Layered subsurface in Utopia Basin of Mars revealed by Zhurong rover radar.

Exploring the subsurface structure and stratification of Mars advances our understanding of Martian geology, hydrological evolution and palaeoclimatic changes, and has been a main task for past and continuing Mars exploration missions1-10. Utopia Planitia, the smooth plains of volcanic and sedimentary strata that infilled the Utopia impact crater, has been a prime target for such exploration as it is inferred to have hosted an ancient ocean on Mars11-13. However, 45 years have passed since Viking-2 provided ground-based detection results. Here we report an in situ ground-penetrating radar survey of Martian subsurface structure in a southern marginal area of Utopia Planitia conducted by the Zhurong rover of the Tianwen-1 mission. A detailed subsurface image profile is constructed along the roughly 1,171 m traverse of the rover, showing an approximately 70-m-thick, multi-layered structure below a less than 10-m-thick regolith. Although alternative models deserve further scrutiny, the new radar image suggests the occurrence of episodic hydraulic flooding sedimentation that is interpreted to represent the basin infilling of Utopia Planitia during the Late Hesperian to Amazonian. While no direct evidence for the existence of liquid water was found within the radar detection depth range, we cannot rule out the presence of saline ice in the subsurface of the landing area.

Modulation of amyloid precursor protein cleavage by γ-secretase activating protein through phase separation.

Aberrant cleavage of amyloid precursor protein (APP) by γ-secretase is closely associated with Alzheimer's disease (AD). γ-secretase activating protein (GSAP) specifically promotes γ-secretase­mediated cleavage of APP. However, the underlying mechanism remains enigmatic. Here, we demonstrate that the 16-kDa C-terminal fragment of GSAP (GSAP-16K) undergoes phase separation in vitro and forms puncta-like condensates in cells. GSAP-16K exerts dual modulation on γ-secretase cleavage; GSAP-16K in dilute phase increases APP­C-terminal 99-residue fragment (C99) cleavage toward preferred production of ß-amyloid peptide 42 (Aß42), but GSAP-16K condensates reduce APP-C99 cleavage through substrate sequestration. Notably, the Aß42/Aß40 ratio is markedly elevated with increasing concentrations of GSAP-16K. GSAP-16K stably associates with APP-C99 through specific sequence elements. These findings mechanistically explain GSAP-mediated modulation of γ-secretase activity that may have ramifications on the development of potential therapeutics.

[The efficacy and safety of unmanipulated haploidentical peripheral blood stem cell transplantation on hematologic diseases].

OBJECTIVE: To evaluate the efficacy and safety of unmanipulated haploidentical allogeneic peripheral blood stem cells transplantation (PBSCT) on hematologic diseases. METHODS: Patients who underwent unmanipulated HLA-mismatched/haploidentical PBSCT from July 2007 to December 2011 were investigated retrospectively. RESULT: Forty-nine patients with hematologic diseases underwent unmanipulated human leukocyte antigen (HLA)-mismatched/haploidentical PBSCT with myeloablative conditioning. All patients were mismatched at the allele level for HLA-A, HLA-B, HLA-Cw, HLA-DRB1 and HLA-DQ1. Fifteen patients were mismatched in 5 loci, 11 patients in 4 loci, 7 patients in 3 loci, 5 patients in 2 loci, and 11 patients in 1 locus. The median numbers of mononuclear cells and CD34⁺ cells infused at transplantation were 10.01(7.05-25.34) × 108/kg and 4.51 (2.01-11.47) × 106/kg, respectively. Patients achieved myeloid and platelet engraftment at a median of 14 (10-25) days and 22 (10-135) days, respectively. The cumulative incidence of acute graft versus host disease (aGVHD) on day 100 was (61.6 ± 7.3)%, and the 2-year cumulative incidence of chronic graft versus host disease (cGVHD) was (42.6 ± 8.5)%. One hundred-day transplantation related mortality (TRM) rate and 2-year cumulative TRM rate were (14.7 ± 5.1)% and (30.9 ± 8.8)%, respectively. The 2-year cumulative incidence estimate of relapse was (25.4 ± 7.0)%. The 2-year cumulative overall survival rate was (58.1 ± 8.8)% and 2-year disease-free survival rate was (53.9 ± 8.4)% with an 11.5-months median follow-up. CONCLUSION: Unmanipulated PBSCT is a promising protocol for patients with hematologic diseases in HLA-mismatched/haploidentical transplant settings.

