Understanding how the coronaviruses invade our body is an essential point, and the expression profile of coronaviruses receptor may help us to find where the coronavirus infects our body. We found that the coronavirus receptors, including angiotensin-converting enzyme 2 (ACE2) for SARS-CoV and SARS-Cov-2, are digestion-related enzymes in human enterocytes. Coronaviruses are continually altering the binding receptor and binding modes during their evolution, but the potential target cell in the small intestine is constant when in the lung is inconstant. Enterocytes may act as a conserved cell reservoir for coronaviruses, which may be partially explained by the Red Queen hypothesis. We also found that coronaviruses receptors could be elevated in the presence of both invasive bacteria and their counterpart, probiotics. We demonstrated here that enterocytes act as a conserved cell reservoir for coronaviruses during their evolutions, which should not be ignored in the investigation of coronavirus diagnosis and treatment strategies.

In this paper, a novel permanent magnet-assisted synchronous reluctance machine (PMASynRM) with rare-earth PMs and ferrite magnets is proposed. The performance of PMASynRM is discussed with respected to the different magnet ratio of rare-earth PMs and ferrite magnets. Some characteristics including the flux density, output torque, cogging torque, output power, power factor, torque ripple, loss, efficiency, and demagnetization are calculated by 2-D finite element analysis (FEA). The analysis results show that the excellent performance can be obtained by using hybrid magnet of rare-earth PMs and ferrite magnets with the suitable magnet ratio, and provide some desirable cost-performance trade-off.

Natural fibers are a gift from nature that we yet fully utilized until now. It can be classified into several groups and bast fibers are the group having the most promising performance when reinforced in polymer composites. However, numerous factors have been reported that influences mechanical properties of fiber reinforcements in the composite. In this review, bast fiber retting process and the effect of enzymatic retting on fiber and fibers reinforced polymer composites have been discussed and reviewed for the latest researches. Retting precedes mechanical processing (i.e. scutching) of the fiber from the stem and is essential for reduction of fiber breakage. All retting methods except chemical retting process are involving secretes of enzymes by bacteria or fungi under controlled (enzymatic retting) or random conditions (water and dew retting). Besides, enzymatic retting is claimed to have more environmentally friendly wastewater products, shorter retting period and controllable fiber biochemical components under mild incubation conditions. This review comprehensively assesses the enzymatic retting process for producing high-quality bast fiber and will become a reference for future development on bast fiber reinforced polymer composites.

Purpose: Acute kidney injury (AKI) is a severe symptom of the 2019 novel coronavirus disease (COVID-19), especially for patients in a critical condition.This study explored the potential mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on AKI at the single-cell level. Methods: 15 normal human kidney samples were collected and analyzed using single-cell RNA sequencing (scRNA-seq). Subsequently, we analyzed the components and proportions of kidney cells expressing the host cellular receptor ACE2 and the key protease TMPRSSs family, and analyzed the expression differences in Occidental and Asian populations. Results: We drafted the currently available world's largest human kidney cell atlas with 42,589 cells and identified 19 clusters through unsupervised hierarchical clustering analysis. ACE2 and TMPRSSs genes were significantly co-expressed in podocytes and proximal convoluted tubules as potential host cells targeted by SARS-CoV-2. Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. In addition, given the high expression of ACE2 and kidney disease-related genes in Occidental donors relative to Asian donors, Occidental populations with SARS-CoV-2 infection might be a higher risk of of kidney injury.

The coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the chief concern of the international community in almost no time. As of May 9th, 2021, more than 150 million cases and 3.2 million deaths have been recorded. Considering the early struggle in treating COVID-19 patients, the researchers and clinicians have decided to try the previously available drugs according to their mechanisms of action. Hence, many antivirals, antibiotics, antiparasitics, and antipyretics have been proposed. Pregnant women, fetuses, and infants are known high-risk populations that are threatened during disease outbreaks. Therefore, this article reviews the safety of potential drugs for COVID-19 patients during pregnancy and breastfeeding.

In the face of the newly emergent COVID-19 pandemic, researchers around the world are racing to identify efficacious drugs capable of preventing or treating its infection. They are doing that by testing already available and approved antimicrobials for their rapid repurposing against COVID-19. Using the data emerging on the comparable efficacy of various compounds having different mechanisms of action and indications, I suggest in this report, their potential mechanistic convergence. Specifically, I highlight the lysosome as a key possible therapeutic target for COVID-19, proposing one of the lysosomal storage disorders, Niemann-Pick type C disease (NPC), as a prototypical condition with inherent resistance or an “unfavorable” host cell environment for viral propagation. The included reasoning evolves from previously generated data in NPC, along with the emerging data on COVID-19. The aim of this report is to suggest that pharmacological induction of a “transient” NPC-like lysosomal dysfunction, could hold answers for targeting the ongoing COVID-19 pandemic.

Among the plant nutrients potassium (K) is one of the vital elements required for plant growth and physiology. Potassium is not only a constituent of plant structure but also plays regulatory function in several biochemical processes related to protein synthesis, carbohydrate metabolism, enzyme activation. There are several physiological processes like stomatal regulation and photosynthesis are dependent on K. In the recent decades K was found to provide abiotic stress tolerance. Under salt stress, K helps in maintaining ion homeostasis and regulation of osmotic balance. Under drought stress condition K regulates the stomatal opening and makes the plants adaptive to water deficit. Many reports provided the notion that K enhances the antioxidant defense in plants and therefore, protects the plants from oxidative stress under various environmental adversities. Also, it provides some cellular signaling alone or in association with other signaling molecules and phytohormones. Although a considerable progress in understanding K-induced abiotic stress tolerance in plants has been achieved the exact molecular mechanisms of such protections are still under research. In this review, we summarized the recent literature on the biological functions of K, its uptake, and translocation and its role in plant abiotic stress tolerance.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

Not a lot is known about either death or the dying process. Politicians and many in the medical profession in the UK tend to shy away from interfering with it by not allowing euthanasia as an end of life option for the patient. This is the first paper in a series of two, comparing the situation in human medicine and veterinary medicine, in which euthanasia is well practiced for relieving suffering at the end of an animal’s life. This first part takes the form of a literature review including best practice around end of life care, its deficiencies and the need for assisted dying. Veterinary surgeons are well trained in the ethics of euthanasia and put it to good use in the best interest of their animal patients. In countries which have legalized physician assisted suicide for the terminally ill reporting indicates that it works well, without increases in involuntary euthanasia and most importantly without intimidation of the vulnerable. However, there is still an ever increasing tendency to overuse sedation and opioids at the end of life, which merits further investigation. With advances in medical science able to significantly prolong the dying process, patient autonomy demands a review of the law in the UK.

Based on the demographic shift and the related challenges resulting from the growing number of elderly and persons with chronic diseases, the idea of smart home that supports its inhabitants in the daily life, gains importance. The purpose of this paper was to examine in a prototypic Ambient Assisted Living environment if users after interaction with different health-supporting applications intend to use such in the future. Two experimental studies exemplary show possible applications of home-integrated technology that can support, assist and accompany the target group in different contexts, and examine to what extent participants are willing to future use such sophisticated technology at home. The results show that people in general, but especially the old and chronically ill ones are quite fascinated of health-supporting ambient technology and the majority intends to use such ambient assistance in the future (study I). Moreover, serious games for healthcare are shown as a hedonic use of technology in smart homes that have a great potential to retain or improve the physical health, mobility and the overall well-being of the inhabitants (study II). The article provides two examples of ambient technology to leverage the demographic change and presents important user factors for facilitating high user acceptance.

The present grievous situation of the tuberculosis disease can be improved by efficient case management and timely follow-up evaluations. With the advent of digital technology this can be achieved by quick summarization of the patient-centric data. The aim of our study was to assess the effectiveness of the ODK Scan paper-to-digital system during testing period of three months. A sequential, explanatory mixed-method research approach was employed to elucidate technology use. Training, smartphones, application and 3G enabled SIMs were provided to the four field workers. At the beginning, baseline measures of the data management aspects were recorded and compared with endline measures to see the impact of ODK Scan. Additionally, at the end, users’ feedback was collected regarding app usability, user interface design and workflow changes. 122 patients’ records were retrieved from the server and analysed for quality. It was found that ODK Scan recognized 99.2% of multiple choice bubble responses and 79.4% of numerical digit responses correctly. However, the overall quality of the digital data was decreased in comparison to manually entered data. Using ODK Scan, a significant time reduction is observed in data aggregation and data transfer activities, however, data verification and form filling activities took more time. Interviews revealed that field workers saw value in using ODK Scan, however, they were more concerned about the time consuming aspects of the use of ODK Scan. Therefore, it is concluded that minimal disturbance in the existing workflow, continuous feedback and value additions are the important considerations for the implementing organization to ensure technology adoption and workflow improvements.

β-Lactams are pharmacologically important compounds because of their various biological uses, including antibiotic and so on. β-Lactams were synthesized from benzylidene-inden derivatives and acetoxyacetyl chloride. The inhibitory effect of these compounds was also examined for human carbonic anhydrase I and II (hCA I, and II) and acetylcholinesterase (AChE). The results reveal that β-lactams are inhibitors of hCA I, II and AChE. The K_i values of β-lactams (2a-k) were 0.44-6.29 nM against hCA I, 0.93-8.34 nM against hCA II, and 0.25-1.13 nM against AChE. Our findings indicate that β-lactams (2a-k) inhibit both CA isoenzymes and AChE at low nanomolar concentrations.

This study was designed for the first time to improve phenolic yield and antioxidant activity of ultrasonic-assisted extraction from Acer truncatum leaves (ATL) using response surface methodology, and phenolic composition in ATL extracted under the optimized condition were characterized by UPLC-QTOF-MS/MS. Solvent and extraction time were selected based on preliminary experiments, and a four-factors-three-levels central composite design was conducted to optimize solvent concentration (X₁), material-to-liquid ratio (X₂), ultrasonic temperature (X₃) and power (X₄) for an optimal total phenol yield (Y₁) and DPPH• antioxidant activity (Y₂). The results showed that the optimal combination was ethanol: water (v:v) 66.21%, material-to-liquid ratio 1:15.31 g/mL, ultrasonic temperature 60 °C, power 267.30 W, and time 30 min with three extractions, giving a maximal total phenol yield of 7593.62 mg gallic acid equivalent /100 g d.w. and a maximal DPPH• antioxidant activity of 74241.61 μmol Trolox equivalent/100 g d.w.. Furthermore, 22 phenolics were first identified in ATL extract obtained under the optimized conditions, indicating that gallates, gallotannins, quercetin, myricetin and chlorogenic acid derivatives were the main phenolic composition in ATL. What’s more, a gallotannins pathway existing in ATL from gallic acid to penta-O-galloyl-glucoside was interpreted. All these results provided practical information aiming at full utilization of phenolics in ATL, together with fundamental knowledge for further research.

The role of the Renin-Angiotensin-Aldosterone System (RAAS) in Corona Virus Disease 2019 (COVID-19) infection has become a controversial topic of discussion. RAAS inhibitors, such as Angiotensin Converting Enzyme (ACE) inhibitors and Angiotensin II receptor blockers (ARBs), which are used to treat cardiovascular diseases, have been implicated in potentially increasing cell surface levels of ACE2. ACE2 is the host receptor for COVID-19 that was discovered in Wuhan, China in December 2019. Since December, COVID-19 has transmitted rapidly across the world and has become a global pandemic. COVID-19 is similar to the Middle East respiratory syndrome coronavirus (MERS-CoV) with the first case reported in Saudi Arabia in September 2012. COVID-19, also known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is also similar to SARS-CoV, which first infected humans in the Guangdong province of southern China in 2002, and caused an epidemic between November 2002 and July 2003. Both SARS-CoV and COVID-19 use ACE2 to enter host cells. ACE2 is primarily expressed in the mouth, lung, heart, esophagus, kidney, bladder, and intestines, and is a component of RAAS, which serves to maintain vascular tone and blood volume. Inhibition or activation of other components of RAAS has been shown to directly increase or decrease the expression and/or activity of ACE2. Furthermore, RAAS-targeting therapeutics, such as ACE inhibitors and ARBs, have also been shown to regulate the expression and/or activity of ACE2, albeit in animal models. Although these changes in ACE2 have been demonstrated only in animal models, there is no evidence that administration of RAAS-targeting therapeutics to humans for the treatment of hypertension, diabetes, and other cardiovascular diseases (e.g., myocardial infarction and heart failure) causes changes in ACE2 expression. Nor is there clinical evidence that RAAS-targeting therapeutics augment COVID-19 infection, morbidity, or mortality. However, clinical evidence does suggest that ACE2 expression may protect against respiratory distress caused by a variety of noxious agents. This review attempts to provide a balanced overview of the potential role of RAAS in regulating ACE2, and the role of ACE2 during COVID-19 infection. Evidence is provided to show that the expression of ACE2 may mediate both positive and negative outcomes, depending on the timing of ACE2 expression.

