兰州唐古特白刺根际微生物分离鉴定

【目的】从兰州唐古特白刺根际分离得到对植物有潜在促生效果的功能微生物，为研发相关菌种制剂的研究奠定基础。【方法】通过平板划线法从其根际分离纯化出6株细菌，并对菌株进行形态特征观察、革兰氏染色等一系列生理生化试验。用藜麦检测各菌株的促生功能，并对具有优良促生作用的1个菌株16S rRNA基因进行分子鉴定及基因草图绘制。【结果】根据生化鉴定结果，6株细菌分别属于不动杆菌属(Acinetobacter)、土壤杆菌属(Agrobacterium)、类芽孢杆菌属(Paenibacillus)、芽孢杆菌属(Bacillus)、鞘氨醇单胞菌属(Sphingomonas)和假单胞菌属(Pseudomonas)。其中，16S rRNA基因鉴定BC4属于肠杆菌属(Enterobacter)，具有较好的促生效果。【结论】BC4具有较好的促生效果，为兰州唐古特白刺菌种资源的开发和利用提供了一定的理论依据。     

Response of grazing snails to phosphorus enrichment of modern stromatolitic microbial communities

1. The effects of added phosphorus (P) on the growth, P and RNA : DNA contents, and survivorship of snails grazing on laminated microbial mats (living ‘stromatolites’) were examined in the Rio Mesquites at Cuatro Ciénegas, Mexico (total P, c. 0.60 μmol L^?1) to test the hypothesis that strong P‐limitation of microautotroph growth produces a stoichiometric constraint on herbivores because of mineral P‐limitation. 2. In a 3‐week experiment performed in summer 2001, addition of phosphorus (+15 μmol L^?1) resulted in a strong decline in stromatolite biomass C : P ratio from very high levels (c. 2300 : 1 by atoms) to moderate levels (c. 550 : 1). The endemic hydrobiid snail Mexithauma quadripaludium responded to P‐enrichment with elevated body P content and higher RNA : DNA ratios, especially for small animals likely to be actively growing. This positive response is consistent with the existence of a stoichiometric constraint on snail growth. 3. In a longer experiment (8 weeks) involving a more moderate P enrichment (+5 μmol L^?1) in summer 2002, P enrichment reduced stromatolite C : P ratio from moderate values in control treatments (c. 750) to very low values (<100 : 1). Snails responded to stromatolite P‐enrichment with increased body P content but, in contrast to the first experiment, with lower RNA : DNA ratio, lower growth rates, and higher mortality. 4. These contrasting results suggest that both very high and very low biomass C : P ratios in stromatolites are detrimental to M. quadripaludium performance, leading us to hypothesise that these herbivores live on a ‘stoichiometric knife edge’.     

Inhibition of α-SMA by the Ectodomain of FGFR2c Attenuates Lung Fibrosis

The soluble ectodomain of fibroblast growth factor receptor-IIIc (sFGFR2c) is able to bind to fibroblast growth factor (FGF) ligands and block the activation of the FGF-signaling pathway. In this study, sFGFR2c inhibited lung fibrosis dramatically in vitro and in vivo. The upregulation of α-smooth muscle actin (α-SMA) in fibroblasts by transforming growth factor-β1 (TGF-β1) is an important step in the process of lung fibrosis, in which FGF-2, released by TGF-β1, is involved. sFGFR2c inhibited α-SMA induction by TGF-β1 via both the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad3 pathways in primary mouse lung fibroblasts and the proliferation of mouse lung fibroblasts. In a mouse model of bleomycin (BLM)-induced lung fibrosis, mice were treated with sFGFR2c from d 3 or d 10 to 31 after BLM administration. Then we used hematoxylin and eosin staining, Masson staining and immunohistochemical staining to evaluate the inhibitory effects of sFGFR2c on lung fibrosis. The treatment with sFGFR2c resulted in significant attenuation of the lung fibrosis score and collagen deposition. The expression levels of α-SMA, p-FGFRs, p-ERK1/2 and p-Smad3 in the lungs of sFGFR2c-treated mice were markedly lower. sFGFR2c may have potential for the treatment of lung fibrosis as an FGF-2 antagonist.     

