Gu-4 Suppresses Affinity and Avidity Modulation of CD11b and Improves the Outcome of Mice with Endotoxemia and Sepsis

BACKGROUND: Systemic leukocyte activation and disseminated leukocyte adhesion will impair the microcirculation and cause severe decrements in tissue perfusion and organ function in the process of severe sepsis. Gu-4, a lactosyl derivative, could selectively target CD11b to exert therapeutic effect in a rat model of severe burn shock. Here, we addressed whether Gu-4 could render protective effects on septic animals. METHODOLOGY/PRINCIPAL FINDINGS: On a murine model of endotoxemia induced by lipopolysaccharide (LPS), we found that the median effective dose (ED50) of Gu-4 was 0.929 mg/kg. In vivo treatment of Gu-4 after LPS challenge prominently attenuated LPS-induced lung injury and decreased lactic acid level in lung tissue. Using the ED50 of Gu-4, we also demonstrated that Gu-4 treatment significantly improved the survival rate of animals underwent sepsis induced by cecal ligation and puncture. By adhesion and transwell migration assays, we found that Gu-4 treatment inhibited the adhesion and transendothelial migration of LPS-stimulated THP-1 cells. By flow cytometry and microscopy, we demonstrated that Gu-4 treatment inhibited the exposure of active I-domain and the cluster formation of CD11b on the LPS-stimulated polymorphonuclear leukocytes. Western blot analyses further revealed that Gu-4 treatment markedly inhibited the activation of spleen tyrosine kinase in LPS-stimulated THP-1 cells. CONCLUSIONS/SIGNIFICANCE: Gu-4 improves the survival of mice underwent endotoxemia and sepsis, our in vitro investigations indicate that the possible underlying mechanism might involve the modulations of the affinity and avidity of CD11b on the leukocyte. Our findings shed light on the potential use of Gu-4, an interacting compound to CD11b, in the treatment of sepsis and septic shock

Cognitive vision system for control of dexterous prosthetic hands: Experimental evaluation

<p>Abstract</p> <p>Background</p> <p>Dexterous prosthetic hands that were developed recently, such as SmartHand and i-LIMB, are highly sophisticated; they have individually controllable fingers and the thumb that is able to abduct/adduct. This flexibility allows implementation of many different grasping strategies, but also requires new control algorithms that can exploit the many degrees of freedom available. The current study presents and tests the operation of a new control method for dexterous prosthetic hands.</p> <p>Methods</p> <p>The central component of the proposed method is an autonomous controller comprising a vision system with rule-based reasoning mounted on a dexterous hand (CyberHand). The controller, termed cognitive vision system (CVS), mimics biological control and generates commands for prehension. The CVS was integrated into a hierarchical control structure: 1) the user triggers the system and controls the orientation of the hand; 2) a high-level controller automatically selects the grasp type and size; and 3) an embedded hand controller implements the selected grasp using closed-loop position/force control. The operation of the control system was tested in 13 healthy subjects who used Cyberhand, attached to the forearm, to grasp and transport 18 objects placed at two different distances.</p> <p>Results</p> <p>The system correctly estimated grasp type and size (nine commands in total) in about 84% of the trials. In an additional 6% of the trials, the grasp type and/or size were different from the optimal ones, but they were still good enough for the grasp to be successful. If the control task was simplified by decreasing the number of possible commands, the classification accuracy increased (e.g., 93% for guessing the grasp type only).</p> <p>Conclusions</p> <p>The original outcome of this research is a novel controller empowered by vision and reasoning and capable of high-level analysis (i.e., determining object properties) and autonomous decision making (i.e., selecting the grasp type and size). The automatic control eases the burden from the user and, as a result, the user can concentrate on what he/she does, not on how he/she should do it. The tests showed that the performance of the controller was satisfactory and that the users were able to operate the system with minimal prior training.</p

Overexpression of sphingosine kinase 1 is associated with salivary gland carcinoma progression and might be a novel predictive marker for adjuvant therapy

