has tremendous potential. However, it is challenging to obtain angstrom-sized pore structures with internal mass transfer and surface/interface properties matching the application conditions. Herein, a two-dimensional (2D) zeolite-like carbon structure (Carzeo-ANG) was constructed with unique angstrom-sized pores in the zeolite structure; then, the surface/interfacial transport behavior and percolation effect of the Carzeo-ANG desalination membrane were evaluated by density functional theory (DFT) calculations and classical molecular dynamics. The first-principles calculations in density functional theory were implemented through the Vienna ab initio simulation package (VASP), which is a commercial package for the simulation of carbon-based materials. The results show that Carzeo-ANG is periodically distributed with angstrom-sized pores (effective diameter = 5.4 Å) of dodecacyclic carbon rings, which ensure structural stability while maintaining sufficient mechanical strength. The remarkable salt-ion adsorption properties and mass transfer activity combined with the reasonable density distribution and free energy barrier for water molecules endow the membrane with superior desalination ability. At the pressure of 80 MPa, the rejection efficiency of Cl- and Na+ were 100% and 96.25%, and the membrane could achieve a water flux of 132.71 L cm-2 day-1 MPa-1. Moreover, the interconnected electronic structure of Carzeo-ANG imparts a self-cleaning effect.

Insight into the Fe atom-FeS cluster synergistic catalysis mechanism for the oxygen evolution reaction in NiS2-based electrocatalysts.

The development of highly active oxygen evolution reaction (OER) catalysts with fast kinetics is crucial for the advancement of clean energy and fuel conversion to achieve a sustainable energy future. Recently, the synergistic effect of single-atom doping and multicomponent clusters has been demonstrated to significantly improve the catalytic activity of materials. However, such synergistic effects involving multi-electron and proton transfer processes are quite complex and many crucial mechanistic details need be well comprehended. We ingeniously propose a catalyst, (Fed-FeSc)@NiS2 (d stands for doping and c stands for clustering), with Fe and FeS acting synergistically on a NiS2 substrate. Specifically, fully dynamic monitoring of multiple active sites at the (Fed-FeSc)@NiS2 interface using metadynamics is innovatively performed. The results show that the rate determining step value at the overpotential of 1.23 V for the synergistic (Fed-FeSc)@NiS2 is 1.55 V, decreased by 6.67% and 35.29% compared to those of the independently acting single-atom doping and multi-clusters. The unique synergistic structure dramatically increases the d-band centre of the Fe site (-1.45 eV), endowing (Fed-FeSc)@NiS2 with more activity than conventional commercial Ir-C catalysts. This study provides insights into the synergistic effects of single-atom doping and multi-component clusters, leading to exploratory inspiration for the design of highly efficient OER catalysts.

Metabolomics analysis of the serum metabolic signature of nonalcoholic fatty liver disease combined with prediabetes model rats after the intervention of Lycium barbarum polysaccharides combined with aerobic activity.

Metabolic disorders accompany nonalcoholic fatty liver disease (NAFLD), associated with prediabetes. Lycium barbarum polysaccharides (LBP) seem to be a potential prebiotic, and aerobic exercise has shown protective effects on NAFLD with prediabetes. However, their combined effects on NAFLD and prediabetes remain unclear. This study investigated the effects of LBP and aerobic exercise alone, and their combined effects on the metabolomics of serum, and explored the potential mechanisms utilizing a high-fat diet-induced rat model of NAFLD and prediabetes. It provided the metabolic basis for the pathogenesis and early diagnosis of prediabetes complicated with NAFLD. Untargeted metabolomics profiling was performed using ultra-high-performance liquid chromatography coupled with quadrupole Orbitrap mass spectrometry to analyze the changes in overall metabolites in each group of samples. An orthogonal partial least squares-discriminant analysis model with variable importance on projection >1 and p < 0.05 were used as the screening criteria to screen the significant differential metabolites and analyze the expression changes and functional pathways. Different intervention treatments showed clear discrimination by univariate and multivariate analyses. The model group had a high relative level of expression of lipids. Comparison between the two groups showed steroids with high expression after LBP and aerobic exercise treatment separately and alkaloids and fatty acyls with high expression after aerobic exercise and the combination intervention, respectively. Comparison of the five groups showed some of the metabolites to be differently expressed after the intervention improved lipid and fatty acid metabolism. The three types of intervention had sound effects on the changes in liver index for the diseases studied. Furthermore, the combination treatment may be a better choice for disease prevention and treatment than a single treatment. Our analysis of metabolomics confirmed that the different treatments had significant regulatory effects on the metabolic pathways. Our findings strongly support the possibility that aerobic exercise combined with LBP can be regarded as a potential therapeutic method for NAFLD in prediabetics.