SARS-CoV-2, the newly identified human coronavirus causing severe pneumonia epidemic, was probably originated from Chinese horseshoe bats. However, direct transmission of the virus from bats to humans is unlikely due to lack of direct contact, implying the existence of unknown intermediate hosts. Angiotensin converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2, but only ACE2s of certain species can be utilized by SARS-CoV-2. Here, we evaluated and ranked the receptor-utilizing capability of ACE2s from various species by phylogenetic clustering and sequence alignment with the currently known ACE2s utilized by SARS-CoV-2, predicting potential intermediate hosts of SARS-CoV-2.

This is the second of a series of two papers comparing the end of life issues in human and veterinary medicine. We outline the main differences between human and animal patients such as patient communication, finance and ‘conflicts of interest’ between animal, owner and veterinarian. We discuss striking similarities between human and veterinary issues such as assessing quality of life and the primary role of the attending veterinarian or doctor being the welfare and care of the patient. This paper takes the form of an ethical argument in favour of allowing euthanasia in human medicine, by providing insights into end of life issues for humans from an independent veterinary perspective. Veterinary surgeons are well trained in the ethics of euthanasia and put it to good use in the best interest of their animal patients. Doctors in the UK are limited and unwilling to put forward a case for the option of euthanasia for those patients who face a slow and agonizing death. With advances in medical science being able to significantly prolong the dying process, autonomy for the patient demands a review of the law regarding patient choice in the UK.

G protein-coupled receptors (GPCRs) comprise the largest family of membrane receptors that control many cellular processes and consequently often serve as drug targets. These receptors undergo a strict regulation by mechanisms such as internalization and desensitization, which are strongly influenced by posttranslational modifications. Ubiquitination is a posttranslational modification with a broad range of functions that is currently gaining increased appreciation as a regulator of GPCR activity. The role of ubiquitination in directing GPCRs for lysosomal degradation has already been well-established. Furthermore, this modification can also play a role in targeting membrane and endoplasmic reticulum-associated receptors to the proteasome. Most recently, ubiquitination was also shown to be involved in GPCR signaling. In this review, we present current knowledge on the molecular basis of GPCR regulation by ubiquitination, and highlight the importance of E3 ubiquitin ligases, deubiquitinating enzymes and β-arrestins. Finally, we discuss classical and newly-discovered functions of ubiquitination in controlling GPCR activity.

Infertility affects approximately 15% of couples worldwide, an estimated 30% of which is related to male factor infertility. Application of low level laser therapy (LLLT) to improve fertility status is a rapidly growing discipline in medicine. Laser therapy triggers a variety of biological processes through interaction with primary cellular photoacceptors. The present review aims at evaluating the literature available in the MEDLINE/ PubMed on cellular and molecular mechanisms of photobiomodulation in the domains of reproductive and veterinary medicine. We primarily focused on the clinical application of laser treatment on seminal quality, in particular its role in promoting spermatozoa motility, as well as the role of phototherapy in modulating assisted reproduction (ART). Additionally, we investigated the strength of evidence in support of the positive impact of photobiomodulation on facilitating ART.

We discuss the role of water bridging the DNA-enzyme interaction by resorting to recent 1 results showing that London dispersion forces between delocalized electrons of base pairs of DNA 2 are responsible for the formation of dipole modes that can be recognized by Taq polymerase. 3 We describe the dynamical origin of the high efficiency and precise targeting of Taq activity in 4 PCR. The spatiotemporal distribution of interaction couplings, frequencies, amplitudes, and phase 5 modulations comprise a pattern of fields instantiating the electromagnetic image of DNA in its 6 water environment, which is what the polymerase enzyme actually recognizes at long range. The 7 experimental realization of PCR amplification, achieved through replacement of the DNA template 8 by the treatment of pure water with electromagnetic signals recorded from viral and bacterial DNA 9 solutions, is found consistent with the gauge theory paradigm of quantum fields.

One of the hallmarks of the SARS-CoV-2 infection has been the inflammatory process that played a role in its pathogenesis, resulting in mortality within susceptible individuals. This uncontrolled inflammatory process leads to severe systemic symptoms via multiple pathways, however, the role of endothelial dysfunction and thrombosis have not been truly explored. This review aims to highlight the pathogenic mechanisms of these inflammatory triggers leading to thrombogenic complications. There are direct and indirect pathogenic pathways of the infection that are examined in detail. We also describe the case of carotid artery thrombosis in a patient following the SARS-CoV-2 infection, while reviewing the literature on the role of ACE2, the endothelium, and the different mechanisms by which SARS-CoV-2 may manifest both acutely and chronically. We also highlight differences from the other coronaviruses that have made this infection pandemic with similarities to the influenza virus.

There are currently around 78 Nuclear Power Plants (NPP) in the world based on Boiling Water Reactors (BWR). The current parameter to assess BWR instability issues is the linear Decay Ratio (DR). However, it is well known that BWRs are complex non-linear dynamical systems that may even exhibit chaotic dynamics that normally preclude the use of the DR when the BWR is working at a specific operating point during instability. In this work a novel methodology based on an adaptive Shannon Entropy estimator and on Noise Assisted Empirical Mode Decomposition variants is presented. This methodology was developed for real-time implementation of a stability monitor. This methodology was applied to a set of signals stemming from several NPPs reactors (Ringhals-Sweden, Forsmark-Sweden and Laguna Verde-Mexico) under commercial operating conditions, that experienced instabilities events, each one of a different nature

SARS-CoV-2 causes severe pneumonia epidemics and probably originated in horseshoe bats, but the intermediate host is unknown. The interaction of SARS-CoV-2 spike protein and its acceptor protein ACE2 is an important issue in determining viral host range and cross-species infection, while the binding capacity of Spike protein to ACE2 of different species is unknown. Here, we used the atomic structure model of SARS-CoV-2 and human ACE2 to assess the receptor utilization capacity of ACE2s from different species including cats, chimpanzees, dogs, cattles. Our results show, domestic cats (Felis catusc) and dogs (Canis lupus familiaris) are more susceptible to infection by SARS-CoV-2 and that they can efficiently transmit the virus to previously uninfected animals that are housed with them. Especially, cats could be a choice of animal model for screening antiviral drugs or vaccine candidates against SARS-CoV-2.

Aims: Spironolactone is a steroidal mineralocoricosteroid receptor antagonist (MRA) used for treatment of resistant hypertension, heart failure and edema. It exerts class specific adverse effects that are shared by other MRAs. Additionally, it exerts unique “off target” steroidal effects that include gynecomastia, impotence and loss of libido in males and menstrual irregularity in females. Together, these have led to a poor tolerability and limited use despite positive results in many randomized, controlled clinical trials. We review the off-target effects of spironolactone that may summate with its MRA action to provide an advantageous profile for prevention or treatment of patients with COVID-19. Methods: Literature review using PubMed Central. Results: The blockade by spironolactone of the androgen receptor should diminish the expression of transmembrane protease serine 2 (TMPRSS2) that has an androgen promoter while its MRA action should enhance the expression of protease nexin1 (PN1) that inhibits furin and plasmin. TMPRSS2, furin and plasmin cooperated to process the SARS-CoV-2 spike protein to increase its high affinity binding to the angiotensin converting enzyme 2 (ACE2) and thereby promote viral cell entry. Its actions as an MRA may reduce inflammation and preserve pulmonary, cardiac and vascular functions. Its anti-plasmin action may combat hemostatic dysfunction. Conclusion: The hypothesis that the off-target effects of spironolactone summate with its MRA actions to provide special benefits for COVID-19 is worthy of direct investigation and clinical trial.

Cannabis is a flowering plant that has long been used for medicinal, therapeutic, and recreational purposes. Cannabis contains more than 500 different compounds, including a unique class of terpeno-phenolic compounds known as cannabinoids; Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most prevalent cannabinoids and have been associated with the therapeutic and medicinal properties of the cannabis plant. In this paper, continuous flow microwave assisted extraction (MAE) is presented and compared with other methods for commercial cannabis extraction. The practical issues of each extraction method are discussed. The main advantages of MAE are: continuous-flow method which allows for higher volumes of biomass to be processed in less time than existing extraction methods, improved extraction efficiency leading to increased final product yields, improved extract consistency and quality because the process does not require stopping and restarting material flows, and ease of scale-up to industrial scale without the use of pressurised batch vessels. Moreover, due to the flexibility of changing the operation conditions, MAE eliminates additional steps required in most extraction methods, such as biomass decarboxylation, winterisation, which typically adds at least a half day to the extraction process. Another factor that sets MAE apart is the ability to achieve high extraction efficiency even at the industrial scale. Whereas the typical recovery of active compounds using supercritical CO¬2 remains around 70-80%, via MAE up to 95% of the active compounds from cannabis biomass can be recovered at the industrial scale.

Puerarin (PUE) is a compound isolated from the roots of Pueraria lobata. We studied the pharmacokinetics and tissue distribution kinetics of PUE in Sprague-Dawley rats following intraperitoneal administration of three concentrations. Indirect competitive ELISA based on an anti-PUE monoclonal antibody was used to determine the concentration of PUE in the blood, heart, liver, spleen, lung, kidney, hippocampus, cerebral cortex, and striatum. The plasma and tissue distribution kinetic characteristics following a single injection of PUE (20, 40, and 80 mg/kg) were calculated using a non-compartment model. In the high-dose (80 mg/kg) and medium-dose (40 mg/kg) groups, the kinetic profile of PUE in blood and kidney samples showed two absorption peaks, while that of the other tissues showed only one peak. In the low-dose (20 mg/kg) group, there was only one peak, irrespective of the sample type. Pharmacokinetic parameters such as the area under the curve, C_max, and T_max varied according to the administered dose. AUC and C_max values increased dose-dependently. PUE was widely distributed in areas of the brain such as the hippocampus, cerebral cortex, and striatum, providing a foundation for guiding the use of PUE in the treatment of cerebral ischaemic stroke and neurodegenerative diseases.

Enzymes are in high demand for very diverse biotechnological applications. However, natural biocatalysts often need to be engineered for fine-tuning their properties towards the end applications, such as the activity, selectivity, stability to temperature or co-solvents, and solubility. Computational methods are increasingly used in this task, providing predictions that narrow down the space of possible mutations significantly and can enormously reduce the experimental burden. Many computational tools are available as web-based platforms, making them accessible to non-expert users. These platforms are typically user-friendly, contain walk-throughs, and do not require deep expertise and installations. Here we describe some of the most recent outstanding web-tools for enzyme engineering and formulate future perspectives in this field.

ω-Transaminases have been immobilized on macrocellular silica monoliths and used as heterogeneous biocatalysts in a continuous flow mode enantioselective transamination reaction. The support was prepared by a sol-gel method based on emulsion templating. The enzyme was immobilized on the structured silica monoliths both by adsorption, and by covalent grafting using amino-functionalized silica monoliths and glutaraldehyde as a coupling agent. A simple reactor set-up based on the use of a heat-shrinkable Teflon tube is presented and successfully used for the continuous flow kinetic resolution of a chiral amine, 4-bromo-α-methylbenzylamine. The porous structure of the supports ensures effective mass transfer and the reactor works in the plug flow regime without preferential flow paths. When immobilized in the monolith and used in the flow reactor, transaminases retain their activity and their enantioselectivity. The solid biocatalyst is also shown to be stable both on stream and during storage. These essential features pave the way to the successful development of an environmentally friendly process for chiral amines production.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

The outbreak of a novel coronavirus (SARS-CoV2) associated with acute respiratory disease called COVID-19 marked the introduction of the third spillover of an animal CoV to humans in the last 2 decades. The SARS-CoV2 genome analysis with various bioinformatics tools revealed that it belongs to beta CoVs genera, with highly similar genome as bat coronavirus and receptor binding domain (RBD) of spike glycoprotein as Malayan pangolin coronavirus. Based on its genetic proximity, SARS-CoV2 is likely to be originated from bat derived CoV and transmitted to humans via an unknown intermediate mammalian host, probably Malayan pangolin. Further spike protein S1/S2 cleavage site of SARS-CoV2 has acquired polybasic furin cleavage site which is absent in bat and pangolin suggesting natural selection either in an animal host before zoonotic transfer or in humans following zoonotic transfer. In the current review, we recapitulate a preliminary opinion about the disease, origin and life cycle of SARS-CoV2, roles of virus proteins in pathogenesis, commonalities and differences between different corona viruses. We have also highlighted the evidences regarding the potential drugs and vaccine candidates with their modes of action to cope with this viral outbreak. Our review provides comprehensive up-dated information on molecular aspects of the SARS-CoV2.

