Merger rate of supermassive primordial black hole binaries

The probability that the primordial black hole (PBH) binaries formed in the early Universe can be affected by the Hubble expansion of background, which is non-negligible when the number density of PBHs is very low (it is actually this case for supermassive PBHs). In this paper, taking into account the effect of cosmic expansion on the comoving distance of PBH pairs, we worked out the merger rate of PBHs with any extended mass function. The torques by all PBHs and linear density perturbations are also considered. It is found that the merger rate of PBH, $M\gtrsim 10^6M_\odot$, binaries is significantly lower for $f_\text{pbh}\lesssim 0.01$ than expected.Comment: 16 pages, 5 figure

Interpretable rumor detection in microblogs by attending to user interactions

We address rumor detection by learning to differentiate between the community's response to real and fake claims in microblogs. Existing state-of-the-art models are based on tree models that model conversational trees. However, in social media, a user posting a reply might be replying to the entire thread rather than to a specific user. We propose a post-level attention model (PLAN) to model long distance interactions between tweets with the multi-head attention mechanism in a transformer network. We investigated variants of this model: (1) a structure aware self-attention model (StA-PLAN) that incorporates tree structure information in the transformer network, and (2) a hierarchical token and post-level attention model (StA-HiTPLAN) that learns a sentence representation with token-level self-attention. To the best of our knowledge, we are the first to evaluate our models on two rumor detection data sets: the PHEME data set as well as the Twitter15 and Twitter16 data sets. We show that our best models outperform current state-of-the-art models for both data sets. Moreover, the attention mechanism allows us to explain rumor detection predictions at both token-level and post-level

Integrating TSPO PET imaging and transcriptomics to unveil the role of neuroinflammation and amyloid-β deposition in Alzheimer's disease.

PURPOSE Despite the revealed role of immunological dysfunctions in the development and progression of Alzheimer's disease (AD) through animal and postmortem investigations, direct evidence regarding the impact of genetic factors on microglia response and amyloid-β (Aβ) deposition in AD individuals is lacking. This study aims to elucidate this mechanism by integrating transcriptomics and TSPO, Aβ PET imaging in clinical AD cohort. METHODS We analyzed 85 patients with PET/MR imaging for microglial activation (TSPO, [18F]DPA-714) and Aβ ([18F]AV-45) within the prospective Alzheimer's Disease Immunization and Microbiota Initiative Study Cohort (ADIMIC). Immune-related differentially expressed genes (IREDGs), identified based on AlzData, were screened and verified using blood samples from ADIMIC. Correlation and mediation analyses were applied to investigate the relationships between immune-related genes expression, TSPO and Aβ PET imaging. RESULTS TSPO uptake increased significantly both in aMCI (P < 0.05) and AD participants (P < 0.01) and showed a positive correlation with Aβ deposition (r = 0.42, P < 0.001). Decreased expression of TGFBR3, FABP3, CXCR4 and CD200 was observed in AD group. CD200 expression was significantly negatively associated with TSPO PET uptake (r =-0.33, P = 0.013). Mediation analysis indicated that CD200 acted as a significant mediator between TSPO uptake and Aβ deposition (total effect B = 1.92, P = 0.004) and MMSE score (total effect B =-54.01, P = 0.003). CONCLUSION By integrating transcriptomics and TSPO PET imaging in the same clinical AD cohort, this study revealed CD200 played an important role in regulating neuroinflammation, Aβ deposition and cognitive dysfunction

Efficacy and Safety of Tribendimidine Against Clonorchis sinensis

In this randomized open-label trial, tribendimidine was shown to have an efficacy comparable to praziquantel for the treatment of Clonorchis sinensis infection. Patients treated with praziquantel experienced significantly more adverse events than tribendimidine recipient

Towards Al3+-Induced Manganese-Containing Superoxide Dismutase Inactivation and Conformational Changes: An Integrating Study with Docking Simulations