Multi-omics data reveals the disturbance of glycerophospholipid metabolism and linoleic acid metabolism caused by disordered gut microbiota in PM2.5 gastrointestinal exposed rats.

The relationships between fine particulate matter (PM2.5) exposure and health effects are complex and incompletely understood. Evidence suggests that PM2.5 exposure alters gut microbiota composition and metabolites, but the connections between these changes remain unclear. The aim of our study was to investigate how gut microbiota are involved in the systemic metabolic changes following PM2.5 gastrointestinal exposure. We used multi-omics approaches, including 16S rRNA sequencing and serum metabolomics, to identify alterations in gut microbes and metabolites of PM2.5-exposed rats. We then explored correlations between perturbed gut microbiota and metabolic changes, and conducted pathway analyses to determine critical metabolic pathways impacted by PM2.5 exposure. To verify links between gut microbiome and metabolome disruptions, we performed fecal microbiota transplantation (FMT) experiment. A total of 30 differential gut microbe taxa were identified between PM2.5 and control groups, primarily in Firmicutes, Acidobacteria, and Proteobacteria phyla. We also identified 30 differential metabolites, including glycerophospholipids, fatty acyls, amino acids and others. Pathway analysis revealed disruptions in glycerophospholipid metabolism, steroid hormone biosynthesis, and linoleic acid metabolism. Through FMT, we confirmed PM2.5 altered phosphatidylcholine and linoleic acid metabolism by changing specific gut bacteria. Our results suggest that PM2.5 gastrointestinal exposure triggers systemic metabolic changes by disrupting the gut microbiome, especially glycerophospholipid and linoleic acid metabolism pathways.

Toward the efficient direct regeneration of spent cathode materials through the effect of residual sodium ions analysis.

Recycling spent lithium-ion batteries is an important means for promoting sustainability within the energy industry. In this study, the effects of residual sodium on the regeneration process and the performance of spent LiNi0.5Co0.2Mn0.3O2 were explored. An appropriate amount of residual sodium was found to improve the properties of the regenerated material, with the best cycle performance and rate performance at a residual sodium of 3 mol %. The first-cycle and 100-cycle discharge capacities were 136.4 mA h g-1 and 120 mA h g-1, respectively, with a capacity retention rate of 87.98% after 100 cycles at a rate of 1 C. The electrochemical performance of the regenerated cathode materials was improved because sodium occupied the lithium sites in the crystal structure, providing a channel for lithium deintercalation. These results indicate that the residual sodium ions should be monitored in appropriate quantities to improve the efficiency of recycling spent lithium-ion batteries.

Amblyseius orientalis shows high consumption and reproduction on Polyphagotarsonemus latus in China.

The broad mite, Polyphagotarsonemus latus (Banks) (Acari: Tarsonemidae), is a cosmopolitan pest that infests many greenhouse crops. Biological control is an important way to control P. latus, with predatory mites being the most widely used natural enemies of this pest. The purpose of this study is to evaluate the capabilities of three native phytoseiids in China (Neoseiulus californicus, Neoseiulus barkeri and Amblyseius orientalis) in controlling P. latus, using Amblyseius swirskii as a control, a commercial biocontrol agent of this pest widely used in Europe. Consumption, development, and reproduction of the four species when fed with P. latus were assessed, and their life table parameters were estimated and compared. Among the three native species, A. orientalis has the highest consumption rate of P. latus (29.0 per day), the shortest developmental duration (5.3 days), and the highest cumulative fecundity (13.5 eggs/female). Overall, its intrinsic rate of increase (rm) is 0.12, comparable to that of A. swirskii. Among the three candidates, A. orientalis is the only one whose population increase might be expected when fed with P. latus. Therefore, we propose A. orientalis to be a potential biocontrol agent for this pest in China.

