A universal interface for plug-and-play assembly of stretchable devices.

Stretchable hybrid devices have enabled high-fidelity implantable1-3 and on-skin4-6 monitoring of physiological signals. These devices typically contain soft modules that match the mechanical requirements in humans7,8 and soft robots9,10, rigid modules containing Si-based microelectronics11,12 and protective encapsulation modules13,14. To make such a system mechanically compliant, the interconnects between the modules need to tolerate stress concentration that may limit their stretching and ultimately cause debonding failure15-17. Here, we report a universal interface that can reliably connect soft, rigid and encapsulation modules together to form robust and highly stretchable devices in a plug-and-play manner. The interface, consisting of interpenetrating polymer and metal nanostructures, connects modules by simply pressing without using pastes. Its formation is depicted by a biphasic network growth model. Soft-soft modules joined by this interface achieved 600% and 180% mechanical and electrical stretchability, respectively. Soft and rigid modules can also be electrically connected using the above interface. Encapsulation on soft modules with this interface is strongly adhesive with an interfacial toughness of 0.24 N mm-1. As a proof of concept, we use this interface to assemble stretchable devices for in vivo neuromodulation and on-skin electromyography, with high signal quality and mechanical resistance. We expect such a plug-and-play interface to simplify and accelerate the development of on-skin and implantable stretchable devices.

Water-responsive supercontractile polymer films for bioelectronic interfaces.

Connecting different electronic devices is usually straightforward because they have paired, standardized interfaces, in which the shapes and sizes match each other perfectly. Tissue-electronics interfaces, however, cannot be standardized, because tissues are soft1-3 and have arbitrary shapes and sizes4-6. Shape-adaptive wrapping and covering around irregularly sized and shaped objects have been achieved using heat-shrink films because they can contract largely and rapidly when heated7. However, these materials are unsuitable for biological applications because they are usually much harder than tissues and contract at temperatures higher than 90 °C (refs. 8,9). Therefore, it is challenging to prepare stimuli-responsive films with large and rapid contractions for which the stimuli and mechanical properties are compatible with vulnerable tissues and electronic integration processes. Here, inspired by spider silk10-12, we designed water-responsive supercontractile polymer films composed of poly(ethylene oxide) and poly(ethylene glycol)-α-cyclodextrin inclusion complex, which are initially dry, flexible and stable under ambient conditions, contract by more than 50% of their original length within seconds (about 30% per second) after wetting and become soft (about 100 kPa) and stretchable (around 600%) hydrogel thin films thereafter. This supercontraction is attributed to the aligned microporous hierarchical structures of the films, which also facilitate electronic integration. We used this film to fabricate shape-adaptive electrode arrays that simplify the implantation procedure through supercontraction and conformally wrap around nerves, muscles and hearts of different sizes when wetted for in vivo nerve stimulation and electrophysiological signal recording. This study demonstrates that this water-responsive material can play an important part in shaping the next-generation tissue-electronics interfaces as well as broadening the biomedical application of shape-adaptive materials.

Staphylococcal enterotoxin B exposed to pregnant rats inhibits the hedgehog signaling pathway in thymic T lymphocytes of the offspring.

The Hedgehog (Hh) signaling pathway is involved in T cell differentiation and development and plays a major regulatory part in different stages of T cell development. A previous study by us suggested that prenatal exposure to staphylococcal enterotoxin B (SEB) changed the percentages of T cell subpopulation in the offspring thymus. However, it is unclear whether prenatal SEB exposure impacts the Hh signaling pathway in thymic T cells. In the present study, pregnant rats at gestational day 16 were intravenously injected once with 15 µg SEB, and the thymi of both neonatal and adult offspring rats were aseptically acquired to scrutinize the effects of SEB on the Hh signaling pathway. It firstly found that prenatal SEB exposure clearly caused the increased expression of Shh and Dhh ligands of the Hh signaling pathway in thymus tissue of both neonatal and adult offspring rats, but significantly decreased the expression levels of membrane receptors of Ptch1 and Smo, transcription factor Gli1, as well as target genes of CyclinD1, C-myc, and N-myc in Hh signaling pathway of thymic T cells. These data suggest that prenatal SEB exposure inhibits the Hh signaling pathway in thymic T lymphocytes of the neonatal offspring, and this effect can be maintained in adult offspring via the imprinting effect.

