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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19), which has become a public health emergency of international concern 1 . Angiotensin-converting enzyme 2 (ACE2) is the cell-entry receptor for severe acute respiratory syndrome coronavirus (SARS-CoV) 2 . Here we infected transgenic mice that express human ACE2 (hereafter, hACE2 mice) with SARS-CoV-2 and studied the pathogenicity of the virus. We observed weight loss as well as virus replication in the lungs of hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of considerable numbers of macrophages and lymphocytes into the alveolar interstitium, and the accumulation of macrophages in alveolar cavities. We observed viral antigens in bronchial epithelial cells, macrophages and alveolar epithelia. These phenomena were not found in wild-type mice infected with SARS-CoV-2. Notably, we have confirmed the pathogenicity of SARS-CoV-2 in hACE2 mice. This mouse model of SARS-CoV-2 infection will be valuable for evaluating antiviral therapeutic agents and vaccines, as well as understanding the pathogenesis of COVID-19. Infection with SARS-CoV-2 causes interstitial pneumonia and viral replication in the lungs of transgenic mice that express a human version of ACE2, confirming the pathogenicity of the virus in this model.

SARS-CoV-2, a β-coronavirus, has rapidly spread across the world, highlighting its high transmissibility, but the underlying morphogenesis and pathogenesis remain poorly understood. Here, we characterize the replication dynamics, cell tropism and morphogenesis of SARS-CoV-2 in organotypic human airway epithelial (HAE) cultures. SARS-CoV-2 replicates efficiently and infects both ciliated and secretory cells in HAE cultures. In comparison, HCoV-NL63 replicates to lower titers and is only detected in ciliated cells. SARS-CoV-2 shows a similar morphogenetic process as other coronaviruses but causes plaque-like cytopathic effects in HAE cultures. Cell fusion, apoptosis, destruction of epithelium integrity, cilium shrinking and beaded changes are observed in the plaque regions. Taken together, our results provide important insights into SARS-CoV-2 cell tropism, replication and morphogenesis. Here, the authors characterize replication of SARS-CoV-2 in human airway epithelial (HAE) cultures and show that it can infect ciliated and secretory cells, affects transepithelial electrical resistance and causes plaque-like cytopathic effects associated with apoptosis.

A frame-shift mutation in MATRILINEAL, a pollen-specific phospholipase, triggers haploid induction in maize, which may be useful in developing improved haploid induction systems for crop breeding. Haploid induction in maize Haploid inbred lines are a valuable tool for genetic research and the hybrid breeding of crop plants. Timothy Kelliher et al . now examine the genetic basis of haploid induction in maize, and find that a frame-shift mutation in MATRILINEAL , a pollen-specific phospholipase, triggers haploid induction in these lines. This finding may be useful for the development of improved haploid induction systems for crop breeding. Sexual reproduction in flowering plants involves double fertilization, the union of two sperm from pollen with two sex cells in the female embryo sac. Modern plant breeders increasingly seek to circumvent this process to produce doubled haploid individuals, which derive from the chromosome-doubled cells of the haploid gametophyte. Doubled haploid production fixes recombinant haploid genomes in inbred lines, shaving years off the breeding process 1 . Costly, genotype-dependent tissue culture methods are used in many crops 2 , while seed-based in vivo doubled haploid systems are rare in nature 3 and difficult to manage in breeding programmes 4 . The multi-billion-dollar maize hybrid seed business, however, is supported by industrial doubled haploid pipelines using intraspecific crosses to in vivo haploid inducer males derived from Stock 6, first reported in 1959 (ref. 5 ), followed by colchicine treatment. Despite decades of use, the mode of action remains controversial 6 , 7 , 8 , 9 , 10 . Here we establish, through fine mapping, genome sequencing, genetic complementation, and gene editing, that haploid induction in maize ( Zea mays ) is triggered by a frame-shift mutation in MATRILINEAL ( MTL ), a pollen-specific phospholipase, and that novel edits in MTL lead to a 6.7% haploid induction rate (the percentage of haploid progeny versus total progeny). Wild-type MTL protein localizes exclusively to sperm cytoplasm, and pollen RNA-sequence profiling identifies a suite of pollen-specific genes overexpressed during haploid induction, some of which may mediate the formation of haploid seed 11 , 12 , 13 , 14 , 15 . These findings highlight the importance of male gamete cytoplasmic components to reproductive success and male genome transmittance. Given the conservation of MTL in the cereals, this discovery may enable development of in vivo haploid induction systems to accelerate breeding in crop plants.

