A Computationally Informed Unified View on the Effect of Polarity and Sterics on the Glass Transition in Vinyl-based Polymer Melts.

We unveil a unified view on the effect of side chains on the glass transition temperatures (Tg) in polymer melts by using molecular dynamics simulations, density functional theory calculations, and available experimental data. We use acrylates as a model system and evaluate the effect of n-alkyl side chains on Tg. We find that backbone dihedral angle fluctuations follow established patterns due to sterics, as expected. However, we also find that the dihedral angle orthogonal to the backbone, which normally is neglected when discussing the effect on Tg, introduces a secondary rotational degree of freedom which strongly impacts Tg. These results are in agreement with experiments and generalize to multiple other polymer systems, as is demonstrated using available experimental data. Conversely, n-alkyl pendant groups attached to the side group reduce Tg. Our work establishes a coherent framework that unifies previously established trends, emphasizing the polarity and size effects of n-alkyl chains on Tg.

Dynamic transformation of bio-inspired single-chain nanoparticles at interfaces.

The interfacial behavior of macromolecules dictates their intermolecular interactions, which can impact the processing and application of polymers for pharmaceutical and synthetic use. Using molecular dynamics simulations, we observe the evolution of a random heteropolymer in the presence of liquid-liquid interfaces. The system of interest forms single-chain nanoparticles through hydrophobic collapse in water, lacking permanent crosslinks and making their morphology mutable in new environments. Complex amphiphilic polymers are shown to be capable of stabilizing high interfacial tension water-hexane interfaces, often unfolding to maximize surface coverage. Despite drastic changes to polymer conformation, monomer presence in the water phase is generally maintained and most changes are due to increased hydrophobic solvent exposure toward the oil phase. These results are then compared to the behavior at the water-graphene interface, where the macromolecules adsorb but do not remodel. The polymer's behavior is shown to depend significantly on both its own amphiphilic character and the deformability of the interface.

Light transmittance in human atrial tissue and transthoracic illumination in rats support translatability of optogenetic cardioversion of atrial fibrillation.

BACKGROUND: Optogenetics could offer a solution to the current lack of an ambulatory method for the rapid automated cardioversion of atrial fibrillation (AF), but key translational aspects remain to be studied. OBJECTIVE: To investigate whether optogenetic cardioversion of AF is effective in the aged heart and whether sufficient light penetrates the human atrial wall. METHODS: Atria of adult and aged rats were optogenetically modified to express light-gated ion channels (i.e., red-activatable channelrhodopsin), followed by AF induction and atrial illumination to determine the effectivity of optogenetic cardioversion. The irradiance level was determined by light transmittance measurements on human atrial tissue. RESULTS: AF could be effectively terminated in the remodeled atria of aged rats (97%, n = 6). Subsequently, ex vivo experiments using human atrial auricles demonstrated that 565-nm light pulses at an intensity of 25 mW/mm2 achieved the complete penetration of the atrial wall. Applying such irradiation onto the chest of adult rats resulted in transthoracic atrial illumination as evidenced by the optogenetic cardioversion of AF (90%, n = 4). CONCLUSION: Transthoracic optogenetic cardioversion of AF is effective in the aged rat heart using irradiation levels compatible with human atrial transmural light penetration.

Molecular signatures of the glass transition in polymers.

The glass transition temperature (T_{g}) is one of the most fundamental properties of polymers. T_{g} is predicted by some theories as a sudden change in a "macroscopic" quantity (e.g., compressibility). However, for systems with "soft" glass transitions where the change is gradual it becomes hard to pinpoint precisely the transition temperature as well as the set of molecular changes occurring during this transition. Here, we introduce two new molecular signatures for the glass transition of polymers that exhibit clear changes as one approaches T_{g}: (i) differential change of the probability distribution of dihedral angles as a function of temperature and (ii) the distribution of fractional of the time spent in the different torsional states. These new signatures provide insights into the glass transition in polymers by directly exhibiting the concept of spatial heterogeneity and dynamical ergodicity breaking in such systems, as well as provide a key step to quantitatively obtain the transition temperature from molecular characteristics of the polymeric systems.

