Development of Dual Reconstituted Humanized Mice for Studies of HIV-1 Neuropathogenesis

Extensive research have been conducted to dissect the rapidly evolving mechanism of human immunodeficiency virus (HIV-1) neuropathogenesis, and to investigate the viral reservoirs in the central nervous system (CNS), which is considered as a major barrier for the viral eradication. These efforts have been hindered due to the paucity of relevant animal models of progressive HIV-1 brain infections. Therefore, we developed a brand new mouse model reconstituted with both a human immune system and human glia (primarily astrocyte and oligodendrocyte lineage) in the brain. We transplanted newborn NOD/SCID/IL2Rγc−/− (NSG) mice with human neural progenitor cells (NPCs) in the lateral ventricle and hematopoietic stem cells (HSCs) in the liver at birth. Human astrocytes repopulated the white matter and periventricular mouse brain regions in an anatomically symmetrical manner, with the highest level of reconstitution in corpus callosum and periventricular region, and relatively low levels in other regions like frontal cortex, striatum and brain stem. Human glial engraftment induced transcriptional changes associated with multiple biological processes, including synaptic transportation, angiogenesis, and axon growth, ion channel activities, compared to non-reconstituted mice, as determined by next generation RNA sequencing. We then investigated the effects of HIV-1 infection on immune and glial cells pathological and molecular changes. The immune analyses of these HIV-1-infected mice showed increased meningeal and perivascular infiltration by human HLA-DR+ cells and surveillance by activated immune cells in brain tissue. The species-specific transcriptome analysis revealed alterations that were linked to interferon (IFN) type 1 and 2 signaling pathways (STAT1, 2, IRF9, MX1, ISG15, IFI6, CMPK2) and a range of host antiviral responses. Differentially expressed mouse genes in the hippocampus reflected tissue remodeling while down-regulated human genes were linked to altered cell growth, glial cytoskeleton reorganization, oligodendrocyte differentiation and myelin ensheathment (MBP, MOBP, PLP1, MAG and ZNF488). The results overlapped with the disease profile observed by others in human HIV-1 encephalitic brains. Therefore, this new model provided a promising future for study of human-specific viral-immune-glial interactions and discovery of new therapeutic targets for HIV-1 nervous system infection

Street Stall Economy in China in the COVID-19 Era: Dilemmas and the International Experience of Promoting the Normalization of Street Stall Economy

Compared with those major policies that need to be practiced over the years, the street stall economy is more like a special means after the epidemic, resulting in a “short and brilliant” heat. Nevertheless, the street stall economy revives is facing several dilemmas. This paper reveals the dilemma of the prosperity and development of the stall economy before and after the epidemic, followed by the international experience and enlightenment of promoting the normalization of street stall economy, ranging from street vendor’s legal status and road administrative promotion to street food safety and environmental protection. To sum up, employment is the foundation of people’s livelihood and the source of wealth, hence, stall economy plays an indispensable role to create a win-win working world and promote the formation of a sustainable economic

RGB-based Category-level Object Pose Estimation via Decoupled Metric Scale Recovery

While showing promising results, recent RGB-D camera-based category-level object pose estimation methods have restricted applications due to the heavy reliance on depth sensors. RGB-only methods provide an alternative to this problem yet suffer from inherent scale ambiguity stemming from monocular observations. In this paper, we propose a novel pipeline that decouples the 6D pose and size estimation to mitigate the influence of imperfect scales on rigid transformations. Specifically, we leverage a pre-trained monocular estimator to extract local geometric information, mainly facilitating the search for inlier 2D-3D correspondence. Meanwhile, a separate branch is designed to directly recover the metric scale of the object based on category-level statistics. Finally, we advocate using the RANSAC-P$n$P algorithm to robustly solve for 6D object pose. Extensive experiments have been conducted on both synthetic and real datasets, demonstrating the superior performance of our method over previous state-of-the-art RGB-based approaches, especially in terms of rotation accuracy. Code: https://github.com/goldoak/DMSR

Bi-level Actor-Critic for Multi-agent Coordination

Coordination is one of the essential problems in multi-agent systems. Typically multi-agent reinforcement learning (MARL) methods treat agents equally and the goal is to solve the Markov game to an arbitrary Nash equilibrium (NE) when multiple equilibra exist, thus lacking a solution for NE selection. In this paper, we treat agents \emph{unequally} and consider Stackelberg equilibrium as a potentially better convergence point than Nash equilibrium in terms of Pareto superiority, especially in cooperative environments. Under Markov games, we formally define the bi-level reinforcement learning problem in finding Stackelberg equilibrium. We propose a novel bi-level actor-critic learning method that allows agents to have different knowledge base (thus intelligent), while their actions still can be executed simultaneously and distributedly. The convergence proof is given, while the resulting learning algorithm is tested against the state of the arts. We found that the proposed bi-level actor-critic algorithm successfully converged to the Stackelberg equilibria in matrix games and find an asymmetric solution in a highway merge environment

Combining river replenishment and restrictions on groundwater pumping to achieve groundwater balance in the Juma River Plain, North China Plain

In recent years, to alleviate the decline in groundwater levels, extensive restrictions on groundwater pumping have been implemented in the North China Plain (NCP). In September 2018, a large-scale ecological water replenishment project was executed involving 22 rivers and lakes. How to adjust the layout of reduction on groundwater pumping within the context of ecological water replenishment is a key issue to be addressed in the study of groundwater level recovery in the NCP. This study adopted the Juma River Plain in Baoding city as a case study, established a numerical model of river replenishment of groundwater, predicted groundwater level changes over the next 15 years (2021–2035) and quantitatively calculated the impact of river replenishment on groundwater levels. To achieve the goal of an overall groundwater balance by 2035, a suitable groundwater pumping restriction scenario was defined based on the impact of river replenishment on groundwater levels. The results indicated that by 2035, the relative rise in groundwater levels attributed to river replenishment and restrictions on groundwater pumping could reach 3.51 and 2.28 m, respectively. River replenishment significantly impacts groundwater levels, especially those near the river. Under the current groundwater exploitation conditions, river replenishment could ensure groundwater level recovery near the river, which accounts for 15% of the total study area. The goal of an overall groundwater balance by 2035 could be achieved if restrictions on groundwater pumping were superimposed, with an average annual reduction of 56 million m3. This study provides valuable insights into groundwater management across the NCP. The proposed methods are useful for the management of other depleted aquifers recharged via ecological water replenishment

Comparative analysis of aroma components and quality of Geotrichum candidum after space mutation breeding

AimThe aroma-producing strain of Geotrichum candidum GDMCC60675 was taken as the research object, the composition of aroma-producing substances of G. candidum was studied, and the target strains of G. candidum suitable for food additives were screened out by mutagenesis.MethodsMutants were obtained by space breeding. The colony morphology and cell morphology of the mutant strain were identified, the phylogenetic tree of the two strains was constructed, and the whole-genome sequences of the wild strain and the mutant strain were compared. The aroma components and key odor compounds of the two strains were analyzed and compared by HS-SPME-GC-MS and E-nose detection, and the data were processed by using the relative odor activity value (ROAV) analysis method.ResultsA mutant strain of G. candidum was found with different characteristics of aroma production compared with wild-type G. candidum. It was found that its colony morphology and cell morphology were similar. However, it was found that the aroma-producing substances produced by the two strains were different, and the key difference compound was phenyl ethyl alcohol, which also proved that the two strains were different, and the main aroma note was different