Amyloid Protein Cross-Seeding Provides a New Perspective on Multiple Diseases In Vivo.

Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

Does the COVID-19 pandemic derail US-China collaboration on carbon neutrality research? A survey

The COVID-19 pandemic has seriously impacted scientific research activities, especially international cooperation in scientific research. Using bibliometric methods and scientific knowledge graph software, and by calculating collaboration indicators such as international collaboration rates, this work conducts a comprehensive review of carbon neutrality publications in the Web of Science database before and during the COVID-19 pandemic, aiming to explore whether the COVID-19 pandemic derail China-U.S. collaboration on carbon neutrality research. The results show that (i) During the COVID-19 pandemic, more extensive research on carbon neutrality was carried out around the world, with China and the United States leading the way in carbon neutrality scientific output. (ii) Following the outbreak of the COVID-19, the global center of global carbon neutrality shifted from the United States to China. (iii) During the COVID-19 pandemic, research ties between China and the United States strengthened. The number of joint publications on carbon neutrality between China and the United States has greatly increased during the COVID-19 pandemic compared to those before. (iv) The proportion of China-U.S. cooperation in China's international cooperation has decreased, while it is the opposite for the United States. At the end of the article, we put forward relevant suggestions for realizing the sustainable development goals of climate change in the post-epidemic era for policymakers' reference. This paper provides offers important insights into the theoretical research of scholars in the field of carbon neutrality.

Does marine environmental research meet the challenges of marine pollution induced by the COVID-19 pandemic? Comparison analysis before and during the pandemic based on bibliometrics.

The outbreak of the COVID-19 pandemic has brought enormous challenges to the global marine environment. Various responses to the COVID-19 pandemic have led to increased marine pollution. Has the COVID-19 pandemic affected marine pollution research? This work comprehensively reviewed marine pollution publications in the Web of Science database before and during the COVID-19 pandemic. Results show that the COVID-19 outbreak has influenced the marine pollution research by: (i) increasing the number of publications; (ii) reshaping different countries' roles in marine pollution research; (iii) altering the hotspots of marine pollution research. The ranking of countries with high productivity in the marine pollution research field changed, and developed economies are the dominant players both before and after the outbreak of the COVID-19 pandemic in this field. Other high-productivity countries, with the exception of China, have higher international cooperation rates in marine pollution research than those before the pandemic. Microplastic pollution has been the biggest challenge of marine pollution and has been aexplored in greater depth during the COVID-19 pandemic. Furthermore, the mining results of marine pollution publications show the mitigation of plastic pollution in the marine environment remains the main content requires future research. Finally, this paper puts forward corresponding suggestions for the reference of researchers and practitioners to improve the global ability to respond to the challenges posed by the pandemic to the marine environment.

A paper-based assay for the colorimetric detection of SARS-CoV-2 variants at single-nucleotide resolution.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has highlighted the need for versatile diagnostic assays that can discriminate among emerging variants of the virus. Here we report the development and performance benchmarking of an inexpensive (approximately US$0.30 per test) assay for the rapid (sample-to-answer time within 30 min) colorimetric detection of SARS-CoV-2 variants. The assay, which we integrated into foldable paper strips, leverages nucleic acid strand-displacement reactions, the thermodynamic energy penalty associated with single-base-pair mismatches and the metal-ion-controlled enzymatic cleavage of urea to amplify the recognition of viral RNAs for the colorimetric readout of changes in pH via a smartphone. For 50 throat swab samples, the assay simultaneously detected the presence of SARS-CoV-2 and mutations specific to the SARS-CoV-2 variants Alpha, Beta and Gamma, with 100% concordance with real-time quantitative polymerase chain reaction and RNA sequencing. Customizable and inexpensive paper-based assays for the detection of viruses and their variants may facilitate viral surveillance.

The negative impact of the COVID-19 on renewable energy growth in developing countries: Underestimated.

