The use of SARS-CoV-2-related coronaviruses from bats and pangolins to polarize mutations in SARS-Cov-2

正Dear Editor,The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 coronavirus has become a global pandemic.The SARS-CoV-2 genome has a similarity of 96.2%to that of RaTG13, a bat SARS-CoV-2-related coronavirus detected in Rhinolophus affinis (Paraskevis et al., 2020; Zhou et al.,2020). The SARS-CoV-2 genome also has 85.5%-92.4%     

Variation in the phenology of photosynthesis among eastern white pine provenances in response to warming

In higher‐latitude trees, temperature and photoperiod control the beginning and end of the photosynthetically active season. Elevated temperature (ET) has advanced spring warming and delayed autumn cooling while photoperiod remains unchanged. We assessed the effects of warming on the length of the photosynthetically active season of three provenances of Pinus strobus L. seedlings from different latitudes, and evaluated the accuracy of the photochemical reflectance index (PRI) and the chlorophyll/carotenoid index (CCI) for tracking the predicted variation in spring and autumn phenology of photosynthesis among provenances. Seedlings from northern, local and southern P. strobus provenances were planted in a temperature‐free‐air‐controlled enhancement (T‐FACE) experiment and exposed to ET (+1.5/3°C; day/night). Over 18 months, we assessed photosynthetic phenology by measuring chlorophyll fluorescence, gas exchange, leaf spectral reflectance and pigment content. During autumn, all seedlings regardless of provenance followed the same sequence of phenological events with the initial downregulation of photosynthesis, followed by the modulation of non‐photochemical quenching and associated adjustments of zeaxanthin pool sizes. However, the timing of autumn downregulation differed between provenances, with delayed onset in the southern provenance (SP) and earlier onset in the northern relative to the local provenance, indicating that photoperiod at the provenance origin is a dominant factor controlling autumn phenology. Experimental warming further delayed the downregulation of photosynthesis during autumn in the SP. A provenance effect during spring was also observed but was generally not significant. The vegetation indices PRI and CCI were both effective at tracking the seasonal variations of energy partitioning in needles and the differences of carotenoid pigments indicative of the stress status of needles. These results demonstrate that PRI and CCI can be useful tools for monitoring conifer phenology and for the remote monitoring of the length of the photosynthetically active season of conifers in a changing climate.     

Phosphorus alleviation of nitrogen‐suppressed methane sink in global grasslands

Grassland ecosystems account for more than 10% of the global CH₄ sink in soils. A 4‐year field experiment found that addition of P alone did not affect CH₄ uptake and experimental addition of N alone significantly suppressed CH₄ uptake, whereas concurrent N and P additions suppressed CH₄ uptake to a lesser degree. A meta‐analysis including 382 data points in global grasslands corroborated these findings. Global extrapolation with an empirical modelling approach estimated that contemporary N addition suppresses CH₄ sink in global grassland by 11.4% and concurrent N and P deposition alleviates this suppression to 5.8%. The P alleviation of N‐suppressed CH₄ sink is primarily attributed to substrate competition, defined as the competition between ammonium and CH₄ for the methane mono‐oxygenase enzyme. The N and P impacts on CH₄ uptake indicate that projected increases in N and P depositions might substantially affect CH₄ uptake and alter the global CH₄ cycle.     

Xanthomonas campestris sensor kinase HpaS co-opts the orphan response regulator VemR to form a branched two-component system that regulates motility

Xanthomonas campestris pv. campestris (Xcc) controls virulence and plant infection mechanisms via the activity of the sensor kinase and response regulator pair HpaS/hypersensitive response and pathogenicity G (HrpG). Detailed analysis of the regulatory role of HpaS has suggested the occurrence of further regulators besides HrpG. Here we used in vitro and in vivo approaches to identify the orphan response regulator VemR as another partner of HpaS and to characterize relevant interactions between components of this signalling system. Bacterial two-hybrid and protein pull-down assays revealed that HpaS physically interacts with VemR. Phos-tag SDS-PAGE analysis showed that mutation in hpaS reduced markedly the phosphorylation of VemR in vivo. Mutation analysis reveals that HpaS and VemR contribute to the regulation of motility and this relationship appears to be epistatic. Additionally, we show that VemR control of Xcc motility is due in part to its ability to interact and bind to the flagellum rotor protein FliM. Taken together, the findings describe the unrecognized regulatory role of sensor kinase HpaS and orphan response regulator VemR in the control of motility in Xcc and contribute to the understanding of the complex regulatory mechanisms used by Xcc during plant infection.     