This review focuses on the regulation and modulation of human DNA polymerase δ (Pol δ). The emphasis is on mechanisms that regulate the activity and properties of Pol δ in DNA repair and replication. The areas covered are the degradation of the p12 subunit of Pol δ, which converts it from a heterotetramer (Pol δ4) to a heterotrimer (Pol δ3), in response to DNA damage and also during the cell cycle. The biochemical mechanisms that lead to degradation of p12 are reviewed, as well as the properties of Pol δ4 and Pol δ3 that provide insights into their functions in DNA replication and repair. The second focus of the review involves the functions of two Pol δ binding proteins, PDIP46 and PDIP38, both of which are multi-functional proteins. PDIP46 is a novel activator of Pol δ4, and the impact of this function is discussed in relation to its potential roles in DNA replication. Several new models for the roles of Pol δ3 and Pol δ4 in leading and lagging strand DNA synthesis that integrate a role for PDIP46 are presented. PDIP38 has multiple cellular localizations including the mitochondria, the splicesosomes and the nucleus. It has been implicated in a number of cellular functions, including the regulation of specialized DNA polymerases, mitosis, the DNA damage response, Mdm2 alternative splicing and the regulation of the Nox4 NADPH oxidase.

Metabolic enzymes are often targeted for drug development programs of metabolic diseases such as diabetes and its complications. Many secondary metabolites isolated from natural products have shown therapeutic action against these enzymes. However, some commercially available synthetic drugs have shown unfriendly impacts with various side effects. Thus, this research has focused on a comprehensive study of secondary metabolites showing better inhibitory activities towards metabolic enzymes such as α-amylase, α-glucosidase, aldose reductase, and lipase. Further receptor-based virtual screening was performed against the various secondary metabolites database designed in-silico. Using Gold combined with subsequent post-docking analyses, the score was obtained as methyl xestospongic ester (Gold score 65.83), 2,″4″-O-diacetylquercitrin (Gold score 65.15), kaempferol-3-O-neohesperidoside (Gold score 53.37) and isosalvianolic acid C methyl ester (Gold score 53.44) for lipase, aldol reductase, α-amylase, and α-glucosidase, respectively. Besides, vitexin and isovitexin for α-amylase; N-trans-Caffeoyl-tyramin for α-glucosidase; purpurolide F and schaftoside for lipase; acteoside and orientin for aldose reductase could be potential drugs for respective enzymes based on in-silico analyses, supported by experimental IC₅₀ values reported. They could bind to the competitive sites of the various targets of metabolic enzymes, and finally, toxicity analysis using ProTox-II was also performed.

Electric field assisted combustion is an important means to improve fuel combustion efficiency. This paper conducts extensive research on flame characteristics under different forms and different application methods of electric fields, emission of soot particles and simulation status. Different flame parameter measurement methods will lead to different degrees of error, and perfect numerical simulation can make simple predictions on experimental data. Most of the current numerical simulations are in two dimensions, and it is necessary to develop a complete and accurate three-dimensional model to simulate and predict the characteristics of the flame under an electric field. The emission of soot particles is also affected by the electric field, and reasonable electric field parameters can greatly reduce the emission of soot particles. It is recommended to conduct centralized measurement of different fuels under the electric field under high pressure and temperature conditions, so as to be able to develop a wider and more accurate flame dynamics and chemical model under the electric field.

Due to the increasing importance of mangroves in climate change mitigation projects, more accurate and cost-effective aboveground biomass (AGB) monitoring methods are required. However, field measurement of AGB may be a challenge because of its remote location and the difficulty to walk in these areas. This study is based on the Livelihoods Fund’ Oceanium project of 10,000 hectare mangrove plantations monitoring. In a first step, the possibility of replacing traditional field measurements of sample plots in a young mangrove plantation by a semiautomatic processing of UAV-based photogrammetric point clouds was assessed. In a second step, Sentinel-1 radar and Sentinel-2 optical imagery were used as auxiliary information to estimate AGB and its variance for the entire study area under a model-assisted framework. AGB was measured using UAV imagery in a total of 95 sample plots. UAV plot data was used in combination with non-parametric Support Vector Regression (SVR) models for the estimation of the study area AGB using model-assisted estimators. Purely UAV-based AGB estimates and their associated standard error (SE) were compared with model-assisted estimates using (1) Sentinel-1, (2) Sentinel-2 and (3) a combination of Sentinel-1 and Sentinel-2 data as auxiliary information. The validation of the UAV-based individual tree height and crown diameter measurements showed a root mean square error (RMSE) of 0.21 m and 0.32 m respectively. Relative efficiency of the three model-assisted scenarios ranged between 1.61 and 2.15. Although all SVR models improved the efficiency of the monitoring over UAV-based estimates, the best results were achieved when a combination of Sentinel-1 and Sentinel-2 data was used. Results indicated that the methodology used in this research can provide accurate and cost-effective estimates of AGB in mangrove young plantations.

The ectoparasitic mite Varroa destructor is the most significant pathological threat to the western honey bee, Apis mellifera, leading to the death of most colonies if left untreated. An alternative approach to chemical treatments is to selectively enhance heritable honey bee traits of resistance or tolerance to the mite through breeding programs, or select for naturally surviving untreated colonies. We conducted a literature review of all studies documenting traits of A. mellifera populations either selectively bred or naturally selected for resistance and tolerance to mite parasitism. This allowed us to conduct an analysis of the diversity, distribution and importance of the traits in different honey bee populations that can survive V. destructor throughout the globe. In a second analysis, we investigated the genetic bases of these different phenotypes by comparing ’omics studies (genomics, transcriptomics, and proteomics) of A. mellifera resistance and tolerance to the parasite. Altogether, this review provides a detailed overview of the current state of the research projects and breeding efforts against the most devastating parasite of A. mellifera. By highlighting the most promising traits of varroa-surviving bees and our current knowledge on their genetic bases, this work will help direct future research efforts and selection programs to control this pest. Additionally, by comparing the diverse populations of honey bees that exhibit the traits, this review highlights the consequences of anthropogenic and natural selection on the interactions between hosts and parasites.

A recent breakthrough in preparation of immobilized enzyme based biocatalysts achieving highly enhanced enzymatic activities and stabilities has become a great alternative to conventional immobilization techniques. The functional hybrid nanobiocatalysts (FHNs) fabricated in this immobilization composed of organic components (amino acid, peptide, protein, enzyme and plant extract) and inorganic components (various metal ions) give flower-like morphology with narrow size distribution and porous structure. The enzyme incorporated FHNs exhibite greatly enhanced catalytic activities and stabilities compared to free and conventionally immobilized enzymes under various experimental conditions. In addition to that, the FHNs consisting of other organic components act as Fenton-like reagents and show peroxidase-like activity owing to presence of metal ions and porous structure in the FHNs. This report basically focuses on preparation, characterization, and bioanalytical applications of the FHNs and explain mechanism of the FHNs formation and thier enhanced activities and stabilities.

This study investigated the effects of soil crust development on the underlying soil properties. The field sampling work was conducted in June 2016 in the Hobq Desert in Inner Mongolia, North China. Soil crust samples and 0–6, 6–12, 12–18, 18–24, 24–30 cm deep underlying soil samples were taken from five representative areas of different soil crust development stages. All samples were analyzed for physicochemical properties including water content, bulk density, aggregate content, organic matter content, enzyme activities, and microbial biomass carbon and nitrogen. The results showed that the thickness, water content, macroaggregate (>250 μm) content, organic matter content, microbial biomass and enzyme activities of the soil crusts gradually increased along the soil crust development gradient, while the bulk density of the soil crusts decreased. Meanwhile, the physicochemical and biological properties of the soils below the algal and moss crusts were significantly ameliorated when compared with the physical crust. Moreover, the amelioration effects were significant in the upper horizons (approx. 0–12 cm deep) and diminished quickly in the deeper soil layers.

A literature review was conducted to summarize the frequency of the D-allele of the angiotensin-converting enzyme-1 in all countries with available data. Using an ecological study design limited to high income countries, we found that the country-level frequency of the D-allele was associated with increased COVID-19 incidence and mortality.

Sustainable agricultural production is endangered by several ecological factors such as drought, extreme temperatures, excessive salts, parasitic ailments, and insect pest infestation. These challenging environmental factors may have adverse effects on future agriculture production in many countries. In modern agriculture, conventional crop breeding techniques alone are inadequate for achieving the increasing population’s food demand on a sustainable basis. The advancement of molecular genetics and related technologies are promising tools for the selection of new crop species. Gene pyramiding through marker assisted selection (MAS) and other techniques have accelerated the development of durable resistant/tolerant lines with high accuracy in the shortest possible period of time for agricultural sustainability. Gene stacking has not been fully utilized for biotic stress resistance development and quality improvement in most of the major cultivated crops. This review emphasizes on gene pyramiding techniques that are being successfully deployed in modern agriculture for improving crop tolerance to abiotic and biotic stresses for sustainable crop improvement.

Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has high infectivity in humans, attributed to the strong affinity of its spike (S) protein to human angiotensin-converting enzyme 2 (ACE2). Here, we analyzed the structural similarity of the S protein between SARS-CoV-2 and other SARS-related coronaviruses (CoVs). Methods We performed multiple alignment analysis of nine amino acid sequences of CoV S proteins from NCBI with MAFFT web-based software, followed by phylogeny analysis. Three-dimensional structure modeling was performed by SWISS-MODEL. We calculated the template modeling score between the S protein of SARS-CoV-2 and that of other SARS-related CoVs. Results The S1 domain of the unclassified CoV RaTG13 (the host of which is the intermediate horseshoe bat) was structurally very similar to that of SARS-CoV-2, implying that RaTG13 could be the origin of SARS-CoV-2. In addition, the folding property of the entire S protein was nearly the same between SARS-CoV-2 and RaTG13 after the PRRA amino acid insertion was removed from SARS-CoV-2. Conclusions RaTG13 could have a high binding affinity to ACE2, similar to SARS-CoV-2, and it is therefore highly likely to infect other animals. Therefore, massive research and monitoring of CoVs in animals is necessary to prevent future COVID-19-like disasters.

Optical and mechanical properties of multilayer coatings depend on the selected layer materials and the deposition technology; therefore, knowledge of the performances of thin films is essential. In the present work, titanium dioxide (TiO2) and silicon dioxide (SiO2) thin films have been prepared by plasma ion-assisted deposition (PIAD). The optical, structural, and mechanical properties of thin films have been investigated using spectrometer/ellipsometer, X-ray diffraction (XRD), atomic force microscopy (AFM), and laser interferometer. The results show that TiO2 film fabricated by PIAD induces a high refractive index, wide optical band gap, amorphous structure, smooth surface, and tensile stress. In the case of SiO2 film, high bias voltage leads to dense structure and compressive stress. As an application, a three-wavelength high reflectance at 632.8, 808, and 1550nm is optimized and deposited. The dependence of total stress in the multilayer on the substrate temperature is studied as well. In conclusion, it is demonstrated that PIAD is an effective method for the preparation of ultralow stress TiO2/SiO2 multilayer films. The achieved stress is as low as 1.4Mpa. The result could provide guidance to the stress optimization of most optical components without prefiguring, backside coating, and post-deposition treatments.

This paper first discusses a fractional-order Liu system of order as low as 2.7 and shows its chaotic characteristics by carrying out numerical simulations such as Lyapunov exponents, bifurcation diagrams and phase portraits. Then, by using the topological horseshoe theory and computer-assisted proof, the existence of chaos in the system is verified theoretically. Finally, the fractional-order system is implemented on a Field Programmable Gate Array (FPGA) and the results obtained show that the fractional-order Liu system is indeed chaotic.

The spike protein of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2), which is mediated by the receptor binding domain (RBD) of the spike protein. Recently, an analysis based on decade-long structural studies of SARS was reported to illustrate with atomic-level details receptor recognition by the novel coronavirus from Wuhan, i.e., 2019-nCoV. Here, this article reports a comprehensive set of structural electrostatic analysis of all SARS-CoV spike protein RBD-related structures as of February 13, 2020, aiming at identifying the electrostatic hot spots for SARS-CoV spike protein to be complexed with ACE2 and its neutralizing antibodies. First, this article identified a structural action mechanism of the F26G19 antibody (of SARS-CoV spike protein), where its Asp56 residue binds to the Arg426 of the SARS-CoV spike protein RBD against the formation of the interfacial Arg426-Glu329 salt bridges between ACE2 and the SARS-CoV spike protein RBD. Second, a hypothesis is reported that a pair of electrostatic clips exist at the interface between ACE2 and the SARS-CoV spike protein RBD, including both Arg426-Glu329 and His445-Glu23-Lys447 salt bridges. Last, this article reports a structurally identified interfacial Glu35-Arg479 salt bridge which helps stabilize the complex structure of ACE2 and the SARS-CoV spike protein RBD. Overall, the structurally identified electrostatic hot spots reported here may be useful for the design of SARS-CoV-neutralizing antibodies in future.

