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Background: Desert hedgehog (DHH), as a member of the Hedgehog (HH) family, is mainly involved in testicular development and peripheral nerve sheath formation. A DHH variant has been identified in patients with 46, XY gonadal dysgenesis (46, XY GD) with or without neuropathy, but few reports mention the involvement of other complications.Case presentation: Here, we report a Chinese female patient who was hospitalized at 14.3 years old due to slow breast development for more than 1 year. She had a female genitalia phenotype and breast development started at 13 years old but progressed slowly. She was not yet menarche on admission, and she had intermittent muscle cramps in her hands and feet. Her karyotype analysis was 46, XY and the SRY gene was positive. Surgical exploration revealed no uterus or ovaries, and the pathology of bilateral gonads was dysplastic testis tissue, which was consistent with partial gonadal dysgenesis (PGD). Genetic analysis identified a homozygous pathogenic variant in DHH exon 3 (c.1027T>C, p. Cys343Arg). During the 6-year follow-up, she received estrogen replacement therapy, resulting in breast development progression without gender dysphoria. However, her peripheral neuropathy became more obvious, and a nerve conduction study (NCS) indicated decreased nerve conduction velocity and action potential. In addition, she also suffered complications such as obesity, insulin resistance, fatty liver, and gastric ulcers.Conclusion: In the present study, we reported a case of 46, XY GD with minifascicular neuropathy caused by a DHH homozygous variant, and we summarized the reported cases worldwide. For the first time in such patients, we showed a comparison of NCS changes with age as well as the presence of multiple complications not previously reported.

Xiuli Yuan,1,* Uet Yu,1,* Senmin Chen,1 Huanli Xu,1 Meng Yi,1 Xianping Jiang,2 Jianming Song,1 Xiaowen Chen,3 Shiyang Chen,3 Zhenhu Lin,3 Changgang Li,1 Feiqiu Wen,1 Sixi Liu1 1Department of Hematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 2Department of Pathology, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China; 3Institute for Medical Research, Shenzhen Children’s Hospital, Shenzhen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sixi LiuDepartment of Hematology and Oncology, Shenzhen Children’s Hospital, Yitian Road No. 7019, Futian, Shenzhen, Guangdong 518038, People’s Republic of ChinaTel +86 189-3869-0206Email tiger647@126.comAbstract: Here, we report a rare case of a 12-year-old boy who was initially diagnosed with B cell lymphoblastic lymphoma (BLBL) and developed myeloid sarcoma (MS) eight months after chemotherapy. Next-generation sequencing (NGS) showed mutations of KRAS and NRAS genes in both the bone marrow and lymph node. He presented an abnormal karyotype of 46, XY, − 9, der (16) t (9; 16) (q13; q12), +mar. He received chemotherapy according to the South China Children’s Leukemia Group 2016 protocol. Complete remission was achieved by the 15th day post-treatment. Eight months later and immediately prior to the start of maintenance therapy, the patient developed fever, skin nodules in both upper arms, and enlargement of bilateral testes. Pathological analysis of skin and testicular biopsies suggested the diagnosis of myeloid sarcoma (MS). Again, NGS examination showed mutations of KRAS and NRAS genes. The patient underwent haploidentical hematopoietic stem cell transplantation but unfortunately did not survive. The interval of eight-month interval between the initial disease onset and MS brings into question whether MS developed as part of the initial onset of disease or as a secondary tumor in association with chemotherapy. Thus, understanding the pathogenesis of MS involving abnormalities of lymphoid progenitors may assist in the prediction of prognosis and development of novel target therapies.Keywords: B cell lymphoblastic lymphoma, myeloid sarcoma, KRAS, NRAS, case report

In this paper, we propose pyramid appearance and global structure action descriptors on both RGB and depth motion history images and a model-free method for human action recognition. In proposed algorithm, we firstly construct motion history image for both RGB and depth channels, at the same time, depth information is employed to filter RGB information, after that, different action descriptors are extracted from depth and RGB MHIs to represent these actions, and then multimodality information collaborative representation and recognition model, in which multi-modality information are put into object function naturally, and information fusion and action recognition also be done together, is proposed to classify human actions. To demonstrate the superiority of the proposed method, we evaluate it on MSR Action3D and DHA datasets, the well-known dataset for human action recognition. Large scale experiment shows our descriptors are robust, stable and efficient, when comparing with the-state-of-the-art algorithms, the performances of our descriptors are better than that of them, further, the performance of combined descriptors is much better than just using sole descriptor. What is more, our proposed model outperforms the state-of-the-art methods on both MSR Action3D and DHA datasets.

