Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

WWP2 promotes degradation of transcription factor OCT4 in human embryonic stem cells

POU transcription factor OCT4 not only plays an essential role in maintaining the pluripotent and self-renewing state of embryonic stem （ES） cells but also acts as a cell fate determinant through a gene dosage effect. However, the molecular mechanisms that control the intracellular OCT4 protein level remain elusive. Here, we report that human WWP2, an E3 ubiquitin （Ub）-protein ligase, interacts with OCT4 specifically through its WW domain and enhances Ub modification of OCT4 both in vitro and in vivo. We first demonstrated that endogenous OCT4 in hu- man ES cells can be post-translationally modified by Ub. Furthermore, we found that WWP2 promoted degradation of OCT4 through the 26S proteasome in a dosage-dependent manner, and the active site cysteine residue of WWP2 was required for both its enzymatic activity and proteolytic effect on OCT4. Remarkably, our data show that the en- dogenous OCT4 protein level was significantly elevated when WWP2 expression was downregulated by specific RNA interference （RNAi）, suggesting that WWP2 is an important regulator for maintaining a proper OCT4 protein level in human ES cells. Moreover, northern blot analysis showed that the WWP2 transcript was widely present in diverse human tissues/organs and highly expressed in undifferentiated human ES cells. However, its expression level was quickly decreased after human ES cells differentiated, indicating that WWP2 expression might be developmentally regulated. Our findings demonstrate that WWP2 is an important regulator of the OCT4 protein level in human ES cells.

CONVEX MAPPINGS ASSOCIATED WITH THE ROPER-SUFFRIDGE EXTENSION OPERATOR

Let λG（z）|dz| be the hyperbolic metric on a simply connected proper domain G?C containing the origin, and let ■be the Banach norms of Cnj for j = 1, 2,…,k.This note is to prove that if f is a normalized biholomorphic convex function on G, then ■is a normalized biholomorphic convex mapping on ■where N = 1+n1 + … + nk and the branch is chosen such that ■,j = 1,…, k. Applying to the Roper-Suffridge extension operator, we obtain a new convex mappings construction of an unbounded domain and a refinement of convex mappings construction on a Reinhardt domain, respectively.

FreeformNet:fast and automatic generation of multiple-solution freeform imaging systems enabled by deep learning

Using freeform optical surfaces in lens design can lead to much higher system specifications and performance while significantly reducing volume and weight.However,because of the complexity of freeform surfaces,freeform optical design using traditional methods requires extensive human effort and sufficient design experience,while other design methods have limitations in design efficiency,simplicity,and versatility.Deep learning can solve these issues by summarizing design knowledge and applying it to design tasks with different system and structure parameters.We propose a deep-learning framework for designing freeform imaging systems.We generate the data set automatically using a combined sequential and random system evolution method.We combine supervised learning and unsupervised learning to train the network so that it has good generalization ability for a wide range of system and structure parameter values.The generated network FreeformNet enables fast generation(less than 0.003 s per system)of multiple-solution systems after we input the design requirements,including the system and structure parameters.We can filter and sort solutions based on a given criterion and use them as good starting points for quick final optimization(several seconds for systems with small or moderate field-of-view in general).The proposed framework presents a revolutionary approach to the lens design of freeform or generalized imaging systems,thus significantly reducing the time and effort expended on optical design.

Fekete and Szego problem for a subclass of quasi-convex mappings in several complex variables

Let K be the familiar class of normalized convex functions in the unit disk. Keogh and Merkes proved the well-known result that maxf∈A ｜a3 - λa22｜ ≤ max{1/3, ｜λ - 1}, ,λ ∈ C, and the estimate is sharp for each ∈. We investigate the corresponding problem for a subclass of quasi-convex mappings of type B defined on the unit ball in a complex Banach space or on the unit polydisk in Cn. The proofs of these results use some restrictive assumptions, which in the case of one complex variable are automatically satisfied.