Unavoidable exposure to radiosensitive normal tissues around cancerous tumor during the radiotherapy can cause side effects such as self-limited acute toxicities, mild chronic symptoms, or severe organ dysfunction. Nevertheless, clinical use of currently available radiation protective agents is limited because of their generic cytotoxicity. A study on radiation protective effect of delphinidin was conducted with proton-beam-exposed human colon cells (CCD-18Co). The measurement in changes of survival fractions of CCD-18Co with/without delphinidin administration at different radiation doses were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. The changes in expression of reactive oxygen species (ROS) and in activities of antioxidant enzymes were measured by colorimetric assays using pertinent assay kits. The measurement of pro-apoptosis/pro-survival protein expressions using Western blot assay and the measurement of DNA damage using comet assay were also fulfilled to evaluate the molecular level of radiation damages in CCD-18Co cells. The experimental results revealed that the pre-administration of delphinidin regulated antioxidant enzymes, reduced ROS, decreased DNA damage, regulated pro-apoptosis/pro-survival proteins, and eventually reduced apoptosis of CCD-18Co cells. In conclusion, it is claimed that delphinidin is nontoxic natural radiation protective compound, and thus delphinidin can be used to protect normal colon tissues during the proton beam therapy.

The chemical graph theory is a subfield of mathematical chemistry which applies classic graph theory to chemical entities and phenomena. Chemical graphs are main data structures to represent chemical structures in cheminformatics. Computable properties of graphs lay the foundation for (quantitative) structure activity and structure property predictions - a core discipline of cheminformatics. It has a historic relevance for natural sciences, such as chemistry, biochemistry and biology, and is in the heart of modern disciplines, such as cheminformatics and bioinformatics. This review first covers the history of chemical graph theory, then provides an overview of its various techniques and applications for CASE, and finally summarises modern tools using chemical graph theory for CASE.

Renal artery thrombosis is a sporadic serious clinical condition which potentially cause renal infarction. Diagnosis of renal infarction can be delayed or missed due to non specific clinical presentation and overlapping appearance of medical and surgical phenomena. Early diagnosis supported by biochemical and radiological findings while appropriate management potentially improve morbidity and mortality. Persistent abdominal or flank pain with raised LDH and proteinuria on background of thromboembolism risk factors supports the diagnosis. Despite the rarity of the disease rapid identification with prompt medical or endovascular intervention could prevent irreversible renal parenchymal damage.

The exploitation of lipid membranes in biosensors has provided the ability to reconstitute a considerable part of their functionality to detect trace of food toxicants and environmental pollutants. Nanotechnology enabled sensor miniaturization and extended the range of biological moieties that could be immobilized within a lipid bilayer device. This chapter reviews recent progress in biosensor technologies based on lipid membranes suitable for environmental applications and food quality monitoring. Numerous biosensing applications are presented, putting emphasis on novel systems, new sensing techniques and nanotechnology-based transduction schemes. The range of analytes that can be currently detected include, insecticides, pesticides, herbicides, metals, toxins, antibiotics, microorganisms, hormones, dioxins, etc. Technology limitations and future prospects are discussed, focused on the evaluation/ validation and eventually commercialization of the proposed sensors.

Plants have evolved tightly regulated strategies to adapt and acclimate to a changing environment to ensure their survival. Various environmental factors affect plant distribution, growth and yield. Low temperature belongs to those abiotic factors which significantly constrain range boundaries of plant species. Exposing plants to low but non-freezing temperature induces a multigenic processes termed cold acclimation, which finally results in an increased freezing tolerance. Cold acclimation comprises reprogramming of the transcriptome, proteome and metabolome and affects communication and signaling between subcellular organelles. Reprogramming of the central carbohydrate metabolism plays a key role in cold acclimation. This review summarizes current knowledge about the role of carbohydrate metabolism in plant cold acclimation. A focus is laid on subcellular metabolic reprogramming, its thermodynamic constraints under low temperature and mathematical modelling of metabolism.

Lignin has interesting functionalities to be exploited in adhesives for medicine, foods and textiles. Nanoparticles (NPs) <100 nm coated with poly(L-lysine), PL and poly(L-glutamic acid) PGA were prepared from the laccase treated lignin to coat nanocellulose fibrils (CNF) with heat. NPs ca. 300 nm were prepared, β-casein coated and cross-linked with transglutaminase (Tgase) to agglutinate chamois specimens. Size exclusion chromatography (SEC) and Fourier-transform infrared (FTIR) spectroscopy were used to characterize polymerized lignin, zetapotential and dynamic light scattering (DLS) to ensure coating of colloidal lignin particles (CLPs). Protein adsorption on lignin was studied by quartz crystal microbalance (QCM). Atomic force microscopy (AFM) was exploited to examine interactions between different polymers and to image NPs with transmission electron microscopy (TEM). Tensile testing showed, when using CLPs for the adhesion, the stress improved ca. 10 and strain ca. 6 times compared to polymeric lignin. For the β-casein NPs the values were 20 and 8, respectively, and for the β-casein coated CLPs between these two cases. When NPs were dispersed in adhesive formulation, the Young's moduli confirmed significant improvement in the elasticity of the joints over the adhesive alone. Exploitation lignin in nanoparticulate morphology is a potential method to prepare bionanomaterials for advanced applications.

Black horehound (Ballota nigra L.) is one of the important medicinal plants, which is a rich source of health-promoting essential oils. Salinity stress affects plant development and alters the quality and quantity of plants extracts and their composition. This study was aimed to investigate the effect of salinity on morphological, physiological characteristics, and secondary metabolites of B. nigra under greenhouse, and in vitro culture conditions. The plants were treated with different concentrations of NaCl (25, 50, 75, 100 mM) and fresh and dry weight of leaf and stem were measured as well as morphological characteristics of the plant. Plant growth was reduced with the increased salinity concentrations. The results showed that all growth-related traits and SPAD were decreased both in vivo and in vitro. Additionally, increased salt concentration affected the cell membrane integrity. Total phenolics content of plants growing in the greenhouse, increased by 21% at 50 mM NaCl, but at higher stress levels (100 mM NaCl), the amounts were decreased significantly. Total flavonoids contents followed similar patterns, with a slight difference. In addition, the maximum and minimum total phenolics contents of plants growing under in vitro condition were observed at 50 mM NaCl and control treatments, respectively. Increasing the salt concentration significantly affected the total flavonoids content, and as a result, the highest amount was observed in 50 and 75 mM NaCl treatments. Antioxidant activity was also measured. Among the NaCl treatments, the highest DPPH scavenging activities (IC50) under greenhouse and in vitro conditions were detected at 50 mM and 25 mM concentrations, respectively. In general, based on the results, with increasing the salinity level to 75 mM, the activities of CAT and APX were significantly upregulated in both greenhouse and in vitro culture conditions. A correlation between total phenolics and flavonoids contents as well as antioxidant activity were obtained. With shifting salinity stress, the type and the amount of the identified essential oil compounds changed. Compounds such as styrene, tridecanol, germacrene-D, beta-Ionone, beta-bisabolene, and caryophyllene oxide increased compared to the controlled treatment.

SARS-CoV-2 is a newly emerging, highly transmissible, and pathogenic coronavirus in humans, which has caused global public health emergency and economic crisis. To date, millions of infections and thousands of deaths have been reported worldwide, and the numbers continue to rise. Currently, there is no specific drug or vaccine against this deadly virus; therefore, there is a pressing need to understand the mechanism through which this virus enters the host cell. Viral entry into the host cell is a multistep process in which SARS-CoV-2 utilizes the receptor binding domain of the spike glycoprotein (S) to recognize ACE2 receptors on the human cells; this initiates host cell entry by promoting viral-host cell membrane fusion through large scale conformational changes in the S protein. Receptor recognition and fusion are critical and essential steps of viral infections and are key determinants of the viral host range and cross-species transmission. In this review, we summarize the current knowledge on the origin and evolution of SARS-CoV-2 and the roles of key viral factors. We discuss the RNA dependent RNA polymerase structure of SARS-CoV-2, its significance in drug discovery, and explain the receptor recognition mechanisms of coronaviruses. We provide a comparative analysis of the SARS-CoV and SARS-CoV-2 S proteins, receptor-binding specificity, and discuss the differences in their antigenicity based on biophysical and structural characteristics.

This paper presents a system developed for the assistance with a collaborative robot in hand-assisted laparoscopic surgery (HALS). The system includes a sensing glove with piezoresistive sensors which capture continuously the flexion degree of the surgeon's fingers. These data are analyzed using an algorithm that detects and recognize the selected movements. This information is sent as commands to the collaborative robot throughout the surgical operation. The bending patterns, speed and execution times of the movements are modelled in a pre-phase in which it will extract all the necessary information for later detection during the motion execution. The results obtained with 10 different volunteers show a high degree of accuracy and a low false discovery rate.

This paper aims to study the surface homogenization and integrity of Ti-6Al-4V alloy by longitudinal-torsional coupled ultrasonic vibration assisted ball-end milling. A method of continuous processing between the flat surface and freeform surface connection is proposed by using ultrasonic vibration assisted ball-end precision milling, during this process, it is not necessary to exchange the cutting tool. The way has been explored for changing the homogenization of surface on Ti-6Al-4V by ultrasonic vibration-assisted milling (UVAM). Cutting experiments employing three parameters, cutting speed, feed rate and depth of cut and two types of machining forms using ball-end milling with UVAM and conventional milling (CM) respectively. The high frequency cutting force, finished surface roughness, topography and residual stresses on the surface and tool wear have been measured by advanced instruments. Particularly, adopting the high frequency cutting force measurement system, it is concluded cutting force in ball-end milling decreased significantly using UVAM as against CM. Moreover, the surface roughness by UVAM with ball-end milling is much better than the CM at a high cutting speed. However, an opposite trend is observed at a low cutting speed. Especially, there is a steep decrease from Ra 0.828 μm average value at 4000 rpm to Ra 0.129 μm average value at 5000 rpm. At the same time, the homogenization of surface roughness and residual stresses decrease significantly in UVAM as compared to which in CM when taking the transversal-longitudinal ratio into consideration. Cutting experiments and measuring results are demonstrated the validity and feasibility of UVAM with ball-end milling, and this method enjoys significant advantages compared to CM process.

The persistent issue of bacterial and fungal colonization of artificial implantable materials and decreasing efficacy of conventional systemic antibiotics used to treat implant-associated infections has led to the development of a wide range of antifouling and antibacterial strategies. This article reviews one such strategy where inherently biologically active renewable resources, i.e. secondary plant metabolites (SPMs) and their naturally occurring combinations (i.e. essential oils) are used for surface functionalization and synthesis of polymer thin films. With a distinct mode of antibacterial activity, broad spectrum of action and diversity of available chemistries, secondary plant metabolites present an attractive alternative to conventional antibiotics. However, their conversion from liquid to solid phase without significant loss of activity is not trivial. Using select examples, this article shows how plasma techniques provide a sufficiently flexible and chemically reactive environment to enable the synthesis of biologically-active polymer-coatings from volatile renewable resources.

The SARS (severe acute respiratory syndrome)-CoV (Coronavirus)-2 S(spike)-protein mRNA/cDNA currently being used as vaccines are antigenic but not antigens against SARS-CoV-2, that causes COVID (Coronavirus Disease) -19. Furthermore, the mRNA and cDNA antigenic vaccines also have potentials for homologous as well as heterologous recombination, primarily into the somatic cell DNA of the vaccine recipients. On the contrary, a SARS-CoV-2 RBD-protein antigen, a part of the S-protein, will directly stimulate antibody production against SARS-CoV-2. Hence, a vaccine composed of SARS-CoV-2 RBD-protein as a safer, fast acting, and effective vaccine against SARS-CoV-2 and thus against COVID-19. This is also useful for some immune compromised individuals.

Alfalfa (Medicago sativa L.) is a perennial, outcrossing legume crop predominantly grown for hay, silage, or pasture. Intensive selection has resulted in dramatic improvement in fitness traits, including winter survival and disease resistance. However, there has been minimal improvement in other economically important traits, such as hay yield, which is still comparable to 30 years ago. Intensive phenotyping costs on this type of trait hinder high selection pressure to identify superior outcross individuals. Severe inbreeding depression inhibits the development of inbred lines with accumulated favorable alleles that exhibit heterosis. This review highlights the outcomes of inbreeding depression as well as the causes, including unmasking deleterious alleles and triggering self-incompatibility. We tracked the research efforts that unveil the genetic bases underlying deleterious alleles and self-incompatibility. The magnitudes of inbreeding depression were compared with the rate of heterozygous halved time in diploid and tetraploid organisms. To fill in the gaps between the controversy and existing hypotheses, we theorized a dosage dominant model of inheritance. The dosage dominant model is similar to the Mendelian dominance model, in which a genotype exhibits a dominant phenotype if there is a dominant allele (alphabet dominant). The difference is that in the dosage dominant model, a genotype will result in a dominant phenotype if the number of dominant alleles is equal to or greater than the number of recessive alleles. This review also includes a discussion on the development of pseudo inbreds and a hypothesis to identify deleterious alleles using bulked segregant analysis and consequently to purge deleterious alleles using marker-assisted selection, to progress toward the successful development of pure inbred lines in alfalfa.