Programmable living assembly of materials by bacterial adhesion.

The field of engineered living materials aims to construct functional materials with desirable properties of natural living systems. A recent study demonstrated the programmed self-assembly of bacterial populations by engineered adhesion. Here we use this strategy to engineer self-healing living materials with versatile functions. Bacteria displaying outer membrane-anchored nanobody-antigen pairs are cultured separately and, when mixed, adhere to each other to enable processing into functional materials, which we term living assembled material by bacterial adhesion (LAMBA). LAMBA is programmable and can be functionalized with extracellular moieties up to 545 amino acids. Notably, the adhesion between nanobody-antigen pairs in LAMBA leads to fast recovery under stretching or bending. By exploiting this feature, we fabricated wearable LAMBA sensors that can detect bioelectrical or biomechanical signals. Our work establishes a scalable approach to produce genetically editable and self-healable living functional materials that can be applied in biomanufacturing, bioremediation and soft bioelectronics assembly.

Improvement of Cancer Prevention and Control: Reflection on the Role of Emerging Information Technologies.

Cancer has become an important public health problem affecting the health of Chinese residents, as well as residents all over the world. With the improvement of cancer prevention and treatment, the growth of the mortality rate of cancers has slowed down gradually, but the incidence rate is still increasing rapidly, and cancers still impose heavy disease and economic burdens. Cancer screening and early cancer diagnosis and treatment are important ways to reduce the burden of cancer-related diseases. At present, various projects for early cancer diagnosis and treatment have been implemented in China. With the expansion of the coverage of these projects, the problems related to project implementation, operation, and management have emerged gradually. In recent years, emerging information technologies have been applied in the field of health and have facilitated health management and clinical decision-making. Meanwhile, China announced multiple policies to encourage and promote the application of information technologies in the field of health. Therefore, combined with the analysis of major problems in cancer prevention and control projects, this paper probes into how to apply information technologies such as biological information mining, artificial intelligence, and electronic information collection technology to various stages of cancer prevention and control. Information technologies realize the integrated management of prevention and control processes, for example, mobilization and preliminary identification, high-risk assessment, clinical screening, clinical diagnosis and treatment, tracking and follow-up, and biological sample management of high-risk groups, and promote the efficient implementation of cancer prevention and control projects in China.

Trial frame for evaluating eye movements.

Eye movement research is an established methodology and widely used in fundamental research fields such as psychology or neuroscience. Most research is performed in controlled environments with screen-based eye trackers, but demand for a wearable requirement is on the rise. Yet, a state of the art wearable eye tracking system thus far has not been feasible for subjects with refractive errors; therefore, a trial frame is proposed for researching the eye movement of people with or without refractive errors. Two iris cameras and several infrared radiation LEDs were fixed behind the frame for recording eye images. The images were sent to a host computer using 2.4G wireless, which was also fixed on the frame. The entire electronic system in the trial frame was driven using a battery. Eye position in the images was recognized and segmented by a model that was trained through machine learning. Then the pupil and blinks were detected from the segmented eye area using ellipse fitting and the eye aspect ratio. Experiments showed that the correct rate of pupil and blink detections were 97.24% and 96.14%, respectively.

A Potential ABA Analog to Increase Drought Tolerance in Arabidopsis thaliana.

Abscisic acid (ABA) plays an important role in the response of plants to drought stress. However, the chemical structure of ABA is unstable, which severely limits its application in agricultural production. Here, we report the identification of a small molecule compound of tetrazolium as an ABA analog (named SLG1) through virtual screening. SLG1 inhibits the seedling growth and promotes drought resistance of Arabidopsis thaliana with higher stability. Yeast two-hybrid and PP2C inhibition assays show that SLG1 acts as a potent activator of multiple ABA receptors in A. thaliana. Results of molecular docking and molecular dynamics show that SLG1 mainly binds to PYL2 and PYL3 through its tetrazolium group and the combination is stable. Together, these results demonstrate that SLG1, as an ABA analogue, protects A. thaliana from drought stress. Moreover, the newly identified tetrazolium group of SLG1 that binds to ABA receptors can be used as a new option for structural modification of ABA analogs.