<p>Abstract</p> <p>Background</p> <p>Overexpression of sphingosine kinase-1 (SPHK1) has been demonstrated to be associated with the development and progression in various types of human cancers. The current study was to characterize the expression of SPHK1 in salivary gland carcinomas (SGC) and to investigate the association between SPHK1 expression and progression of SGC.</p> <p>Methods</p> <p>The expression of SPHK1 was examined in 2 normal salivary gland tissues, 8 SGC tissues of various clinical stages, and 5 pairs of primary SGC and adjacent salivary gland tissues from the same patient, using real-time PCR and western blot analysis. Furthermore, the SPHK1 protein expression was analyzed in 159 clinicopathologically characterized SGC cases by immunohistochemistry. Statistical analyses were performed to determine the prognostic and diagnostic associations.</p> <p>Results</p> <p>SPHK1 expression was found to be markedly upregulated in SGC tissues than that in the normal salivary gland tissues and paired adjacent salivary gland tissues, at both mRNA and protein levels. Statistical analysis revealed a significant correlation of SPHK1 expression with the clinical stage (<it>P </it>= 0.005), T classification (<it>P </it>= 0.017), N classification (<it>P </it>= 0.009), M classification (<it>P </it>= 0.002), and pathological differentiation (<it>P </it>= 0.013). Patients with higher SPHK1 expression had shorter overall survival time, whereas patients with lower SPHK1 expression had better survival. Importantly, patients in the group without adjuvant therapy who exhibited high SPHK1 expression had significantly lower overall survival rates compared with those with low SPHK1 expression. Moreover, multivariate analysis suggested that SPHK1 expression might be an independent prognostic indicator for the survival of SGC patients.</p> <p>Conclusions</p> <p>Our results suggest that SPHK1 expression is associated with SGC progression, and might represent as a novel and valuable predictor for adjuvant therapy to SGC patients.</p

Identification of miRs-143 and -145 that Is Associated with Bone Metastasis of Prostate Cancer and Involved in the Regulation of EMT

The principal problem arising from prostate cancer (PCa) is its propensity to metastasize to bone. MicroRNAs (miRNAs) play a crucial role in many tumor metastases. The importance of miRNAs in bone metastasis of PCa has not been elucidated to date. We investigated whether the expression of certain miRNAs was associated with bone metastasis of PCa. We examined the miRNA expression profiles of 6 primary and 7 bone metastatic PCa samples by miRNA microarray analysis. The expression of 5 miRNAs significantly decreased in bone metastasis compared with primary PCa, including miRs-508-5p, -145, -143, -33a and -100. We further examined other samples of 16 primary PCa and 13 bone metastases using real-time PCR analysis. The expressions of miRs-143 and -145 were verified to down-regulate significantly in metastasis samples. By investigating relationship of the levels of miRs-143 and -145 with clinicopathological features of PCa patients, we found down-regulations of miRs-143 and -145 were negatively correlated to bone metastasis, the Gleason score and level of free PSA in primary PCa. Over-expression miR-143 and -145 by retrovirus transfection reduced the ability of migration and invasion in vitro, and tumor development and bone invasion in vivo of PC-3 cells, a human PCa cell line originated from a bone metastatic PCa specimen. Their upregulation also increased E-cadherin expression and reduced fibronectin expression of PC-3 cells which revealed a less invasive morphologic phenotype. These findings indicate that miRs-143 and -145 are associated with bone metastasis of PCa and suggest that they may play important roles in the bone metastasis and be involved in the regulation of EMT Both of them may also be clinically used as novel biomarkers in discriminating different stages of human PCa and predicting bone metastasis

Significantly improved dehydrogenation of LiBH4 destabilized by TiF3

The hydrogen storage properties of LiBH4 ball milled with TiF3 were investigated. It was found that the LiBH4–TiF3 mixture exhibited significantly improved dehydrogenation properties. For example, the LiBH4–TiF3 (mole ratio: 3:1) sample started to release hydrogen at around 100 °C, and the hydrogen desorption capacity reached 5.0 wt% at 250 °C. Furthermore, the dehydrogenated product can be partially rehydrogenated at 100 atm H2 and 350 °C. X-Ray diffraction (XRD), infrared (IR) spectroscopy and X-ray photoelectron spectroscopy (XPS) characterizations revealed that the decreased dehydrogenation conditions in the LiBH4–TiF3 system resulted from an exothermic reaction of 3LiBH4 + TiF3 → 3LiF + TiB2 + B + 6H2, which improved both its thermodynamics and kinetics. As the above reaction is exothermic, the reverse reaction is not feasible, further investigations indicated that the rehydrogenation may be due to the formation of another borohydrid

Mispila elongata Breuning 1938

Mispila (s. str.) elongata Breuning, 1938 (Figure 10a–g) Mispila elongata Breuning, 1938: 380; Kariyanna et al., 2017: 193. Mispila (Mispila) elongata: Breuning, 1961a: 281; Breuning, 1963b: 488. Type material examined. India: Holotype, female: ‘ Type [p, label circular, red framed]; H. L. Andrewes / Nilgiri Hills [p]; Andrewes / Bequest. / B. M. 1922–221. [p]; Mispila / elongata / mihi Typ. [h] / det. Breuning [p]; NHMUK014596479 ’. Non-type material examined. India: 1 male: ‘ H. L. Andrewes / Nilgiri Hills [p]; Andrewes / Bequest. / B. M. 1922–221. [p]; NHMUK014596478 [p]’.Published as part of Xie, Guanglin, Barclay, Maxwell V. L. & Wang, Wenkai, 2023, The collection of the genus Mispila Pascoe, 1864 housed in the Natural History Museum, London (Coleoptera: Cerambycidae), pp. 245-265 in Zootaxa 5352 (2) on page 256, DOI: 10.11646/zootaxa.5352.2.6, http://zenodo.org/record/840724