Sonar imaging technology is widely used in the field of marine and underwater monitoring because sound waves can be transmitted in elastic media, such as the atmosphere and seawater, without much interference. In underwater object detection, due to the unique characteristics of the monitored sonar image, and since the target in an image is often accompanied by its own shadow, we can use the relative relationship between the shadow and the target for detection. To make use of shadow-information-aided detection and realize accurate real-time detection in sonar images, we put forward a network based on a lightweight module. By using the attention mechanism with a global receptive field, the network can make the target pay attention to the shadow information in the global environment, and because of its exquisite design, the computational time of the network is greatly reduced. Specifically, we design a ShuffleBlock model adapted to Hourglass to make the backbone network lighter. The concept of CNN dimension reduction is applied to MHSA to make it more efficient while paying attention to global features. Finally, CenterNet’s unreasonable distribution method of positive and negative samples is improved. Simulation experiments were carried out using the proposed sonar object detection dataset. The experimental results further verify that our improved model has obvious advantages over many existing conventional deep learning models. Moreover, the real-time monitoring performance of our proposed model is more conducive to the implementation in the field of ocean monitoring.

Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel and highly pathogenic human coronavirus and has quickly spread to other countries in the Middle East, Europe, North Africa and Asia since 2012. Previous studies have shown that MERS-CoV ORF4b antagonizes the early antiviral alpha/beta interferon (IFN-α/β) response, which may significantly contribute to MERS-CoV pathogenesis; however, the underlying mechanism is poorly understood. Here, we found that ORF4b in the cytoplasm could specifically bind to TANK binding kinase 1 (TBK1) and IκB kinase epsilon (IKKε), suppress the molecular interaction between mitochondrial antiviral signaling protein (MAVS) and IKKε and inhibit IFN regulatory factor 3 (IRF3) phosphorylation and subsequent IFN-β production. Further analysis showed that ORF4b could also inhibit IRF3 and IRF7-induced production of IFN-β, whereas deletion of the nuclear localization signal of ORF4b abrogated its ability to inhibit IRF3 and IRF7-induced production of IFN-β, but not IFN-β production induced by RIG-I, MDA5, MAVS, IKKε and TBK-1, suggesting that ORF4b could inhibit the induction of IFN-β in both the cytoplasm and nucleus. Collectively, these results indicate that MERS-CoV ORF4b inhibits the induction of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. Viruses have evolved multiple strategies to evade or thwart a host’s antiviral responses. A novel human coronavirus (HCoV), Middle East respiratory syndrome coronavirus (MERS-CoV), is distinguished from other coronaviruses by its high pathogenicity and mortality. However, virulence determinants that distinguish MERS-CoV from other HCoVs have yet to be identified. MERS-CoV ORF4b antagonizes the early antiviral response, which may contribute to MERS-CoV pathogenesis. Here, we report the identification of the interferon (IFN) antagonism mechanism of MERS-CoV ORF4b. MERS-CoV ORF4b inhibits the production of type I IFN through a direct interaction with IKKε/TBK1 in the cytoplasm and also in the nucleus with unknown mechanism. These findings provide a rationale for the novel pathogenesis of MERS-CoV as well as a basis for developing a candidate therapeutic against this virus.