Analysis of Muscular Electrical Activity and Blood Perfusion of Upper Extremity in Patients with Hemiplegic Shoulder Pain: A Pilot Study.

Background: Hemiplegic shoulder pain (HSP) is a common symptom for post-stroke patients, which has a severely adverse impact on their rehabilitation outcomes. However, the cause of HSP has not been clearly identified due to its complicated multifactorial etiologies. As possible causes of HSP, the abnormality of both muscular electrical activity and blood perfusion remains lack of investigations. Objective: This study aimed to analyze the alteration of muscular electrical activity and blood perfusion of upper extremity in patients with HSP by using surface electromyography (sEMG) and laser speckle contrast imaging (LSCI) measurement techniques, which may provide some insight into the etiology of HSP. Methods: In this observational and cross-sectional study, three groups of participants were recruited. They were hemiplegic patients with shoulder pain (HSP group), hemiplegic patients without shoulder pain (HNSP group), and healthy participants (Healthy group). The sEMG data and blood perfusion data were collected from all the subjects and used to compute three different physiological measures, the root-mean-square (RMS) and median-frequency (MDF) parameters of sEMG recordings, and the perfusion unit (PU) parameter of blood perfusion imaging. Results: The RMS parameter of sEMG showed significant difference (p < 0.05) in the affected side between HSP, HNSP, and Healthy groups. The MDF parameter of sEMG and PU parameter of blood perfusion showed no significant difference in both sides among the three groups (p > 0.05). The RMS parameter of sEMG showed a statistically significant correlation with the pain intensity (r = -0.691, p =0.012). Conclusion: This study indicated that the muscular electrical activity of upper extremity had a correlation with the presence of HSP, and the blood perfusion seemed to be no such correlation. The findings of the study suggested an alternative way to explore the mechanism and treatment of HSP.

Genome-Wide Characterization and Expression Analysis of KH Family Genes Response to ABA and SA in Arabidopsis thaliana.

K-homologous (KH) family is a type of nucleic acid-binding protein containing the KH domain and has been found to affect splicing and transcriptional regulation. However, KH family genes haven't been investigated in plant species systematically. In this study, we identified 30 genes that belonged to the KH family based on HMM of the KH domain in Arabidopsis thaliana. Phylogenetic tree analysis showed that the KH family is grouped into three subgroups. Synteny analysis showed that AtKH9 and AtKH29 have the conserved synteny relationship between A. thaliana and the other five species. The AtKH9 and AtKH29 were located in the cytoplasm and nucleus. The seed germination rates of the mutants atkh9 and atkh29 were higher than wild-type after abscisic acid (ABA) and salicylic acid (SA) treatments. In addition, the expression of ABA-related genes, such as ABRE-binding factor 2 (ABF2), ABRE-binding factor 4 (ABF4), and delta 1-pyrroline-5-carboxylate synthase (P5CS), and an SA-related gene pathogenesis-related proteins b (PR1b) were downregulated after ABA and SA treatments, respectively. These results suggested that atkh9 and atkh29 mutants inhibit the effect of ABA and SA on seed germination. In conclusion, our results provide valuable information for further exploration of the function of KH family genes and propose directions and ideas for the identification and characterization of KH family genes in other plants.

PCirc: random forest-based plant circRNA identification software.