The present study was conducted to evaluate the effects of dietary supplementation of tea polyphenol （TP） on serum hormone, serum enzyme activity, antioxidant-related and immune-related gene expression of laying hens under heat stress. A total of 288 Chinese yellow chicken (186 days old) were randomly distributed among two treatments, each of which included 6 replicates of 24 hens. Dietary treatments were that the basal diet was supplemented with 200 mg / kg tea polyphenol. The study lasted for 7 weeks, including 1 week of adaptation and 6 weeks of the formal test. The content of high-density lipoprotein cholesterol (HDL-C) and total protein (TP) in serum significantly decreased by dietary supplementation with tea polyphenol. Dietary tea polyphenol supplementation improved serum superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzyme activity and decreased serum malondialdehyde (MDA) content in treatments compared to the control. However, supplementation of tea polyphenol did not affect the activity of serum catalase (CAT). The results indicated that long-term feeding of tea polyphenols help to increase the amount of hormones (FSH, E2) associated with reproduction in laying hens and thus improve egg production. It also improved the immune function of laying hens in high temperature environments. Adding tea polyphenols to the diet can significantly increase the serum IgG, IgM content of the laying hens and can upregulate the IgA content. Dietary supplementation of tea polyphenols in the laying hens significantly increased the expression of antioxidant enzyme-related genes (SOD, CAT and GPX1) in the liver. Moreover, the addition of tea polyphenols significantly increased the expression of immune-related genes (Interferon-γ (INF-γ), Interleukin 2 (IL-2) and Interleukin 4 (IL-4)) in the spleen. It is concluded that addition of tea polyphenols has a positive effect on antioxidant activity and immune function of laying hens.

MAPLE (matrix assisted pulsed laser evaporation) depositions of Candida Rugosa lipase were carried out from ice matrices whose composition is optimized in order to minimize conformational damage of the protein, which strongly influences its catalytic activity. To induce lid opening and to protect lipase during the MAPLE process, pentane and m-DOPA amino acid were added to the liquid matrix giving a target formed by a frozen water-lipase-pentane microemulsion. FTIR and AFM were used to investigate the structure of MAPLE deposited lipase films. The ability of MAPLE films to promote transesterification was determined by thin layer chromatography. It was shown that m-DOPA has influence on the aggregation but not on the unfolding of lipase induced by MAPLE, while the microemulsion formed by the addition of pentane to the target composition is effective in protecting lipase during the MAPLE process. MAPLE deposited lipases showed a modified specificity.

Bottom-up systems biology entails the construction of kinetic models of cellular pathways by collecting kinetic information on the pathway components (e.g. enzymes) and collating this into a kinetic model, based for example on ordinary differential equations. This requires integration and data transfer between a variety of tools, ranging from data acquisition in kinetics experiments, to fitting and parameter estimation, to model construction, evaluation and validation. Here, we present a workflow that uses the Python programming language, specifically the modules from the SciPy stack, to facilitate this task. Starting from raw kinetics data, acquired either from spectrophotometric assays with microtitre plates or from NMR spectroscopy time courses, we demonstrate the fitting and construction of a kinetic model using scientific Python tools. The analysis takes place in a Jupyter notebook, which keeps all information related to a particular experiment together in one place and thus serves as an e-labbook, enhancing reproducibility and traceability. The Python programming language serves as an ideal foundation for this framework because it is powerful yet relatively easy to learn for the non-programmer, has a large library of scientific routines and active user community, is open-source and extensible, and many computational systems biology software tools are written in Python or have a Python API. Our workflow thus enables investigators to focus on the scientific problem at hand rather than worrying about data integration between disparate platforms.

Recent digital transformations have significantly impacted the current society, economy, and culture. This includes adoption of rapidly emerging technologies, such as artificial intelligence (AI), immersive technology (e.g., virtual, augmented, mixed and extended reality (VR/AR/MR/XR)), cloud services, and internet of things, in our day-to-day life. `Metaverse’ has emerged as a technology that incorporates many of these transforming technologies to deliver personalised immersive experience related to specific application areas. A potential major beneficiary of Metaverse is the educational ecosystem, where highly immersive learning experiences can be delivered to students, catering to their personal learning needs and train them on life skills such as empathy, ethical qualities, and communication skills. The present-day Metaverse allows physical engagement, enabling users to utilise limb movements to interact with the presented materials. However, ethical concerns and technical limitations impede the widespread implementation of the Metaverse in the real-world. This paper provides a comprehensive survey of the existing literature covering the architecture, type and components of Metaverse, followed by practical aspects of metaverse implementation. The paper is concluded by discussing on the open challenges and issues along with their mitigation strategies and future research directions after the detailed usecase of Metaverse in Education.

Carbonic Anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life kingdoms, classified into seven genetically different families (α-θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or the progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) are used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

Electroless etching of semiconductors was elevated to an advanced micromachining process by the addition of a structured metal catalyst. Patterning of the catalyst by lithographic techniques facilitates the patterning of crystalline and polycrystalline wafer substrates. Galvanic deposition of metals on semiconductors has a natural tendency to produce nanoparticles rather than flat uniform films. This characteristic makes possible the etching of not only wafers but also particles with arbitrary shape. While it has been widely recognized that spontaneous deposition of metal nanoparticles can be used in connection with etching to porosify wafers, it is also possible to produced nanostructured powders. MACE can be controlled to produce (1) etch track pores with shapes and sizes closely related to the shape and size of the metal nanoparticle, (2) hierarchically porosified substrates exhibiting combinations of large etch track pores and mesopores, and (3) nanowires with either solid or mesoporous cores. This review discussed the mechanisms of porosification, processing advances and the properties of the etch product with special emphasis on the etching of silicon powders.

We hypothesize that the reason severe COVID-19 is closely linked to a limited number of conditions such as obesity, hypertension, older age and diabetes is that these conditions are characterized by a pro-inflammatory state in general and an angiotensin converting enzyme-1-bias in particular. We review recent evidence that this pro-inflammatory state can be reversed via regular exercise and a healthy diet. Studies are suggested that could test this hypothesis.

Field cricket (Gryllus bimaculatus) is newly emerged as an edible insect in several countries. Anti-inflammatory effect of glycosaminoglycan derived this cricket was not fully investigated on chronic disease animal model such as diabetic mouse. For potential therapeutic agents, anti-diabetic activities of field cricket glycosaminoglycan (GbG) was evaluated in diabetic mice based on their abilities to reduce glucose, ALT, AST, LDL-cholesterol, and BUN levels, compared with dung beetle (Catharsius molossus) glycosaminoglycan (CaG) as a positive control glycosaminoglycan. Db mice were orally administered for one month according to their groups: Db Hetero (normal), Db Homo (type-2 diabetic), CaG (5 mg/kg), GbG (5 mg/kg), and metformin (10 mg/kg). Blood glucose level was decreased after 1^st week treatment with GbG. It also inhibited LDL-cholesterol and alkaline phosphatase levels. Regarding oxidative damage of diabetic state, levels of hepatocellular biomarkers levels and protein carbonyl content were reduced in db mice treated with GbG. Especially anti-oxidative activities of catalase, superoxide dismutase, and glutathione peroxidase were significantly increased in GbG treated group compared to those in the control. GbG was composed of heparin disaccharides and main N-glycan was identified as Hex₉GlcNAc₂ (m/z 1905.7) of with neutral mono-sugar mainly comprising of hexose, L (+) rhamnose by mass spectroscopy. These results from sero-biochemical, hepatocellular anti-oxidant assay in db mice data suggest cricket (G. bimaculatus) glycosaminoglycan might play a role in its anti-diabetic action.

Enzyme replacement therapy (ERT) improves the somatic manifestations in mucopolysaccharidoses (MPS))．However, because intravenously administered enzymes cannot cross the blood brain barrier (BBB), ERT is ineffective against the progressive neurodegeneration and resultant severe central nervous system (CNS) symptoms observed in patients with neuronopathic MPS. Attempts to surmount this problem have been made with intrathecal and intracerebroventricular ERT intend to achieve CNS effects, but the burdens on patients are inimical to long-term multiple administrations. However, after pabinafusp alfa, a human iduronate-2-sulfatase fused with a BBB-crossing anti-transferrin receptor antibody, showed both central and peripheral efficacy in mice model, subsequent clinical trials in a total of 62 patients with MPS-II (Hunter syndrome) in Japan and Brazil substantiated this dual efficacy and provided an acceptable safety profile. To date, pabinafusp alfa is the only approved intravenous ERT effective against both the somatic and CNS symptoms of patients with MPS-II. This article summarizes the hitherto obtained preclinical and clinical evidence associated with this drug, and discusses the preclinical, translational and clinical challenges of evaluating, ameliorating and preventing the neurodegeneration in patients with MPS-II.

Background and Objectives: Acute compartment syndrome (ACS) is an emergency condition of the lower limb in which prophylactic fasciotomy is required to prevent complications. A negative pressure wound therapy (NPWT) used to the treatment of fasciotomy wounds provide beneficial clinical results. This study aimed to exchange the authors’ experience of using the NPWT installation system on the lower limb wounds after fasciotomy in ACS. Materials and Methods: This is a retrospective study enrolled consecutive patients with ACS, who underwent fasciotomy and was treated with the NPWT installation system at Department of Vascular Surgery, Provincial Hospital in Kielce from April 2016 to July 2017. Results: The study enrolled 15 patients with a diagnosis of ACS (87% men, mean age 65 years old). An open four-compartment fasciotomy (87%) or two-compartment fasciotomy (13%) was performed. The NPWT was applied on the first day after fasciotomy in 87% of patients. Therapy was initiated by the negative pressure of 125 mm Hg, which maintained at this level until the therapy was finalized. In 80% of patients, the vacuum-assisted wound closure (VAC) dressing changes were performed every 3 days. The first approximation of fasciotomy wounds margins occurred on the 4th day after surgery among 67% of individuals. The average time of using VAC on fasciotomy wounds was 9 days. The average time to definitive closure edges of fasciotomy wounds was 12 days. The average time of hospital stay was 17 days. Conclusions: Our experience indicates the legitimacy of using NPWT in wound treatment after fasciotomy in ACS. The NPWT enables faster primary closure of wounds, reduces edema, as well as decreases hospitalization time.

Aims: Angiotensin-converting enzyme 2 (ACE2) plays an important role in the entry of coronaviruses into host cells. This paper described how carnosine, a naturally occurring supplement, can be an effective drug candidate for coronavirus disease (COVID-19) on the basis of molecular docking and modeling to host ACE2 co-crystallized with COVID-19 spike protein. Methods: First, the starting point was ACE2 inhibitors and their structure-activity relationship (SAR). Next, chemical similarity (or diversity) and PubMed searches made it possible to repurpose and assess approved or experimental drugs for COVID-19. In parallel, at all stages, authors performed bioactivity scoring to assess potential repurposed inhibitors at ACE2. Finally, investigators performed molecular docking and modeling of the identified drug candidate to host ACE2 co-crystallized with COVID-19 spike protein. Results: Carnosine emerged as the best known drug candidate to match ACE2 inhibitor structure. Preliminary docking was more optimal to ACE2 than the known typical angiotensin-converting enzyme 1 (ACE1) inhibitor (enalapril) and quite comparable to known or presumed ACE2 inhibitors. Viral spike protein elements binding to ACE2 were retained in the best carnosine pose in SwissDock at 1.75 Angstroms. Out of the three main areas of attachment expected to the co-crystallized protein structure, carnosine bind with higher affinity to two compared to the known ACE2 active site. LibDock score was 92.40 for site 3, 90.88 for site 1, and inside the active site 85.49. Conclusion: Carnosine has promising inhibitory interactions with host ACE2 co-crystallized with COVID-19 spike protein and hence could offer potential mitigating effect against current COVID-19 pandemic.

