Exploring gut-lung axis crosstalk in SARS-CoV-2 infection: Insights from a hACE2 mouse model.

Based on the forefront of clinical research, there is a growing recognition that the gut microbiota, which plays a pivotal role in shaping both the innate and adaptive immune systems, may significantly contribute to the pathogenesis of coronavirus disease 2019 (COVID-19). Although an association between altered gut microbiota and COVID-19 pathogenesis has been established, the causative mechanisms remain incompletely understood. Additionally, the validation of the precise functional alterations within the gut microbiota relevant to COVID-19 pathogenesis has been limited by a scarcity of suitable animal experimental models. In the present investigation, we employed a newly developed humanized ACE2 knock-in (hACE2-KI) mouse model, capable of recapitulating critical aspects of pulmonary and intestinal infection, to explore the modifications in the gut microbiota following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Examination of fecal samples using 16S rRNA gene profiling unveiled a notable reduction in species richness and conspicuous alterations in microbiota composition at 6 days postinfection (dpi). These alterations were primarily characterized by a decline in beneficial bacterial species and an escalation in certain opportunistic pathogens. Moreover, our analysis entailed a correlation study between the gut microbiota and plasma cytokine concentrations, revealing the potential involvement of the Lachnospiraceae_NK4A136_group and unclassified_f_Lachnospiraceae genera in attenuating hyperinflammatory responses triggered by the infection. Furthermore, integration of gut microbiota data with RNA-seq analysis results suggested that the increased presence of Staphylococcus in fecal samples may signify the potential for bacterial coinfection in lung tissues via gut translocation. In summary, our hACE2-KI mouse model effectively recapitulated the observed alterations in the gut microbiota during SARS-CoV-2 infection. This model presents a valuable tool for elucidating gut microbiota-targeted strategies aimed at mitigating COVID-19.

How many authors does it take to publish a high profile or classic paper?

Although the process of publishing a scientific paper has gotten simpler, it is increasingly difficult to publish a paper in high profile journals. We have analyzed the publishing data in the cell biology field and found several alarming trends developing over the last two decades. There is an emerging divide between scientist-run journals and professional-run high profile journals. How did this happen? What should we do? The core issue is whether the current standard for high profile journals hurts rather than helps the scientific discovery process. In this regard, we suggest that the editors and scientists should direct their focus on the potential impact and rigor of the work instead of the "perfection" or "completeness" of the study.

Metabolite Characteristics Analysis of Siliques and Effects of Lights on the Accumulation of Glucosinolates in Siliques of Rapeseed.

Glucosinolates (GSLs) are naturally occurring secondary metabolites found in the Brassicaceae family, which mainly synthesize in the siliques with a wide range of functions. In this study, we investigated the effects of lights on metabolites in siliques of rapeseed through ultra high-performance liquid chromatography (UPLC)-heated electrospray ionization (HESI)-tandem mass spectrometry (MS/MS). A total of 249 metabolites, including 29 phenolic acids, 38 flavonoids, 22 GSLs, 93 uncalculated and 67 unknown compounds, were identified in siliques of rapeseed. Meanwhile, 62 metabolites showed significant differences after shading treatment, which were mainly GSLs and unknown compounds. Interestingly, the amounts of 10 GSLs had high accumulation levels in siliques, while the expression levels of their corresponding biosynthetic genes (AOP, GSL-OH, IGMT, and ST5a) were obviously reduced after shading treatment. Further evidence showed that the amounts of GSLs were significantly reduced in seeds, in accordance with the expression profiles of transporter genes (BnaGTRs). Our findings indicated that lights could affect the accumulation and transportation of GSLs from siliques to seeds in rapeseed. Therefore, this study facilitates a better understanding of metabolic characteristics of siliques and provides insight into the importance of light for GSLs accumulation and transportation in siliques and seeds of rapeseed.

Scientific prizes and the extraordinary growth of scientific topics.

