Equilibrium problems on Riemannian manifolds with applications

We study the equilibrium problem on general Riemannian manifolds. The results on existence of solutions and on the convex structure of the solution set are established. Our approach consists in relating the equilibrium problem to a suitable variational inequality problem on Riemannian manifolds, and is completely different from previous ones on this topic in the literature. As applications, the corresponding results for the mixed variational inequality and the Nash equilibrium are obtained. Moreover, we formulate and analyze the convergence of the proximal point algorithm for the equilibrium problem. In particular, correct proofs are provided for the results claimed in J. Math. Anal. Appl. 388, 61-77, 2012 (i.e., Theorems 3.5 and 4.9 there) regarding the existence of the mixed variational inequality and the domain of the resolvent for the equilibrium problem on Hadamard manifolds.National Natural Science Foundation of ChinaNatural Science Foundation of Guizhou Province (China)Dirección General de Enseñanza SuperiorJunta de AndalucíaNational Science Council of Taiwa

Single-Cell RNA Sequencing of hESC-Derived 3D Retinal Organoids Reveals Novel Genes Regulating RPC Commitment in Early Human Retinogenesis.

The development of the mammalian retina is a complicated process involving the generation of distinct types of neurons from retinal progenitor cells (RPCs) in a spatiotemporal-specific manner. The progression of RPCs during retinogenesis includes RPC proliferation, cell-fate commitment, and specific neuronal differentiation. In this study, by performing single-cell RNA sequencing of cells isolated from human embryonic stem cell (hESC)-derived 3D retinal organoids, we successfully deconstructed the temporal progression of RPCs during early human retinogenesis. We identified two distinctive subtypes of RPCs with unique molecular profiles, namely multipotent RPCs and neurogenic RPCs. We found that genes related to the Notch and Wnt signaling pathways, as well as chromatin remodeling, were dynamically regulated during RPC commitment. Interestingly, our analysis identified that CCND1, a G1-phase cell-cycle regulator, was coexpressed with ASCL1 in a cell-cycle-independent manner. Temporally controlled overexpression of CCND1 in retinal organoids demonstrated a role for CCND1 in promoting early retinal neurogenesis. Together, our results revealed critical pathways and novel genes in early retinogenesis of humans

Viruses mobilize plant immunity to deter nonvector insect herbivores.

A parasite-infected host may promote performance of associated insect vectors; but possible parasite effects on nonvector insects have been largely unexplored. Here, we show that Begomovirus, the largest genus of plant viruses and transmitted exclusively by whitefly, reprogram plant immunity to promote the fitness of the vector and suppress performance of nonvector insects (i.e., cotton bollworm and aphid). Infected plants accumulated begomoviral βC1 proteins in the phloem where they were bound to the plant transcription factor WRKY20. This viral hijacking of WRKY20 spatiotemporally redeployed plant chemical immunity within the leaf and had the asymmetrical benefiting effects on the begomoviruses and its whitefly vectors while negatively affecting two nonvector competitors. This type of interaction between a parasite and two types of herbivores, i.e., vectors and nonvectors, occurs widely in various natural and agricultural ecosystems; thus, our results have broad implications for the ecological significance of parasite-vector-host tripartite interactions

Re-evaluation of the carcinogenic significance of hepatitis B virus integration in hepatocarcinogenesis

To examine the role of hepatitis B virus (HBV) integration in hepatocarcinogenesis, a systematic comparative study of both tumor and their corresponding non-tumor derived tissue has been conducted in a cohort of 60 HBV associated hepatocellular carcinoma (HCC) patients. By using Alu-polymerase chain reaction (PCR) and ligation-mediated PCR, 233 viral-host junctions mapped across all human chromosomes at random, no difference between tumor and non-tumor tissue was observed, with the exception of fragile sites (P = 0.0070). HBV insertions in close proximity to cancer related genes such as hTERT were found in this study, however overall they were rare events. No direct correlation between chromosome aberrations and the number of HBV integration events was found using a sensitive array-based comparative genomic hybridization (aCGH) assay. However, a positive correlation was observed between the status of several tumor suppressor genes (TP53, RB1, CDNK2A and TP73) and the number of chromosome aberrations (r = 0.6625, P = 0.0003). Examination of the viral genome revealed that 43% of inserts were in the preC/C region and 57% were in the HBV X gene. Strikingly, approximately 24% of the integrations examined had a breakpoint in a short 15 nt viral genome region (1820-1834 nt). As a consequence, all of the confirmed X gene insertions were C-terminal truncated, losing their growth-suppressive domain. However, the same pattern of X gene C-terminal truncation was found in both tumor and non-tumor derived samples. Furthermore, the integrated viral sequences in both groups had a similar low frequency of C1653T, T1753V and A1762T/G1764A mutations. The frequency and patterns of HBV insertions were similar between tumor and their adjacent non-tumor samples indicating that the majority of HBV DNA integration events are not associated with hepatocarcinogenesis

Survival outcomes of autologous breast reconstruction after mastectomy: A matched case-control study

BackgroundDue to the lack of strong evidence-based medical evidence, the relationship between autologous breast reconstruction (ABR) after mastectomy and long-term prognosis is unclear. This study aims to explore if ABR after mastectomy is associated with the prognosis of breast cancer (BC) patients based on the data from the Surveillance, Epidemiology, and End Results (SEER) database.MethodsWe collected data for all cases diagnosed with BC who underwent or did not undergo ABR after mastectomy from 2010-2015 in the SEER database. The primary outcome of our study was overall survival (OS) and cancer specific survival (CSS). The Propensity Score-Matched (PSM) analysis was used to eliminate the effects of non-random statistics, setting the caliper as 0.0001 to balance the baseline variables within the groups. Chi-square test, Kaplan-Meier method, univariate and multivariate cox regression analysis were used to analyze the data and subgroup analysis was performed to find the subgroups of people who might benefit from ABR.ResultOf 27893 eligible patients, 11038 patients were matched. The cohort consisted of 5519 (50%) ABR patients and 5519 (50%) non-ABR patients after PSM. After PSM, on multivariate cox regression analysis, ABR still exerted a significant influence on the OS (hazard ratio (HR), 0.83, P< 0.05). However, no statistical difference was shown on CSS (HR, 0.93, P = 0.31). Kaplan-Meier survival analysis showed ABR group had better OS (P = 0.001), but similar CSS (P = 0.174) between ARB and mastectomy groups. Subgroup analysis showed that after matching, those with 50-59 years old, earlier stages of disease, without a marital partner and living in urban areas had better OS after ABR.ConclusionsABR after mastectomy was associated with better OS, but not affect CSS