Recent advances in structural studies of the CRISPR-Cas-mediated genome editing tools

Clustered regularly interspaced short palindromic repeats (CRISPR) and accompanying CRISPR-associated (Cas) proteins provide RNA-guided adaptive immunity for prokaryotes to defend themselves against viruses. The CRISPR-Cas systems have attracted much attention in recent years for their power in aiding the development of genome editing tools. Based on the composition of the CRISPR RNA-effector complex, the CRISPR-Cas systems can be divided into two classes and six types. In this review, we summarize recent advances in the structural biology of the CRISPR-Cas-mediated genome editing tools, which helps us to understand the mechanism of how the guide RNAs assemble with diverse Cas proteins to cleave target nucleic acids.     

Nanotechnology for the management of COVID-19 during the pandemic and in the post-pandemic era

Following the global COVID-19 pandemic, nanotechnology has been at the forefront of research efforts and enables the fast development of diagnostic tools, vaccines and antiviral treatment for this novel virus (SARS-CoV-2). In this review, we first summarize nanotechnology with regard to the detection of SARS-CoV-2, including nanoparticle-based techniques such as rapid antigen testing, and nanopore-based sequencing and sensing techniques. Then we investigate nanotechnology as it applies to the development of COVID-19 vaccines and anti-SARS-CoV-2 nanomaterials. We also highlight nanotechnology for the post-pandemic era, by providing tools for the battle with SARS-CoV-2 variants and for enhancing the global distribution of vaccines. Nanotechnology not only contributes to the management of the ongoing COVID-19 pandemic but also provides platforms for the prevention, rapid diagnosis, vaccines and antiviral drugs of possible future virus outbreaks.     

Review on COVID-19 Etiopathogenesis,Clinical Presentation and Treatment Available with Emphasis on ACE2

In December 2019, Wuhan city in the Hubei province of China reported for the first time a cluster of patients infected with a novel coronavirus, since then there has been an outburst of this disease across the globe affecting millions of human inhabitants. Severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), is a member of beta coronavirus family which upon exposure caused a highly infectious disease called novel coronavirus disease-2019 (COVID-19). COVID-19, a probably bat originated disease was declared by World Health Organization (WHO) as a global pandemic in March 2020. Since then, despite rigorous global containment and quarantine efforts, the disease has affected nearly 56,261,952 laboratory confirmed human population and caused deaths of over 1,349,506 lives worldwide. Virus passes in majority through respiratory droplets and then enters lung epithelial cells by binding to angiotensin converting enzyme 2 (ACE2) receptor and there it undergoes replication and targeting host cells causing severe pathogenesis. Majority of human population exposed to SARS-CoV-2 having fully functional immune system undergo asymptomatic infection while 5–10% are symptomatic and only 1–2% are critically affected and requires ventilation support. Older people or people with co-morbidities are severely affected by COVID-19. These categories of patients also display cytokine storm due to dysfunctional immune response which brutally destroys the affected organs and may lead to death in some. Real time PCR is still considered as standard method of diagnosis along with other serology, radiological and biochemical investigations. Till date, no specific validated medication is available for the treatment of COVID-19 patients. Thus, this review provides detailed knowledge about the different landscapes of disease incidence, etiopathogenesis, involvement of various organs, diagnostic criteria’s and treatment guidelines followed for management of COVID-19 infection since its inception. In conclusion, extensive research to recognize novel pathways and their cross talk to combat this virus in precarious settings is our future positive hope.     