Interventions to prevent surface transmission of an infectious virus based on real human touch behavior: a case study of the norovirus.

OBJECTIVES: Infectious viruses (e.g., SARS-CoV-2, norovirus) can transmit through surfaces. Norovirus has infected millions of individuals annually. Interventions on norovirus transmission in high-risk indoor environment are important. METHODS: This study focused on a restaurant in Guangzhou, China. More than 41,000 touches by both diners and staff members were collected using video cameras. A surface transmission model was developed and combined with these real human touch behaviors to analyze the effectiveness of different norovirus prevention strategies. RESULTS: When the virus carrier was a diner, the virus intake fraction of diners in the same table was the highest. Increasing the touch frequency on personal private surfaces would reduce the virus exposure. The virus intake fraction was reduced by 18.4% on average if public surfaces were not touched. Optimization on surface materials could reduce the virus intake fraction by 86.6%. Additionally, disinfecting tablecloths, clothes of diners, and chairs were the three most effective surface disinfection strategies. CONCLUSION: Controlling human touch behavior (e.g., reducing the self-touches on mucous membranes) is more effective than surface disinfection in controlling norovirus transmission, but surface disinfection cannot be ignored because human behavior is difficult to be controlled.

Optimization of COVID-19 prevention and control with low building energy consumption.

COVID-19 is a global threat. Non-pharmaceutical interventions were commonly adopted for COVID-19 prevention and control. However, during stable periods of the pandemic, energy would be inevitably wasted if all interventions were implemented. The study aims to reduce the building energy consumption when meet the demands of epidemic prevention and control under the stable period of COVID-19. Based on the improved Wells-Riley model considering dynamic quanta generation and pulmonary ventilation rate, we established the infection risk - equivalent fresh air volume - energy consumption model to analyze the infection risk and building energy consumption during different seasons and optimized the urban building energy consumption according to the spatio-temporal population distribution. Shopping centers and restaurants contributed the most in urban energy consumption, and if they are closed during the pandemic, the total infection risk would be reduced by 25%-40% and 15%-25% respectively and the urban energy consumption would be reduced by 30%-40% and 13%-20% respectively. If people wore masks in all public indoor environments (exclude restaurants and KTV), the infection risk could be reduced by 60%-70% and the energy consumption could be reduced by 20%-60%. Gyms pose the highest risk for COVID-19 transmission. If the energy consumption kept the same with the current value, after the optimization, infection risk in winter, summer and the transition season could be reduced by 65%, 53% and 60%, respectively. After the optimization, under the condition of R t  < 1, the energy consumption in winter, summer, and the transition season could be reduced by 72%, 64%, and 68% respectively.

Close contact behavior-based COVID-19 transmission and interventions in a subway system.

During COVID-19 pandemic, analysis on virus exposure and intervention efficiency in public transports based on real passenger's close contact behaviors is critical to curb infectious disease transmission. A monitoring device was developed to gather a total of 145,821 close contact data in subways based on semi-supervision learning. A virus transmission model considering both short- and long-range inhalation and deposition was established to calculate the virus exposure. During rush-hour, short-range inhalation exposure is 3.2 times higher than deposition exposure and 7.5 times higher than long-range inhalation exposure of all passengers in the subway. The close contact rate was 56.1 % and the average interpersonal distance was 0.8 m. Face-to-back was the main pattern during close contact. Comparing with random distribution, if all passengers stand facing in the same direction, personal virus exposure through inhalation (deposition) can be reduced by 74.1 % (98.5 %). If the talk rate was decreased from 20 % to 5 %, the inhalation (deposition) exposure can be reduced by 69.3 % (73.8 %). In addition, we found that virus exposure could be reduced by 82.0 % if all passengers wear surgical masks. This study provides scientific support for COVID-19 prevention and control in subways based on real human close contact behaviors.