Antagonistic substrate binding by a group II intron ribozyme.

In this study, the thermodynamic properties of substrate-ribozyme recognition were explored using a system derived from group II intron ai5gamma. Substrate recognition by group II intron ribozymes is of interest because any nucleic ac?id sequence can be targeted, the recognition sequence can be quite long (>/=13 bp), and reaction can proceed with a very high degree of sequence specificity. Group II introns target their substrates throug?h the formation of base-pairing interactions with two regions of the intron (EBS1 and EBS2), which are usually located far apart in the secondary structure. These structures pair with adjacent, corresponding sites (IBS1 and IBS2) on the substrate. In order to understand the relative energetic contribution of each base-pairing interaction (EBS1-IBS1 or EBS2-IBS2) to substrate binding energy, the free energy of each helix was measured. The individual helices were found to have base-pairing free energies similar to those calculated for regular RNA duplexes of the same sequence, suggesting that each recognition helix derives its binding energy from base-pairing interactions alone and that each helix can form independently. Most interestingly, it was found that the sum of the measured individual free energies (approximately 20 kcal/mol) was much higher than the known free energy for substrate binding (approximately 12 kcal/mol). This indicates that certain group II intron ribozymes can bind their substrates in an antagonistic fashion, paying a net energetic penalty upon binding the full-length substrate. This loss of binding energy is not due to weakening of individual helices, but appears to be linked to ribozyme conformational changes induced by substrate binding. This coupling between substrate binding and ribozyme conformational rearrangement may provide a mechanism for lowering overall substrate binding energy while retaining the full information content of 13 bp, thus resulting in a mechanism for ensuring sequence specificity.     

Intravenous injection of the oncolytic virus M1 awakens antitumor T cells and overcomes resistance to checkpoint blockade

Reversing the highly immunosuppressive tumor microenvironment (TME) is essential to achieve long-term efficacy with cancer immunotherapy. Despite the impressive clinical response to checkpoint blockade in multiple types of cancer, only a minority of patients benefit from this approach. Here, we report that the oncolytic virus M1 induces immunogenic tumor cell death and subsequently restores the ability of dendritic cells to prime antitumor T cells. Intravenous injection of M1 disrupts immune tolerance in the privileged TME, reprogramming immune-silent (cold) tumors into immune-inflamed (hot) tumors. M1 elicits potent CD8⁺ T cell-dependent therapeutic effects and establishes long-term antitumor immune memory in poorly immunogenic tumor models. Pretreatment with M1 sensitizes refractory tumors to subsequent checkpoint blockade by boosting T-cell recruitment and upregulating the expression of PD-L1. These findings reveal the antitumor immunological mechanism of the M1 virus and indicated that oncolytic viruses are ideal cotreatments for checkpoint blockade immunotherapy.Subject terms: Cancer microenvironment, Targeted therapies     

A cross-talk between epithelium and endothelium mediates human alveolar–capillary injury during SARS-CoV-2 infection

COVID-19, caused by SARS-CoV-2, is an acute and rapidly developing pandemic, which leads to a global health crisis. SARS-CoV-2 primarily attacks human alveoli and causes severe lung infection and damage. To better understand the molecular basis of this disease, we sought to characterize the responses of alveolar epithelium and its adjacent microvascular endothelium to viral infection under a co-culture system. SARS-CoV-2 infection caused massive virus replication and dramatic organelles remodeling in alveolar epithelial cells, alone. While, viral infection affected endothelial cells in an indirect manner, which was mediated by infected alveolar epithelium. Proteomics analysis and TEM examinations showed viral infection caused global proteomic modulations and marked ultrastructural changes in both epithelial cells and endothelial cells under the co-culture system. In particular, viral infection elicited global protein changes and structural reorganizations across many sub-cellular compartments in epithelial cells. Among the affected organelles, mitochondrion seems to be a primary target organelle. Besides, according to EM and proteomic results, we identified Daurisoline, a potent autophagy inhibitor, could inhibit virus replication effectively in host cells. Collectively, our study revealed an unrecognized cross-talk between epithelium and endothelium, which contributed to alveolar–capillary injury during SARS-CoV-2 infection. These new findings will expand our understanding of COVID-19 and may also be helpful for targeted drug development.Subject terms: Mechanisms of disease, Viral infection     