Spectrum Analysis for Fully Connected Neural Networks.

This article studies the meaning of parameters of fully connected neural networks with single hidden layer from the perspective of spectrum. Under the constraints of numerical range, the corresponding relationship between parameters and the spectrum of network function can be established by the Fourier series coefficients of the activation function, which is truncated and periodically extended. This work is substantiated on the Mixed National Institute of Standards and Technology (MNIST) handwritten dataset and two illustrative examples with certain spectra. The simulations complete the conversion between spectrum and parameters with high precision and give the significance of hidden nodes to the spectrum of network function. Some algorithms derived from these properties, such as the parameter initialization method using spectrum and the pruning method by sorting amplification weights, are also presented to introduce how spectrum analysis affects neural network decision-making. Thus, spectrum analysis has great potential in network interpretation.

Molecular basis for isoform-selective inhibition of presenilin-1 by MRK-560.

Inhibition of γ-secretase activity represents a potential therapeutic strategy for Alzheimer's disease (AD). MRK-560 is a selective inhibitor with higher potency for Presenilin 1 (PS1) than for PS2, the two isoforms of the catalytic subunit of γ-secretase, although the underlying mechanism remains elusive. Here we report the cryo-electron microscopy (cryo-EM) structures of PS1 and PS2-containing γ-secretase complexes with and without MRK-560 at overall resolutions of 2.9-3.4 Å. MRK-560 occupies the substrate binding site of PS1, but is invisible in PS2. Structural comparison identifies Thr281 and Leu282 in PS1 to be the determinant for isoform-dependent sensitivity to MRK-560, which is confirmed by swapping experiment between PS1 and PS2. By revealing the mechanism for isoform-selective inhibition of presenilin, our work may facilitate future drug discovery targeting γ-secretase.

Sub-microscopic magnetite and metallic iron particles formed by eutectic reaction in Chang'E-5 lunar soil.

Ferric iron as well as magnetite are rarely found in lunar samples, and their distribution and formation mechanisms on the Moon have not been well studied. Here, we discover sub-microscopic magnetite particles in Chang'E-5 lunar soil. Magnetite and pure metallic iron particles are embedded in oxygen-dissolved iron-sulfide grains from the Chang'E-5 samples. This mineral assemblage indicates a FeO eutectoid reaction (4FeO = Fe3O4 + Fe) for formation of magnetite. The iron-sulfide grains' morphology features and the oxygen's distribution suggest that a gas-melt phase reaction occurred during large-impact events. This could provide an effective method to form ubiquitous sub-microscopic magnetite in fine lunar soils and be a contributor to the presentation of ferric iron on the surface of the Moon. Additionally, the formation of sub-microscopic magnetite and metallic iron by eutectoid reaction may provide an alternative way for the formation of magnetic anomalies observed on the Moon.

Outcomes of peripheral blood stem cell transplantation in patients from human leukocyte antigen matched or mismatched unrelated donors.