According to the United Nations Environment Programme, the COVID-19 pandemic has created challenges for the economy and the energy sector, as well as uncertainty for the renewable energy industry. However, the impact on renewable energy during the pandemic has not been consistently determined. Instead of relying on data from year-to-year comparisons, this study redesigned the analytical framework for assessing the impact of a pandemic on renewable energy. First, this research designed an "initial prediction-parameter training-error correction-assignment combination" forecasting approach to simulate renewable energy consumption in a "no pandemic" scenario. Second, this study calculates the difference between the "pandemic" and "no pandemic" scenarios for renewable energy consumption. This difference represents the change in renewable energy due to the COVID-19 pandemic. Various techniques such as nonlinear grey, artificial neural network and IOWGA operator were incorporated. The MAPEs were controlled to within 5% in 80% of the country samples. The conclusions indicated that renewable energy in China and India declined by 8.57 mtoe and 3.19 mtoe during COVID-19 period. In contrast, the rise in renewable energy in the US is overestimated by 8.01 mtoe. Overall, previous statistics based on year-to-year comparisons have led to optimistic estimates of renewable energy development during the pandemic. This study sheds light on the need for proactive policy measures in the future to counter the global low tide of renewable energy amid COVID-19.

Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay† † Electronic supplementary information (ESI) available: ESI 1 and ESI file 2. See DOI: 10.1039/d1ra00426c

The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to the cell receptor and affect the potency of vaccines and antibodies. Here we used an in silico approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2). The effect of all single point mutations on the interface was predicted. SPR assay results show that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated the in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit the development of broadly neutralizing vaccine and antibody. The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates viral cell attachment and serves as a promising target for therapeutics development.

Epidemiological features and dynamic changes in blood biochemical indices for COVID-19 patients in Hebi.

BACKGROUND: Millions of people have died of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and retrospective studies of the disease in local regions are necessary. AIM: To characterize the epidemiological features and dynamic changes in blood biochemical indices for SARS-CoV-2-infected patients in Hebi, a representative city with a large floating population in North China. METHODS: From January 25 to February 10, 2020, the clinical data of patients who tested positive for SARS-CoV-2 by quantitative real-time polymerase chain reaction in Hebi city (China) were evaluated at admission, and laboratory data for hematologic parameters, inflammatory indices, coagulation function indices, liver function indices, blood lipid indices, renal function indices, myocardial enzyme activities and five blood biochemical markers of immunity were evaluated at admission, upon hospitalization and before discharge. RESULTS: Sixteen confirmed COVID-19 patients developed pneumonia but were cured after adequate treatment. Fever and fatigue were the common symptoms. The most common laboratory abnormalities of patients at admission were leukopenia, eosinopenia, decreased percentage of eosinophils, elevated high sensitivity C-reactive protein and fibrinogen levels, hypoalbuminemia, mildly increased aspartate transferase activity and levels of bilirubin, and increased levels of ß2-microglobulin. Importantly, aggravated liver dysfunction was detected in most patients, which may be partially attributed to virus infection as well as medicinal treatment. CONCLUSION: This study provides several potential diagnostic markers and dynamic biochemical indices of disease progression to better prevent, diagnose and treat COVID-19 infection.

CRISPR-Cas13a cascade-based viral RNA assay for detecting SARS-CoV-2 and its mutations in clinical samples.

SARS-CoV-2 is one of the greatest threats to global human health. Point-of-care diagnostic tools for SARS-CoV-2 could facilitate rapid therapeutic intervention and mitigate transmission. In this work, we report CRISPR-Cas13a cascade-based viral RNA (Cas13C) assay for label-free and isothermal determination of SARS-CoV-2 and its mutations in clinical samples. Cas13a/crRNA was utilized to directly recognize the target of SARS-CoV-2 RNA, and the recognition events sequentially initiate the transcription amplification to produce light-up RNA aptamers for output fluorescence signal. The recognition of viral RNA via Cas13a-guide RNA ensures a high specificity to distinguish SARS-CoV-2 from MERS-CoV and SARS-CoV, as well as viral mutations. A post transcription amplification strategy was triggered after CRISPR-Cas13a recognition contributes to an amplification cascade that achieves high sensitivity for detecting SARS-CoV-2 RNA, with a limit of detection of 0.216 fM. In addition, the Cas13C assay could be able to discriminate single-nucleotide mutation, which was proven with N501Y in SARS-Cov-2 variant. This method was validated by a 100% agreement with RT-qPCR results from 12 clinical throat swab specimens. The Cas13C assay has the potential to be used as a routine nucleic acid test of SARS-CoV-2 virus in resource-limited regions.