Background Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus (SARS‐CoV‐2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS‐CoV‐2 was a need to explore the possible age‐related phenomena with non‐human primate models. Methods Three 3‐5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS‐CoV‐2, and then analyzed by clinical signs, viral replication, chest X‐ray, histopathological changes and immune response. Results Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS‐CoV‐2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages. Conclusion SARS‐CoV‐2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS‐CoV‐2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS‐CoV‐2 infection.

Background Frailty and sarcopenia are prevalent in chronic kidney disease (CKD) populations and could increase the risk for adverse health outcomes. Few studies assess the correlation between frailty, sarcopenia and CKD in non‐dialysis patients. Therefore, this study aimed to determine frailty‐associated factors in elderly CKD stage I–IV patients, expected to early identify and intervene in the frailty of elderly CKD patients. Methods A total of 774 elderly CKD I–IV patients (>60 years of age) recruited from 29 clinical centers in China between March 2017 and September 2019 were included in this study. We established a Frailty Index (FI) model to evaluate frailty risk and verified the distributional property of FI in the study population. Sarcopenia was defined according to the criteria of the Asian Working Group for Sarcopenia 2019. Multinomial logistic regression analysis was used to assess the associated factors for frailty. Results Seven hundred seventy‐four patients (median age 67 years, 66.0% males) were included in this analysis, with a median estimated glomerular filtration rate of 52.8 mL/min/1.73 m2. The prevalence of sarcopenia was 30.6%. The FI exhibited a right‐skewed distribution. The age‐related slope of FI was 1.4% per year on a logarithmic scale (r2 = 0.706, 95% CI 0.9, 1.8, P < 0.001). The upper limit of FI was around 0.43. The FI was related to mortality (HR = 1.06, 95% CI 1.00, 1.12, P = 0.041). Multivariate multinomial logistic regression analysis showed that sarcopenia, advanced age, CKD stage II–IV, low level of serum albumin and increased waist–hip ratio were significantly associated with high FI status, while advanced age and CKD stage III–IV were significantly associated with for median FI status. Moreover, the results from the subgroup were consistent with the leading results. Conclusions Sarcopenia was independently associated with an increased risk for frailty in elderly CKD I‐IV patients. Patients with sarcopenia, advanced age, high CKD stage, high waist–hip ratio and low serum albumin level should be assessed for frailty.

To date, hydropower dams raise numerous interpretations about their impact on the Lancang-Mekong River. While most research studies analyze the negative aspects of hydropower development on people’s livelihoods and local environments, the hydropower sector was historically one of the most iconic economic segments facilitating transboundary water cooperation for decades. By using the constructive discourse analysis and critical political ecology approach, the presented text (1) outlines the current environmental narratives over the Lancang-Mekong hydropower development and (2) explores the politicization of the Chinese mainstream dams. The data were collected upon the multi-level content analysis of relevant sources and double-checked with the Lancang-Mekong Cooperation and Conflict Database (LMCCD) monitoring over 4000 water-related events among six riparian countries between 1990 and 2021. Our data show that (i) there is a stark contrast in positive and negative narratives over the rapid hydropower development, (ii) the impact of mainstream dams on the river is more often discussed than that of tributary dams, (iii) implications of the hydropower dams are often interpreted upon the non-traditional research inputs rather than widely accepted studies, and (iv) developing the contradictory arguments through social and public media contributes to greater polarization of the multi-stakeholders’ viewpoints in the accountable research dialogue.

