Using genetic variation to disentangle the complex relationship between food intake and health outcomes

Diet is considered as one of the most important modifiable factors influencing human health, but efforts to identify foods or dietary patterns associated with health outcomes often suffer from biases, confounding, and reverse causation. Applying Mendelian randomization in this context may provide evidence to strengthen causality in nutrition research. To this end, we first identified 283 genetic markers associated with dietary intake in 445,779 UK Biobank participants. We then converted these associations into direct genetic effects on food exposures by adjusting them for effects mediated via other traits. The SNPs which did not show evidence of mediation were then used for MR, assessing the association between genetically predicted food choices and other risk factors, health outcomes. We show that using all associated SNPs without omitting those which show evidence of mediation, leads to biases in downstream analyses (genetic correlations, causal inference), similar to those present in observational studies. However, MR analyses using SNPs which have only a direct effect on the exposure on food exposures provided unequivocal evidence of causal associations between specific eating patterns and obesity, blood lipid status, and several other risk factors and health outcomes.     

SARS-CoV-2 envelope protein causes acute respiratory distress syndrome (ARDS)-like pathological damages and constitutes an antiviral target

Cytokine storm and multi-organ failure are the main causes of SARS-CoV-2-related death. However, the origin of excessive damages caused by SARS-CoV-2 remains largely unknown. Here we show that the SARS-CoV-2 envelope (2-E) protein alone is able to cause acute respiratory distress syndrome (ARDS)-like damages in vitro and in vivo. 2-E proteins were found to form a type of pH-sensitive cation channels in bilayer lipid membranes. As observed in SARS-CoV-2-infected cells, heterologous expression of 2-E channels induced rapid cell death in various susceptible cell types and robust secretion of cytokines and chemokines in macrophages. Intravenous administration of purified 2-E protein into mice caused ARDS-like pathological damages in lung and spleen. A dominant negative mutation lowering 2-E channel activity attenuated cell death and SARS-CoV-2 production. Newly identified channel inhibitors exhibited potent anti-SARS-CoV-2 activity and excellent cell protective activity in vitro and these activities were positively correlated with inhibition of 2-E channel. Importantly, prophylactic and therapeutic administration of the channel inhibitor effectively reduced both the viral load and secretion of inflammation cytokines in lungs of SARS-CoV-2-infected transgenic mice expressing human angiotensin-converting enzyme 2 (hACE-2). Our study supports that 2-E is a promising drug target against SARS-CoV-2.Subject terms: Cell death, Molecular biology     

夜间温度升高对双季早晚稻产量的影响

温度是影响水稻生长发育的重要因素,但夜间温度升高对双季水稻产量的影响还不清楚。利用两间玻璃室内夜间不同的温度条件,研究了水稻生长期间夜温升高对双季早、晚稻产量的影响。结果表明,夜间最低温度每升高1℃早稻产量降低5.42%-9.48%,而夜间最低温度每升高1℃晚稻产量提高8.99%-11.28%。夜温升高有利于早、晚稻的分蘖,增加有效穗数,但不利于颖花分化,使每穗粒数减少;夜温升高使早稻结实率下降,但提高晚稻的结实率。     

两种麻疯树苗对盐胁迫的生理生态响应

研究两种不同基因型麻疯树苗(南油2、3号)在不同NaCl浓度下生理生态响应特征,并比较不同基因型麻疯树苗的耐盐差异性。结果表明:①用25、50 mmo.lL-1NaCl处理,南油2号全株干重与对照无显著差异,而南油3号全株干重比对照显著降低。用100 mmol.L-1l或以上浓度的NaCl处理,随着盐度增加,两种树苗全株干重皆比对照显著降低,且3号苗降低的幅度大于2号苗。②在用200 mmol.L-1或以下浓度的NaCl处理,南油2、3号叶片相对含水量(RWC)皆与对照无显著差异,而在用300 mmol.L-1NaCl处理,则分别比对照显著降低5%和8%。③用25、50 mmol.L-1NaCl处理,南油2号可溶性糖(SS)含量比对照显著降低,3号与对照无显著差异;用200、300 mmo.lL-1NaCl处理后,两者SS含量均比对照显著降低。同时,2号苗可溶性蛋白(SP)含量比对照显著增加,3号苗SP含量与对照无显著差异。④随着盐度增加,南油2号苗超氧化物歧化酶(SOD)活性先增加后降低。用300 mmol.L-1NaCl处理,比对照显著降低。随着盐度增加,3号苗的SOD活性递减,皆显著低于对照。用25、50 mmo.lL-1NaCl处理,两种树苗的过氧化物酶(POD)活性与对照无显著差异。随着盐度增加,2号苗的POD活性比对照显著增加,而3号苗比对照显著降低。用25、50 mmo.lL-1NaCl处理,两种树苗的过氧化氢酶(CAT)活性皆比对照显著增加,且随着盐度增加,其变化趋势如SOD活性。结果表明,麻疯树幼苗具有较好的耐盐性,且南油2号比南油3号具有更高的耐盐性,因为前者具有更高的保护酶活性、叶片保水能力和叶片SP含量。     

FERONIA is involved in phototropin 1-mediated blue light phototropic growth in Arabidopsis

Plant shoot phototropism is triggered by the formation of a light-driven auxin gradient leading to bending growth. The blue light receptor phototropin 1(phot1) senses light direction, but how this leads to auxin gradient formation and growth regulation remains poorly understood. Previous studies have suggested phot1’s role for regulated apoplastic acidification, but its relation to phototropin and hypocotyl phototropism is unclear. Herein, we show that blue light can cause phot1 to interact with...     