Immobilization of enzymes is a good field of study to expand the life of enzyme in and lowering the cost of the chemical processes such as separation processes. Urease is an important enzyme with medical and industrial applications. The aim of the present study is to prepare an immobilized urease on a strong cation exchange resin (Amberlite IR120 -Na) and study of its activity and stability. We monitored the liberation of Na ions in the collected fractions and searching for protein in the fractions as an indicators of immobilization by ion exchange phenomenon. Sodium is measured using atomic absorption spectroscopy techniques, while protein tested by Bradford’s method. Immobilized urease activity was evaluated by salicylate-hypochlorite method. The results indicated a complete immobilization of urease enzyme on the resin surface with reserving 92% of the activity of free enzyme. The immobilized urease enzyme on resin showed good stability and it has a 62% of its activity after 154 days of storage at room temperature. It is concluded that a new immobilized urease enzyme system is prepared with good enzyme activity and stability.

Aim: To develop an index for quantitative assessment of the upper limb motor function in children with cerebral palsy before and after robot-assisted therapy. Method: An upper limb motor function index was developed using kinematic, surface electromyography and three-axis inertial measurements unit data collected from 15 children with cerebral palsy (CP) and 15 typically developed children. Children with CP underwent 18 robot-assisted therapy sessions with the REAplan device. All children were evaluated, using kinematic data from the REAplan, electromyography and three-axis inertial measurements unit readings from its accelerometer. A principal component analysis was conducted to produce an evaluation index, which is able to detect the deviation from the upper limb motor function of typically developing children group. Children with CP were evaluated twice before and after the intervention with Box and Blocks test and Finger-To-Nose test. The discriminative and concurrent validity of the upper limb motor function index were investigated. Results: The upper limb motor function index was higher in children with CP post therapy (p<0.001). Finger-To-Nose test values improved after robot-assisted therapy (p<0.03). A weak but positive correlation was observed between upper limb motor function index and clinical tests (r=0.012, p=0.95 and r=0.13, p= 0.54 for Box and Blocks test and Finger-To-Nose test respectively). Interpretation: The upper limb motor function index successfully differentiated between the typically developing children and children with CP and was effective in assessing the improvement of the upper limb motor function after robot-assisted therapy. The upper limb motor function index could be extended to assess and monitor rehabilitation therapies of other populations, such as those with stroke and Parkinson’s disease.

Rice (Oryza sativa L.) supplies nourishment to about half of the population of the world's inhabitants. Of them, more than 2 billion people suffer from "hidden hunger" in which they are unable to meet the recommended nutrients or micronutrients from their daily dietary intake. Bio-fortification refers to developing micronutrient-rich diet foods using traditional breeding methods and modern biotechnology, a promising approach to nutrition enrichment as part of an integrated strategy for food systems. To improve the profile of rice grain for the biofortification related traits, understanding the genetics of important biofortification traits is required. Moreover, these attributes are quantitative in nature and are influenced by several genes and environmental variables. In the course of past decades, several endeavours such, as finding the important quantitative trait loci (QTLs) for improving the nutrient profile of rice seeds were successfully undertaken. In this review, we have presented the information regarding the QTLs identified for the biofortification traits in the rice.

The aim of this study was to investigate the potential of converting potato peel waste into bio ethanol using an in-house produced multi-enzyme preparation. To achieve this, a variety of pre-treatment strategies, including thermal, chemical, and thermo-chemical methods, were applied to the potato peels. These included boiling for 30 and 60 min, steam at varying pressures and times, and different concentrations of chemicals such as H2SO4, HNO3, CH3COOH, HCl, NaOH, Ca(OH)2, KOH, NH3, and H2O2, either alone or in combination with steam. The pre-treated potato peels were then enzymatically hydrolyzed using a crude multi-enzyme cocktail derived from solid-state fermentation of wheat bran by a natural variety of Aspergillus niger P-19, containing cellulases, hemicellulases, pectinase, and amylases. The most effective pre-treatment combination was found to be 3% H2SO4 followed by steam under pressure and enzymatic hydrolysis using the crude multi-enzyme preparation. This combination resulted in the highest yield of reducing sugars (141.04 ±12.31 g/l) with a 98.49% carbohydrate conversion at a 20% substrate loading, giving an ethanol yield of 43.2 g/l. Furthermore, supplementing the medium with peptone, (NH4)(H2PO4), and ZnSO4 at 0.1%w/v each with 22% and 24% solid, respectively, resulted in appreciable yields of 51.67 and 54.75 g/l, further enhancing the ethanol yield.

There is great importance and need of improving existing carbon materials fabrication methods. As such, this work proposes to discuss, interrogate, and propose viable hydrothermal, solvothermal, and other advanced carbon materials synthetic methods. The advanced carbon materials to be interrogated will include the synthesis of carbon dots, carbon nanotubes, nitrogen/titania-doped carbons, graphene quantum dots, and their nanocomposites with solid/polymeric/metal oxide supports. This will be done with special mind to microwave-assisted solvothermal and hydrothermal synthesis due to their favourable properties such as rapidity, low cost, and green/environmentally-friendliness. Thus, these methods are important during the current and future synthesis and modification of advanced carbon materials for application in energy, gas separation, sensing, and water treatment. Simultaneously, the work will pay special cognizance to methods reducing the fabrication costs and environmental impact while enhancing the properties as a direct result of the synthesis methods. As a direct result, the expectation is to impart a significant contribution to the scientific body of work regarding the improvement of the said fabrication methods.

The preparation of new materials based on starch for the development of biodegradable packaging is increasing, however, the poor properties of this biopolymer for this application causes an area of opportunities for the improvement of water vapour permeability (WVP), mechanical properties, thermal properties, hydrophilicity, water absorption, among others. Hence, starch has been combined with other polymers such as polyvinyl alcohol, which has shown an improvement in the mechanical properties of starch, also, the use of clays suggests that the properties of response to water can be improved. Therefore, in this work, the preparation and characterization of starch-PVA-nanoclay films prepared by solvent casting is reported. The results obtained suggest that the sonication of nanoclay is necessary to reach a good dispersion, which promotes a strong interaction among starch-PVA-nanoclay. In addition, the properties of WVP and mechanical properties of films improved with incorporation of nanoclay, the concentration of 0.5% w/v of nanoclay showed to be the best concentration due to concentrations of 1.0 and 1.5% w/v were poorer than 0.5% w/v. Accordingly, the successful incorporation of nanoclays into the matrix starch-PVA suggests that this material is a good candidate for use as packaging.

UAV cooperative control has been an important issue in UAV-assisted sensor network, thanks to the considerable benefit obtained from cooperative mechanism of UAVs being applied as a flying base station. In coverage scenario, the tradeoff between coverage performance and transmission performance often makes deployment of UAVs fall into a dilemma, since both indexes are related to the distance between UAVs. To address this issue, UAV coverage and data transmission mechanism is analyzed in this paper, then an efficient multi-UAV cooperative deployment model is proposed. The problem is also modeled as a coalition formation game (CFG). The CFG with Pareto order is proved to have a stable partition. Then, an effective approach consisting of coverage deployment and coalition selection is designed, wherein UAVs can decide strategies cooperatively to achieve better coverage performance. Combining analysis of game approach, a coalition selection and position deployment algorithm based on Pareto order (CSPDA-PO) is designed to execute coverage deployment and coalition selection. Finally, simulation results are shown to validate the proposed approach based on efficient multi-UAV cooperative deployment model.

Increasing global concern over COVID-19 has recently brought greater attention to studies due to the ease of person-to-person transmission and the current lack of effective antiviral therapy. Here, we proposed the application of the adverse outcome pathway (AOP) framework to support re-search on the pathogenesis of viral disease. We first constructed adverse outcome pathways (AOPs) applicable to COVID-19 management to understand whether the infection causes severe acute respiratory distress. Based on the AOP framework where mechanistic elucidation of the pathway from the interaction of chemicals (or viruses) to apical endpoints is represented, our COVID-19 AOP indicated that the molecular initiating event (MIE) was angiotensin-converting enzyme 2 (ACE2) interaction, and the key events (KEs) were the increased pro-inflammatory cytokines in immune cells, with increased mortality as an apical adverse outcome (AO). However, there is still limited information on the toxicity mechanisms of AOPs in COVID-19; therefore, detailed KEs and AOs on toxicity mechanisms will be required to fill these gaps in the data. This study demonstrated that the COVID-19 AOP framework is a suitable tool to design new drugs and to integrate crowded-sourced information for the battle against the COVID-19 pandemic.

Background: Cardiomyopathy is commonly observed disease that may occurs due to mutations in either susceptible genes or modifier gene. People with broad age group are affected either attributable to spontaneous or inherited mutations of these genes. Various gene mutations are reported so far but only few of them were studied in detail. Methods: In the current study, we evaluated epidemiological variables like age, sex, familial status, parental consanguinity. We also described specific clinical symptoms associated with the cardiomyopathy condition in Indian population. Results: Our studies on mutation screening of phospholamban gene revealed two transitions (4880 C/T, 4887 T/G) in 5’ flanking region which might cause inherited dilated cardiomyopathy with refractory congestive heart failure are We further deliberated the gene polymorphism of renin angiotensin system gene angiotensin-1-converting enzyme as an associated marker/ modifier in cardiomyopathy patients and their family members. Conclusions: Information on epidemiological, clinical statistics, phospholamban gene mutation analysis and angiotensin-1-converting enzyme gene polymorphism is essential to guide the successful execution for future therapies and benefits us to identify those patients at risk for faster disease progression, congestive heart failure, and arrhythmia.

Conventional phenotyping breeding approaches for vegetable crops like Solanaceae, Bulb, Root crops, have made a significant contribution by developing many varieties. Despite this, conventional phenotyping approaches are not sufficient due to the longer time taken to develop a variety, low genetic gain, environmental factors and some other externalities that affect the phenotype-based selection. To address the challenges of conventional phenotype, a new recent method of high throughput phenotyping (HTP) is considered a promising tool. The development of high-throughput phenotyping technology began in the preceding decade as advancements in sensor, computer vision, automation, and advanced machine learning technologies. HTP platforms are being utilized to undertake non-destructive assessments of the complete plant system in a range of crops. HTP provides the precise measurements and suggests the collection of high-quality and accurate data which is necessary for standardizing phenotyping for the collection of genetic dissection and genomic assisted breeding such as genome-wide association studies (GWAS), linkage mapping, marker-assisted selection (MAS), genomic selection (GS). The remainder of this chapter discusses how high-throughput phenotyping technologies can be used in genomic-assisted breeding for vegetable crops

DNA origami has emerged in recent years as a powerful technique for designing and building 2D and 3D nanostructures. While the breadth of structures that have been produced is impressive, one of the remaining challenges, especially for DNA origami structures intended to carry out useful biomedical tasks in vivo, is to endow them with the ability to detect and respond to molecules of interest. Target molecules may be disease indicators or cell surface receptors, and the responses may include conformational changes leading to release of therapeutically relevant cargo. Nucleic acid aptamers are ideally suited to this task and are beginning to be used in DNA origami designs. In this review we consider examples of uses of DNA aptamers in DNA origami structures and summarise what is currently understood regarding aptamer-origami integration. We review three major roles for aptamers in such applications: protein immobilisation, triggering of structural transformation, and cell targeting. Finally, we consider future perspectives for DNA aptamer integration with DNA origami.

We demonstrate hybrid integration of a lithium niobate microring resonator with a silicon nitride waveguide in the vertical configuration to achieve efficient light coupling. The microring resonator is fabricated on a lithium niobate on insulator (LNOI) substrate using photolithography assisted chemo-mechanical etching (PLACE). A fused silica cladding layer is deposited on the LNOI ring resonator. The silicon nitride waveguide is further produced on the fused silica cladding layer by first fabricating a trench in the fused silica using focused ion beam (FIB) etching for facilitating the evanescent coupling, followed by formation of the silicon nitride waveguide on the bottom of the trench. The FIB etching ensures the required high positioning accuracy between the waveguide and the ring resonator. We achieve Q-factors as high as 1.4*10^7 with the vertically integrated device.

Spherical microparticles of TiO₂ were synthesized by the ionic liquid-assisted solvothermal method at different reaction time (3, 6, 12 and 24h). The properties of the prepared photocatalysts were investigated by means of UV-vis diffuse-reflectance spectroscopy (DRS), BET surface area measurements, scanning electron microscopy (SEM), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy (XPS). The results indicated that the efficiency of phenol degradation was related with a time of the solvothermal synthesis as determined for TiO₂_EAN(1:1)_24h sample. Microparticles of TiO₂_EAN(1:1)_3h formed during the only 3h of synthesis time revealed really high photoactivity under visible irradiation – 75%. This value increased to 80% and 82% after 12h and 24h, respectively. The photoactivity increase was accompanied by the increase of the specific surface area thus pores size, as well as ability to absorb UV-vis irradiation. The high efficiency of phenol degradation of IL-TiO₂ photocatalysts was ascribed to the interaction between the surface of TiO₂ and ionic liquid components (carbon and nitrogen).