Optical ventricular cardioversion by local optogenetic targeting and LED implantation in a cardiomyopathic rat model.

AIMS: Ventricular tachyarrhythmias (VTs) are common in the pathologically remodelled heart. These arrhythmias can be lethal, necessitating acute treatment like electrical cardioversion to restore normal rhythm. Recently, it has been proposed that cardioversion may also be realized via optically controlled generation of bioelectricity by the arrhythmic heart itself through optogenetics and therefore without the need of traumatizing high-voltage shocks. However, crucial mechanistic and translational aspects of this strategy have remained largely unaddressed. Therefore, we investigated optogenetic termination of VTs (i) in the pathologically remodelled heart using an (ii) implantable multi-LED device for (iii) in vivo closed-chest, local illumination. METHODS AND RESULTS: In order to mimic a clinically relevant sequence of events, transverse aortic constriction (TAC) was applied to adult male Wistar rats before optogenetic modification. This modification took place 3 weeks later by intravenous delivery of adeno-associated virus vectors encoding red-activatable channelrhodopsin or Citrine for control experiments. At 8-10 weeks after TAC, VTs were induced ex vivo and in vivo, followed by programmed local illumination of the ventricular apex by a custom-made implanted multi-LED device. This resulted in effective and repetitive VT termination in the remodelled adult rat heart after optogenetic modification, leading to sustained restoration of sinus rhythm in the intact animal. Mechanistically, studies on the single cell and tissue level revealed collectively that, despite the cardiac remodelling, there were no significant differences in bioelectricity generation and subsequent transmembrane voltage responses between diseased and control animals, thereby providing insight into the observed robustness of optogenetic VT termination. CONCLUSION: Our results show that implant-based optical cardioversion of VTs is feasible in the pathologically remodelled heart in vivo after local optogenetic targeting because of preserved optical control over bioelectricity generation. These findings add novel mechanistic and translational insight into optical ventricular cardioversion.

Weakening personal protective behavior by Chinese university students after COVID-19 vaccination.

Personal protective behaviors and their dynamic change are known to play a major role in the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causal pathogen of the coronavirus disease 2019 (COVID-19) pandemic. In this study, a total of 3229 students in Chinese universities completed an online survey about their knowledge on transmission and personal protective behavior before and after COVID-19 vaccination. Of the respondents, 87.6% had been vaccinated. Most students believed that the large droplet (97.0%) and short-range airborne (89.3%) routes were the two most likely SARS-CoV-2 transmission routes, whereas only 24.1% considered long-range airborne transmission to be possible. Students who would be expected to possess better knowledge about virus transmission (e.g., students of medicine) reported better personal protective behaviors. Female students reported relatively better personal hygiene practices than male students, so did the confident students than their diffident peers. Students washed their hands on average of 5.76 times per day during the pandemic. Students at universities in southern regions washed their hands more frequently but paid less attention to indoor ventilation than did their northern counterparts. Interestingly, students who are fear of being infected had the bad personal hygiene. University students wore 22% less masks in public indoor environments after vaccination. Chinese university students weakened their personal protective behavior after vaccination and it may increase the potential risk of infection in the new waves of variant virus (e.g. delta).

Predicting Critical Micelle Concentrations for Surfactants Using Graph Convolutional Neural Networks.