Background and aims The cardiotoxicity related to 5-Fluorouracil (5-FU) in cancer patients has garnered widespread attention. The systemic immune-inflammation index (SII) has recently been identified as a novel predictive marker for the development of cardiovascular illnesses in individuals without pre-existing health conditions. However, it remains unclear whether the levels of SII are linked to cardiotoxicity related to 5-FU. This retrospective study aims to fill this knowledge gap by examining the correlation between SII and cardiotoxicity related to 5-FU in a colorectal cancer cohort. Methods The study comprised colorectal cancer patients who received 5-FU-based chemotherapy at the affiliated cancer hospital of Guizhou Medical University between January 1, 2018 and December 31, 2020. After adjustment for confounders and stratification by tertiles of the interactive factor, linear regression analyses, curve fitting and threshold effect analyses were conducted. Results Of the 754 patients included final analysis, approximately 21% ( n  = 156) of them ultimately experienced cardiotoxicity related to 5-FU. Monocytes (M) was found as an influential element in the interaction between SII and cardiotoxicity related to 5-FU. In the low tertile of M (T1: M ≤ 0.38 × 10 9 /L), increasing log SII was positively correlated with cardiotoxicity related to 5-FU (Odds Ratio [OR], 8.04; 95% confidence interval [95%CI], 1.68 to 38.56). However, a curvilinear relationship between log SII and cardiotoxicity was observed in the middle tertile of M (T2: 0.38 < M ≤ 0.52 × 10 9 /L). An increase in log SII above 1.37 was shown to be associated with a decreased risk of cardiotoxicity (OR, 0.14; 95%CI, 0.02 to 0.88), indicating a threshold effect. In the high tertile of M (T3: M > 0.52 × 10 9 /L), there was a tendency towards a negative linear correlation between the log SII and cardiotoxicity was observed (OR, 0.85; 95%CI, 0.37 to 1.98). Conclusion Our findings suggest that SII may serve as a potential biomarker for predicting cardiotoxicity related to 5-FU in colorectal cancer patients. SII is an independent risk factor for cardiotoxicity related to 5-FU with low monocytes levels (T1). Conversely, in the middle monocytes levels (T2), SII is a protective factor for cardiotoxicity related to 5-FU but with a threshold effect.

Background Helicobacter pylori ( H. pylori ) can disrupt the tight junctions between gastric epithelial cells and penetrate the intercellular spaces acting on epithelial cells, normal fibroblasts (NFs), and cancer-associated fibroblasts (CAFs), but their interaction in gastric cancer tumorigenesis and progression remains unclear. Methods Primary CAFs and NFs were isolated from paired gastric cancer tissues and adjacent normal tissues and identified by immunofluorescence staining and western blot analysis for FSP-1, α-SMA, FAP, and vimentin expression. RNA-sequencing was used to compare the transcriptomes between CAFs and NFs. The expressions of FAP, lumican, and α-SMA, human cytokine array, and Transwell assay were used to assess the transformation of NFs to CAFs. CCK-8 assay, colony formation, flow cytometry, Transwell assay, and nude mouse xenograft model were used to determine the effects of Serpin E1 on cell proliferation and metastasis in vitro and in vivo. Finally, Serpin E1 and/or FAP expression was measured in H. pylori -infected gerbil gastric mucosa and human gastric cancer tissues. Results Gastric CAFs are inflammatory CAFs with α-SMA low FAP high lumican high . The interplay of H. pylori , fibroblasts, and cancer cells promotes the transition of NFs to CAFs by inducing cytokine release, especially Serpin E1. Long-term H. pylori infection and CAFs induce Serpin E1 expression in gerbil gastric tissues and human gastric cancer cells. Serpin E1 overexpression enhances the growth, migration, invasion of gastric cancer cells in vitro, and xenograft tumor growth in nude mice via inducing angiogenesis. Serpin E1 and FAP were highly expressed in cancer cells and CAFs of gastric cancer tissues, respectively, and a good correlation was observed between their expression. Higher Serpin E1 expression is negatively associated with the overall survival of patients with gastric cancer. Conclusions The interplay of H. pylori , fibroblasts, and cancer cells induced Serpin E1 expression to promote the activation of NFs to CAFs and gastric carcinogenesis. Targeting Serpin E1 will provide a promising therapeutic strategy for gastric cancer by disrupting the interaction between H. pylori , CAFs, and gastric cancer cells.