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Provable data possession (PDP) is a crucial means of protecting the integrity of data in the domain of cloud storage. In the post-quantum era, the PDP scheme that uses lattices relies too heavily on the third-party auditor (TPA), which is not entirely trustworthy and is easily affected by a single point of failure. Moreover, the scheme often leads to the leakage of private user data while attempting to satisfy the demand for public verification. In response to the above problems, this paper designs a protocol for post-quantum privacy-preserving PDP and uses it to develop a scheme based on smart contracts. The proposed scheme has the characteristics of being post quantum and can satisfy the demand for public verification while preserving user privacy. The property of noninteraction of the protocol can reduce transaction fees incurred owing to the frequent operation of the blockchain, and the smart contract with a deposit mechanism can ensure fair payments to all parties. The results of a theoretical analysis and experiments show that the proposed scheme is highly secure and efficient.

How species diverge into different lineages is a central issue in evolutionary biology. Despite the increasing evidence indicating that such divergences do not need geographic isolation, the correlation between lineage divergence and the adaptive ecological divergence of phenotype corresponding to distribution is still unknown. In addition, gene flow has been widely detected during and through such diverging processes. We used one widely distributed Aquilegia viridiflora complex as a model system to examine genomic differentiation and corresponding phenotypic variations along geographic gradients. Our phenotypic analyses of 20 populations from northwest to northeast China identified two phenotypic groups along the geographic cline. All examined traits are distinct from each other, although a few intermediate individuals occur in their contacting regions. We further sequenced the genomes of representative individuals of each population. However, four distinct genetic lineages were detected based on nuclear genomes. In particular, we recovered numerous genetic hybrids in the contact regions of four lineages. Gene flow is widespread and continuous between four lineages but much higher between contacting lineages than geographically isolated lineages. Gene flow and natural selection might result in inconsistency between heredity and phenotype. Moreover, many genes with fast lineage-specific mutations were identified to be involved in local adaptation. Our results suggest that both geographic isolation and local selection exerted by the environment and pollinators may together create geographic distributions of phenotypic variations as well as the underlying genomic divergences in numerous lineages.

Type 2 diabetes (T2D) is characterized by the malfunction of pancreatic β cells. Susceptibility and pathogenesis of T2D can be affected by multiple factors, including sex differences. However, the mechanisms underlying sex differences in T2D susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq), we demonstrate the presence of sexually dimorphic transcriptomes in mouse β cells. Using a high-fat diet-induced T2D mouse model, we identified sex-dependent T2D altered genes, suggesting sex-based differences in the pathological mechanisms of T2D. Furthermore, based on islet transplantation experiments, we found that compared to mice with sex-matched islet transplants, sex-mismatched islet transplants in healthy mice showed down-regulation of genes involved in the longevity regulating pathway of β cells. Moreover, the diabetic mice with sex-mismatched islet transplants showed impaired glucose tolerance. These data suggest sexual dimorphism in T2D pathogenicity, indicating that sex should be considered when treating T2D. We hope that our findings could provide new insights for the development of precision medicine in T2D.

The early window of human embryogenesis is largely a black box for developmental biologists. Here we probed the cellular diversity of 4- to 6-week human embryos when essentially all organs are just laid out. Based on over 180,000 single-cell transcriptomes, we generated a comprehensive atlas of 313 cell types in 18 developmental systems, which were annotated with a collection of ontology and markers from 157 publications. Together with spatial transcriptome on embryonic sections, we characterized the molecule and spatial architecture of previously unappreciated cell types. Combined with data from other vertebrates, the rich information shed light on spatial patterning of axes, systemic temporal regulation of developmental progression and potential human-specific regulation. Our study provides a compendium of early progenitor cells of human organs, which can serve as the root of lineage analysis in organogenesis.

Premise Aquilegia is an ideal taxon for studying the evolution of adaptive radiation. Current phylogenies of Aquilegia based on different molecular markers are inconsistent, and therefore a clear and accurate phylogeny remains uncertain. Analyzing the chloroplast genome, with its simple structure and low recombination rate, may help solve this problem. Methods Next-generation sequencing data were generated or downloaded for Aquilegia species, enabling their chloroplast genomes to be assembled. The assemblies were used to estimate the genome characteristics and infer the phylogeny of Aquilegia. Results In this study, chloroplast genome sequences were assembled for Aquilegia species distributed across Asia, North America, and Europe. Three of the genes analyzed (petG, rpl36, and atpB) were shown to be under positive selection and may be related to adaptation. The phylogenetic tree of Aquilegia showed that its member species formed two clades with high support, North American and European species, with the Asian species being paraphyletic; A. parviflora and A. amurensis clustered with the North American species, while the remaining Asian species were found in the European clade. In addition, A. oxysepala var. kansuensis should be considered as a separate species rather than a variety. Discussion The complete chloroplast genomes of these Aquilegia species provide new insights into the reconstruction of the phylogeny of related species and contribute to the further study of this genus.