Surfactants are amphiphilic molecules that are widely used in consumer products, industrial processes, and biological applications. A critical property of a surfactant is the critical micelle concentration (CMC), which is the concentration at which surfactant molecules undergo cooperative self-assembly in solution. Notably, the primary method to obtain CMCs experimentally-tensiometry-is laborious and expensive. In this study, we show that graph convolutional neural networks (GCNs) can predict CMCs directly from the surfactant molecular structure. In particular, we developed a GCN architecture that encodes the surfactant structure in the form of a molecular graph and trained it using experimental CMC data. We found that the GCN can predict CMCs with higher accuracy on a more inclusive data set than previously proposed methods and that it can generalize to anionic, cationic, zwitterionic, and nonionic surfactants using a single model. Molecular saliency maps revealed how atom types and surfactant molecular substructures contribute to CMCs and found this behavior to be in agreement with physical rules that correlate constitutional and topological information to CMCs. Following such rules, we proposed a small set of new surfactants for which experimental CMCs are not available; for these molecules, CMCs predicted with our GCN exhibited similar trends to those obtained from molecular simulations. These results provide evidence that GCNs can enable high-throughput screening of surfactants with desired self-assembly characteristics.

Evidence for lack of transmission by close contact and surface touch in a restaurant outbreak of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is primarily a respiratory disease that has become a global pandemic. Close contact plays an important role in infection spread, while fomite may also be a possible transmission route. Research during the COVID-19 pandemic has identified long-range airborne transmission as one of the important transmission routes although lack solid evidence. METHODS: We examined video data related to a restaurant associated COVID-19 outbreak in Guangzhou. We observed more than 40,000 surface touches and 13,000 episodes of close contacts in the restaurant during the entire lunch duration. These data allowed us to analyse infection risk via both the fomite and close contact routes. RESULTS: There is no significant correlation between the infection risk via both fomite and close contact routes among those who were not family members of the index case. We can thus rule out virus transmission via fomite contact and interpersonal close contact routes in the Guangzhou restaurant outbreak. The absence of a fomite route agrees with the COVID-19 literature. CONCLUSIONS: These results provide indirect evidence for the long-range airborne route dominating SARS-CoV-2 transmission in the restaurant. We note that the restaurant was poorly ventilated, allowing for increasing airborne SARS-CoV-2 concentration.

Patterns of virus growth across the diversity of life.

Although viruses in their natural habitats add up to less than 10% of the biomass, they contribute more than 90% of the genome sequences [1]. These viral sequences or 'viromes' encode viruses that populate the Earth's oceans [2, 3] and terrestrial environments [4, 5], where their infections impact life across diverse ecological niches and scales [6, 7], including humans [8-10]. Most viruses have yet to be isolated and cultured [11-13], and surprisingly few efforts have explored what analysis of available data might reveal about their nature. Here, we compiled and analyzed seven decades of one-step growth and other data for viruses from six major families, including their infections of archaeal, bacterial and eukaryotic hosts [14-191]. We found that the use of host cell biomass for virus production was highest for archaea at 10%, followed by bacteria at 1% and eukarya at 0.01%, highlighting the degree to which viruses of archaea and bacteria exploit their host cells. For individual host cells, the yield of virus progeny spanned a relatively narrow range (10-1000 infectious particles per cell) compared with the million-fold difference in size between the smallest and largest cells. Furthermore, healthy and infected host cells were remarkably similar in the time they needed to multiply themselves or their virus progeny. Specifically, the doubling time of healthy cells and the delay time for virus release from infected cells were not only correlated (r = 0.71, p < 10-10, n = 101); they also spanned the same range from tens of minutes to about a week. These results have implications for better understanding the growth, spread and persistence of viruses in complex natural habitats that abound with diverse hosts, including humans and their associated microbes.

Molecular simulations of lipid membrane partitioning and translocation by bacterial quorum sensing modulators.