BACKGROUND: Allogeneic peripheral blood stem cell transplantation from unrelated donors (UR-PBSCT) is an alternative treatment for many hematologic diseases due to lack of human leukocyte antigen (HLA)-identical sibling donors. This study aimed to evaluate the impact of the degree of the HLA match on the clinical efficacy of UR-PBSCT. METHODS: Patients who underwent UR-PBSCT from September 2003 to September 2012 were retrospectively investigated. They were divided into three groups according to high-resolution molecular typing. SPSS version 17.0 was used to analysis and compare the statistics of engraftment, incidence of GVHD, other complications and survival among the groups. RESULTS: One hundred and eleven patients received UR-PBSCT, 60 of them with an HLA matched donor (10/10), 36 of them with a one locus mismatched donor (9/10), and 15 of them with a two loci mismatched donor (8/10). Similar basic characteristics were found in the three groups. No differences were found in engraftment of myeloid cells or platelets in the three groups (P > 0.05). Two-year cumulative incidence of relapse, overall survival (OS) and disease-free survival (DFS) among those three groups were similar (P > 0.05). The cumulative incidence of 100-day III-IV aGVHD in the HLA matched group and the one HLA locus mismatched group were significantly lower than that in the two HLA loci mismatched group (3.3%, 8.6%, and 26.7%, P = 0.009). The occurrence rate of new pulmonary infections in the HLA matched group was lower than in the two HLA mismatched groups (26.67%, 52.78%, and 41.18%, P = 0.035). The cumulative incidence of 100-day and 2-year transplantation related mortality (TRM) in two HLA loci mismatched group was higher than in the HLA matched group and in the one HLA locus mismatched group, (8.4%, 11.8% and 33.3%, P = 0.016) and (12.3%, 18.7% and 47.5%, P = 0.002). CONCLUSIONS: HLA mismatch will not significantly impact the engraftment or 2-year survival after UR-PBSCT, but two mismatched HLA loci may increase the cumulative incidence of severe aGVHD and TRM.

[Clinical analysis of 10 patients with subcutaneous panniculitis-like T cell lymphoma].

This study was purposed to evaluate the clinical and pathological features, prognosis of patients with subcutaneous panniculitis-time T cell lymphoma (SPTCL). The clinicopathologic features, immunophenotypes and treatment of 10 SPTCL patients which confirmed by pathology were analyzed retrospectively. The results showed that the main clinical manifestations of SPTCL were the single or multiple subcutaneous nodules. Of them 8 cases were found with recurrent high fever, weight loss, injury of liver function, bone marrow involvement and pancytopenia. This disease rapidly advanced. Pathologically, atypical large, medium-size and small-lymphocytes rounded the lipocytes look like rosettes. The reactive proliferation of histiocytes accompanied by phagothrocytic phenomena, polynuclear giant cells and granulomatous reaction. The tumor cells infiltrated into the lipolubuls. This lymphoma expressed the cytotoxic T-cell immunophenotype. CHOP regimen was the most common chemotherapy regimen used. 60% patients achieved a good initial response to chemotherapy. 3-year survival was 10%, with median survival time of 10 months. It is concluded that SPTCL is a specific type of lymphoma involving primarily in subcutaneous fatty tissues, most cases of SPTCL display an aggressive course, the disease may progress rapidly and accompanies with unfavorable prognosis. And the prognosis is poor in SPTCL patients with hemophagocytic syndrome. but the allo-HSCT can improve the outcome of this disease.

[Clinical analysis of 12 patients with angioimmunoblastic T cell lymphoma].

To evaluate the clinical, pathological characters and prognosis of patients with angioimmunoblastic T cell lymphoma (AITL), the clinicopathologic features, immunophenotypes, therapy and survival rate of 12 AITL patients which were confirmed by pathologic examination were retrospectively studied. The results indicated that main symptom was observed as general lymphadenopathy, however, 9 patients had fever. The diagnosis of AITL was based on lymph-node biopsy. The histopathologic characteristics of AITL showed the damage of normal lymphnode structure, the proliferation of immunoblastic cells and arborescent super vascularization. All immunophenotypes were mature peripheral T-cellular. CVP regimen was the most common chemotherapy regimen used for patients. 58% patients have a good initial response to chemotherapy. 3-year survival was 25%, with median survival time of 25 months. In conclusion, most cases of AITL display an aggressive course, therefore, the disease progresses rapidly and has unfavorable prognosis, further studies are required to improve its therapy regimen.