Fast growing scientific topics have famously been key harbingers of the new frontiers of science, yet, large-scale analyses of their genesis and impact are rare. We investigated one possible factor connected with a topic's extraordinary growth: scientific prizes. Our longitudinal analysis of nearly all recognized prizes worldwide and over 11,000 scientific topics from 19 disciplines indicates that topics associated with a scientific prize experience extraordinary growth in productivity, impact, and new entrants. Relative to matched non-prizewinning topics, prizewinning topics produce 40% more papers and 33% more citations, retain 55% more scientists, and gain 37 and 47% more new entrants and star scientists, respectively, in the first five-to-ten years after the prize. Funding do not account for a prizewinning topic's growth. Rather, growth is positively related to the degree to which the prize is discipline-specific, conferred for recent research, or has prize money. These findings reveal new dynamics behind scientific innovation and investment.

The emergency surgical infection management checklist of hospitalized patients with coronavirus disease 2019 (COVID-19) in Zhejiang, China.

The novel coronavirus disease 2019 (COVID-19) epidemic broke out in 2019, it is highly contagious, and the infection rate among medical staff is high. The management of infection prevention and control during emergency surgery of COVID-19 patients has been outlined and the perioperative infection management checklist for emergency surgery of COVID-19 patients has been summarized and validated. There have been 13 emergency surgeries performed on COVID-19 patients at our hospital during this time. Two cases were cured and discharged, and the others were discharged after improvement and transferred to further rehabilitation, 30-day mortality of the emergency surgical is 0%. Once the emergency surgery protocol in the hospital is successfully established, emergency surgery can be performed as soon as the surgical planning decision is made, and the operating room can be prepared for use at any time. The incidence of surgical site infection (SSI) was largely higher than that of ordinary patients in the same time; however, the successful implementation of emergency surgery for COVID-19 had positive significance in reducing the incidence of death, risk of bleeding, and hypoxia. The current cumulative cure rate of COVID-19 in our hospital is 98%, patient mortality rate is 0%, and the incidence of COVID-19 infection in medical staff is 0%. The emergency surgical infection management checklist is feasible and effective in guiding the preoperative and intraoperative surgical procedures.

Optimization of Cellulase Immobilization with Sodium Alginate-Polyethylene for Enhancement of Enzymatic Hydrolysis of Microcrystalline Cellulose Using Response Surface Methodology.

A novel method of immobilizing cellulase on sodium alginate (SA)-polyethylene glycol (PEG) enabled the cellulase to be used repeatedly. The matrix of the immobilized cellulase was detected and characterized using Fourier transform infrared spectroscopy and scanning electron microscopy. In comparison with SA-immobilized cellulase, the relative enzyme activity and immobilization rate increased by 25% and 18%, respectively. The application range of the immobilized enzyme in terms of temperature and pH was larger than that of the free enzyme, and its thermal stability increased. The immobilized enzyme was used in enzymatic hydrolysis, in which MCC was used as the substrate. The optimal conditions for enzymatic hydrolysis were as follows: the dosage of SA-PEG-immobilized cellulase was 3.55 g/g total solids of the substrate, the concentration of the substrate was 13.16%, and the pH was 5.11. In comparison with the yield of reducing sugars in the first round of hydrolysis of MCC by SA-immobilized cellulase, the yield in the hydrolysis of MCC by SA-PEG-immobilized cellulase increased by 133%. After five cycles of repeated use, the total yield of reducing sugars when MCC was hydrolyzed by SA-PEG-immobilized cellulase was similar to that achieved with free cellulase. In comparison with the free enzyme, the highest yield when the immobilized enzyme was used was 22.68%. Therefore, the immobilized cellulase exhibited high performance in enzymatic hydrolysis.

E-Scooter safety: The riding risk analysis based on mobile sensing data.

