Optimized empirical model based on whale optimization algorithm for simulate daily reference crop evapotranspiration in different climatic regions of China

• The accuracy of the temperature, radiation and hybrid models improved by 12.05 %, 11.06% and 10.46% after being optimized by WOA. • The estimation accuracy of the temperature, radiation and hybrid models optimized by the whale algorithm were higher than the prediction result of the ELM model. • The empirical model with more input parameters has higher estimation accuracy than the empirical model with fewer parameters. The accurate estimation of reference crop evapotranspiration (ET 0) is of great significance to improve agricultural water use efficiency and optimize regional water resources management. At present, the applicability evaluation system of ET 0 models is still lacking in several climate regions in China, leading to the confusion in application of the ET 0 model in some specific regions. In this study, the daily meteorological data of 84 representative stations in four climate regions of China during the past 30 years (1991–2019) were selected to evaluate the ET 0 simulation results of twelve empirical models (four temperature models, five radiation models, and three hybrid models) on the daily scale, and the optimal models suitable for each climate region were screened. Whale optimization algorithm (WOA) was used to optimize the optimal model to improve the simulation accuracy, and the ET 0 results were compared with those predicted by extreme learning machine (ELM). The results showed that the estimation accuracy of the hybrid model was the best throughout China, followed by the radiation model, and the temperature model was relatively poor, with R2 ranges of 0.77–0.88, 0.60–0.86, and 0.58–0.82, respectively. Among the temperature-based models, Hargreaves-Samani and Improve Baier-Robertson model had the highest accuracy, with R2 of 0.80 and 0.79. Among the radiation-based models, Priestley-Taylor and Jensen-Haise models had the best accuracy, with R2 of 0.82 and 0.79. Among the hybrid models, Penman model had the highest accuracy, with R2 of 0.84. The accuracy of Hargreaves-Samani and Improve Baier-Robertson model in SMZ climate region was higher than TCZ, TMZ, and MPZ, and the accuracy of Jensen-Haise model in TCZ was the highest. The estimation accuracy of Priestley-Taylor and Penman models was similar in SMZ, TCZ, TMZ and MPZ. Using WOA to optimize the optimal temperature, radiation, and hybrid models, the prediction accuracy was improved by 12.05 %, 11.06 %, and 10.46 %, which were higher than the result of ELM model, with R2 of 0.90, 0.91, 0.95 and 0.90, respectively. Therefore, it is recommended to adopt WOA to optimize the empirical model to estimate the ET 0 all over China. [ FROM AUTHOR] Copyright of Journal of Hydrology is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Exploring the Regulatory Function of the N‐terminal Domain of SARS‐CoV‐2 Spike Protein through Molecular Dynamics Simulation

SARS‐CoV‐2 is what has caused the COVID‐19 pandemic. Early viral infection is mediated by the SARS‐CoV‐2 homo‐trimeric Spike (S) protein with its receptor binding domains (RBDs) in the receptor‐accessible state. Molecular dynamics simulation on the S protein with a focus on the function of its N‐terminal domains (NTDs) is performed. The study reveals that the NTD acts as a “wedge” and plays a crucial regulatory role in the conformational changes of the S protein. The complete RBD structural transition is allowed only when the neighboring NTD that typically prohibits the RBD's movements as a wedge detaches and swings away. Based on this NTD “wedge” model, it is proposed that the NTD–RBD interface should be a potential drug target. The Spike protein of SARS‐CoV‐2 plays a key role in the infection process. The N‐terminal domain (NTD) of the Spike protein plays a regulatory function by the “wedge” model: it typically wedges in to prohibit receptor binding domain's (RBD's) movements and occasionally moves out to allow RBD to tilt downward. Potential drugs are virtually screened for the NTD‐RBD interface.

Exploring the Regulatory Function of the N-terminal Domain of SARS-CoV-2 Spike Protein through Molecular Dynamics Simulation (Adv. Theory Simul. 10/2021)

N-terminal Domain of SARS-CoV-2 Spike Protein In article number 2100152, Yao Li, Tong Wang, Haipeng Gong, and co-workers propose the ?wedge? model to demonstrate the regulatory function of the N-terminal domain (NTD) of SARS-CoV-2 Spike protein. The NTD typically wedges in to prohibit receptor binding domain's (RBD's) movements and it occasionally moves out to allow RBD to tilt downward.