Mosaic Recombination Inflicted Various SARS-CoV-2 Lineages to Emerge into Novel Virus Variants: a Review Update

Human Coronaviruses (hCoVs) belongs to the enormous and dissimilar family of positive-sense, non-segmented, single-stranded RNA viruses. The RNA viruses are prone to high rates of mutational recombination resulting in emergence of evolutionary variant to alter various features including transmissibility and severity. The evolutionary changes affect the immune escape and reduce effectiveness of diagnostic and therapeutic measures by becoming undetectable by the currently available diagnostics and refractory to therapeutics and vaccines. Whole genome sequencing studies from various countries have adequately reported mosaic recombination between different lineage strain of SARS-CoV-2 whereby RNA dependent RNA polymerase (RdRp) gene reconnects with a homologous RNA strand at diverse position. This all lead to evolutionary emergence of new variant/ lineage as evident with the emergence of XBB in India at the time of writing this review. The continuous periodical genomic surveillance is utmost required for understanding the various lineages involved in recombination to emerge into hybrid variant. This may further help in assessing virus transmission dynamics, virulence and severity factor to help health authorities take appropriate timely action for prevention and control of any future COVID-19 outbreak.     

浅谈公共卫生与疾病预防控制体系建设

此次新冠肺炎疫情传播速度快、影响范围广、防控难度大,在没有特异性治疗药物和疫苗的情况下,我国通过最全面彻底的、以"非医疗干预"手段为主的防控举措,全社会动员,全民参与,科学防治、精准防治,有效遏制了本土疫情,取得了阶段性重要成效。在此次疫情防控中,我国各级公共卫生与疾病预防控制(以下简称"疾控")体系起到了重要作用,但也暴露出了诸多短板和不足。文章梳理了现阶段我国疾控体系、公共卫生法律法规建设、卫生应急管理政策保障3个方面存在的突出问题,提出了新时代疾控体系的职能任务发展、关键科研技术建设和专业人才资源储备3个方面的具体建议。     

Circulating Cell-Free DNA Level in Prediction of COVID-19 Severity and Mortality: Correlation of with Haematology and Serum Biochemical Parameters

Lymphocyte dysregulation in coronavirus disease-19 (COVID-19) is a major contributing factor linked to disease severity and mortality. Apoptosis results in the accumulation of cell-free DNA (cfDNA) in circulation. COVID-19 has a heterogeneous clinical course. The role of cfDNA levels was studied to assess the severity and outcome of COVID-19 patients and correlated with other laboratory parameters. The current case series included 100 patients with mild COVID-19 (MCOV-19) and 106 patients with severe COVID-19 (SCOV-19). Plasma cfDNA levels were quantified using SYBR green quantitative real-time PCR through amplification of the β-actin gene. CfDNA level was significantly higher in SCOV-19 at 706.7 ng/ml (522.6–1258) as compared to MCOV-19 at 219.8 ng/ml (167.7–299.6). The cfDNA levels were significantly higher in non-survivor than in survivors (p = 0.0001). CfDNA showed a significant correlation with NLR, ferritin, LDH, procalcitonin, and IL-6. The diagnostic sensitivity and specificity of cfDNA in the discrimination of SCOV-19 from MCOV-19 were 90.57% & 80%, respectively. CfDNA showed a sensitivity of 94.74% in the differentiation of non-survivors from survivors. CfDNA levels showed a significant positive correlation with other laboratory and inflammatory markers of COVID-19. CfDNA levels, NLR, and other parameters may be used to stratify and monitor COVID-19 patients and predict mortality. CfDNA may be used to predict COVID-19 severity with higher diagnostic sensitivity.     

On the syndemic nature of crises: A Freeman perspective

In this paper we draw a parallel between the insights developed within the framework of the current COVID-19 health crisis and the views and insights developed with respect to the long term environmental crisis, the implications for science, technology and innovation (STI) policy, Christopher Freeman analyzed already in the early 90′s. With at the time of writing, the COVID-19 pandemic entering in many countries a third wave with a very differentiated implementation path of vaccination across rich and poor countries, drawing such a parallel remains of course a relatively speculative exercise. Nevertheless, based on the available evidence of the first wave of the pandemic, we feel confident that some lessons from the current health crisis and its parallels with the long-term environmental crisis can be drawn. The COVID-19 pandemic has also been described as a “syndemic”: a term popular in medical anthropology which marries the concept of ‘synergy’ with ‘epidemic’ and provides conceptually an interesting background for these posthumous Freeman reflections on crises. The COVID-19 crisis affects citizens in very different and disproportionate ways. It results not only in rising structural inequalities among social groups and classes, but also among generations. In the paper, we focus on the growing inequality within two particular groups: youngsters and the impact of COVID-19 on learning and the organization of education; and as mirror picture, the elderly many of whom witnessed despite strict confinement in long-term care facilities, high mortality following the COVID-19 outbreak. From a Freeman perspective, these inequality consequences of the current COVID-19 health crisis call for new social STI policies: for a new “corona version” of inclusion versus exclusion.     