The emergence of shared electric scooter (E-Scooter) systems offers a new micro-mobility mode in many urban areas worldwide. These systems have rapidly attracted numerous trips on various types of facilities such as sidewalks and bike lanes. After their burst of popularity, there are also growing safety concerns about E-Scooter riding. Consequently, a few cities have banned or temporarily suspended E-Scooters as severe crashes occurred. As an emerging micro-mobility mode, its safety performance is significantly understudied as compared to other travel modes such as cars and bicycles. The lack of crash records further prevents it from understanding the underlying mechanisms that drive the occurrences of E-Scooter crashes. The overarching goal of this paper is to probe the safety risk when riding E-Scooters. Specifically, it aims to study the interactions between e-scooter riding and the environment settings through naturalistic riding experiments. Rather than focusing on the analysis of individual riders' heterogeneous behavior (e.g., swinging, hard braking, etc.) and rider characteristics (e.g., age, gender, etc.), the naturalistic riding study examines the riding process in different riding circumstances. A mobile sensing system has been developed to collect data for quantifying the surrogate safety metrics in terms of experienced vibrations, speed changes, and proximity to surrounding objects. The results from naturalistic riding experiments show that E-Scooters can experience notable impacts from different riding facilities. Specifically, compared to bicycle riding, more severe vibration events were associated with E-Scooter riding, regardless of the pavement types. Riding on concrete pavements was found to experience a multiple times higher frequency of vibration events when compared to riding on asphalt pavements of the same length. Riding on both sidewalks and vehicle lanes can both encounter high-frequency close contacts in terms of proximity with other objects. These experimental results suggest that E-Scooters are subject to increased safety challenges due to the increased vibrations, speed variations, and constrained riding environments.

[Perioperative infection prevention strategies for double-lung transplantation in elderly patients with COVID-19].

OBJECTIVE: To summarize the experience of perioperative prevention during double-lung transplantation for elderly patients with coronavirus disease 2019 (COVID-19). METHODS: Clinical data of 2 elderly patients with COVID-19 who underwent double-lung transplantation in the First Affiliated Hospital of Zhejiang University School of Medicine in March 2020 were retrospectively reviewed. Perioperative protective measures were introduced in terms of medical staffing, respiratory tract, pressure injuries, air in operating room, instruments and equipment, pathological specimens, and information management. RESULTS: Two cases of double-lung transplantation were successfully completed, and the patients had no operation-related complications. Extracorporeal membrane oxygenator was successfully removed 2 to 4 days after surgery and the patients recovered well. There was no infection among medical staff. CONCLUSIONS: Adequate preoperative preparation, complete patient transfer procedures, proper placement of instruments and equipment, strengthening of intraoperative care management, and attention to prevention of pressure injury complications can maximize the safety of COVID-19 patients and medical staff.

Importance of scientific collaboration in contemporary drug discovery and development: a detailed network analysis.

BACKGROUND: Growing evidence shows that scientific collaboration plays a crucial role in transformative innovation in the life sciences. For example, contemporary drug discovery and development reflects the work of teams of individuals from academic centers, the pharmaceutical industry, the regulatory science community, health care providers, and patients. However, public understanding of how collaborations between academia and industry catalyze novel target identification and first-in-class drug discovery is limited. RESULTS: We perform a comprehensive network analysis on a large scientific corpus of collaboration and citations (97,688 papers with 1,862,500 citations from 170 million scientific records) to quantify the success trajectory of innovative drug development. By focusing on four types of cardiovascular drugs, we demonstrate how knowledge flows between institutions to highlight the underlying contributions of many different institutions in the development of a new drug. We highlight how such network analysis could help to increase industrial and governmental support, and improve the efficiency or accelerate decision-making in drug discovery and development. CONCLUSION: We demonstrate that network analysis of large public databases can identify and quantify investigator and institutional relationships in drug discovery and development. If broadly applied, this type of network analysis may help to enhance public understanding of and support for biomedical research, and could identify factors that facilitate decision-making in first-in-class drug discovery among academia, the pharmaceutical industry, and healthcare systems.

Mentorship and protégé success in STEM fields.