水杨酸调控盐胁迫下羽衣甘蓝种子萌发的机理

盐胁迫是植物种子萌发与植株生长的重要限制因子。以羽衣甘蓝(Brassica oleracea var.acephala)名古屋为材料,研究不同盐分对其种子萌发的影响,探索水杨酸(SA)及其合成抑制剂氨基茚磷酸(AIP)处理对羽衣甘蓝种子萌发的调控效应。实验结果表明,150与200 mmol·L^–1 NaCl处理后的羽衣甘蓝种子活力显著降低。盐胁迫显著降低种子的吸水速率、种子活力与幼苗质量,降低苯丙氨酸裂解酶活性与内源SA含量,提高过氧化氢(H2O2)与超氧阴离子(O2^–.)含量。SA可以缓解盐胁迫对羽衣甘蓝种子活力的抑制作用,通过促进内源SA合成,从而提高种子吸水率与种子活力,促进种子对K^+、Mg^2+的吸收,降低Na+含量。此外,外源施加SA能够显著增强超氧化物歧化酶和过氧化物酶活性,降低H2O2与O2^–.的积累。相反,氨基茚磷酸(AIP)处理能够增强盐胁迫对种子萌发的抑制作用,推测这与AIP处理能够显著降低种子内源SA含量密切相关。研究表明外源SA主要通过提高保护酶活性、降低活性氧积累和维持体内离子平衡来增强羽衣甘蓝的耐盐性。     

Survivorship of geographic Pomacea canaliculata populations in responses to cold acclimation

1. Pomacea canaliculata, a freshwater snail from South America, has rapidly established natural populations from south to north subtropical region in China, since its original introductions in the 1980s. Low temperature in winter is a limiting factor in the geographic expansion and successfully establishment for apple snail populations. There have been some studies on population level of low temperature tolerance for P. canaliculata, yet little is quantified about its life‐history traits in responses to cold temperatures. Whether these responses vary with the acclimation location is also unclear. We investigated the survivorship and longevity of P. canaliculata in responses to cold temperatures and examine whether these responses vary with the location and snail size. We hypothesized that survival of the snails depends on their shell height and the level of low temperature, and P. canaliculata population from the mid-subtropical zone may exhibit the highest viability over the cold thermal range.
2. We sampled P. canaliculata populations from five latitude and longitude ranges of subtropical China: Guangzhou population in southernmost (SM‐GZ), three populations of Yingtan (MR‐YT), Ningbo (MR‐NB), Ya'an (MR‐YA) in midrange, and Huanggang population in northernmost (NM‐HG) subtropical zone. For each P. canaliculata population, survival and longevity at six cold acclimation temperature levels (12, 9, 6, 3, 0, and ?3°C) were quantified, and the effects of location and shell height were examined.
3. The MR‐YA population from mid-subtropical zone of China exhibited the highest survival rate and prolonged survival time regardless of the temperature acclimation treatments, whereas the SM‐GZ population from southern subtropical was the most sensitive to cold temperatures, particular temperatures below 9°C. No individuals of the SM‐GZ population could survive after stressed for 30 days (3°C), 5 days (0°C) and 2 days (?3°C), respectively. For each experimental P. canaliculata population held at 3, 0, and ?3°C, individuals with intermediate shell height of 15.0–25.0 mm had significantly higher survivals.
4. The results highlight a request of a more thorough investigation on acclimation responses in each of the life table demographic parameters for P. canaliculata, and pose the question of whether natural selection or some genetic changes may have facilitated adaptation in invasive locations.