Superoxide dismutase (SOD, EC 1.15.1.1) plays an important antioxidant defense role in skins exposed to oxygen. We studied the inhibitory effects of Al3+ on the activity and conformation of manganese-containing SOD (Mn-SOD). Mn-SOD was significantly inactivated by Al3+ in a dose-dependent manner. The kinetic studies showed that Al3+ inactivated Mn-SOD follows the first-order reaction. Al3+ increased the degree of secondary structure of Mn-SOD and also disrupted the tertiary structure of Mn-SOD, which directly resulted in enzyme inactivation. We further simulated the docking between Mn-SOD and Al3+ (binding energy for Dock 6.3: −14.07 kcal/mol) and suggested that ASP152 and GLU157 residues were predicted to interact with Al3+, which are not located in the Mn-contained active site. Our results provide insight into the inactivation of Mn-SOD during unfolding in the presence of Al3+ and allow us to describe a ligand binding via inhibition kinetics combined with the computational prediction

Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>CD8⁺effector cells often have an antitumor function in patients with cancer. However, CD8⁺Foxp3⁺regulatory T cells (Tcregs) and interleukin (IL)-17-producing CD8⁺T cells (Tc17 cells) also derive from the CD8⁺T cell lineage. Their role in the antitumor response remains largely unknown. In the present study, we aimed to investigate the distribution, characterization, and generation of CD8⁺Tcregs and Tc17 cells in NPC patients.</p> <p>Methods</p> <p>Peripheral blood and tumor biopsy tissues from 21 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were collected, along with peripheral blood from 21 healthy donors. The biological characteristics of Tcregs and Tc17 cells from blood and tumor tissues were examined by intracellular staining, tetramer staining and fluorescence-activated cell sorting (FACS) analysis. The suppressive function of Tcregs was investigated using a proliferation assay that involved co-culture of sorted CD8⁺CD25⁺T cells with naïve CD4⁺T cells <it>in vitro</it>.</p> <p>Results</p> <p>We observed an increased prevalence of Tcregs and Tc17 cells among tumor-infiltrating lymphocytes (TILs) and different distribution among peripheral blood mononuclear cells (PBMCs) in NPC patients. Cytokine profiles showed that the Tcregs expressed a high level of IL-10 and low level of transforming growth factor β, whereas Tc17 cells expressed a high level of tumor necrosis factor α. Interestingly, both subsets expressed a high level of interferon γ in TILs, and the Tcregs suppressed naïve CD4⁺T cell proliferation by a cell contact-dependent mechanism <it>in vitro</it>. Moreover, we demonstrated the existence of Epstein-Barr virus latent membrane protein (LMP) 1 and LMP2 antigen-specific Tcregs in NPC.</p> <p>Conclusions</p> <p>Our data provide new insights into the composition and function of CD8⁺T-cell subsets in NPC, which may have an important influence on NPC immunotherapy.</p

Recurrent DNMT3A R882 Mutations in Chinese Patients with Acute Myeloid Leukemia and Myelodysplastic Syndrome

Somatic mutations of DNMT3A gene have recently been reported in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We examined the entire coding sequences of DNMT3A gene by high-resolution melting analysis and sequencing in Chinese patients with myeloid malignancies. R882 mutations were found in 12/182 AML and in 4/51 MDS, but not in either 79 chronic myeloid leukemia (CML), or 57 myeloproliferative neoplasms (MPNs), or 4 chronic monomyelocytic leukemia. No other DNMT3A mutations were detected in all patients. R882 mutations were associated with old age and more frequently present in monoblastic leukemia (M4 and M5, 7/52) compared to other subtypes (5/130). Furthermore, 14/16 (86.6%) R882 mutations were observed in patients with normal karyotypes. The overall survival of mutated MDS patients was shorter than those without mutation (median 9 and 25 months, respectively). We conclude that DNMT3A R882 mutations are recurrent molecular aberrations in AML and MDS, and may be an adverse prognostic event in MDS