Einstein believed that mentors are especially influential in a protégé's intellectual development, yet the link between mentorship and protégé success remains a mystery. We marshaled genealogical data on nearly 40,000 scientists who published 1,167,518 papers in biomedicine, chemistry, math, or physics between 1960 and 2017 to investigate the relationship between mentorship and protégé achievement. In our data, we find groupings of mentors with similar records and reputations who attracted protégés of similar talents and expected levels of professional success. However, each grouping has an exception: One mentor has an additional hidden capability that can be mentored to their protégés. They display skill in creating and communicating prizewinning research. Because the mentor's ability for creating and communicating celebrated research existed before the prize's conferment, protégés of future prizewinning mentors can be uniquely exposed to mentorship for conducting celebrated research. Our models explain 34-44% of the variance in protégé success and reveals three main findings. First, mentorship strongly predicts protégé success across diverse disciplines. Mentorship is associated with a 2×-to-4× rise in a protégé's likelihood of prizewinning, National Academy of Science (NAS) induction, or superstardom relative to matched protégés. Second, mentorship is significantly associated with an increase in the probability of protégés pioneering their own research topics and being midcareer late bloomers. Third, contrary to conventional thought, protégés do not succeed most by following their mentors' research topics but by studying original topics and coauthoring no more than a small fraction of papers with their mentors.

Prospective study evaluating post-operative central nervous system infections following cranial surgery.

AIMS: To evaluate the efficacy of our methods for decreasing the incidence of post-operative central nervous system infections (PCNSI) and to assess the type of microbiology and risk factors associated with PCNSI. METHODS: This prospective study was performed at First Affiliated Hospital, College of Medicine, Zhejiang University, which is a major medical centre in eastern China. The study included adult patients who underwent cranial surgery from January 2014 to October 2015 at this institution and survived for more than 7 days . The demographic information and clinical data of the patients were recorded for every operation and the incidence of PCNSI and the type of microbiology were analysed separately for patients undergoing craniotomy and those undergoing cranial burr-hole surgery. Prior to initiation of the study, our research team had developed and implemented a series of methods for reducing infection rates in our department. RESULTS: A total of 1,616 cranial surgery procedures were assessed in the present study; 1,236 craniotomy/craniectomy operations and 380 cranial burr-hole surgery operations. Of these procedures, 29 were complicated by PCNSI (27 cases with meningitis/ventriculitis and two with intracranial abscess/empyema). The overall incidence of PCNSI was 1.8%, while the incidence of craniotomy/craniectomy operations was 2.0% (25 cases) and that of burr-hole surgery operations was 1.1% (four cases); the most common microorganism was Staphylococcus. Of the patients who underwent cranial burr-hole surgery, the only independent risk factor for PCNSI was the absence of prophylactic antibiotics. There were no independent risk factors for craniotomy/craniectomy operations. CONCLUSIONS: In the present large-sample study, the incidence of PCNSI was 1.8%, which was dramatically lower than that of a previous study performed by our research group.

Scientific prize network predicts who pushes the boundaries of science.

Scientific prizes confer credibility to persons, ideas, and disciplines, provide financial incentives, and promote community-building celebrations. We examine the growth dynamics and interlocking relationships found in the worldwide scientific prize network. We focus on understanding how the knowledge linkages among prizes and scientists' propensities for prizewinning relate to knowledge pathways between disciplines and stratification within disciplines. Our data cover more than 3,000 different scientific prizes in diverse disciplines and the career histories of 10,455 prizewinners worldwide for over 100 years. We find several key links between prizes and scientific advances. First, despite an explosive proliferation of prizes over time and across the globe, prizes are more concentrated within a relatively small group of scientific elites, and ties among elites are highly clustered, suggesting that a relatively constrained number of ideas and scholars push the boundaries of science. For example, 64.1% of prizewinners have won two prizes and 13.7% have won five or more prizes. Second, certain prizes strongly interlock disciplines and subdisciplines, creating key pathways by which knowledge spreads and is recognized across science. Third, genealogical and coauthorship networks predict who wins multiple prizes, which helps to explain the interconnectedness among celebrated scientists and their pathbreaking ideas.

Bevacizumab for the Treatment of Gammaknife Radiosurgery-Induced Brain Radiation Necrosis.

BACKGROUND: Radiation necrosis is one of the complications of Gammaknife radiosurgery. The traditional treatment of radiation necrosis carries a high risk of failure, Bevacizumab is an antiangiogenic monoclonal antibody against vascular endothelial growth factor, a known mediator of cerebral edema. It can be used to successfully treat brain radiation necrosis. PATIENT DESCRIPTION: Two patients with a history of small cell lung cancer presented with metastatic disease to the brain. They underwent Gammaknife radiosurgery to brain metastases. Several months later, magnetic resonance imaging showed radiation necrosis with significant surrounding edema. The patients had a poor response to treatment with dexamethasone. They were eventually treated with bevacizumab (5 mg/kg every 2 weeks, 7.5 mg/kg every 3 weeks, respectively), and the treatment resulted in significant clinical and radiographic improvement. CONCLUSION: Bevacizumab can be successfully used to treat radiation necrosis induced by Gammaknife radiosurgery in patients with cerebral metastases. It is of particular benefit in patients with poor reaction to corticosteroids and other medications.

