Characterization of an EPS-producing bifidobacterial strain based on integration of phenotypic and complete genome sequencing data.

Bifidobacterium and Lactobacillus are known to be common members of the human intestinal microbiota, which play important roles in maintaining the homeostasis of host gut microenvironment. Several bifidobacterial and lactobacilli strains have been used as probiotics for health benefits. The exopolysaccharides (EPSs) produced by strains from Bifidobacterium and Lactobacillus are considered as beneficial traits mediating these beneficial effects. In this study, 21 strains belonging to Bifidobacterium and Lactobacillus were isolated from healthy infants' stool and were screened for EPS-producing ability. Among these strains, Bifidobacterium longum XZM1 showed the highest EPS productivity, which was further confirmed and characterized. The complete genome of strain XZM1 was sequenced, which revealed the presence of a gene cluster for EPS production. Furthermore, comparative genome analysis was performed among XZM1 and other strains from B. longum species. Following purification, the molecular weight (Mw) of EPS from XZM1 was determined as 4023 Da (Mw) through gel permeation chromatography. Analysis of the EPS hydrolysates revealed that the EPS was composed of mannose, glucose, galactose, arabinose, and fucose. Additionally, the EPS exhibited higher scavenging abilities toward hydroxyl than 1,1-diphenyl-2-picrylhydrazyl free radical. Overall, these results suggest that XZM1 from B. longum species may be a promising probiotic candidate.

Identification of common pathway and hub genes in the degeneration of both annulus fibrosus and nucleus pulposus in intervertebral disc.

PURPOSE: This study aimed to identify the common pathways and hub genes related to oxidative stress (OS) and autophagy of both annulus fibrosus (AF) and nucleus pulposus (NP) in intervertebral disc degeneration (IDD) based on the data obtained from the Gene Expression Omnibus (GEO) database. METHODS: The Gene expression data for human intervertebral discs was obtained from the GEO database, including the AF and NP of both non-degenerated disc and degenerated disc. The differentially expressed genes (DEGs) were identified using the limma package in R language. DEGs related to OS and autophagy were obtained using Gene Ontology (GO) database. Analyses of the GO, signaling pathways, protein-protein interaction (PPI) networks, and hub genes were performed using AnnotationDbi package, DAVID, GSEA, STRING database, and Cytoscape software, respectively. Finally, the online tool of NetworkAnalyst and the Drug Signatures database (DSigDB) were used to screen for transcriptional factors and potential drugs of the hub genes. RESULTS: There were 908 genes associated with OS and autophagy found. A total of 52 DEGs were identified, included five upregulated and 47 downregulated genes. These DEGs were mainly involved in mTOR signaling pathway and the NOD-like receptor signaling pathway. The top 10 hub genes were CAT, GAPDH, PRDX1, PRDX4, TLR4, GPX7, GPX8, MSRA, RPTOR, GABARAPL1. Besides, FOXC1, PPARG, RUNX2, JUN, and YY1 were identified as the key regulatory factors of hub genes. L-cysteine, oleanolic acid, and berberine were potential therapeutic agents for the treatment of IDD. CONCLUSIONS: Common hub genes, signaling pathways, transcription factors, and potential drugs associated with OS and autophagy were identified, which provides significant basis for further mechanism research and drug screening of IDD.

Reliability and Validity Analysis of Pelvic Sagittal Inclination Calculated by Inverse Cosine Function Method on Pelvic Anteroposterior Radiographs.

OBJECTIVE: Evaluation of sagittal pelvic tilt is significant for hip surgeons. However, the accurate measurement of pelvic sagittal inclination (PSI) is still a challenge. The objective of this study is to propose a new method for measurement of PSI from pelvic anteroposterior radiograph based on the inverse cosine function obtained from individualized pelvic model. METHODS: Collecting the imaging data of 30 patients with both pelvic CT and full-length spine radiographs. Establishing pelvic model by customized 3D reconstruction software. The length of three groups of longitudinal and transverse line segments (A'p and B') were measured from full-length spine anteroposterior radiographs. The corresponding anatomical parameters, including A, B, b, ∠α, ∠γ, were measured and calculated on the same patient's pelvic model. The estimated PSI (ePSI) based on three groups of anatomical landmarks, including ePSI-1, ePSI-2, and ePSI-3, were calculated by equation, ePSI = arccos A ' p b * B ' - ∠ α , and compared with the actual PSI (aPSI) measured by Surgamap software. For the reliability and validation evaluation, three observers measured these parameters in two rounds. Intra-class correlation and inter-class correlation were both calculated. Bland-Altman method was used to evaluate the consistency between the estimated PSI (ePSI) and the actual PSI (aPSI). RESULTS: ePSI-1 and ePSI-2 showed excellent intra-observer reliability (0.921-0.997, p < 0.001) and inter-observer reliability (0.801-0.977, p < 0.001). ePSI-3 had a fair inter-observer reliability (0.239-0.823, p < 0.001). ePSI-1 showed the strongest correlation with aPSI (r = 0.917, p < 0.001). Mean (maximum) absolute difference of ePSI-1, ePSI-2, and ePSI-3 is 2.62° (7.42°), 4.23° (13.78°), and 7.74° (31.47°), respectively. The proportion of cases with absolute difference less than 5° in three groups were 86.7% (ePSI-1), 66.7% (ePSI-2), 56.7% (ePSI-3). CONCLUSION: This new method based on inverse cosine function has good reliability and validity when used in the evaluation of PSI on pelvic anteroposterior radiographs.

