FHPM: Fine-grained Huge Page Management For Virtualization

As more data-intensive tasks with large footprints are deployed in virtual machines (VMs), huge pages are widely used to eliminate the increasing address translation overhead. However, once the huge page mapping is established, all the base page regions in the huge page share a single extended page table (EPT) entry, so that the hypervisor loses awareness of accesses to base page regions. None of the state-of-the-art solutions can obtain access information at base page granularity for huge pages. We observe that this can lead to incorrect decisions by the hypervisor, such as incorrect data placement in a tiered memory system and unshared base page regions when sharing pages. This paper proposes FHPM, a fine-grained huge page management for virtualization without hardware and guest OS modification. FHPM can identify access information at base page granularity, and dynamically promote and demote pages. A key insight of FHPM is to redirect the EPT huge page directory entries (PDEs) to new companion pages so that the MMU can track access information within huge pages. Then, FHPM can promote and demote pages according to the current hot page pressure to balance address translation overhead and memory usage. At the same time, FHPM proposes a VM-friendly page splitting and collapsing mechanism to avoid extra VM-exits. In combination, FHPM minimizes the monitoring and management overhead and ensures that the hypervisor gets fine-grained VM memory accesses to make the proper decision. We apply FHPM to improve tiered memory management (FHPM-TMM) and to promote page sharing (FHPM-Share). FHPM-TMM achieves a performance improvement of up to 33% and 61% over the pure huge page and base page management. FHPM-Share can save 41% more memory than Ingens, a state-of-the-art page sharing solution, with comparable performance

Specific TLR-mediated HSP70 activation plays a potential role in host defense against the intestinal parasite Giardia duodenalis

Giardia duodenalis, an important flagellated noninvasive protozoan parasite, infects the upper small intestine and causes a disease termed giardiasis globally. Few members of the heat shock protein (HSP) family have been shown to function as potential defenders against microbial pathogens, while such information is lacking for Giardia. Here we initially screened and indicated that in vitro Giardia challenge induced a marked early upregulation of HSP70 in intestinal epithelial cells (IECs). As noted previously, apoptotic resistance, nitric oxide (NO)-dependent cytostatic effect and parasite clearance, and epithelial barrier integrity represent effective anti-Giardia host defense mechanisms. We then explored the function of HSP70 in modulating apoptosis, NO release, and tight junction (TJ) protein levels in Giardia-IEC interactions. HSP70 inhibition by quercetin promoted Giardia-induced IEC apoptosis, viability decrease, NO release reduction, and ZO-1 and occludin downregulation, while the agonist celastrol could reverse these Giardia-evoked effects. The results demonstrated that HSP70 played a previously unrecognized and important role in regulating anti-Giardia host defense via attenuating apoptosis, promoting cell survival, and maintaining NO and TJ levels. Owing to the significance of apoptotic resistance among those defense-related factors mentioned earlier, we then elucidated the anti-apoptotic mechanism of HSP70. It was evident that HSP70 could negatively regulate apoptosis in an intrinsic way via direct inhibition of Apaf-1 or ROS-Bax/Bcl-2-Apaf-1 axis, and in an extrinsic way via cIAP2-mediated inhibition of RIP1 activity. Most importantly, it was confirmed that HSP70 exerted its host defense function by downregulating apoptosis via Toll-like receptor 4 (TLR4) activation, upregulating NO release via TLR4/TLR2 activation, and upregulating TJ protein expression via TLR2 activation. HSP70 represented a checkpoint regulator providing the crucial link between specific TLR activation and anti-Giardia host defense responses. Strikingly, independent of the checkpoint role of HSP70, TLR4 activation was proven to downregulate TJ protein expression, and TLR2 activation to accelerate apoptosis. Altogether, this study identified HSP70 as a potentially vital defender against Giardia, and revealed its correlation with specific TLR activation. The clinical importance of HSP70 has been extensively demonstrated, while its role as an effective therapeutic target in human giardiasis remains elusive and thus needs to be further clarified