欧盟“工业5.0”对我国制造业高质量发展的影响与启示——基于智库双螺旋法的应用探索研究

当今世界，正经历百年未有之大变局和世纪疫情交织叠加冲击，主要经济体开始前瞻布局后疫情时代的战略调整、经济重振和转型升级。“工业5.0”作为欧盟谋划“新工业革命”、推进欧洲工业转型的战略新部署，引起国际社会的广泛关注并成为智库研究的热点。文章运用智库双螺旋法，从系统性、主体性、科学性、全局性、实践性5个角度构建了研究工业战略及其涉及的国际关系、科技战略、经济社会发展等复杂性系统问题的新思路，分析了欧盟“工业5.0”的宗旨、目的和意义，以及对我国制造业高质量发展的影响、启示和借鉴，提出了我国的因应之策，并揭示了智库双螺旋法在拓展相关问题研究视野中的价值意义。     

新冠肺炎疫情对全球生产体系的冲击和我国产业链加速外移的风险分析

新冠肺炎疫情短期内严重冲击了我国生产供应,加大了国内产业链加速外移的风险。文章基于当前疫情导致我国短期生产与出口供给缺口的研究,结合我国在全球生产网络和亚洲生产链的枢纽位置,就疫情对全球产业链的冲击及其引发的我国产业链加速外移风险进行了剖析。研究结果表明,疫情引起的产能缺口将对全球生产体系产生冲击,跨国企业将加快生产链布局调整,需密切关注疫情造成部分产业链加速外移的风险。最后,就企业复工保障、疫情防控和产业链布局等方面提出相关政策建议。     

Complete blood count alterations in COVID-19 patients: A narrative review

Coronavirus disease 2019 (COVID-19) pandemic represents a scientific and social crisis. One of the main unmet needs for coronavirus disease 2019 is its unpredictable clinical course, which can rapidly change in an irreversible outcome. COVID-19 patients can be classified into mild, moderate, and severe. Several haematological parameters, such as platelets, white blood cell total count, lymphocytes, neutrophils, (together with neutrophil-lymphocyte and platelet-lymphocyte ratio), and haemoglobin were described to be associated with COVID-19 infection and severity. The purpose of these review is to describe the current state of the art about complete blood count alterations during COVID-19 infection, and to summarize the crucial role of some haematological parameters during the course of the disease. Decreased platelet, lymphocyte, haemoglobin, eosinophil, and basophil count, increased neutrophil count and neutrophil-lymphocyte and platelet-lymphocyte ratio have been associated with COVID-19 infection and a worse clinical outcome. Our study adds some novelty about the identification of effective biomarkers of progressive disease, and might be helpful for diagnosis, prevention of complications, and effective therapy.     

A Pilot Study on COVID-19 Positive Subjects: An Excerpt of Post-Infection-Pro-Diabetic Disposition & Related Consequences in Correlation to Hepato-Pancreatic Bio-Markers,Pro-Inflammatory Cytokines and Other Risk Factors

COVID-19, a global pandemic that led to increased morbidity and mortality worldwide since its outcome at the end of the year 2019. A newly discovered variant of severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) was the arbitrator for spreading the syndrome by droplet transmission causing multi-organ failure in many occasions. A post-infection-pro-diabetic disposition was found evident in this study with the persistence of hepato-pancreatic aberrations in respect of reference range of tissue specific bio-markers in hospital admitted COVID-19 cases. The results of this study show that hyperglycemia is a risk factor in precipitating disease oriented complications to the patients with COVID-19 disease. A post-infection follow- up on glycemic-index and related complexities is a vital need to the COVID-19 infected convalescent subjects. Implementation of guidelines on social measure and awareness of anti-viral interventions may be the only way to prevent COVID-19 transmission.     