Preventing a rebound in carbon intensity post-COVID-19 - lessons learned from the change in carbon intensity before and after the 2008 financial crisis.

The carbon emission rebound of the post-2008 financial crisis teaches us a lesson that avoiding a rebound in carbon intensity is key to prevent the carbon emission increase afterward. Although how carbon emission will change the world after the COVID-19 pandemic is unknown, it is urgent to learn from the past and avert or slow down the potential rebound effect. Therefore, this study aims to identify key drivers of carbon intensity changes of 55 sectors, applying the decomposition techniques and the world input-output data. Our results demonstrate that global carbon intensity fluctuates drastically when shocked by the global financial crisis, presenting an inversed-V shape for the period 2008-2011. Industrial carbon emission and gross output vary among different industries, the growth rate of industrial carbon intensity varies from -55.55% to 23.77%. The energy intensity effect and economic structure effect have opposite impacts on carbon intensity decrease, accelerating and hindering the decreasing carbon intensity, respectively. However, the energy mix effect has a minor impact on carbon intensity decrease. The industrial carbon intensity decomposition results show the impact of technological and structural factors are significantly different among industries. Moreover, the impact of energy intensity is slightly stronger than the energy mix. More measures targeting avoiding the rebound in carbon intensity should be developed.

Single point mutations can potentially enhance infectivity of SARS-CoV-2 revealed by in silico affinity maturation and SPR assay.

The RBD (receptor binding domain) of the SARS-CoV-2 virus S (spike) protein mediates viral cell attachment and serves as a promising target for therapeutics development. Mutations on the S-RBD may alter its affinity to the cell receptor and affect the potency of vaccines and antibodies. Here we used an in silico approach to predict how mutations on RBD affect its binding affinity to hACE2 (human angiotensin-converting enzyme2). The effect of all single point mutations on the interface was predicted. SPR assay results show that 6 out of 9 selected mutations can strengthen binding affinity. Our prediction has reasonable agreement with the previous deep mutational scan results and recently reported mutants. Our work demonstrated the in silico method as a powerful tool to forecast more powerful virus mutants, which will significantly benefit the development of broadly neutralizing vaccine and antibody.

Abnormal apelin-ACE2 and SGLT2 signaling contribute to adverse cardiorenal injury in patients with COVID-19.

BACKGROUND: Angiotensin converting enzyme 2 (ACE2) has recently been identified as the functional receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent response for novel coronavirus disease 2019 (COVID-19). This study aimed to explore the roles of ACE2, apelin and sodium-glucose cotransporter 2 (SGLT2) in SARS-CoV-2-mediated cardiorenal damage. METHODS AND RESULTS: The published RNA-sequencing datasets of cardiomyocytes infected with SARS-CoV-2 and COVID-19 patients were used. String, UMAP plots and single cell RNA sequencing data were analyzed to show the close relationship and distinct cardiorenal distribution patterns of ACE2, apelin and SGLT2. Intriguingly, there were decreases in ACE2 and apelin expression as well as marked increases in SGLT2 and endothelin-1 levels in SARS-CoV-2-infected cardiomyocytes, animal models with diabetes, acute kidney injury, heart failure and COVID-19 patients. These changes were linked with downregulated levels of interleukin (IL)-10, superoxide dismutase 2 and catalase as well as upregulated expression of profibrotic genes and pro-inflammatory cytokines/chemokines. Genetic ACE2 deletion resulted in upregulation of pro-inflammatory cytokines containing IL-1ß, IL-6, IL-17 and tumor necrosis factor α. More importantly, dapagliflozin strikingly alleviated cardiorenal fibrosis in diabetic db/db mice by suppressing SGLT2 levels and potentiating the apelin-ACE2 signaling. CONCLUSION: Downregulation of apelin and ACE2 and upregulation of SGLT2, endothelin-1 and pro-inflammatory cytokines contribute to SARS-CoV-2-mediated cardiorenal injury, indicating that the apelin-ACE2 signaling and SGLT2 inhibitors are potential therapeutic targets for COVID-19 patients.