Quorum sensing (QS) is a bacterial communication process mediated by both native and non-native small-molecule quorum sensing modulators (QSMs), many of which have been synthesized to disrupt QS pathways. While structure-activity relationships have been developed to relate QSM structure to the activation or inhibition of QS receptors, less is known about the transport mechanisms that enable QSMs to cross the lipid membrane and access intracellular receptors. In this study, we used atomistic MD simulations and an implicit solvent model, called COSMOmic, to analyze the partitioning and translocation of QSMs across lipid bilayers. We performed umbrella sampling at atomistic resolution to calculate partitioning and translocation free energies for a set of naturally occurring QSMs, then used COSMOmic to screen the water-membrane partition and translocation free energies for 50 native and non-native QSMs that target LasR, one of the LuxR family of quorum-sensing receptors. This screening procedure revealed the influence of systematic changes to head and tail group structures on membrane partitioning and translocation free energies at a significantly reduced computational cost compared to atomistic MD simulations. Comparisons with previously determined QSM activities suggest that QSMs that are least likely to partition into the bilayer are also less active. This work thus demonstrates the ability of the computational protocol to interrogate QSM-bilayer interactions which may help guide the design of new QSMs with engineered membrane interactions.

COVID-19 Vaccination Did Not Change the Personal Protective Behaviors of Healthcare Workers in China.

Personal protective behaviors of healthcare workers (HCWs) and dynamic changes in them are known to play a major role in the hospital transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, 1,499 HCWs in Chinese hospitals completed an online survey about their knowledge on SARS-CoV-2 transmission and their personal protective behaviors before and after coronavirus disease 2019 (COVID-19) vaccination. Of all the respondents, 89% were vaccinated at the time of the survey and 96% believed that the vaccine was effective or highly effective. Further, 88% of the vaccinated HCWs expressed that they would get revaccinated if the vaccination failed. Compared with HCWs with a lower education level, those with a higher education level had less fear of being infected with SARS-CoV-2 and reported a lower negative impact of the pandemic on how they treated patients. Physicians and nurses were willing to believe that short-range airborne and long-range fomite are possible transmission routes. HCWs with a higher education level had a better knowledge of COVID-19 but worse personal protective behaviors. The fact that HCWs with a longer work experience had worse personal protective behaviors showed that HCWs gradually relax their personal protective behaviors over time. Moreover, vaccination reduced the negative effects of the COVID-19 pandemic on how the HCWs treated patients. Importantly, the survey revealed that after vaccination, HCWs in China did not relax their personal protective behaviors, and it may bring a low potential risk for following waves of variant virus (e.g., delta).

Extracellular expression of a novel ß-agarase from Microbulbifer sp. Q7, isolated from the gut of sea cucumber.

A novel endo-type ß-agarase was cloned from an agar-degrading bacterium, Microbulbifer sp. Q7 (CGMCC No. 14061), that was isolated from sea cucumber gut. The agarase-encoding gene, ID2563, consisted of 1800 bp that encoded a 599-residue protein with a signal peptide of 19 amino acids. Sequence analysis suggested that the agarase belongs to the GH16 family. The agarase was expressed in Escherichia coli with a total activity of 4.99 U/mL in fermentation medium. The extracellular enzyme activity accounted for 65.73% of the total activity, which indicated that the agarase can be extracellularly secreted using the wild-type signal peptide from Microbulbifer sp. Q7. The agarase exhibited maximal activity at approximately 40 °C and pH 6.0. It was stable between pH 6.0 and pH 9.0, which was a much wider range than most of the reported agarases. The agarase was sensitive to some metal ions (Cu2+, Zn2+ and Fe3+), but was resistant to urea and SDS. The agarase hydrolyzed ß-1,4-glycosidic linkages of agarose, primarily yielding neoagarotetraose and neoagarohexaose as the final products. These indicate that this recombinant agarase can be an effective tool for the preparing functional neoagaro-oligosaccharides.

Chitosan Influences the Expression of P-gp and Metabolism of Norfloxacin in Grass Carp.