Comparison of percutaneous endoscopic and open posterior lumbar interbody fusion for the treatment of single-segmental lumbar degenerative diseases.

BACKGROUND: Endoscopic lumbar interbody fusion has become an emerging technique. Some researchers have reported the technique of percutaneous endoscopic transforaminal lumbar interbody fusion. We propose percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) as an alternative approach. The purpose of this study was to assess the clinical efficacy of PE-PLIF by comparing percutaneous endoscopic and open posterior lumbar interbody fusion (PLIF). METHODS: Thirty patients were enrolled in each group. Demographic data, perioperative data, and radiological parameters were collected prospectively. The clinical outcomes were evaluated by visual analog scale (VAS) and Oswestry Disability Index (ODI) scores. RESULTS: The background data were comparable between the two groups. The mean operation time was longer in the PE-PLIF group. The PE-PLIF group showed benefits in less blood loss and shorter hospital stay. VAS and ODI scores significantly improved in both groups. However, the VAS score of low-back pain was lower in the PE-PLIF group. The satisfaction rate was 96.7% in both groups. The radiological outcomes were similar in both groups. In the PE-PLIF group, the fusion rate was 93.3%, and the cage subsidence rate was 6.7%; in the open PLIF group, the fusion and cage subsidence rates were 96.7% and 16.7%. There were minor complications in one patient in the PE-PLIF group and two in the open PLIF group. CONCLUSIONS: The current study revealed that PE-PLIF is safe and effective compared with open PLIF. In addition, this minimally invasive technique may enhance postoperative recovery by reducing tissue damage and blood loss.

Mori fructus aqueous extracts attenuate carbon tetrachloride-induced renal injury via the Nrf2 pathway and intestinal flora.

Mori fructus aqueous extracts (MFAEs) have been used as a traditional Chinese medicine for thousands of years with the function of strengthening the liver and tonifying the kidney. However, its inner mechanism to alleviative renal injury is unclear. To investigate the attenuation of MFAEs on nephrotoxicity and uncover its potential molecular mechanism, we established a nephrotoxicity model induced by carbon tetrachloride (CCl4). The mice were randomly divided into control group, CCl4 model group (10% CCl4), CCl4 + low and high MFAEs groups (10% CCl4 + 100 mg/kg and 200 mg/kg MFAEs). We found that MFAEs decreased the kidney index of mice, restored the pathological changes of renal structure induced by CCl4, reduced cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (Kim-1) blood urea nitrogen and creatinine contents in serum, promoted the nuclear transportation of Nrf2 (nuclear factor erythroid derived 2 like 2), elevated the expression of HO-1 (heme oxygenase 1), GPX4 (glutathione peroxidase 4), SLC7A11 (solute carrier family 7 member 11), ZO-1 (zonula occludens-1) and Occludin, suppressed the expression of Keap1 (kelch-like ECH-associated protein 1), HMGB1 (High Mobility Group Protein 1), ACSL4 (acyl-CoA synthetase long chain family member 4) and TXNIP (thioredoxin interacting protein), upregulated the flora of Akkermansia, Anaerotruncus, Clostridium_sensu_stricto, Ihubacter, Alcaligenes, Dysosmobacter, and downregulated the flora of Clostridium_XlVa, Helicobacter, Paramuribaculum. Overlapped with Disbiome database, Clostridium_XlVa, Akkermansia and Anaerotruncus may be the potential genera treated with renal injury. It indicated that MFAEs could ameliorate kidney injury caused by CCl4 via Nrf2 signaling.

Effects of different frequencies of Er:YAG laser on the bonding properties of zirconia ceramic.