Effect of pharmaceutical care on the treatment of COVID-19: A protocol for systematic review and meta analysis.

BACKGROUND: We aimed to conduct a meta-analysis to assess the effect of pharmaceutical care on the treatment of coronavirus disease 2019 (COVID-19). METHODS: All case-controlled studies related to pharmaceutical care on the treatment of COVID-19 will be included in this review. We will use index words related to pharmaceutical care and COVID-19 to perform literature searches in PubMed, Embase, MEDLINE, CNKI, and Wanfang databases, to include articles indexed as of October 20, 2020 in English and Chinese language. Two reviewers will select trials independently for inclusion and assess trial quality. Two pairs of review authors will independently extract information for each included trials. Primary outcomes are clinical outcomes, average hospital stays, costs, patient satisfaction, and incidence of adverse drug reactions. We will evaluate the risk of bias of the included studies based on Cochrane assessment tool. Revman 5.3 (the Cochrane collaboration, Oxford, UK) will be used for heterogeneity assessment, generating funnel-plots, data synthesis, subgroup analysis, and sensitivity analysis. RESULTS: We will provide targeted and practical results assessing the effect of pharmaceutical care on the treatment of COVID-19. CONCLUSION: The stronger evidence about the effect of pharmaceutical care on the treatment of COVID-19 will be provided for clinicians. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020214223 ETHICS AND DISSEMINATION:: There is no need for ethical approval, and the review will be reported in a peer-reviewed journal.

Therapeutic experience of an 89-year-old high-risk patient with incarcerated cholecystolithiasis: A case report and literature review.

BACKGROUND: The global pandemic of coronavirus disease 2019 pneumonia poses a particular challenge to the emergency surgical treatment of elderly patients with high-risk acute abdominal diseases. Elderly patients are a high-risk group for surgical treatment. If the incarceration of gallstones cannot be relieved, emergency surgery is unavoidable. CASE SUMMARY: We report an 89-year-old male patient with acute gangrenous cholecystitis and septic shock induced by incarcerated cholecystolithiasis. He had several coexisting, high-risk underlying diseases, had a history of radical gastrectomy for gastric cancer, and was taking aspirin before the operation. Nevertheless, he underwent emergency laparoscopic cholecystectomy, with maintenance of postoperative heart and lung function, successfully recovered, and was discharged on day 8 after the operation. CONCLUSION: Emergency surgery for elderly patients with acute abdominal disease is safe and feasible during the coronavirus disease 2019 pandemic, the key is to abide strictly by the hospital's epidemic prevention regulations, fully implement the epidemic prevention procedure for emergency surgery, fully prepare before the operation, accurately perform the operation, and carefully manage the patient postoperatively.

Effects of meteorological conditions and air pollution on COVID-19 transmission: Evidence from 219 Chinese cities.

The spatial distribution of the COVID-19 infection in China cannot be explained solely by geographical distance and regulatory stringency. In this research we investigate how meteorological conditions and air pollution, as concurring factors, impact COVID-19 transmission, using data on new confirmed cases from 219 prefecture cities from January 24 to February 29, 2020. Results revealed a kind of nonlinear dose-response relationship between temperature and coronavirus transmission. We also found that air pollution indicators are positively correlated with new confirmed cases, and the coronavirus further spreads by 5-7% as the AQI increases by 10 units. Further analysis based on regional divisions revealed that in northern China the negative effects of rising temperature on COVID-19 is counteracted by aggravated air pollution. In the southern cities, the ambient temperature and air pollution have a negative interactive effect on COVID-19 transmission, implying that rising temperature restrains the facilitating effects of air pollution and that they jointly lead to a decrease in new confirmed cases. These results provide implications for the control and prevention of this disease and for the anticipation of another possible pandemic.