Gene editing in plants: progress and challenges

The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) genome editing system is a powerful tool for targeted gene modifications in a wide range of species, including plants. Over the last few years, this system has revolutionized the way scientists perform genetic studies and crop breeding, due to its simplicity, flexibility, consistency and high efficiency. Considerable progress has been made in optimizing CRISPR/Cas9 systems in plants, particularly for targeted gene mutagenesis. However, there are still a number of important challenges ahead, including methods for the efficient delivery of CRISPR and other editing tools to most plants, and more effective strategies for sequence knock-ins and replacements. We provide our viewpoint on the goals, potential concerns and future challenges for the development and application of plant genome editing tools.     

Impact of COVID-19 pandemic on information management research and practice: Transforming education,work and life

The COVID-19 pandemic has forced many organisations to undergo significant transformation, rethinking key elements of their business processes and use of technology to maintain operations whilst adhering to a changing landscape of guidelines and new procedures. This study offers a collective insight to many of the key issues and underlying complexities affecting organisations and society from COVID-19, through an information systems and technological perspective. The views of 12 invited subject experts are collated and analysed where each articulate their individual perspectives relating to: online learning, digital strategy, artificial intelligence, information management, social interaction, cyber security, big data, blockchain, privacy, mobile technology and strategy through the lens of the current crisis and impact on these specific areas. The expert perspectives offer timely insight to the range of topics, identifying key issues and recommendations for theory and practice.     

Aberrant methylation patterns in cancer: a clinical view

Epigenetic mechanisms, such as DNA methylation, DNA hydroxymethylation, post-translational modifications (PTMs) of histone proteins affecting nucleosome remodelling, and regulation by small and large non-coding RNAs (ncRNAs) work in concert with cis and trans acting elements to drive appropriate gene expression. Advances in detection methods and development of dedicated platforms and methylation arrays resulted in an explosion of information on aberrantly methylated sequences linking deviations in epigenetic landscape with the initiation and progression of complex diseases. Here, we consider how DNA methylation changes in malignancies, such as breast, pancreatic, colorectal, and gastric cancer could be exploited for the purpose of developing specific diagnostic tools. DNA methylation changes can be applicable as biomarkers for detection of malignant disease in easily accessible tissues. Methylation signatures are already proving to be an important marker for determination of drug sensitivity. Even more, promoter methylation patterns of some genes, such as MGMT, SHOX2, and SEPT9, have already been translated into commercial clinical assays aiding in patient assessment as adjunct diagnostic tools. In conclusion, the changes in DNA methylation patterns in tumour cells are slowly gaining entrance into routine diagnostic tests as promising biomarkers and as potential therapeutic targets.Key words: biomarkers, CpG islands, DNA methylation, molecular diagnostics, epigenetics     

Interleukin-6 Perpetrator of the COVID-19 Cytokine Storm

COVID-19 has emerged as a global pandemic. It is mainly manifested as pneumonia which may deteriorate into severe respiratory failure. The major hallmark of the disease is the systemic inflammatory immune response characterized by Cytokine Storm (CS). CS is marked by elevated levels of inflammatory cytokines, mainly interleukin-6 (IL-6), IL-8, IL-10, tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Of these, IL-6 is found to be significantly associated with higher mortality. IL-6 is also a robust marker for predicting disease prognosis and deterioration of clinical profile. In this review, the pivotal role played by IL-6 in the immuno-pathology of COVID-19 has been illustrated. The role of IL-6 as a pleiotropic cytokine executing both pro and anti-inflammatory activities has been reviewed. ADAM 10, a metalloproteinase switches the anti-inflammatory pathway of IL-6 to pro inflammatory hence blocking the action of ADAM 10 could be a new therapeutic strategy to mitigate the proinflammatory action of IL-6. Furthermore, we explore the role of anti-IL6 agents, IL-6 receptor antibodies which were being used for autoimmune diseases but now are being repurposed for the therapy of COVID-19.     

