Unconstrained Piezoelectric Vascular Electronics for Wireless Monitoring of Hemodynamics and Cardiovascular Health.

The patient-centered healthcare requires timely disease diagnosis and prognostic assessment, calling for individualized physiological monitoring. To assess the postoperative hemodynamic status of patients, implantable blood flow monitoring devices are highly expected to deliver real time, long-term, sensitive, and reliable hemodynamic signals, which can accurately reflect multiple physiological conditions. Herein, an implantable and unconstrained vascular electronic system based on a piezoelectric sensor immobilized is presented by a "growable" sheath around continuously growing arterial vessels for real-timely and wirelessly monitoring of hemodynamics. The piezoelectric sensor made of circumferentially aligned polyvinylidene fluoride nanofibers around pulsating artery can sensitively perceive mechanical signals, and the growable sheath bioinspired by the structure and function of leaf sheath has elasticity and conformal shape adaptive to the dynamically growing arterial vessels to avoid growth constriction. With this integrated and smart design, long-term, wireless, and sensitive monitoring of hemodynamics are achieved and demonstrated in rats and rabbits. It provides a simple and versatile strategy for designing implantable sensors in a less invasive way.

Can global or national disability weights represent provincial level?

BACKGROUND: A universal set of disability weights(DWs) is mainly based on the survey of North America, Australia and Europe, whereas the participants in Asia was limited. The debate hasn't yet settled whether a universal DW is desirable or useful.The focus of the debate is its representativenes-s.After all, the DWs come from people's subjective evaluation of pain, and they may vary according to cultural background.The differences of the DWs could have implications for the magnitude or ranking of disease burdens.The DWs of Anhui Province has not been completely presented.This paper aims to obtain the DWs suitable for the general population of Anhui Province of China, and attempts to explore the differences between different DWs by comparing the DWs with the similar-cultural background and the DWs with cross-cultural background. METHODS: A web-based survey was conducted to estimate the DWs for 206 health states of Anhui province in 2020. Paired comparison (PC) data were analyzed and anchored by probit regression and fitting loess model. We compared the DWs in Anhui with other provinces in China and those in Global burden of disease (GBD) and Japan. RESULTS: Compared with Anhui province, the proportion of health states which showed 2 times or more differences ranged from 1.94% (Henan) to 11.17% (Sichuan) in China and domestic provinces. It was 19.88% in Japan and 21.51% in GBD 2013 respectively. In Asian countries or regions, most of the health states with top 15 DWs belonged to the category of mental, behavioral, and substance use disorders. But in GBD, most were infectious diseases and cancer. The differences of DWs in neighboring provinces were smaller than other geographically distant provinces or countries. CONCLUSION: PC responses were largely consistent across very distinct settings,but the exceptions do need to be faced squarely.The differences of DWs among similar-cultural regions were smaller than cross-cultural regions. There is an urgent need for relevant gold standards.

Evaluation of the Mini-Mental State Examination and the Montreal Cognitive Assessment for Predicting Post-stroke Cognitive Impairment During the Acute Phase in Chinese Minor Stroke Patients.

Objective: To assess the value of the Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) during acute phase in predicting post-stroke cognitive impairment (PSCI) at 3-6 months. Methods: We prospectively recruited 229 patients who had suffered their first-ever ischemic stroke. PSCI was determined in 104 of these patients by a comprehensive neuropsychological battery performed at 3-6 months. Receiver operating characteristic (ROC) curve analysis was then performed to compare the discriminatory ability of the MMSE and MoCA. Also, we applied a decision tree generated by the classification and regression tree methodology. Results: In total, 66 patients had PSCI when evaluated 3-6 months after the onset of minor stroke. Logistic regression analysis revealed that education, body mass index (BMI), and baseline MoCA scores were independently associated with PSCI. ROC curve analysis showed that the ability to predict PSCI was similar when compared between baseline MoCA scores [area under curve (AUC), 0.821; 95% confidence interval (CI), 0.743-0.898] and baseline MMSE scores (AUC, 0.809; 95% CI, 0.725-0.892, P = 0.75). Both MMSE and MoCA exhibited similar predictive values at their optimal cut-off points (MMSE ≤27; sensitivity, 0.682; specificity, 0.816; MoCA ≤21; sensitivity, 0.636; specificity, 0.895). Classification and regression tree-derived analysis yielded an AUC of 0.823 (sensitivity, 0.803; specificity, 0.842). Conclusion: When applied within 2 weeks of stroke, the MMSE and MoCA are both useful and have similar predictive value for PSCI 3-6 months after the onset of minor stroke.

