Klebsiella pneumoniae-caused liver abscess (KLA) is an emerging infectious disease. However, factors other than K1-specific loci that contribute to the pathogenesis of this disease have not been identified. pLVPK is a 219,385-bp plasmid of K. pneumoniae CG43, an invasive K2 strain associated with KLA. We aimed in this study to evaluate the involvement of pLVPK in K. pneumoniae virulence and its clinical significance in abscess formation. A pLVPK-cured CG43 was isolated and its virulence was examined in a mouse model. The prevalence of pLVPK-derived loci terW, iutA, rmpA, silS, and repA was investigated in 207 clinical isolates by screening with specific primers. Loss of pLVPK abolished the ability of K. pneumoniae to disseminate into extraintestinal sites and, consequently, attenuated abscess formation in mice. Primary K. pneumoniae abscess isolates (n = 94) were more likely to be terW (+)-iutA (+)-rmpA (+)-silS (+) than those related to non-abscess infections (n = 113) (62% vs. 27%; p < 0.0001). Logistic regression analysis indicated that the presence of the terW-rmpA-iutA-silS loci was a significant risk factor (odds ratio, 4.12; 95% confidence interval, 2.02-8.4; p < 0.0001) for abscess formation. pLVPK is a determinant for K. pneumoniae virulence and infection with strains carrying the pLVPK-derived terW-rmpA-iutA-silS loci may predispose patients to abscess formation.

Incorporating two-dimensional (2D) graphene sheets into a 3D graphene structure provides porous structures to bind enzyme but with low enzyme affinity and unstable structure because of removal of the surficial functional group and the flexibility of graphene sheets. To address this issue, we herein constructed a 3D porous Ti3C2T x MXene–graphene (MG) hybrid film through a facile mixing–drying process. Ti3C2T x MXene nanosheets (MNS) with hydrophilic groups on the rigid flakes endowed the MG hybrid film with open porous structure and a highly hydrophilic miroenvironment. By simply controlling the content of Ti3C2T x MNS and graphene sheets, the sizes of the internal pores were accordingly tunable. The 3D porous hybrid film, fabricated from Ti3C2T x MNS and graphene sheets (weight ratios of 1:2 abd 1:3), supplied more open structure to facilitate the glucose oxidase (GOx) entering the internal pores, which probably enhanced the stable immobilization and retaining of the GOx in the film. As a result, the as-proposed biosensor exhibited prominent electrochemical catalytic capability toward glucose biosensing, which was finally applied for glucose assay in sera. The preparation of the size-controlled 3D porous hybrid film provided a method for effectively binding enzymes/protein further to develop elegant biosensors.

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Chronic low back pain (CLBP), lasting >3 months, is the end result of multiple pathogenic factors. Unfortunately, little is known about CLBP pathogenesis, which limits its advancements in clinical therapy and disease management. This paper summarizes the known pathological axes of CLBP, involving both peripheral and central systems. In particular, this paper details injurious nerve stimulation, inflammation-induced peripheral pathway, and central sensitization. Lumbar components, such as intervertebral disc (IVD), facet joints, muscles, fascia, ligaments, and joint capsules, contain pain receptors called nociceptors. Degeneration of the aforementioned lumbar components activates inflammatory pathways, which can directly damage nerves, lower nociceptor threshold to fire action potentials (AP), and cause pain. Additionally, damaged lumbar IVDs and endplates can also lead to the pathologic invasion of nerve growth and innervation, followed by the compression of herniated IVDs on nerve roots, thereby causing traumatic neuropathic pain. The central mechanism of CLBP involves alteration of the sensory processing of the brain and malfunction of the descending pain modulatory system, which facilitates pain amplification in the center nervous system (CNS). Lastly, abnormalities in the brain biochemical metabolism, activation of glial cells, and subsequent inflammation also play important roles in CLBP development. Taken together, inflammation plays an important role in both peripheral and central sensitization of CLBP. Due to the heterogeneity of CLBP, its pathological mechanism remains complex and difficult to understand. Therefore, it is a worthy field for future research into the subcomponents of CLBP pathogenesis, in order to distinguish the specific form of the disease, identify its origins, and develop corresponding highly effective comprehensive therapy against CLBP.

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Brain ischemia-reperfusion (IR) triggers a complex series of biochemical events including inflammation. To test the neuroprotective efficacy of Cordyceps sinensis mycelium (CSM) in a rat model of focal cerebral IR, ischemic animals were treated with CSM. They were evaluatedat 24 h after reperfusion for neurological deficit score. Furthermore, the mechanism of the anti-inflammatory potential of CSM in the regulation of nuclear factor kappaB, polymorphonuclear cells (PMN), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), adhesion molecule (ICAM-1), and cyclooxygenase-2 (COX-2) was determined by ELISA and immunohistochemistry. CSM significantly inhibited IR-induced up-regulation of NF-kappaB activation and the brain production of IL-1β, TNF-α, iNOS, ICAM-1, and COX-2. Moreover, CSM suppressed infiltration of PMN. The study demonstrates the neuroprotective potential of CSM inhibition through anti-inflammation in a rat model of ischemia-reperfusion.

BackgroundIschemic hypoxic brain injury often causes irreversible brain damage. The lack of effective and widely applicable pharmacological treatments for ischemic stroke patients may explain a growing interest in traditional medicines. From the point of view of "self-medication" or "preventive medicine," Cordyceps sinensis was used in the prevention of cerebral ischemia in this paper.MethodsThe right middle cerebral artery occlusion model was used in the study. The effects of Cordyceps sinensis (Caterpillar fungus) extract on mortality rate, neurobehavior, grip strength, lactate dehydrogenase, glutathione content, Lipid Peroxidation, glutathione peroxidase activity, glutathione reductase activity, catalase activity, Na+K+ATPase activity and glutathione S transferase activity in a rat model were studied respectively.ResultsCordyceps sinensis extract significantly improved the outcome in rats after cerebral ischemia and reperfusion in terms of neurobehavioral function. At the same time, supplementation of Cordyceps sinensis extract significantly boosted the defense mechanism against cerebral ischemia by increasing antioxidants activity related to lesion pathogenesis. Restoration of the antioxidant homeostasis in the brain after reperfusion may have helped the brain recover from ischemic injury.ConclusionsThese experimental results suggest that complement Cordyceps sinensis extract is protective after cerebral ischemia in specific way. The administration of Cordyceps sinensis extract significantly reduced focal cerebral ischemic/reperfusion injury. The defense mechanism against cerebral ischemia was by increasing antioxidants activity related to lesion pathogenesis.