A tyrosine catabolic intermediate 4-hydroxyphenylpyruate attenuates murine endotoxic shock by blocking NLRP3 inflammasome activation.

The metabolic alterations of amino acid metabolism are closely associated with inflammatory response. However, relatively little is known about the roles of phenylalanine (Phe)/tyrosine (Tyr) catabolites during inflammation. Nitisinone (NTBC) is an orphan drug used to treat hereditary tyrosinemia type I potentially by changing Phe/Tyr metabolic flow. In this study, we used NTBC as a tool to investigate the potential role of the Phe/Tyr catabolic pathway in inflammatory responses. We found that NTBC was effective in tempering the bacterial endotoxin lipopolysaccharide (LPS)-induced septic shock in mice. Mechanistically, the protective effect was related to the accumulation of a Phe/Tyr catabolic intermediate, 4-hydroxyphenylpyruvate (4-HPP), induced by the NTBC treatment. 4-HPP could inhibit NLRP3 inflammasome priming and activation processes and therefore reduce IL-1ß release and pyroptosis. Like NTBC, 4-HPP was also effective in attenuating endotoxic shock in mice. Our results suggest the Phe/Tyr catabolic pathway as a potential immunoregulatory hub that may be exploited therapeutically to alleviate inflammation.

Anti-Apoptosis and Autophagy Effects of Melatonin Protect Rat Chondrocytes against Oxidative Stress via Regulation of AMPK/Foxo3 Pathways.

OBJECTIVE: Emerging evidence has indicated that excessive reactive oxygen species (ROS) have detrimental effects on osteoarthritis (OA). This study aimed to elucidate the effects of melatonin (MT), an antioxidant indolamine secreted from the pineal gland, on chondrocyte senescence and cartilage degeneration, thereby clarifying the underlying mechanisms of ROS-induced OA pathogenesis. DESIGN: Hydrogen peroxide (H2O2) was used to induce oxidative stress in rat chondrocytes. ROS levels were evaluated using cytometry and immunofluorescence. Cell viability was detected using the Cell Counting Kit-8 (CCK-8) assay. Western blotting and qPCR (Quantiative Real-Time Polymerase Chain Reaction) were used to examine apoptosis and autophagy. For in vivo experiments, male Sprague-Dawley rats were randomly divided into a sham-operated group, DMM (destabilization of the medial meniscus) surgery group, and surgery groups that received melatonin. Knee joints were collected and stained for histological analysis. RESULTS: The data demonstrated that melatonin treatment significantly suppressed H2O2-induced matrix degradation and apoptosis, and maintained mitochondrial redox homeostasis. In addition, an enhancement of autophagic flux was observed through western blotting. These findings corresponded with activation of the AMPK/Foxo3 signaling pathways upon melatonin treatment. Histological staining and transmission electron microscopy (TEM) micrographs also demonstrated that melatonin alleviated cartilage ossification and chondrocyte hypertrophy in vivo. CONCLUSIONS: Our results indicated that melatonin protected chondrocytes via mitochondrial redox homeostasis and autophagy. The effects of melatonin on senescence may apply to other age-related diseases. Thus, melatonin may have multiple potential therapeutic applications.

Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy.

BACKGROUND: Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. RESULTS: The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment. CONCLUSIONS: By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited.

Simulation Analysis of Limit Operating Specifications for Onshore Spoolable Reinforced Thermoplastic Pipes.