Human embryonic stem cells (hESCs) derived β cells (SC-β cells) hold great promise for diabetes treatment, yet how to achieve functional maturation of these SC-β cells and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remain elusive. By single cell RNA-seq pseudotime analysis, we revealed that ZnT8 is involved in SC-β cells functional maturation process and its loss of function (LOF) accelerates functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) and enhances proinsulin to insulin conversion efficiency in SC-β cells, both in vitro and in vivo, by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, SC-β cells with ZnT8 LOF are resistant to metabolic stresses induced cell death, as lipotoxicity or glucotoxicity, displaying higher survival. Most importantly, transplantation of SLC30A8-/- SC-β cells into diabetic mice significantly improves glycemia restoration and SC-β cell survival with long-term stability. Therefore, our study offers an advanced cell replacement therapy for diabetes with both improved SC-β cell survival and function against metabolic stress.

Human embryonic stem cell-derived β cells (SC-β cells) hold great promise for treatment of diabetes, yet how to achieve functional maturation and protect them against metabolic stresses such as glucotoxicity and lipotoxicity remains elusive. Our single-cell RNA-seq analysis reveals that ZnT8 loss of function (LOF) accelerates the functional maturation of SC-β cells. As a result, ZnT8 LOF improves glucose-stimulated insulin secretion (GSIS) by releasing the negative feedback of zinc inhibition on insulin secretion. Furthermore, we demonstrate that ZnT8 LOF mutations endow SC-β cells with resistance to lipotoxicity/glucotoxicity-triggered cell death by alleviating endoplasmic reticulum (ER) stress through modulation of zinc levels. Importantly, transplantation of SC-β cells with ZnT8 LOF into mice with preexisting diabetes significantly improves glycemia restoration and glucose tolerance. These findings highlight the beneficial effect of ZnT8 LOF on the functional maturation and survival of SC-β cells that are useful as a potential source for cell replacement therapies.

scRNA-seq of an invariant cell lineage reveals insights into asymmetric cell division, FGF signaling, and notochord specification., Progressive unfolding of gene expression cascades underlies diverse embryonic lineage development. Here, we report a single-cell RNA sequencing analysis of the complete and invariant embryonic cell lineage of the tunicate Ciona savignyi from fertilization to the onset of gastrulation. We reconstructed a developmental landscape of 47 cell types over eight cell cycles in the wild-type embryo and identified eight fate transformations upon fibroblast growth factor (FGF) inhibition. For most FGF-dependent asymmetric cell divisions, the bipotent mother cell displays the gene signature of the default daughter fate. In convergent differentiation of the two notochord lineages, we identified additional gene pathways parallel to the master regulator T/Brachyury. Last, we showed that the defined Ciona cell types can be matched to E6.5-E8.5 stage mouse cell types and display conserved expression of limited number of transcription factors. This study provides a high-resolution single-cell dataset to understand chordate early embryogenesis and cell lineage differentiation.

Type 2 diabetes, characterized by malfunction of pancreatic β cells, is affected by multiple cues including sex differences. Nevertheless, mechanisms of sex differences in type 2 diabetes susceptibility and pathogenesis remain unclear. Using single-cell RNA sequencing (scRNA-seq) technology, we showed that sexual dimorphism of transcriptome exists in both mouse and human β cells, and differs significantly in human under diabetic condition. Our analysis further revealed the existence of sex-dependent type 2 diabetes altered genes in both mice and human beings, suggesting divergences in pathological mechanisms of type 2 diabetes between sexes. Our results indicated that sex should be taken into consideration when treating diabetes, which was further validated by the sex-matched and sex-mismatched islet transplantation in mice. Compared to sex-matched transplants, sex-mismatched transplants showed downregulation of genes involved in the longevity regulating pathway in β cells and led to impaired glucose tolerance in diabetic mice. Taken together, our findings could advance current understanding of type 2 diabetes pathogenesis with sexually dimorphic perspectives and provide new insights to the development of precision medicine.

This paper proposes an improved gray model of equal dimensional innovation based on time-varying parameters and the gray characteristics of small sample and poor information of the safety monitoring data during underground cavern construction, so as to predict and judge the deformation of surrounding rocks in underground caverns and to obtain relatively reliable results in the analysis of uncertain systems. Under certain conditions, the improved gray model of equal dimensional innovation based on time-varying parameters can be used to predict the deformation of surrounding rocks during the excavation of underground caverns, thereby providing mathematical analysis tools for safe construction.

Motivation It is well known that batch effects exist in RNA-seq data and other profiling data. Although some methods do a good job adjusting for batch effects by modifying the data matrices, it is still difficult to remove the batch effects entirely. The remaining batch effect can cause artifacts in the detection of patterns in the data. Results In this study, we consider the batch effect issue in the pattern detection among the samples, such as clustering, dimension reduction and construction of networks between subjects. Instead of adjusting the original data matrices, we design an adaptive method to directly adjust the dissimilarity matrix between samples. In simulation studies, the method achieved better results recovering true underlying clusters, compared to the leading batch effect adjustment method ComBat. In real data analysis, the method effectively corrected distance matrices and improved the performance of clustering algorithms. Availability and implementation The R package is available at: https://github.com/tengfei-emory/QuantNorm. Supplementary information Supplementary data are available at Bioinformatics online.