The effects of Er:YAG laser with different frequencies on zirconia ceramic's bonding properties were studied. In total, 42 Y-TZP (yttrium-stabilized tetragonal zirconia polycrystals, UPCERA ST) with 3 mm × 3 mm × 2 mm divided into 6 groups (n = 7): control (C), sandblasting (SB), and Er:YAG laser (A1-A4), which the frequencies correspond to 5 Hz, 10 Hz, 15 Hz, and 20 Hz, IPS e.max Press ceramics were B. Scanning electron microscope (SEM) images were recorded. The ceramics were bonded to enamel from extracted teeth. After being constantly stored at 37 ℃ for 24 h, the shear test was performed with a universal testing machine. Stereomicroscope evaluated fracture modes. Stereomicroscope evaluated fracture modes. Data were analyzed by SPSS26.0 statistical software; the standard was P = 0.05. (1) The SEM showed the surface of A1-A4 became rough compared with C. (2) The shear test showed that the highest bonding strength for B was 13.15 ± 2.97 MPa, followed by SB was 7.78 ± 0.97 MPa, and A2 was 7.13 ± 0.75 MPa. However, there was no significant difference between SB and A2 (P > 0.05). Fracture modes of C were the interface fracture of Y-TZP and resin adhesive; most of A1-A4 and SB also were interface fracture, a few mixed fractures, and cohesion fracture of resin adhesive; B were all mixed fracture. Er:YAG laser with 10 Hz could be used as an alternative to sandblasting with Al2O3 for surface modification of Y-TZP to increase the bonding strength.

Increased glycolysis in skeletal muscle coordinates with adipose tissue in systemic metabolic homeostasis.

Insulin-independent glucose metabolism, including anaerobic glycolysis that is promoted in resistance training, plays critical roles in glucose disposal and systemic metabolic regulation. However, the underlying mechanisms are not completely understood. In this study, through genetically manipulating the glycolytic process by overexpressing human glucose transporter 1 (GLUT1), hexokinase 2 (HK2) and 6-phosphofructo-2-kinase-fructose-2,6-biphosphatase 3 (PFKFB3) in mouse skeletal muscle, we examined the impact of enhanced glycolysis in metabolic homeostasis. Enhanced glycolysis in skeletal muscle promoted accelerated glucose disposal, a lean phenotype and a high metabolic rate in mice despite attenuated lipid metabolism in muscle, even under High-Fat diet (HFD). Further study revealed that the glucose metabolite sensor carbohydrate-response element-binding protein (ChREBP) was activated in the highly glycolytic muscle and stimulated the elevation of plasma fibroblast growth factor 21 (FGF21), possibly mediating enhanced lipid oxidation in adipose tissue and contributing to a systemic effect. PFKFB3 was critically involved in promoting the glucose-sensing mechanism in myocytes. Thus, a high level of glycolysis in skeletal muscle may be intrinsically coupled to distal lipid metabolism through intracellular glucose sensing. This study provides novel insights for the benefit of resistance training and for manipulating insulin-independent glucose metabolism.

NMR spectroscopy based metabolomics confirms the aggravation of metabolic disorder in metabolic syndrome combined with hyperuricemia.

BACKGROUND AND AIMS: Hyperuricemia (HUA) were associated with Metabolic syndrome (MetS) and its components. However, the molecular mechanism of uric acid in the development of MetS was not well elucidated. The aim of this study was developing a systemic metabolic profile by using metabolomics approach to explore the molecular mechanism of uric acid in the development of MetS. METHODS AND RESULTS: Anthropometric, clinical biochemical data, and serum samples were collected from patients with MetS, MetS combined with HUA (MetS & HUA) and healthy controls. 1H nuclear magnetic resonance (NMR) spectroscopy was used to detect endogenous small molecule metabolites of serum samples, then multivariate statistical analysis was applied to distinguish samples of different groups. In addition, pathway analysis was performed to contribute to understanding the metabolic change. By serum metabolic profiling, a total of 20 identified metabolites including lipids, amino acids, and organic acids were significantly altered in MetS and MetS & HUA patients. MetS & HUA patients presented a more severe disorder in both identified metabolites and BMI and biochemical indexes. According to pathway analysis, there were 3 and 5 metabolic pathways remarkably perturbed in MetS and MetS & HUA group respectively. CONCLUSION: Taken together, we identified disordered metabolites and related pathways for both MetS and MetS & HUA patients, and found a more severe metabolic disorder in MetS patients who has a higher serum uric acid. Our study provides biochemical insights into the metabolic alteration for the progress of MetS.

Percutaneous endoscopic posterior lumbar interbody fusion for the treatment of degenerative lumbar diseases: a technical note and summary of the initial clinical outcomes.