Spoolable reinforced plastic line pipes (RTPs), exhibiting a series of advantages such as good flexibility, few joints, long single length, light weight, easy installation, etc., have been widely used in the onshore oil and gas industry such as oil and gas gathering and transportation, high pressure alcohol injection, water injection, sewage treatment, and other fields. However, due to the lack of clear standard specificationof the limit operating properties for RTPs, three typical failure modes, i.e., tensile, flexure, and torsion, frequently occur in terrain changes, construction operation, and subsequent application, which seriously affects the promotion and use of RTPs. In this paper, the stress distribution of a non-bonded polyester fiber reinforced high-density polyethylene (HDPE) pipe (DN 150, PN 2.5 MPa) was systematically studied by the finite element method (FEM), and then the limit operating values under the axial tensile, coiled bending, and torsion load were determined. The corresponding experiments were conducted to validate the reliability and accuracy of the FEM model. The FEM results showed that the critical strain for axial tensile was 3%, the minimum respooling bend radius was 1016.286 mm, and the limit torsion angle of this RTP was 58.77°, which are very close to the experimental results. These limit values will be useful to establish normative guidelines for field construction and failure prevention of onshore RTP.

Subdural fluid collection rather than meningitis contributes to hydrocephalus after cervical laminoplasty: A case report.

BACKGROUND: Hydrocephalus following dural tear after spinal surgery is rare. Although a few cases of obstructive hydrocephalus caused by subdural fluid collection and communicating hydrocephalus associated with meningitis have been reported, the mechanism remains uncertain. Herein we describe a patient complicated with hydrocephalus after cervical laminoplasty in whom subdural fluid collection in the cervical spine and posterior cranial fossa rather than chronic meningitis was the main mechanism. CASE SUMMARY: A 45-year-old man underwent cervical laminoplasty for cervical spondylotic myelopathy at a local hospital. Ten days postoperatively, a high fever occurred and magnetic resonance imaging (MRI) showed cerebrospinal fluid (CSF) leakage. Pseudomeningocele liquid test showed high levels of protein and white blood cell (WBC) count with negative bacterial culture. The patient was treated with short-term intravenous antibiotic and discharged with normal body temperature. The patient was uneventful during the first 8 mo follow-up although repeated MRI showed persistent pseudomeningocele. At the 9th mo postoperatively, the patient gradually presented with dizziness and headache accompanied by recurrent weakness of his left arm. Imaging examinations demonstrated hydrocephalus and a cystic lesion around the cervical spinal cord. CSF test from lumbar puncture indicated chronic meningitis. MRI on 1 d after pseudomeningocele drainage showed a significant decrease in the cystic volume, suggesting that the cystic lesion would be subdural fluid collection rather than adhesive arachnoiditis. After dural defect repair, the patient's symptoms completely resolved and hydrocephalus gradually disappeared. CSF analysis at the 21-mo follow-up revealed significantly decreased protein level and WBC count. CONCLUSION: Subdural fluid collection rather than meningitis contributes to the hydrocephalus formation after cervical laminoplasty.

Credit contingent interest rate swap pricing.

Credit value adjustment (CVA) is an adjustment to an existing trading price based on the counterparty-risk premium. Currently, CVA is computed with an implicit assumption that the replacement contract is default-free after the original counterparty defaults, with the assumption that those trades will not re-assigned. In the actual counterparty default settlement, it is the norm that trades will be re-assigned, especially on the buy side. Since the counterparty of the replacement contract could also default within the lifetime of an existing contract, ignoring the possibility of counterparty defaults of replacement contracts will either under or over estimate the cost of the risk. An important practical question is, therefore, how to estimate under/over pricing of CVA under current practice. In this paper, we considered the pricing of credit contingent interest rate swap (CCIRS) or credit contingent default swap (CCDS), which is considered the CVA hedge for interest rate swaps (IRS). We derived partial differential Eqs. (PDEs) satisfied by the approximated CVA with the assumption that the replacement contracts do not default. For comparison purposes, we also derived the PDEs for the cost of CVA by relaxing the assumption of default-free replacement contracts with a finite number of counterparty defaults. It shows that the no-default and two default cases can be derived within the same analytical solution framework, similar to the Funding Valuation Adjustment (FVA) problem where continuous funding is a reasonable assumption. The finite number of default case is non-trivial. The PDE for the two default case is derived in this paper. We calibrate our model based on market data and carry out extensive computations for the purpose of comparing these three CVAs. Our basic finding is that the values of the two CVAs are close for top rated counterparties. On the other hand, for counterparties with lower credit ratings, the difference among the two CVAs can be significant.