Berberine ameliorates cellular senescence and extends the lifespan of mice via regulating p16 and cyclin protein expression

Although aging and senescence have been extensively studied in the past few decades, however, there is lack of clinical treatment available for anti‐aging. This study presents the effects of berberine (BBR) on the aging process resulting in a promising extension of lifespan in model organisms. BBR extended the replicative lifespan, improved the morphology, and boosted rejuvenation markers of replicative senescence in human fetal lung diploid fibroblasts (2BS and WI38). BBR also rescued senescent cells with late population doubling (PD). Furthermore, the senescence‐associated β‐galactosidase (SA‐β‐gal)‐positive cell rates of late PD cells grown in the BBR‐containing medium were ~72% lower than those of control cells, and its morphology resembled that of young cells. Mechanistically, BBR improved cell growth and proliferation by promoting entry of cell cycles from the G₀ or G₁ phase to S/G₂‐M phase. Most importantly, BBR extended the lifespan of chemotherapy‐treated mice and naturally aged mice by ~52% and ~16.49%, respectively. The residual lifespan of the naturally aged mice was extended by 80%, from 85.5 days to 154 days. The oral administration of BBR in mice resulted in significantly improved health span, fur density, and behavioral activity. Therefore, BBR may be an ideal candidate for the development of an anti‐aging medicine.     

Aging shifts mitochondrial dynamics toward fission to promote germline stem cell loss

Changes in mitochondrial dynamics (fusion and fission) are known to occur during stem cell differentiation; however, the role of this phenomenon in tissue aging remains unclear. Here, we report that mitochondrial dynamics are shifted toward fission during aging of Drosophila ovarian germline stem cells (GSCs), and this shift contributes to aging‐related GSC loss. We found that as GSCs age, mitochondrial fragmentation and expression of the mitochondrial fission regulator, Dynamin‐related protein (Drp1), are both increased, while mitochondrial membrane potential is reduced. Moreover, preventing mitochondrial fusion in GSCs results in highly fragmented depolarized mitochondria, decreased BMP stemness signaling, impaired fatty acid metabolism, and GSC loss. Conversely, forcing mitochondrial elongation promotes GSC attachment to the niche. Importantly, maintenance of aging GSCs can be enhanced by suppressing Drp1 expression to prevent mitochondrial fission or treating with rapamycin, which is known to promote autophagy via TOR inhibition. Overall, our results show that mitochondrial dynamics are altered during physiological aging, affecting stem cell homeostasis via coordinated changes in stemness signaling, niche contact, and cellular metabolism. Such effects may also be highly relevant to other stem cell types and aging‐induced tissue degeneration.     

Genetically Encoded FRET Biosensor Detects the Enzymatic Activity of Prostate-Specific Antigen

Prostate cancer is the most common cancer among men beyond 50 years old, and ranked the second in mortality. The level of Prostate-specific antigen (PSA) in serum has been a routine biomarker for clinical assessment of the cancer development, which is detected mostly by antibody-based immunoassays. The proteolytic activity of PSA also has important functions. Here a genetically encoded biosensor based on fluorescence resonance energy transfer (FRET) technology was developed to measure PSA activity. In vitro assay showed that the biosensor containing a substrate peptide ‘RLSSYYSGAG’ had 400% FRET change in response to 1 µg/ml PSA within 90 min, and could detect PSA activity at 25 ng/ml. PSA didn’t show enzymatic activity toward the biosensor in serum solution, likely reflecting the existence of other inhibitory factors besides Zn2+. By expressing the biosensor on cell plasma membrane, the FRET responses were significant, but couldn’t distinguish well the cultured prostate cancer cells from non-prostate cancer cells under microscopy imaging, indicating insufficient speci- ficity to PSA. The biosensor with the previously known ‘HSSKLQ’ substrate showed little response to PSA in solution. In summary, we developed a genetically encoded FRET biosensor to detect PSA activity, which may serve as a useful tool for relevant applications, such as screening PSA activation substrates or inhibitors; the purified biosensor protein can also be an alternative choice for measuring PSA activity besides currently commercialized Mu-HSSKLQ-AMC substrate from chemical synthesis.     

Protosappanin‐A and oleanolic acid protect injured podocytes from apoptosis through inhibition of AKT‐mTOR signaling

Protosappanin‐A (PrA) and oleanolic acid (OA), which are important effective ingredients isolated from Caesalpinia sappan L., exhibit therapeutic potential in multiple diseases. This study focused on exploring the mechanisms of PrA and OA function in podocyte injury. An in vitro model of podocyte injury was induced by the sC5b‐9 complex and assays such as cell viability, apoptosis, immunofluorescence, quantitative real‐time polymerase chain reaction, and western blot were performed to further investigate the effects and mechanisms of PrA and OA in podocyte injury. The models of podocyte injury were verified to be successful as seen through significantly decreased levels of nephrin, podocin, and CD2AP and increased level of desmin. The sC5b‐9‐induced podocyte apoptosis was inhibited in injured podocytes treated with PrA and OA, accompanied by increased protein levels of nephrin, podocin, CD2AP, and Bcl2 and decreased levels of desmin and Bax. The p‐AKT/p‐mTOR levels were also reduced by treatment of PrA and OA while AKT/mTOR was unaltered. Further, the effects of PrA and OA on injured podocytes were similar to that of LY294002 (a PI3K‐AKT inhibitor). PrA and OA were also seen to inhibit podocyte apoptosis and p‐AKT/p‐mTOR levels induced by IGF‐1 (a PI3K‐AKT activator). Our data demonstrate that PrA and OA can protect podocytes from injury or apoptosis, which may occur through inhibition of the abnormal activation of AKT‐mTOR signaling.