: The effect that the microstructure exerts on the TRIP phenomenon and on the mechanical properties in a multiphase steel was studied. Samples of an initially cold-rolled ferrite-pearlite steel underwent different intercritical annealing treatments at 750 °C until an equal fractions of austenite/ferrite was reached; the intercritical treatment was followed by isothermal bainitic treatments before cooling the samples to room temperature. Samples in the first treatment were heated directly to the intercritical temperature, whereas other samples were heated to either 900 or 1100 °C to obtain a fully homogenized, single phase austenitic microstructure prior to the conducting the intercritical treatment. The high temperature homogenization of austenite resulted in the decrease in its stability, so a considerable austenite fraction transformed into martensite by cooling to room temperature after the bainitic heat treatment. Most of the retained austenite transformed during the tensile tests, and as a consequence, the previously homogenized steels showed the highest UTS. In turn, the steel with a ferritic-pearlitic initial microstructure, exhibited higher ductility than the other steels and texture components that favor forming processes.

This paper questions the potential shift of reproduction towards assisted reproductive technologies due to benefits provided by genetic manipulation of embryos. In order to examine the viability of such a shift and its implications from a regulatory perspective, we relied on two panels of experts from Israel and Spain, using the Delphi method and a series of in-depth interviews. We anticipate, at a first stage, a continuous-steady growth in the use of IVF, supplemented by preimplantation genetic diagnosis and the introduction of CRISPR/Cas. At a second stage, attracting a growing share of fertile people would require developments in genomics. While it is unclear whether these developments will fully materialize, they could be replaced by technoscientific imaginaries generating perceived benefits. We conclude that the regulation of reproductive genetics is becoming more critical and complex. The aim should be to ensure good practices and equity, while providing more information to the public. A broad and inclusive societal debate may overcome the difficulty of drawing a clear line between medical uses and non-medical uses of genetic selection and engineering and may contribute to finding the right balance between allowing autonomous decisions of patients and protecting the public interest.

Successful engineering of a microbial host for efficient production of a target product from a given substrate can be viewed as an extensive optimization task. Such a task involves the selection of high activity enzymes as well as their gene expression regulatory control elements (i.e., promoters and ribosome binding sites). Finally, there is also the need to tune expression of multiple genes along a heterologous pathway to relieve constraints from rate-limiting step and help reduce metabolic burden on cells from unnecessary over-expression of high activity enzymes. While the aforementioned tasks could be performed through combinatorial experiments, such an approach incurs significant cost, time and effort, which is a handicap that can be relieved by application of modern machine learning tools. Such tools could attempt to predict high activity enzymes from sequence, but they are currently most usefully applied in classifying strong promoters from weaker ones as well as combinatorial tuning of expression of multiple genes. This perspective reviews the application of machine learning tools to aid metabolic pathway optimization through identifying challenges in metabolic engineering that could be overcome with the help of machine learning tools.

myfood24 is a comprehensive self-completed online 24-hour dietary recall tool currently used for nutritional assessments in epidemiological research. However, its clinical application has been unexplored. This mixed methods prospective observational study explores the acceptability and usability of myfood24 in a clinical population, women with gestational diabetes (GDM). Women were recruited at their first diabetes antenatal clinic appointment. To assess acceptability and usability, they were asked to complete five 24-hour dietary recalls using myfood24 over two weeks and a user experience questionnaire; with a subset invited to participate in a one-to-one semi-structured interview. Of the 199 participants, mean maternal age was 33 years, mean booking BMI 29.7kg/m2, 36% primiparous, 57% White, 33% Asian. Of these 121 (61%) completed myfood24 at least once and 73 (37%) completed the user questionnaire; 15 were interviewed. Usability of myfood24 was measured using the System Usability Scale (SUS) and found to be good (mean 70.9, 95%CI 67.1, 74.6). Interviews identified several areas for improvement, including optimising its use for mobile devices. myfood24 appears to be acceptable and have potential to support self-management and behaviour change for women with GDM but requires adaptation to record blood glucose results alongside real-time tracking of diet.

The antioxidant, antimicrobial, antiproliferative, and enzyme inhibitory properties of five extracts from aerial parts of Salvia pachyphylla were examined to assess the prospective of this plant as a source of natural products with therapeutic potential. Those properties were analyzed performing a set of standard assays. The extract obtained with dichloromethane showed the most variety of components, as yielded promising results in all completed assays. Furthermore, the extract obtained with ethyl acetate exhibited that greatest antioxidant activity as well as the best xanthine oxidase inhibitory activity. Remarkably, both extracts obtained with n-hexane or dichloromethane revealed significant antimicrobial activity against the Gram-positive bacteria; also, they showed greater antiproliferative activity against three representative cell lines of the most common types of cancers in women worldwide, and against a cell line that exemplifies cancers that typically develop drug resistance. Despite that other extracts were less active, such as the methanolic or aqueous, their results are promising for the isolation and identification of novel bioactive molecules.

We attempted to establish an objective method to accurately evaluate the motility of bull sperm and examined the effects of media for sperm suspensions and frame rates on data of computer-assisted sperm motility analysis (CASA). Sperm incubated in Brackett and Oliphant medium (BO) more clearly showed hyperactivation-like motility than those in synthetic oviductal fluid. Sperm images captured at 150 frames per second (fps) showed a trajectory that was closer to the real pathway than those at other frame rates (30, 50, and 75 fps). We then examined the characteristics of sex-sorted and non-sorted semen using a cluster analysis followed by a discriminant analysis of sperm motility in BO at 150 fps. The results indicated that sex-sorted semen contained sperm with hyperactivation-like motility as the main subpopulation immediately after thawing and this subpopulation decreased after 2-h incubation. The main subpopulation in non-sorted semen had progressive motility that was maintained during incubation. In conclusion, usage of BO for sperm suspensions and capturing sperm motility at 150 fps by CASA were appropriate for evaluating bovine sperm motility. A discriminant analysis using data from a cluster analysis of motile sperm has the ability to accurately describe differences in the structures of sperm motility subpopulations.

Eating disorders (EDs) are serious, life-threatening psychiatric conditions associated with physical and psychosocial impairments, as well as high morbidity and mortality. Given the chronic refractory nature of EDs and the paucity of evidence-based treatments, there is a pressing need to identify novel approaches for this population. The noncompetitive N-methyl-D-aspartate receptor (NMDAr) antagonist, ketamine, has recently been approved for treatment-resistant depression, exerting rapid and robust antidepressant effects. It is now being investigated for several new indications, including obsessive-compulsive, post-traumatic, and substance use disorder; and shows transdiagnostic potential for EDs, particularly among clinical non-responders. As such, the aim of this review is to examine contemporary findings on the treatment of EDs with ketamine, whether used as a primary, adjunctive, or combination psychopharmacotherapy. Avenues for future research are also discussed. Overall, results are encouraging and point to therapeutic value, yet are limited to case series and reports on anorexia nervosa. Further empirical work is thus needed to explore ketamine efficacy across ED subgroups; establish safety profiles and optimize dosing; and develop theory-driven, targeted treatment strategies at the individual patient level.

Animal-assisted interventions (AAI) use human-animal interactions to positive effect in various contexts including cancer care. This systematic literature review is the first part of a two-part paper series focusing on the research methods and quantitative results of AAI studies in oncology. We find methodological consistency in the use of canines as therapy animals, in the types of high-risk patients excluded from studies, and in the infection precautions taken with therapy animals throughout cancer wards. The investigated patient endpoints are not significantly affected by AAI, with the exceptions of improvements in oxygen consumption, quality of life, depression, mood, and satisfaction with therapy. The AAI field in oncology has progressed significantly since its inception and has great potential to positively impact future patient outcomes. To advance the field, AAI research in oncology should consistently improve the methodological design of studies, report data more completely, and focus on the therapy animal’s well-being.

General–purpose automatic speech recognition (ASR) systems have improved their quality and are being used for pronunciation assessment. However, the assessment of isolated short utterances, as words in minimal pairs for segmental approaches, remains an important challenge, even more for non-native speakers. In this work, we compare the performance of our own tailored ASR system (kASR) with the one of Google ASR (gASR) for the assessment of Spanish minimal pair words produced by 33 native Japanese speakers in a computer-assisted pronunciation training (CAPT) scenario. Participants of a pre/post-test training experiment spanning four weeks were split into three groups: experimental, in-classroom, and placebo. Experimental group used the CAPT tool described in the paper, which we specially designed for autonomous pronunciation training. Statistically significant improvement for experimental and in-classroom groups is revealed, and moderate correlation values between gASR and kASR results were obtained, beside strong correlations between the post-test scores of both ASR systems with the CAPT application scores found at the final stages of application use. These results suggest that both ASR alternatives are valid for assessing minimal pairs in CAPT tools, in the current configuration. Discussion on possible ways to improve our system and possibilities for future research are included.

High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to their glucosinolate amount. Extracts from Sinapis nigra L. and Sinapis alba L. have been obtained from leaves and seeds under different conditions using ethanol/water mixtures because well accepted by food industry. The EtOH/H2O 8:2 mixture gives better yields in glucosinolate amounts from grinded seeds, mainly sinalbin in S. alba and sinigrin in S. nigra. The highest antiproliferative activity in both non-tumour and tumour cell lines was induced by S. alba seeds extract. To evaluate whether Sinapis spp effect was only due to glucosinolate content or it was influenced by the extracts’ complexity, cells were treated with extracts or glucosinolates, in the presence of myrosinase. Pure sinigrin did not modify cell proliferation, while pure sinalbin was less effective than the extract. The addition of myrosinase increased the antiproliferative effects of the S. nigra extract and sinigrin. Antiproliferative activity was correlated to MAPKs modulation, which was cell and extract-dependent. Cell-cycle analysis evidenced a proapoptotic effect of S. alba on both tumour cell lines and of S. nigra only on HCT 116. Both extracts showed good antimicrobial activity in disc diffusion tests and on ready-to-eat fresh salad. These results underline the potential effects of Sinapis spp in chemoprevention and food preservation.

In this research, low-fat dried Chinese sausage was formulated with mango peel pectin (MPP) extracted by microwave assisted extraction (MAE) (0%, 5%, 10% and 15% (w/w). The extractable yield of pectin attained from peel of Nam Dok Mai variety was achieved at 13.85% using 700-watt power. The extracted MPP were of high equivalent weight (1,485.78 mg/mol), degree esterification (77.19%) and methoxyl content (19.33%) with the structure of more porosity as compared to that of the conventional method. Spectrum scans by Fourier transform infrared spectrophotometer (FT-IR) advised that the extracted MPP gave the similar wave number profiles as the commercial pectin. Quality attributes of the Chinese sausages were accessed and compared with the control formula (CTRL). At higher concentrations of MPP, the product had positively increased colour intensity. The texture profile of the sausage illustrated that only the hardness value was comparable with the CTRL, while springiness, cohesiveness, gumminess and chewiness were statistically lower (p < 0.05). Furthermore, the sensory evaluation by experienced panellists (n=12) indicated that 5% MPP similarly represented overall acceptability with the CTRL. Consequently, MPP can be effectively applied at low level as fat replacement in Chinese sausage allowing colour improvement and product of healthier option.

In order to integrate genomics in breeding and development of drought tolerant groundnut genotypes, identification of genomic regions/genetic markers for drought surrogate traits is essential. We used SNP markers for a genetic analysis of the ICRISAT groundnut minicore collection for genome wide marker-trait association for some physiological traits and to determine the magnitude of linkage disequilibrium (LD) present in the genetic resources. The LD analysis showed that about 36% of loci pairs were in significant LD (P < 0.05 and r2 > 0.2) and 3.14% of the pairs were in complete LD. There was rapid decline in LD with distance and the LD was <0.2 at a distance of 41635 bp. The marker trait association (MTAs) studies revealed 20 significant MTAs (p <0.001) with 11 markers for leaf area index (4), canopy temperature (13), chlorophyll content (1) and NDVI (2). The markers explained 2 to 21% of the phenotypic variation observed. Most of the MTAs identified on the A subgenome were also identified on the respective homeologous chromosome on the B subgenome. The duplications of effect observed could be due to common ancestor of the A and B genome which explains the linkage detected between markers lying on different chromosomes seen in the current study. The present study identified a total of 20 highly significant marker trait associations with 11 markers for four physiological traits of importance in groundnut; LAI, CT, SCMR and NDVI. The markers identified in this study can serve as useful genomic resources to initiate marker-assisted selection and trait introgression of groundnut for drought tolerance. The identified markers in this study may be useful for marker assisted selection after further validation.