As an important secondary explosive, cyclotrimethylenetrinitramine (RDX, C3H6O6N6) is extensively used in military and industrial applications due to its high energy density and low sensitivity to external stimulations. Considerable attention has been devoted to the study of the detonation initiation, with particular interest in the mechanism by which energy is transferred from a shock wave to the internal molecular vibrations so as to begin endothermic decomposition. During the whole process, phonons as the primary carriers of heat may play an important role. Experimentally, inelastic neutron scattering (INS) technique provides a means of studying the dynamics of motions of atoms and molecules in the crystal, especially in the low frequency region which contains most phonon lattice modes. In this work, neutron diffraction pattern of polycrystalline RDX under ambient condition has been measured and compared with the calculated results, showing reasonable agreement with and thus confirming the structure of RDX. Subsequently, the vibrational INS spectrum of RDX has been measured at T=10 K over the region of 10-104~cm-1 by using cold neutron triple-axis spectrometer. On the basis of the solid-state density functional calculations with the generalized gradient approximation (BLYP and BP functionals), it is possible to perform normal-mode analysis, which agrees with previous assignments. A total of 9 phonon lattice modes and 3 internal vibrations have been identified. Eight possible doorway modes may be predicted in the energy range between 100 and 148~cm-1, which arise from the combinations of phonon lattice modes 38.3, 40.3, 50.2, 61.5~cm-1 and fundamental vibrations 86.6, 88.6, 101.4~cm-1. The doorway modes are the proposed bridge by which the energy of initial shockwave can pass from the external degrees of freedom into those of the molecule. It is shown that all of these eight modes have fundamental vibrational components that consist of nitro-group deformation vibrations. This point is of particular importance and supports the theory that the initial bond broken in detonation is the NN bond. This work may shed light on the mechanism of detonation initiation from a microscopic viewpoint.

The use of tissue- or tumor-selective promoters in targeted gene therapy for prostate cancer depends on strong and selective activity. The -426 to +28 bp probasin (PB) promoter has the potential to target selected genes to the prostatic epithelial cells. We showed that in the assay of luciferase reporter gene driven by PB promoter, activation of luciferase expression was 1.5-fold increase in human prostate cancer cell LNCaP relative to non-small cell lung cancer cell H460. Significant increase of luciferase activity was observed in both cell lines when infection with ICP27 (-) HSV-1 was added to PBluciferase plasmid transfected LNCaP and H460 cells. In addition, an expression vector (PB-ICP27) was generated in which one of the herpes simplex virus type 1 (HSV-1) immediate early (IE) genes required for viral replication~ICP27 was regulated by PB promoter. This vector was transfected into LNCaP, H460 and one other nonprostate cancer cell HepG2 (hepatoma), the cell lines were then infected with ICP27 (-) HSV-1 and resulting viral stock from these cells were used to infect ICP27 expression 2-2 cell. The plaque yields from infected 2-2 cells were counted and reflected the production of ICP27 (-) HSV-1 replication in PB-ICP27 vector transfected cells that can express ICP27 protein. Although we found that the profound viral replication was observed in LNCaP cells compared to that of HepG2 cells, the production of viral replication in H460 cells was surprisingly significant higher than that in LNCaP cells and was contrasted to our PB-driven luciferase assay result. Our study demonstrates that (1). -426 to +28 bp PB promoter shows relative tissue-specific activity; (2). Infection with ICP27 (-) HSV-1 can enhance the expression levels of reporter gene driven by PB promoter and ICP27 (-) HSV-1 can only replicate in the cells expressing ICP27 protein; (3). The vector construct containing ICP27 gene driven by PB promoter may not be an ideal delivery system for the purpose of prostate tissue-specific gene expression.

Using density functional theory, the structural parameters of α-U and bcc phases were obtained separately, in reasonable agreement with previous experimental and theoretical results. The enthalpy-pressure curve showed that the phase transition pressure was approximately 111 GPa. The structural behavior of γ-U under extreme loading conditions was exhibited by the ideal strength calculations. In addition, by analyzing the energy-strain relationship we found that the strain corresponding to the shear modulus c’ could decrease the total energy of U-Nb (6.25 at.%) alloy, indicating the instability of this structure.

Having read Comrade Yuan Gongming's article "Is Teaching at a Primary School a Job of No Promise and No Future?" I would like to express some of my own opinions.