A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2

The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-CoV-2 variants, including Omicron, are required to be identified as soon as the samples are identified as ‘positive’. Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time, we have developed MOPCS (Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) with the ‘gene scissors’ clustered regularly interspaced short palindromic repeat (CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification, within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-CoV-2, and mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) and BA.1 (a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.     

Current status of the lateral flow immunoassay for the detection of SARS-CoV-2 in nasopharyngeal swabs

Early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and diagnosis of coronavirus disease 2019 (COVID-19) are priorities during the pandemic. Symptomatic and suspected asymptomatic individuals should be tested for COVID-19 to confirm infection and to be excluded from social interactions. As molecular testing capacity is overloaded during the pandemic, rapid antigen tests, such as lateral flow immunoassays (LFIAs), can be a useful tool as they allow greater test availability and obtain results in a very short time. This short review aims to present the analytical properties of LFIAs in the detection of SARS-CoV-2 in nasopharyngeal swabs. Lateral flow immunoassay is a method that combines thin-layer chromatography and indirect immunochemical sandwich method and allows the detection of a specific SARS-CoV-2 antigen in nasopharyngeal swabs. Swab specimens should be adequately collected and tested as soon as possible. Users should pay attention to quality control and possible interferences. Antigen tests for SARS-CoV-2 show high sensitivity and specificity in cases with high viral loads, and should be used up to five days after the onset of the first symptoms of COVID-19. False positive results may be obtained when screening large populations with a low prevalence of COVID-19 infection, while false negative results may happen due to improper specimen collection or insufficient amount of antigen in the specimen. So as to achieve reliable results, a diagnostic accuracy study of a specific rapid antigen test should be performed.     

Agile and adaptive governance in crisis response: Lessons from the COVID-19 pandemic

Countries around the world have had to respond to the COVID-19 outbreak with limited information and confronting many uncertainties. Their ability to be agile and adaptive has been stressed, particularly in regard to the timing of policy measures, the level of decision centralization, the autonomy of decisions and the balance between change and stability. In this contribution we use our observations of responses to COVID-19 to reflect on agility and adaptive governance and provide tools to evaluate it after the dust has settled. Whereas agility relates mainly to the speed of response within given structures, adaptivity implies system-level changes throughout government. Existing institutional structures and tools can enable adaptivity and agility, which can be complimentary approaches. However, agility sometimes conflicts with adaptability. Our analysis points to the paradoxical nature of adaptive governance. Indeed, successful adaptive governance calls for both decision speed and sound analysis, for both centralized and decentralized decision-making, for both innovation and bureaucracy, and both science and politics.     

新冠疫情与情报智慧:突发公共卫生事件疾控应急工作情报能力评价

【目的/意义】评价我国突发公共卫生事件疾控应急工作情报能力现状,识别肺炎鏖战中情报能力的问题,对指导现实工作具有重要意义。【方法/过程】本文以新型冠状病毒肺炎疫情为具体问题,推演疾控应急工作情报智慧树模型,设计因应的情报能力评价体系,改进熵权法来测定指标权重及评价结果。通过比较权重的位序与增量来发现疫情任务情报能力的重点,以及情报能力在该问题中和既往工作的差异,利用短板参量分析肺炎鏖战中情报能力的不足。【结果/结论】研究发现:本次任务对情报保障和利用能力具有较高要求,较与以往疾控应急工作,对情报加工和传递能力的需求加剧;情报决策、情报处理与分析、情报劳动者和情报政策成为疾控应急工作情报能力的重要因素;短板问题存在于应急队伍、开展应用性应急课题研究和应急情报管理机制之中,另有待优化问题存在于应急预案、公众引导、应急制度等项目之中。本研究根据上述分析结果对肺炎鏖战中的情报能力治理提出对策建议。