The aim of this study was to investigate the relationship between the administration of chitosan (CTS), expression of permeability glycoprotein (P-gp), and the metabolism of norfloxacin (NOR) in Grass Carp Ctenopharyngodon idella. Fish were administrated with a single dose of either NOR, CTS, 1:5 NOR-CTS or 1:10 NOR-CTS. The P-gp expression was analyzed by immunohistochemistry and real time-PCR. The concentration of NOR was determined using HPLC. The mRNA and protein expression of P-gp in the fish intestine was significantly enhanced following a single dosage of 40 mg/kg NOR, and peak expression occurred at 3 h after drug administration (P < 0.05). A single dosage of both 1:5 NOR-CTS and 1:10 NOR-CTS reduced the intestinal P-gp expression to levels significantly lower than that from NOR alone (P < 0.05), but significantly higher than that from the control (P < 0.05). Interestingly, CTS alone also led to a slight decrease in P-gp expression. In addition, pharmacokinetic assays revealed a marked increase in area under the curve (AUC) of NOR with 1:5 and 1:10 NOR-CTS, by approximately 1.5-fold and threefold, respectively. Finally, the relative bioavailability of NOR after a single oral dosage of 1:5 and 1:10 NOR-CTS was enhanced to 148.02% and 304.98%, respectively. In this study, we demonstrated that the transmembrane glycoprotein P-gp regulates NOR metabolism in the intestine of Grass Carp, suggesting that NOR may be a direct substrate of P-gp. More importantly, we showed that CTS can inhibit P-gp expression in a dose-dependent manner and improve the relative bioavailability of NOR in this species.

Low-Molecular-Weight Peptides from Salmon Protein Prevent Obesity-Linked Glucose Intolerance, Inflammation, and Dyslipidemia in LDLR-/-/ApoB100/100 Mice.

BACKGROUND: We previously reported that fish proteins can alleviate metabolic syndrome (MetS) in obese animals and human subjects. OBJECTIVES: We tested whether a salmon peptide fraction (SPF) could improve MetS in mice and explored potential mechanisms of action. METHODS: ApoB(100) only, LDL receptor knockout male mice (LDLR(-/-)/ApoB(100/100)) were fed a high-fat and -sucrose (HFS) diet (25 g/kg sucrose). Two groups were fed 10 g/kg casein hydrolysate (HFS), and 1 group was additionally fed 4.35 g/kg fish oil (FO; HFS+FO). Two other groups were fed 10 g SPF/kg (HFS+SPF), and 1 group was additionally fed 4.35 g FO/kg (HFS+SPF+FO). A fifth (reference) group was fed a standard feed pellet diet. We assessed the impact of dietary treatments on glucose tolerance, adipose tissue inflammation, lipid homeostasis, and hepatic insulin signaling. The effects of SPF on glucose uptake, hepatic glucose production, and inducible nitric oxide synthase activity were further studied in vitro with the use of L6 myocytes, FAO hepatocytes, and J774 macrophages. RESULTS: Mice fed HFS+SPF or HFS+SPF+FO diets had lower body weight (protein effect, P = 0.024), feed efficiency (protein effect, P = 0.018), and liver weight (protein effect, P = 0.003) as well as lower concentrations of adipose tissue cytokines and chemokines (protein effect, P ≤ 0.003) compared with HFS and HFS+FO groups. They also had greater glucose tolerance (protein effect, P < 0.001), lower activation of the mammalian target of rapamycin complex 1/S6 kinase 1/insulin receptor substrate 1 (mTORC1/S6K1/IRS1) pathway, and increased insulin signaling in liver compared with the HFS and HFS+FO groups. The HFS+FO, HFS+SPF, and HFS+SPF+FO groups had lower plasma triglycerides (protein effect, P = 0.003; lipid effect, P = 0.002) than did the HFS group. SPF increased glucose uptake and decreased HGP and iNOS activation in vitro. CONCLUSIONS: SPF reduces obesity-linked MetS features in LDLR(-/-)/ApoB(100/100) mice. The anti-inflammatory and glucoregulatory properties of SPF were confirmed in L6 myocytes, FAO hepatocytes, and J774 macrophages.