Mapping of Cu and Pb Contaminations in Soil Using Combined Geochemistry, Topography, and Remote Sensing: A Case Study in the Le’an River Floodplain, China

Heavy metal pollution in soil is becoming a widely concerning environmental problem in China. The aim of this study is to integrate multiple sources of data, namely total Cu and Pb contents, digital elevation model (DEM) data, remote sensing image and interpreted land-use data, for mapping the spatial distribution of total Cu and Pb contamination in top soil along the Le’an River and its branches. Combined with geographical analyses and watershed delineation, the source and transportation route of pollutants are identified. Regions at high risk of Cu or Pb pollution are suggested. Results reveal that topography is the major factor that controls the spatial distribution of Cu and Pb. Watershed delineation shows evidence that the streamflow resulting from rainfall is the major carrier of metal pollutants

Study on diversity, nitrogen-fixing capacity, and heavy metal tolerance of culturable Pongamia pinnata rhizobia in the vanadium-titanium magnetite tailings

IntroductionThe diversity, nitrogen-fixing capacity and heavy metal tolerance of culturable rhizobia in symbiotic relationship with Pongamia pinnata surviving in vanadium (V) - titanium (Ti) magnetite (VTM) tailings is still unknown, and the rhizobia isolates from the extreme barren VTM tailings contaminated with a variety of metals would provide available rhizobia resources for bioremediation.MethodsP. pinnata plants were cultivated in pots containing the VTM tailings until root nodules formed, and then culturable rhizobia were isolated from root nodules. The diversity, nitrogen-fixing capacity and heavy metal tolerance of rhizobia were performed.ResultsAmong 57 rhizobia isolated from these nodules, only twenty strains showed different levels of tolerance to copper (Cu), nickel (Ni), manganese (Mn) and zinc (Zn), especially strains PP1 and PP76 showing high tolerance against these four heavy metals. Based on the phylogenetic analysis of 16S rRNA and four house-keeping genes (atpD, recA, rpoB, glnII), twelve isolates were identified as Bradyrhizobium pachyrhizi, four as Ochrobactrum anthropic, three as Rhizobium selenitireducens and one as Rhizobium pisi. Some rhizobia isolates showed a high nitrogen-fixing capacity and promoted P. pinnata growth by increasing nitrogen content by 10%-145% in aboveground plant part and 13%-79% in the root. R. pachyrhizi PP1 showed the strongest capacity of nitrogen fixation, plant growth promotion and resistance to heavy metals, which provided effective rhizobia strains for bioremediation of VTM tailings or other contaminated soils. This study demonstrated that there are at least three genera of culturable rhizobia in symbiosis with P. pinnata in VTM tailings.DiscussionAbundant culturable rhizobia with the capacity of nitrogen fixation, plant growth promotion and resistance to heavy metals survived in VTM tailings, indicating more valuable functional microbes could be isolated from extreme soil environments such as VTM tailings

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs

Different Temporal Stability and Responses to Droughts between Needleleaf Forests and Broadleaf Forests in North China during 2001–2018

Droughts can affect the physiological activity of trees, damage tissues, and even trigger mortality, yet the response of different forest types to drought at the decadal time scale remains uncertain. In this study, we used two remote sensing-based vegetation products, the MODIS enhanced vegetation index (EVI) and MODIS gross primary productivity (GPP), to explore the temporal stability of deciduous needleleaf forests (DNFs) and deciduous broadleaf forests (DBFs) in droughts and their legacy effects in North China from 2001 to 2018. The results of both products showed that the temporal stability of DBFs was consistently much higher than that of DNFs, even though the DBFs experienced extreme droughts and the DNFs did not. The DBFs also exhibited similar patterns in their legacy effects from droughts, with these effects extending up to 4 years after the droughts. These results indicate that DBFs have been better acclimated to drought events in North China. Furthermore, the results suggest that the GPP was more sensitive to water variability than EVI. These findings will be helpful for forest modeling, management, and conservation