Neural Cognitive Diagnosis for Intelligent Education Systems

Cognitive diagnosis is a fundamental issue in intelligent education, which aims to discover the proficiency level of students on specific knowledge concepts. Existing approaches usually mine linear interactions of student exercising process by manual-designed function (e.g., logistic function), which is not sufficient for capturing complex relations between students and exercises. In this paper, we propose a general Neural Cognitive Diagnosis (NeuralCD) framework, which incorporates neural networks to learn the complex exercising interactions, for getting both accurate and interpretable diagnosis results. Specifically, we project students and exercises to factor vectors and leverage multi neural layers for modeling their interactions, where the monotonicity assumption is applied to ensure the interpretability of both factors. Furthermore, we propose two implementations of NeuralCD by specializing the required concepts of each exercise, i.e., the NeuralCDM with traditional Q-matrix and the improved NeuralCDM+ exploring the rich text content. Extensive experimental results on real-world datasets show the effectiveness of NeuralCD framework with both accuracy and interpretability

Zinc inhibits TRPV1 to alleviate chemotherapy-induced neuropathic pain

Zinc is a transition metal that has a long history of use as an anti-inflammatory agent. It also soothes pain sensations in a number of animal models. However, the effects and mechanisms of zinc on chemotherapy-induced peripheral neuropathy remain unknown. Here we show that locally injected zinc markedly reduces neuropathic pain in male and female mice induced by paclitaxel, a chemotherapy drug, in a TRPV1-dependent manner. Extracellularly applied zinc also inhibits the function of TRPV1 expressed in HEK293 cells and mouse DRG neurons, which requires the presence of zinc-permeable TRPA1 to mediate entry of zinc into the cytoplasm. Moreover, TRPA1 is required for zinc-induced inhibition of TRPV1-mediated acute nociception. Unexpectedly, zinc transporters, but not TRPA1, are required for zinc-induced inhibition of TRPV1-dependent chronic neuropathic pain produced by paclitaxel. Together, our study demonstrates a novel mechanism underlying the analgesic effect of zinc on paclitaxel-induced neuropathic pain that relies on the function of TRPV1

The immunosuppressive effects and mechanisms of loureirin B on collagen-induced arthritis in rats

IntroductionRheumatoid arthritis (RA) is a common disease mainly affecting joints of the hands and wrists. The discovery of autoantibodies in the serum of patients revealed that RA belonged to the autoimmune diseases and laid a theoretical basis for its immunosuppressive therapy. The pathogenesis of autoimmune diseases mainly involves abnormal activation and proliferation of effector memory T cells, which is closely related to the elevated expression of Kv1.3, a voltage-gated potassium (Kv) channel on the effector memory T cell membrane. Drugs blocking the Kv1.3 channel showed a strong protective effect in RA model animals, suggesting that Kv1.3 is a target for the discovery of specific RA immunosuppressive drugs.MethodsIn the present study, we synthesized LrB and studied the effects of LrB on collagen- induced arthritis (CIA) in rats. The clinical score, paw volume and joint morphology of CIA model rats were compared. The percentage of CD3+, CD4+ and CD8+ T cells in rat peripheral blood mononuclear and spleen were analyzed with flow cytometry. The concentrations of inflammatory cytokines interleukin (IL)-1b, IL-2, IL-4, IL-6, IL-10 and IL-17 in the serum of CIA rats were analyzed with enzyme-linked immunosorbent assay. The IL-1b and IL-6 expression in joints and the Kv1.3 expression in peripheral blood mononuclear cells (PBMCs) were quantified by qPCR. To further study the mechanisms of immunosuppressive effects of LrB, western blot and immunofluorescence were utilized to study the expression of Kv1.3 and Nuclear Factor of Activated T Cells 1 (NFAT1) in two cell models - Jurkat T cell line and extracted PBMCs.ResultsLrB effectively reduced the clinical score and relieved joint swelling. LrB could also decrease the percentage of CD4+ T cells, while increase the percentage of CD8+ T cells in peripheral blood mononuclear and spleen of rats with CIA. The concentrations of inflammatory cytokines interleukin (IL)-1b, IL-2, IL-6, IL-10 and IL-17 in the serum of CIA rats were significantly reduced by LrB. The results of qPCR showed that Kv1.3 mRNA in the PBMCs of CIA rats was significantly higher than that of the control and significantly decreased in the LrB treatment groups. In addition, we confirmed in cell models that LrB significantly decreased Kv1.3 protein on the cell membrane and inhibited the activation of Nuclear Factor of Activated T Cells 1 (NFAT1) with immune stimulus.ConclusionIn summary, this study revealed that LrB could block NFAT1 activation and reduce Kv1.3 expression in activated T cells, thus inhibiting the proliferation of lymphocytes and the release of inflammatory cytokines, thereby effectively weakening the autoimmune responses in CIA rats. The effects of immunosuppression due to LrB revealed its potential medicinal value in the treatment of RA