长江江豚感染铜绿假单胞菌肺炎的诊治

本文记录了一例患急性铜绿假单胞菌肺炎的长江江豚诊断、治疗和预后观察过程。病原学鉴定采用鲜血琼脂平板对该江豚鼻腔拭子,在37℃下进行细菌需氧、厌氧培养和分离,并对所分离的细菌种类进行细菌学鉴定,结合血常规和血生化的检测结果,判定病原为铜绿假单胞菌（Pseudomonas aeruginosa,PA）。依据病原菌的药敏试验结果对患病江豚进行治疗,预后良好。通过对整个过程的资料分析以及预后观察,得到如下提示：1）应做好饲养环境的消毒措施,防止江豚出现获得性PA感染;2）对江豚日常呼吸道和粪便中PA的检测,有利于疾病的早期预防和控制;3）江豚呼吸系统疾病的治愈依赖于准确的病原鉴定和及时的治疗,药敏试验对于PA感染的治疗非常必要;4）行为学的改变在江豚呼吸道疾病发病初期以及预后有重要的指示作用。     

Osteoimmunology: The correlation between osteoclasts and the Th17/Treg balance in osteoporosis

Osteoporosis is a bone disease that is caused by disorder of the skeletal microenvironment, and it characterized by a high disability rate and the occurrence of low energy fractures. Studies on osteoporosis and related treatment options have always been hot spots in the field of bone biology. In the past, the understanding of osteoporosis has been rather limited; research has only shown that osteoporosis involves the imbalance of bone resorption and bone formation, and recent studies have not provided cutting‐edge theories of the basic understanding of osteoporosis. Recent studies have shown crosstalk between bone and immune responses. RANKL, an essential factor for osteoclasts (OCs), is associated with the immune system. T helper (Th17)/regulatory T (Treg) cells are two different kinds of T cells that can self‐interact and regulate the differentiation and formation of OCs. Therefore, understanding the correlation between the skeletal and immune systems and further revealing the roles and the cooperation between RANKL and the Th17/Treg balance will help to provide new insights for the treatment of osteoporosis.     

Depression compromises antiviral innate immunity via the AVP-AHI1-Tyk2 axis

Depression is a serious public-health issue. Recent reports have suggested higher susceptibility to viral infections in depressive patients. However, how depression affects antiviral innate immune signaling remains unknown. Here, we revealed a reduction in expression of Abelson helper integration site 1 (AHI1) in the peripheral blood mononuclear cells (PBMCs) and macrophages from the patients with major depressive disorder (MDD), which leads to attenuated antiviral immune response. We found that depression-related arginine vasopressin (AVP) induces reduction of AHI1 in macrophages. Further studies demonstrated that AHI1 is a critical stabilizer of basal type-I-interferon (IFN-I) signaling. Mechanistically, AHI1 recruits OTUD1 to deubiquitinate and stabilize Tyk2, while AHI1 reduction downregulates Tyk2 and IFN-I signaling activity in macrophages from both MDD patients and depression model mice. Interestingly, we identified a clinical analgesic meptazinol that effectively stimulates AHI1 expression, thus enhancing IFN-I antiviral defense in depression model mice. Our study promotes the understanding of the signaling mechanisms of depression-mediated antiviral immune dysfunction, and reveals meptazinol as an enhancer of antiviral innate immunity in depressive patients.Subject terms: Innate immunity, Ubiquitylation, Cell signalling     

Selective pericentromeric heterochromatin dismantling caused by TP53 activation during senescence

Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms that lead to these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive heterochromatin loss, are mechanistically connected during senescence. We show that, at the onset of senescence, pericentromeric heterochromatin is specifically dismantled consisting of chromatin decondensation, accumulation of DNA breakages, illegitimate recombination and loss of DNA. This process is caused by telomere shortening or genotoxic stress by a sequence of events starting from TP53-dependent downregulation of the telomere protective protein TRF2. The resulting loss of TRF2 at pericentromeres triggers DNA breaks activating ATM, which in turn leads to heterochromatin decondensation by releasing KAP1 and Lamin B1, recombination and satellite DNA excision found in the cytosol associated with cGAS. This TP53–TRF2 axis activates the interferon response and the formation of chromosome rearrangements when the cells escape the senescent growth arrest. Overall, these results reveal the role of TP53 as pericentromeric disassembler and define the basic principles of how a TP53-dependent senescence inducer hierarchically leads to selective pericentromeric dismantling through the downregulation of TRF2.