BACKGROUND: Circular RNA (circRNA) is a novel type of RNA with a closed-loop structure. Increasing numbers of circRNAs are being identified in plants and animals, and recent studies have shown that circRNAs play an important role in gene regulation. Therefore, identifying circRNAs from increasing amounts of RNA-seq data is very important. However, traditional circRNA recognition methods have limitations. In recent years, emerging machine learning techniques have provided a good approach for the identification of circRNAs in animals. However, using these features to identify plant circRNAs is infeasible because the characteristics of plant circRNA sequences are different from those of animal circRNAs. For example, plants are extremely rich in splicing signals and transposable elements, and their sequence conservation in rice, for example is far less than that in mammals. To solve these problems and better identify circRNAs in plants, it is urgent to develop circRNA recognition software using machine learning based on the characteristics of plant circRNAs. RESULTS: In this study, we built a software program named PCirc using a machine learning method to predict plant circRNAs from RNA-seq data. First, we extracted different features, including open reading frames, numbers of k-mers, and splicing junction sequence coding, from rice circRNA and lncRNA data. Second, we trained a machine learning model by the random forest algorithm with tenfold cross-validation in the training set. Third, we evaluated our classification according to accuracy, precision, and F1 score, and all scores on the model test data were above 0.99. Fourth, we tested our model by other plant tests, and obtained good results, with accuracy scores above 0.8. Finally, we packaged the machine learning model built and the programming script used into a locally run circular RNA prediction software, Pcirc ( https://github.com/Lilab-SNNU/Pcirc ). CONCLUSION: Based on rice circRNA and lncRNA data, a machine learning model for plant circRNA recognition was constructed in this study using random forest algorithm, and the model can also be applied to plant circRNA recognition such as Arabidopsis thaliana and maize. At the same time, after the completion of model construction, the machine learning model constructed and the programming scripts used in this study are packaged into a localized circRNA prediction software Pcirc, which is convenient for plant circRNA researchers to use.

Identification and Functional Analysis of lncRNAs Responsive to Hypoxia in Eospalax fontanierii.

Subterranean rodents could maintain their normal activities in hypoxic environments underground. Eospalax fontanierii, as one kind of subterranean rodent found in China can survive very low oxygen concentration in labs. It has been demonstrated that long non-coding RNAs (lncRNAs) have important roles in gene expression regulations at different levels and some lncRNAs were found as hypoxia-regulated lncRNAs in cancers. We predicted thousands of lncRNAs in the liver and heart tissues by analyzing RNA-Seq data in Eospalax fontanierii. Those lncRNAs often have shorter lengths, lower expression levels, and lower GC contents than mRNAs. Majors of lncRNAs have expression peaks in hypoxia conditions. We found 1128 DE-lncRNAs (differential expressed lncRNAs) responding to hypoxia. To search the miRNA regulation network for lncRNAs, we predicted 471 and 92 DE-lncRNAs acting as potential miRNA target and target mimics, respectively. We also predicted the functions of DE-lncRNAs based on the co-expression networks of lncRNA-mRNA. The DE-lncRNAs participated in the functions of biological regulation, signaling, development, oxoacid metabolic process, lipid metabolic/biosynthetic process, and catalytic activity. As the first study of lncRNAs in Eospalax fontanierii, our results show that lncRNAs are popular in transcriptome widely and can participate in multiple biological processes in hypoxia responses.

Combinatorial Evolution of a Terpene Synthase Gene Cluster Explains Terpene Variations in Oryza.

Terpenes are specialized metabolites ubiquitously produced by plants via the action of terpene synthases (TPSs). There are enormous variations in the types and amounts of terpenes produced by individual species. To understand the mechanisms responsible for such vast diversity, here we investigated the origin and evolution of a cluster of tandemly arrayed TPS genes in Oryza In the Oryza species analyzed, TPS genes occur as a three-TPS cluster, a two-TPS cluster, and a single TPS gene in five, one, and one species, respectively. Phylogenetic analysis revealed the origins of the two-TPS and three-TPS clusters and the role of species-specific losses of TPS genes. Within the three-TPS clusters, one orthologous group exhibited conserved catalytic activities. The other two groups, both of which contained pseudogenes and/or nonfunctional genes, exhibited distinct profiles of terpene products. Sequence and structural analyses combined with functional validation identified several amino acids in the active site that are critical for catalytic activity divergence of the three orthologous groups. In the five Oryza species containing the three-TPS cluster, their functional TPS genes showed both conserved and species-specific expression patterns in insect-damaged and untreated plants. Emission patterns of volatile terpenes from each species were largely consistent with the expression of their respective TPS genes and the catalytic activities of the encoded enzymes. This study indicates the importance of combinatorial evolution of TPS genes in determining terpene variations among individual species, which includes gene duplication, retention/loss/degradation of duplicated genes, varying selection pressure, retention/divergence in catalytic activities, and divergence in expression regulation.