Structural and Functional Diversity of Acidic Scorpion Potassium Channel Toxins

Background: Although the basic scorpion K + channel toxins (KTxs) are well-known pharmacological tools and potential drug candidates, characterization the acidic KTxs still has the great significance for their potential selectivity towards different K + channel subtypes. Unfortunately, research on the acidic KTxs has been ignored for several years and progressed slowly. Principal Findings: Here, we describe the identification of nine new acidic KTxs by cDNA cloning and bioinformatic analyses. Seven of these toxins belong to three new a-KTx subfamilies (a-KTx28, a-KTx29, and a-KTx30), and two are new members of the known k-KTx2 subfamily. ImKTx104 containing three disulfide bridges, the first member of the a-KTx28 subfamily, has a low sequence homology with other known KTxs, and its NMR structure suggests ImKTx104 adopts a modified cystine-stabilized a-helix-loop-b-sheet (CS-a/b) fold motif that has no apparent a-helixs and b-sheets, but still stabilized by three disulfide bridges. These newly described acidic KTxs exhibit differential pharmacological effects on potassium channels. Acidic scorpion toxin ImKTx104 was the first peptide inhibitor found to affect KCNQ1 channel, which is insensitive to the basic KTxs and is strongly associated with human cardiac abnormalities. ImKTx104 selectively inhibited KCNQ1 channel with a Kd of 11.69 mM, but was less effective against the basic KTxs-sensitive potassium channels. In addition to the ImKTx104 toxin, HeTx204 peptide, containing a cystine-stabilized a-helix-loop-helix (CS-a/a) fold scaffold motif

The Pore Loop Domain of TRPV1 Is Required for Its Activation by the Volatile Anesthetics Chloroform and Isoflurane s

ABSTRACT The environmental irritant chloroform, a naturally occurring small volatile organohalogen, briefly became the world's most popular volatile general anesthetic (VGA) before being abandoned because of its low therapeutic index. When chloroform comes in contact with skin or is ingested, it causes a painful burning sensation. The molecular basis for the pain associated with chloroform remains unknown. In this study, we assessed the role of transient receptor potential (TRP) channel family members in mediating chloroform activation and the molecular determinants of VGA activation of TRPV1. We identified the subpopulation of dorsal root ganglion (DRG) neurons that are activated by chloroform. Additionally, we transiently expressed wild-type or specifically mutated TRP channels in human embryonic kidney cells and used calcium imaging or wholecell patch-clamp electrophysiology to assess the effects of chloroform or the VGA isoflurane on TRP channel activation. The results revealed that chloroform activates DRG neurons via TRPV1 activation. Furthermore, chloroform activates TRPV1, and it also activates TRPM8 and functions as a potent inhibitor of the noxious chemical receptor TRPA1. The results also indicate that residues in the outer pore region of TRPV1 previously thought to be required for either proton or heat activation of the channel are also required for activation by chloroform and isoflurane. In addition to identifying the molecular basis of DRG neuron activation by chloroform and the opposing effects chloroform has on different TRP channel family members, the findings of this study provide novel insights into the structural basis for the activation of TRPV1 by VGAs

Chaerilus pseudoconchiformus sp. n. and an updated key of the chaerilid scorpions from China (Scorpiones, Chaerilidae) Launched to accelerate biodiversity research

Abstract A new species, C. pseudoconchiformus sp. n., is described from Xizang, China. The new species is distinguished from its congeners by a body length of 32−40 mm, carapace with the anterior margin straight, chela with length/width ratio average of 3.3 in males (3.2−3.4, two adults), and 2.5 in females (2.3−2.6, nine adults), eight or nine (eight usually) rows of denticles on fixed and movable fingers of pedipalp chelae, five pectinal teeth in males and three or four in females. To date, the chaerilid species fauna of China consists of nine species. An updated identification key to Chaerilus from China is presented

Chaerilus pseudoconchiformus sp. n. and an updated key of the chaerilid scorpions from China (Scorpiones, Chaerilidae)

A new species, C. pseudoconchiformus sp. n., is described from Xizang, China. The present new species is distinguished from its congeners by a body length of 32−40 mm, carapace with the anterior margin straight, chela with length/width ratio average of 3.3 in males (3.2−3.4, two adults), and 2.5 in females (2.3−2.6, nine adults), eight or nine (eight usually) rows of denticles on fixed and movable fingers of pedipalp chelae, five pectinal teeth in males and three or four in females. To date, the chaerilid species fauna of China consists of nine species. An updated identification key to Chaerilus from China is presented

Scorpiops ingens sp. n. and an updated key to the Scorpiops from China (Scorpiones, Euscorpiidae, Scorpiopinae)

A new species, Scorpiops ingens sp. n., from Xizang, is described and illustrated. Scorpiops ingens sp. n. is characterized by yellow-brown color, large size (length of adults above 70.0 mm), small and dense granules on tegument, a pair of small median eyes, 17 external trichobothria (5 eb, 2 esb, 2 em, 4 est, 4 et), and 7 or 8 (usually 7) ventral trichobothria in the pedipalp patella, chela with a length/width ratio average of 2.2 in males and females, pedipalp chela fingers on adult females and males scalloped, pectinal teeth count 6–8, pectinal fulcra absent. With the description of this new species, the number of known species of Scorpiops from China is raised to 12. An updated identification key to Scorpiops from China is presented

Loureirin B exerts its immunosuppressive effects by inhibiting STIM1/Orai1 and K V 1.3 channels

Loureirin B (LrB) is a constituent extracted from traditional Chinese medicine Resina Draconis. It has broad biological functions and an impressive immunosuppressive effect that has been supported by numerous studies. However, the molecular mechanisms underlying Loureirin B-induced immune suppression are not fully understood. We previously reported that Loureirin B inhibited