Cell-type apoptosis in lung during SARS-CoV-2 infection (preprint)

The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection because fatal COVID-19 cases are commonly linked to respiratory failure due to ARDS. The pathologic alteration known as diffuse alveolar damage in endothelial and epithelial cells is a critical feature of acute lung injury in ARDS. However, the pathogenesis of ARDS following SRAS-CoV-2 infection remains largely unknown. In the present study, we examined apoptosis in post-mortem lung sections from COVID-19 patients and lung tissues from a non-human primate model of SARS-CoV-2 infection, in a cell-type manner, including type 1 and 2 alveolar cells and vascular endothelial cells (ECs), macrophages, and T cells. Multiple-target immunofluorescence (IF) assays and western blotting suggest both intrinsic and extrinsic apoptotic pathways are activated during SARS-CoV-2 infection. Furthermore, we observed that SARS-CoV-2 fails to induce apoptosis in human bronchial epithelial cells (i.e., BEAS2B cells) and primary human umbilical vein endothelial cells (HUVECs), which are refractory to SARS-CoV-2 infection. However, infection of co-cultured Vero cells and HUVECs or Vero cells and BEAS2B cells with SARS-CoV-2 induced apoptosis in both Vero cells and HUVECs/BEAS2B cells, but did not alter the permissiveness of HUVECs or BEAS2B cells to the virus. Post-exposure treatment of the co-culture of Vero cells and HUVECs with an EPAC1-specific activator ameliorated apoptosis in HUVECs. These findings may help to delineate a novel insight into the pathogenesis of ARDS following SARS-CoV-2 infection.

Berberine and obatoclax inhibit SARS-CoV-2 replication in primary human nasal epithelial cells in vitro (preprint)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and has infected an estimated 10% of the global population in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of a specific set of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.

Exploring epitope and functional diversity of anti-SARS-CoV2 antibodies using AI-based methods (preprint)

Since the beginning of the COVID19 pandemics, an unprecedented research effort has been conducted to analyze the antibody responses in patients, and many trials based on passive immunotherapy -notably monoclonal antibodies - are ongoing. Twenty-one antibodies have entered clinical trials, 6 having reached phase 2/3, phase 3 or having received emergency authorization. These represent only the tip of the iceberg, since many more antibodies have been discovered and represent opportunities either for diagnosis purposes or as drug candidates. The main problem facing laboratories willing to develop such antibodies is the huge task of analyzing them and choosing the best candidate for exhaustive experimental validation. In this work we show how artificial intelligence-based methods can help in analyzing large sets of antibodies in order to determine in a few hours the best candidates in few hours. The MAbCluster method, which only requires knowledge of the amino acid sequences of the antibodies, allows to group the antibodies having the same epitope, considering only their amino acid sequences and their 3D structures (actual or predicted), and to infer some of their functional properties. We then use MAbTope to predict the epitopes for all antibodies for which they are not already known. This allows an exhaustive comparison of the available epitopes, but also gives a synthetic view of the possible combinations. Finally, we show how these results can be used to predict which antibodies might be affected by the different mutations arising in the circulating strains of the virus, such as the N501Y mutation that has started to spread in Great-Britain.

EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K/eNOS-dependent manner during inflammation (preprint)

Coagulopathy is associated with both inflammation and infection, including infection with the novel SARS-CoV-2 (COVID-19). Endothelial cells (ECs) fine tune hemostasis via cAMP-mediated secretion of von Willebrand factor (vWF), which promote the process of clot formation. The e xchange p rotein directly a ctivated by c AMP (EPAC) is a ubiquitously expressed intracellular cAMP receptor that plays a key role in stabilizing ECs and suppressing inflammation. To assess whether EPAC could regulate vWF release during inflammation, we utilized our EPAC1 -null mouse model and revealed an increased secretion of vWF in endotoxemic mice in the absence of the EPAC1 gene. Pharmacological inhibition of EPAC1 in vitro mimicked the EPAC1 −/− phenotype. EPAC1 regulated TNFα-triggered vWF secretion from human umbilical vein endothelial cells (HUVECs) in a phosphoinositide 3-kinases (PI3K)/endothelial nitric oxide synthase (eNOS)-dependent manner. Furthermore, EPAC1 activation reduced inflammation-triggered vWF release, both in vivo and in vitro . Our data delineate a novel regulatory role of EPAC1 in vWF secretion and shed light on potential development of new strategies to controlling thrombosis during inflammation. Key Point PI3K/eNOS pathway-mediated, inflammation-triggered vWF secretion is the target of the pharmacological manipulation of the cAMP-EPAC system.