Gold particles decorated reduced graphene oxide for low level mercury vapor detection with rapid response at room temperature.

Rapid and sensitive detection of mercury vapor is of great significance for environmental protection and human health. But the detection method enabling low detection limitation and rapid response at room temperature simultaneously has rarely been reported. In this work, we propose a gold particles decorated reduced graphene oxide sensor for mercury vapor detection. After adding the gold particles, the reduced graphene oxide sensors' response sensitivity increase by more than 16 times and the response time significantly decreases, which is far less below the results reported by others. The sensor performance improvement should attribute to the distribution of the decorated gold particles, which insert into the layered graphene sheets, as demonstrated by the SEM and XRD results. The increased layer spacing of graphene sheets is conductive to the faster entry/exit of mercury vapor and increases the effective sensing area of graphene. What's more, the first-principles calculation results confirm the mercury-philicity of gold particles, which also contributes to the increased sensitivity. We further test more performance of the gold particles decorated reduced graphene oxide sensor to mercury vapor, which shows a linear response, low detection limit and good repeatability. The proposed sensor shows rapid response/recovery (6/8 s), low detection limit (0.01 ng/mL), linear response, good repeatability and room temperature detection simultaneously, which shows great application potential for mercury vapor detection.

Towards optimal selection of stimuli polarity method for effective evoking auditory brainstem responses.

Towards eliminating stimulus artifacts, alternating polarity stimuli have been widely adopted in eliciting the auditory brainstem response. However, considering the difference in the physiologic basis of the positive and negative polarity stimuli on the auditory system, it is unclear whether alternating polarity stimuli would adversely affect the auditory brainstem response characteristics. This research proposes a new polarity method for stimulus artifacts elimination, Sum polarity, that separately utilized the rarefaction and condensation stimuli and then summed the two evoked responses. We compared the waveform morphology and latencies of the auditory brainstem responses evoked by familiar stimuli (including click, tone-burst, and chirp) with different polarity methods in normal-hearing subjects to investigate the new method's effectiveness. The experimental results showed that alternating polarity of the click and chirp had little effect on the auditory brainstem response. In contrast, alternating polarity affected the waveform morphology and latencies of the auditory brainstem responses to the low-frequency tone-burst, with the effect decreasing as the stimulus frequency increased. These results demonstrated the performance of any polarity method is related to the characteristics of the stimulus signal itself, and no polarity method is optimal for all types of stimuli. Based on the analysis of experimental results, a fixed polarity and alternating polarity were recommended for the click and chirp auditory brainstem responses, respectively. Furthermore, considering the apparent latency differences between the responses to opposite polarity stimuli, the Sum polarity was suggested for the tone-burst auditory brainstem responses. Moreover, this work verified the feasibility of the Sum polarity, which offers another choice for eliminating stimulus artifacts in an evoked potential acquisition.

Biochemical Characterization and Function of Eight Microbial Type Terpene Synthases from Lycophyte Selaginella moellendorffii.

Selaginella moellendorffii is a lycophyte, a member of an ancient vascular plant lineage. Two distinct types of terpene synthase (TPS) genes were identified from this species, including S. moellendorffii TPS genes (SmTPSs) and S. moellendorffii microbial TPS-like genes (SmMTPSLs). The goal of this study was to investigate the biochemical functions of SmMTPSLs. Here, eight full-length SmMTPSL genes (SmMTPSL5, -15, -19, -23, -33, -37, -46, and -47) were functionally characterized from S. moellendorffii. Escherichia coli-expressed recombinant SmMTPSLs were tested for monoterpenes synthase and sesquiterpenes synthase activities. These enzymatic products were typical monoterpenes and sesquiterpenes that have been previous shown to be generated by typical plant TPSs when provided with geranyl diphosphate (GPP) and farnesyl diphosphate (FPP) as the substrates. Meanwhile, SmMTPSL23, -33, and -37 were up-regulated when induced by alamethicin (ALA) and methyl jasmonate (MeJA), suggesting a role for these genes in plants response to abiotic stresses. Furthermore, this study pointed out that the terpenoids products of SmMTPSL23, -33, and -37 have an antibacterial effect on Pseudomonas syringae pv. tomato DC3000 and Staphylococcus aureus. Taken together, these results provide more information about the catalytic and biochemical function of SmMTPSLs in S. moellendorffii plants.