Epidemic spreading with activity-driven awareness diffusion on multiplex network.

There has been growing interest in exploring the interplay between epidemic spreading with human response, since it is natural for people to take various measures when they become aware of epidemics. As a proper way to describe the multiple connections among people in reality, multiplex network, a set of nodes interacting through multiple sets of edges, has attracted much attention. In this paper, to explore the coupled dynamical processes, a multiplex network with two layers is built. Specifically, the information spreading layer is a time varying network generated by the activity driven model, while the contagion layer is a static network. We extend the microscopic Markov chain approach to derive the epidemic threshold of the model. Compared with extensive Monte Carlo simulations, the method shows high accuracy for the prediction of the epidemic threshold. Besides, taking different spreading models of awareness into consideration, we explored the interplay between epidemic spreading with awareness spreading. The results show that the awareness spreading can not only enhance the epidemic threshold but also reduce the prevalence of epidemics. When the spreading of awareness is defined as susceptible-infected-susceptible model, there exists a critical value where the dynamical process on the awareness layer can control the onset of epidemics; while if it is a threshold model, the epidemic threshold emerges an abrupt transition with the local awareness ratio α approximating 0.5. Moreover, we also find that temporal changes in the topology hinder the spread of awareness which directly affect the epidemic threshold, especially when the awareness layer is threshold model. Given that the threshold model is a widely used model for social contagion, this is an important and meaningful result. Our results could also lead to interesting future research about the different time-scales of structural changes in multiplex networks.

Contagion processes on the static and activity-driven coupling networks.

The evolution of network structure and the spreading of epidemic are common coexistent dynamical processes. In most cases, network structure is treated as either static or time-varying, supposing the whole network is observed in the same time window. In this paper, we consider the epidemics spreading on a network which has both static and time-varying structures. Meanwhile, the time-varying part and the epidemic spreading are supposed to be of the same time scale. We introduce a static and activity-driven coupling (SADC) network model to characterize the coupling between the static ("strong") structure and the dynamic ("weak") structure. Epidemic thresholds of the SIS and SIR models are studied using the SADC model both analytically and numerically under various coupling strategies, where the strong structure is of homogeneous or heterogeneous degree distribution. Theoretical thresholds obtained from the SADC model can both recover and generalize the classical results in static and time-varying networks. It is demonstrated that a weak structure might make the epidemic threshold low in homogeneous networks but high in heterogeneous cases. Furthermore, we show that the weak structure has a substantive effect on the outbreak of the epidemics. This result might be useful in designing some efficient control strategies for epidemics spreading in networks.

Two-stage effects of awareness cascade on epidemic spreading in multiplex networks.

Human awareness plays an important role in the spread of infectious diseases and the control of propagation patterns. The dynamic process with human awareness is called awareness cascade, during which individuals exhibit herd-like behavior because they are making decisions based on the actions of other individuals [Borge-Holthoefer et al., J. Complex Networks 1, 3 (2013)]. In this paper, to investigate the epidemic spreading with awareness cascade, we propose a local awareness controlled contagion spreading model on multiplex networks. By theoretical analysis using a microscopic Markov chain approach and numerical simulations, we find the emergence of an abrupt transition of epidemic threshold ß(c) with the local awareness ratio α approximating 0.5, which induces two-stage effects on epidemic threshold and the final epidemic size. These findings indicate that the increase of α can accelerate the outbreak of epidemics. Furthermore, a simple 1D lattice model is investigated to illustrate the two-stage-like sharp transition at α(c)≈0.5. The results can give us a better understanding of why some epidemics cannot break out in reality and also provide a potential access to suppressing and controlling the awareness cascading systems.