BACKGROUND: Percutaneous endoscopic lumbar interbody fusion was a new technique that leads to improved visualization, improved safety and less trauma than does the traditional procedure. The purpose of this study was to introduce the technique of percutaneous endoscopic posterior lumbar interbody fusion (PE-PLIF) and determine its efficacy. METHODS: 35 patients with an average age of 52.3±13.7 years were treated with single-segment PE-PLIF. The perioperative parameters and the radiographic parameters were measured. The visual analog scale (VAS) score for low back pain, VAS score for leg pain and Oswestry disability index (ODI) score were used to assess the levels of pain and function. RESULTS: The mean estimated volume of blood loss was 68.6±32.3 ml, operative time was 179.6±31.0 minutes. PE-PLIF significantly reduced the VAS score for low back pain, VAS score for leg pain and ODI score, and improved the posterior disc height, lumbar lordosis angle and segmental lordosis angle (p < 0.05). The rate of satisfaction was 94.3%. One patient suffered a dural tear. There was one case of contralateral radiculopathy that was relieved after conservative treatment. CONCLUSIONS: This research suggests that PE-PLIF is a minimally invasive, safe, and effective treatment for degenerative lumbar diseases requiring interbody fusion.

Noninvasive quantification of intrarenal allograft C4d deposition with targeted ultrasound imaging.

Antibody-mediated rejection (AMR) has emerged as a major cause of renal allograft dysfunction. C4d, a specific marker for AMR diagnosis, was strongly recommended for routine surveillance; however, currently, C4d detection is dependent upon tissue biopsy, which is invasive and provides only local semi-quantitative data. Targeted ultrasound imaging has been used extensively for noninvasive and real-time molecular detection with advantages of high specificity and sensitivity. In this study, we designed C4d-targeted microbubbles (MBC4d ) using a streptavidin-biotin conjugated method and detected C4d deposition in vivo in a rat model of AMR by enhanced ultrasound imaging. This noninvasive procedure allowed successful acquisition of the first qualitative image of C4d deposition in a wide renal allograft section, which reflected real-time C4d distribution in grafts. Moreover, we introduced normal intensity difference for quantitative analysis, which exhibited a nearly linear correlation with the grade of C4d deposition according to pathologic analysis. In addition, this approach showed no influence on survival rates and pathologic features in the microbubble injection groups, thereby demonstrating its safety. These findings demonstrated a simple, noninvasive, quantitative, and safe evaluation method for C4d, with the utility of this approach potentially preventing patients from having to undergo an invasive biopsy.

A Novel Hypothesis on Excessive Activation of Residual B Lymphocytes in Common Variable Immunodeficiency Concurrent with Aseptic, Erosive Polyarthritis.

The aim of this study was to report aseptic, erosive polyarthritis in a patient with common variable immunodeficiency (CVID), which is quite different from the vastly more common nonerosive form. Peripheral blood mononuclear cells of the patient were isolated. Flow cytometry was used to analyze the proportion and function of lymphocytes. A Parker-Pearson needle biopsy was performed on the right knee. Four of her unaffected family members were enrolled as controls. A 21-year-old woman was admitted for recurrent polyarthritis of 3-year duration. The right knee, hip, wrist, proximal interphalangeal joints, and left elbow were involved, with progressive joint destruction. She was diagnosed as having CVID based on her recurrent infections, poor response to vaccines, and marked hypogammaglobulinemia. No bacterium or mycobacterium was detected in synovium or synovial fluid. The synovium was infiltrated by lymphocytes rather than neutrophils. Polyarthritis did not resolve by adequate intravenous immunoglobulin substitution and empirical antibiotic treatment, but resolved gradually after treatment with methylprednisolone and tacrolimus, supporting the diagnosis of aseptic polyarthritis. Further analyses showed that although only 0.5% of residual B lymphocytes were existent in peripheral blood of the patient, expressions of activation marker CD69 and production of IL-1ß, IL-6, and TNF-α were high. Marked infiltration with CD19+B lymphocytes (as well as CD4+ or CD8+ T lymphocytes) was detected in the synovium. The proportion of IL21+CD4+Th cells from peripheral blood of the patient was high. CD4+ Th cells from the patient secreted nearly 3 times more IL-21 than the same cell type analyzed from unaffected family members, perhaps due to excessive compensation to assist the function of residual B lymphocytes. A novel hypothesis in CVID concurrent with aseptic, erosive polyarthritis is that excessive activation of residual B lymphocytes infiltrate into the synovium of the involved joints and lead to polyarthritis and joint destruction.