Computational Determination of Potential Multiprotein Targeting Natural Compounds for Rational Drug Design Against SARS-COV-2.

SARS-CoV-2 caused the current COVID-19 pandemic and there is an urgent need to explore effective therapeutics that can inhibit enzymes that are imperative in virus reproduction. To this end, we computationally investigated the MPD3 phytochemical database along with the pool of reported natural antiviral compounds with potential to be used as anti-SARS-CoV-2. The docking results demonstrated glycyrrhizin followed by azadirachtanin, mycophenolic acid, kushenol-w and 6-azauridine, as potential candidates. Glycyrrhizin depicted very stable binding mode to the active pocket of the Mpro (binding energy, -8.7 kcal/mol), PLpro (binding energy, -7.9 kcal/mol), and Nucleocapsid (binding energy, -7.9 kcal/mol) enzymes. This compound showed binding with several key residues that are critical to natural substrate binding and functionality to all the receptors. To test docking prediction, the compound with each receptor was subjected to molecular dynamics simulation to characterize the molecule stability and decipher its possible mechanism of binding. Each complex concludes that the receptor dynamics are stable (Mpro (mean RMSD, 0.93 Å), PLpro (mean RMSD, 0.96 Å), and Nucleocapsid (mean RMSD, 3.48 Å)). Moreover, binding free energy analyses such as MMGB/PBSA and WaterSwap were run over selected trajectory snapshots to affirm intermolecular affinity in the complexes. Glycyrrhizin was rescored to form strong affinity complexes with the virus enzymes: Mpro (MMGBSA, -24.42 kcal/mol and MMPBSA, -10.80 kcal/mol), PLpro (MMGBSA, -48.69 kcal/mol and MMPBSA, -38.17 kcal/mol) and Nucleocapsid (MMGBSA, -30.05 kcal/mol and MMPBSA, -25.95 kcal/mol), were dominated mainly by vigorous van der Waals energy. Further affirmation was achieved by WaterSwap absolute binding free energy that concluded all the complexes in good equilibrium and stability (Mpro (mean, -22.44 kcal/mol), PLpro (mean, -25.46 kcal/mol), and Nucleocapsid (mean, -23.30 kcal/mol)). These promising findings substantially advance our understanding of how natural compounds could be shaped to counter SARS-CoV-2 infection.

Simultaneous sex and species classification of silkworm pupae by NIR spectroscopy combined with chemometric analysis.

BACKGROUND: Most studies only focus on the sex discrimination of silkworm pupae. However, species differentiation of silkworm pupae is also needed in sericulture. To classify the sex and species at the same time, the present study adopts near infrared (NIR) spectroscopy combined with multivariate analysis. RESULTS: First, spectra samples were acquired using an NIR sensor, comprising female and male silkworm pupae from three species. Second, three different variables selection approaches were used, including a successive projections algorithm, competitive adaptive reweighted sampling (CARS) and interval partial least squares (iPLS). Third, identification models were built based on random forest and partial least squares discriminant analysis (PLSDA). The experimental results show that iPLS-PLSDA model (95.24%) gives a high performance when using the one of the three variable selection methods alone. To further increase the performance, the variable selection methods are optimized. The accuracy of the iPLS-CARS-PLSDA model is as high as 98.41%. CONCLUSION: The present study demonstrates that the optimized variable selection method in combination with NIR spectroscopy represents a suitable strategy for sex and species identification of silkworm pupae. © 2020 Society of Chemical Industry.

Identification and Characterization of circRNAs Responsive to Methyl Jasmonate in Arabidopsis thaliana.