Objectives: Studies evaluating machine learning (ML) algorithms on cross-lingual RadLex® mappings for developing context-sensitive radiological reporting tools are lacking. Therefore, we investigated whether ML-based approaches can be utilized to assist radiologists in providing key imaging biomarkers – such as The Alberta stroke programme early CT score (APECTS). Material and Methods: A stratified random sample (age, gender, year) of CT reports (n=206) with suspected ischemic stroke was generated out of 3997 reports signed off between 2015-2019. Three independent, blinded readers assessed these reports and manually annotated clinico-radiologically relevant key features. The primary outcome was whether ASPECTS should have been provided (yes/no: 154/52). For all reports, both the findings and impressions underwent cross-lingual (German to English) RadLex®-mappings using natural language processing. Well-established ML-algorithms including classification trees, random forests, elastic net, support vector machines (SVMs) and boosted trees were evaluated in a 5 x 5-fold nested cross-validation framework. Further, a linear classifier (fastText) was directly fitted on the German reports. Ensemble learning was used to provide robust importance rankings of these ML-algorithms. Performance was evaluated using derivates of the confusion matrix and metrics of calibration including AUC, brier score and log loss as well as visually by calibration plots. Results: On this imbalanced classification task SVMs showed the highest accuracies both on human-extracted- (87%) and fully automated RadLex® features (findings: 82.5%; impressions: 85.4%). FastText without pre-trained language model showed the highest accuracy (89.3%) and AUC (92%) on the impressions. Ensemble learner revealed that boosted trees, fastText and SVMs are the most important ML-classifiers. Boosted trees fitted on the findings showed the best overall calibration curve. Conclusions: Contextual ML-based assistance suggesting ASPECTS while reporting neuroradiological emergencies is feasible, even if ML-models are restricted to be developed on limited and highly imbalanced data sets.

This research was presented the special designed microfluidic device generated for sperm separation based on assumption of different surface electrical charged of sperms X and Y. However, to avoid ethical problem, the microfluidic chip has been tested with the mimic electrical charged particles, TiO₂-coated Polystyrene beads, (TiO₂-coated Ps-beads), instead of spermatozoa. The work has been separated into three main parts. Firstly, the simply but efficient fabrication of negatively charged TiO₂-coated Ps-beads has been presented. In addition, various characterization techniques such as X-ray diffraction (XRD), Tungsten Scanning Electron Microscopy (W-SEM) with energy-dispersive X-ray spectroscopy (EDS) mode, and X-ray Absorption Spectroscopy (XAS), have been reported in this work to elucidate the reasons behind the persistence of negatively charged on the surface of TiO₂-coated Ps-beads. Results show that the fabricated TiO₂-coated Ps-beads was partly coated in the mixed forms of amorphous Ti⁴⁺ and had caused a negatively charge to appear on the surface after fabrication and had sustained its electrical charged for long. Secondly, process of simulation and fabrication of microfluidic device was presented. Finally the negatively charged TiO₂-coated Ps-beads were tested in this microfluidic devices. For design of microfluidic devices integrated with a couple of microelectrodes, the simulated structures were fabricated by photolithographic technique and tested with the Ps-beads. Percentage of validation for Ps-beads separation indicated that the 100 mm-distance-between-electrodes microfluidic device exhibits to be the highest performance prototype at 86.96%. For further confirmation, another model so called the single path prototype has been established. It is confirmed by 92.59% of validation for the utilization of the device. The successfully designed microfluidic devices can be examined with actual spermatozoa later. Furthermore, process to fabricate the negatively charged TiO₂-coated Ps-beads can be established as testified samples for development of other microfluidic devices.

Study question: What are the current trends of research in Human Assisted Reproduction around the world? Summary answer: USA is the leading country, followed by the UK, China, France and Italy. The largest research area is “laboratory techniques”, although other areas such as “public health”, “quality, ethics and law” and “female factor” are gaining ground worldwide. What is known already: Scientific research, especially in health and medical sciences, aims at addressing specific needs that society (and, especially, patients) perceives as pressing. One of the main challenges for policymakers and research funders alike is therefore to align research priorities to societal needs. We can thus think of research agendas in terms of a demand side (societal needs) and a supply side (research outputs). Research output in Human Assisted Reproduction has expanded in the past years, as indicated by the increasing number of scientific publications in indexed journals in this area. Nevertheless, no map of research related to assisted reproduction has been produced so far, hindering the identification of potential areas of improvement and need. Study design, size, duration: 26,000+ scientific publications (articles, letters, and reviews) on Human Assisted Reproduction produced worldwide between 2005 and 2016 were analyzed. These publications were indexed in PubMed or obtained from reference list of indexed publications included in the analysis.Participants/materials, setting, methods: The corpus of publications was obtained by combining the MeSH terms: “Reproductive techniques”, “Reproductive medicine”, “Reproductive health”, “Fertility”, “Infertility”, and “Germ cells”. Then it was analyzed by means of text mining algorithms (Topic Modeling (TM) based on Latent Dirichlet Allocation (LDA)), in order to obtain the main topics of interest. Finally, these categories were analyzed across world regions and time. Main results and the role of chance: We identified 44 main topics, which were further grouped in 11 macro categories, form larger to smaller: “laboratory techniques”, “male factor”, “quality, ethics and law”, “female factor”, “public health and infectious diseases”, “basic research and genetics”, “pregnancy complications and risks”, “general infertility and ART”, “psychosocial aspects”, “cancer”, and “research methodology”. The USA was the leading country in number of publications, followed by the UK, China, France and Italy. Interestingly, research contents in high income countries is fairly homogeneous across macro-categories, and it is dominated by “laboratory techniques” in Western and Southern Europe, and by “quality, ethics and law” in North America, Australia and New Zealand. In middle income countries we observe that research is mainly performed on “male factor”, and noticeably less on “female factor”. Finally, research on “public health and infectious diseases” predominates in low-income countries. Regarding temporal evolution of research, “laboratory techniques” is the most abundant topic on a yearly basis, and relatively constant over time. However, since production in most of the other categories is increasing, the relative contribution of this research category is actually decreasing. Publication is especially increasing in “public health and infectious diseases” (in all world regions, but especially in low income countries), “quality, ethics and law” (high income countries), and “female factor” (middle income countries). Limitations, reasons for caution: Three main factors might limit the robustness of our work: the textual corpus analyzed is based on abstract and titles, the reproducibility of the stochastic algorithms applied, which may produce slightly differing results at each run, and the interpretation of the topics obtained. Wider implications of the findings: This study should prove beneficial in the design of research strategies and policies that foster the alignment between supply (assisted reproduction research) and demand (society). Study funding/competing interest(s): PTQ-14-06718 of the Spanish MINECO Torres Quevedo programme (FAM).

As part of the ongoing screening research for local edible plants in Thailand, Petroselinum crispum fruit oil was considered as a potential bioinsecticide with proven antimosquito activity against both the pyrethroid susceptible and resistant strains of Aedes aegypti. Due to the comparative mosquitocidal efficacy on these mosquitoes, this plant oil is promoted as a natural alternative and attractive candidate for further study in monitoring resistance of mosquito vectors. Therefore, the aim of this study was to evaluate the impact of P. crispum oil on the biochemical characteristics of the target mosquito larvae of Ae. aegypti, by determining quantitative changes of key enzymes responsible for xenobiotic detoxification, including glutathione-S-transferases (GSTs), α- and β-esterases (α-/β-ESTs), acetylcholinesterase (AChE), acid and alkaline phosphatases (ACP and ALP) and mixed-function oxidases (MFO). Three populations of Ae. aegypti, comprising the pyrethroid susceptible Muang Chiang Mai-susceptible (MCM-S) strain and the pyrethroid resistant Pang Mai Dang-resistant (PMD-R) and Upakut-resistant (UPK-R) strains, were used as test organisms. Biochemical study of Ae. aegypti larvae prior to treatment with P. crispum oil revealed that apart from AChE, the baseline activity of most defensive enzymes, such as GSTs, α-/β-ESTs, ACP, ALP and MFO, in resistant UPK-R or PMD-R, was higher than that determined in susceptible MCM-S. However, after 24-h exposure to P. crispum oil, the pyrethroid susceptible and resistant Ae. aegypti showed similarity in biochemical features, with alterations of enzyme activity in the treated larvae, as compared to the controls. A significant increase in the activity levels of GSTs, α-/β-ESTs, ACP and ALP was recorded in all strains of P. crispum oil-treated Ae. aegypti larvae, whereas MFO and AChE activity in these mosquitoes was decreased. The recognizable larvicidal capability on pyrethroid resistant Ae. aegypti, and the inhibitory effect on AChE and MFO, emphasized the potential of P. crispum oil as an attractive alternative application for management of mosquito resistance in current and future control programs.

Fatty acids (FAs) represent an important class of metabolites, impacting on membrane building blocks and cellular regulatory networks. In nature, prokaryotes are characterized with the most impressing FA structural diversity and the highest relative contents of free fatty acids (FFAs). Thereby, nitrogen-fixing bacteria (order Rhizobiales), often found in symbiosis with legumes, attract a special interest. Indeed, FAs impact on the structure of rhizobial nodulation factors, required for successful infection of plant root. Although the FA patterns can be addressed by GC- and LC-MS, these methods are time-consuming and suffer from compromised sensitivity, low stability of derivatives and artifacts. In contrast, MALDI-TOF-MS represents an excellent platform for high-efficient metabolite fingerprinting, also applicable to FFAs. Therefore, here we propose a simple and straightforward protocol for high-throughput relative quantification of FFAs in rhizobia by the combination of Langmuir technology and MALDI-TOF-MS, which is featured with high sensitivity, accuracy and precision of quantification. Here we propose a step by step procedure comprising rhizobia culturing, pre-cleaning, extraction, sample preparation, mass spectrometric analysis, data processing and post-processing. To demonstrate the analytical potential of the protocol we illustrate it by a case study – comparison the FFA metabolomes of two rhizobia species - Rhizobium leguminosarum and Sinorhizobium meliloti.

To determine the mode of action of the effects of phytoalexins in soybeans, we analyzed enzyme inhibition kinetics using Michaelis–Menten plots and the Lineweaver–Burk plots. The results showed that glyceollin showed competitive inhibition, genistein showed noncompetitive, daidzein was uncompetitive, and luteolin showed a mixed mode of action. The Ki values were determined using a Dixon plot as: glyceollin, 18.99; genistein, 15.42; luteolin, 16.81; and daidzein, 9.99 μM, respectively. Furthermore, potential synergistic effects between glyceollin and the three designated polyphenols were investigated. A combination of glyceollin and luteolin (the ratio of 3:7 of glyceollin and luteolin) had synergistic effects on α-glucosidase inhibition according to combination index (CI)-isobologram equation. Collectively, these results showed that a combination of glyceollin and luteolin has the potential to inhibit α-glucosidase activity via a synergistic mode of action.

With the emergence of the novel corona virus SARS-CoV-2 since December 2019, more than 43 million cases have been reported worldwide. This virus has shown high infectivity and severe symptoms in some cases leading to over 1 million deaths globally. Despite the collaborative and concerted research efforts that has been made, no effective treatment for COVID-19 (corona virus disease-2019) is currently available. SARS-CoV-2 uses the angiotensin converting enzyme 2 (ACE2) as an initial mediator for viral attachment and host cell invasion. ACE2 is widely distributed in human tissues including the cell surface of lung cells which represent the primary site of the infection. Inhibiting or reducing cell surface availability of ACE2 represents a promising therapy for tackling COVID-19. In this context, most ACE2–based therapeutic strategies have aimed to achieve this through the use of angiotensin converting enzyme (ACE) inhibitors or neutralizing the virus by exogenous administration of ACE2. However, through this review, we present another perspective focusing on the subcellular localization and trafficking of ACE2. Membrane targeting of ACE2, shedding and its cellular trafficking pathways including internalization are not well elucidated. Therefore, hereby we present an overview on the fate of newly synthesized ACE2, its post translational modifications, what is known of its trafficking pathways. In addition, we highlight the possibility that some of the identified ACE2 missense variants might affect its trafficking efficiency and localization and hence may explain some of the observed variable severity of SARS-CoV-2 infections. Extensive understanding of these processes is necessary to evaluate the potential use of ACE2 as a credible therapeutic target.

STRAS (Single access Transluminal Robotic Assistant for Surgeons) is a flexible robotic system based on the Anubis® platform of Karl Storz for application to intra-luminal surgical procedures. It consists of three cable-driven systems, one endoscope serving as guide and two inserted instruments. The flexible and bendable instruments have three degrees of freedom and can be teleoperated by a single user via two specially designed master interfaces. In this research, a pair of specific sensor gloves, which ergonomically fit to the master handles of the system was designed and the forces applied by one expert and one novice user during system-specific task execution in a simulator task (4-step-pick-and-drop) were compared. The results show that user expertise is not only reflected by shorter task execution times but also, more importantly, by specific differences in handgrip force profiles for specific sensor locations on anatomically relevant parts of the fingers and hand controlling the surgical instruments of the robotic master/slave system.