Epepeotes desertus subsp. obscurus

&lt;p&gt;Epepeotes desertus obscurus (Aurivillius, 1926)&lt;/p&gt; &lt;p&gt;Fig. 1g, h&lt;/p&gt; &lt;p&gt;Diochares desertus var. obscurus Aurivillius, 1926: 102. Type locality: Buru [Indonesia].&lt;/p&gt; &lt;p&gt;Epepeotes desertus s.- sp. obscurus: Breuning 1943: 229.&lt;/p&gt; &lt;p&gt;Epepeotes desertus ssp. obscurus: Breuning 1961: 326.&lt;/p&gt; &lt;p&gt;Epepeotes desertus obscurus: Bar&scaron;evskis 2020: 180.&lt;/p&gt; &lt;p&gt;Non-type material.&lt;/p&gt; &lt;p&gt; 14 specimens. &lt;b&gt;Indonesia (14)&lt;/b&gt;: Ceram (2 females); Mausela (5 males, 7 females).&lt;/p&gt; &lt;p&gt;Comments.&lt;/p&gt; &lt;p&gt; Breuning (1943) stated that the subspecies &lt;i&gt;E. desertus rhobetor&lt;/i&gt; is distinguished from the subspecies &lt;i&gt;E. d. desertus&lt;/i&gt; by the body usually smaller, the antennae more slender, the body markings yellow, and the elytral spots small and separate, with only a few individuals uniting into narrow transverse bands before and after the middle; the subspecies &lt;i&gt;E. d. obscurus&lt;/i&gt; is separated from the nominate subspecies by the elytron with less concave apex and reduced body markings. However, the holotype of &lt;i&gt;E. d. rhobetor&lt;/i&gt; (Fig. 1d) has the complete premedian transverse band and the postmedian band consisting of several large spots that are not fully fused, which is different from the description and illustration by Breuning (1943). Olivier (1808) illustrated the dorsal view of the species &lt;i&gt;Cerambix fimbriatus&lt;/i&gt; Olivier, 1795 (Fig. 1c, now a synonym of the nominate subspecies), which differs from &lt;i&gt;E. d. rhobetor&lt;/i&gt; and &lt;i&gt;E. d. obscurus&lt;/i&gt; mainly in the large and complete premedian and postmedian transverse bands on the elytra. However, the body markings and size are variable in this species, which make it difficult to accurately distinguish the three subspecies. The taxonomic status of the three subspecies is expected to be resolved by further study of more type and non-type material, perhaps with the possible removal of the subspecies-level status.&lt;/p&gt;Published as part of &lt;i&gt;Xie, Guanglin, Barclay, Maxwell V. L. &amp; Wang, Wenkai, 2023, The collection of the genus Epepeotes Pascoe, 1866 housed in the Natural History Museum, London (Coleoptera, Cerambycidae), pp. 19-39 in ZooKeys 1184&lt;/i&gt; on page 19, DOI: 10.3897/zookeys.1184.11172

Epepeotes ceramensis

&lt;p&gt;Epepeotes ceramensis (Thomson, 1861)&lt;/p&gt; &lt;p&gt;Fig. 5c-f&lt;/p&gt; &lt;p&gt;Rhamses ceramensis Thomson, 1861: 361. Type locality: Ceram [Indonesia].&lt;/p&gt; &lt;p&gt;Pelargoderus Pelargoderus Ceramensis[sic]: Pascoe 1866: 279.&lt;/p&gt; &lt;p&gt;Epepeotes ceramensis: Breuning 1943: 148, 226.&lt;/p&gt; &lt;p&gt;Non-type material.&lt;/p&gt; &lt;p&gt; 14 specimens. &lt;b&gt;Indonesia (14)&lt;/b&gt;: Ceram (7 males, 7 females).&lt;/p&gt; &lt;p&gt;Comments.&lt;/p&gt; &lt;p&gt;The light-colored spots on the elytra are variable, from very distinct to nearly invisible (Fig. 5d, e).&lt;/p&gt;Published as part of &lt;i&gt;Xie, Guanglin, Barclay, Maxwell V. L. &amp; Wang, Wenkai, 2023, The collection of the genus Epepeotes Pascoe, 1866 housed in the Natural History Museum, London (Coleoptera, Cerambycidae), pp. 19-39 in ZooKeys 1184&lt;/i&gt; on page 19, DOI: 10.3897/zookeys.1184.11172