Circular RNAs (circRNAs) are endogenous noncoding RNAs with covalently closed continuous loop structures that are formed by 3'-5' ligation during splicing. These molecules are involved in diverse physiological and developmental processes in eukaryotic cells. Jasmonic acid (JA) is a critical hormonal regulator of plant growth and defense. However, the roles of circRNAs in the JA regulatory network are unclear. In this study, we performed high-throughput sequencing of Arabidopsis thaliana at 24 h, 48 h, and 96 h after methyl JA (MeJA) treatment. A total of 8588 circRNAs, which were distributed on almost all chromosomes, were identified, and the majority of circRNAs had lengths between 200 and 800 bp. We identified 385 differentially expressed circRNAs (DEcircRNAs) by comparing data between MeJA-treated and untreated samples. Gene Ontology (GO) enrichment analysis of the host genes that produced the DEcircRNAs showed that the DEcircRNAs are mainly involved in response to stimulation and metabolism. Additionally, some DEcircRNAs were predicted to act as miRNA decoys. Eight DEcircRNAs were validated by qRT-PCR with divergent primers, and the junction sites of five DEcircRNAs were validated by PCR analysis and Sanger sequencing. Our results provide insight into the potential roles of circRNAs in the MeJA regulation network.

Promising terpenes as SARS-CoV-2 spike receptor-binding domain (RBD) attachment inhibitors to the human ACE2 receptor: Integrated computational approach.

The spike protein receptor binding domain (S-RBD) is a necessary corona-viral protein for binding and entry of coronaviruses (COVs) into the host cells. Hence, it has emerged as an attractive antiviral drug target. Therefore, present study was aimed to target severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S-RBD with novel bioactive compounds to retrieve potential candidates that could serve as anti-coronavirus disease 2019 (COVID-19) drugs. In this paper, computational approaches were employed, especially the structure-based virtual screening followed by molecular dynamics (MD) simulation as well as binding energy analysis for the computational identification of specific terpenes from the medicinal plants, which can block SARS-CoV-2 S-RBD binding to Human angiotensin-converting enzyme 2 (H-ACE2) and can act as potent anti-COVID-19 drugs after further advancements. The screening of focused terpenes inhibitors database composed of ~1000 compounds with reported therapeutic potential resulted in the identification of three candidate compounds, NPACT01552, NPACT01557 and NPACT00631. These three compounds established conserved interactions, which were further explored through all-atom MD simulations, free energy calculations, and a residual energy contribution estimated by MM-PB(GB)SA method. All these compounds showed stable conformation and interacted well with the hot-spot residues of SARS-CoV-2 S-RBD. Conclusively, the reported SARS-CoV-2 S-RBD specific terpenes could serve as seeds for developing potent anti-COVID-19 drugs. Importantly, the experimentally tested glycyrrhizin (NPACT00631) against SARS-CoV could be used further in the fast-track drug development process to help curb COVID-19.

Transcriptome sequencing of Eospalax fontanierii to determine hypoxia regulation of cardiac fibrinogen.

With the increase in blood viscosity, the blood circulation resistance will increase when animals are in hypoxia. However, these phenomenons do not appear in hypoxic-adapted animals. Eospalax fontanierii is a subterranean rodent and is an ideal species for research in hypoxia adaptation. Eighteen healthy adult E. fontanierii individuals were equally divided into three groups that were exposed to 21% O2 for 1 week, 10.5% O2 for 44 h, and 6.5% O2 for 6 h, and then, the hearts were collected for transcriptome sequencing. After differentially expressed analysis, fibrinogen genes were selected for qPCR and Western blot verification. Eighteen healthy adult Sprague-Dawley rats (SD rats) were treated with the same oxygen concentrations, and their hearts were simultaneously subjected to qPCR. The quantitative real-time PCR and Western blot results were completely opposite to those of the rats. E. fontanierii fibrinogen mRNA was significantly downregulated when expressed under the conditions of 10.5% and 6.5% O2 compared with 21% O2. Correspondingly, fibrinogen mRNA in E. fontanierii was expressed at lower levels than SD rats in 10.5% and 6.5% O2. After tail-cutting experiment, the results showed that the coagulation rate of E. fontanierii was slowed down under hypoxic conditions. These results showed that E. fontanierii may downregulate the expression of fibrinogen mRNA in hypoxia to reduce the aggregation of red blood cells and platelets in plasma, which may prevent blood from becoming overly viscous, and at the same time, reduce blood circulation resistance and the probability of thrombosis in hypoxia to protect the heart.