The assessment of transmission efficiency and latent infection period in asymptomatic carriers of SARS-CoV-2 infection.

Few studies have focused on the transmission efficiency of asymptomatic carriers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our follow-up study was performed on 147 asymptomatic carriers in Anhui Province. Of these, 50.0% were male, 50.3% were older than 40 years, 43.8% were farmers, and 68.7% were from the north of Anhui Province. 16 of the 147 asymptomatic carriers developed symptoms in the following 14 days of isolated observation, and were subsequently diagnosed as confirmed cases. The possible latent infection period was found to range from 1-5 days before onset, with a median time of 2 days. The second attack rate for the 16 confirmed cases who had transferred from being asymptomatic carriers was 9.7% (23/236 close contacts), while for the 131 asymptomatic carriers the rate was 2.6% (24/914 close contacts), showing a significant difference in second attack rate between the two groups (p＜0.001). Our study indicated that COVID-19 cases are contagious during the incubation period, and that close contact screening should be extended to include the incubation period. Our results also showed that the transmission efficiency for asymptomatic carriers was lower than that for confirmed case.

Mortality and Disease Burden of Injuries from 2008 to 2017 in Anhui Province, China.

OBJECTIVE: To investigate the temporal trends in mortality and disease burden of injuries in Anhui province from 2008 to 2017, so as to provide reference for injury control and prevention. METHODS: Data of mortality were collected from 9 national surveillance points in Anhui province during 2008-2017 in the Information System for Death Cause Register and Management. The surveillance data were analyzed by using crude mortality, standardized mortality rate (SMR), potential year of life lost (PYLL), PYLL rate (PYLLR), and average of year life lost (AYLL). RESULTS: There were a total of 44855 people died from injury, accounted for 9.44% of the all-cause mortality, ranked as the fifth leading cause of deaths in the whole population, and denoted the first leading cause of deaths in the 0-44 year's group. The leading causes of injury deaths were road traffic accidents, suicide, accidental falls, drowning, and poisoning. Road traffic accidents was the primary cause of injury deaths among the male population, while suicide was the dominate cause of injury deaths among the female population. Drowning, traffic accidents, and suicide accounted for the most injury deaths among the population aged 0-14 years, 15-64 years, and above 60 years, respectively. The road traffic accidents accounted for the largest proportion of injury PYLL and PYLLR, and drowning caused the highest AYLL among injury deaths. CONCLUSION: In Anhui province, road traffic accidents, suicide, accidental falls, drowning, and poisoning were the top five causes of injury deaths that harm the health of local residents; corresponding injury prevention strategies should be formulated.

Binding of two intrinsically disordered peptides to a multi-specific protein: a combined Monte Carlo and molecular dynamics study.

The unique ability of intrinsically disordered proteins (IDPs) to fold upon binding to partner molecules makes them functionally well-suited for cellular communication networks. For example, the folding-binding of different IDP sequences onto the same surface of an ordered protein provides a mechanism for signaling in a many-to-one manner. Here, we study the molecular details of this signaling mechanism by applying both Molecular Dynamics and Monte Carlo methods to S100B, a calcium-modulated homodimeric protein, and two of its IDP targets, p53 and TRTK-12. Despite adopting somewhat different conformations in complex with S100B and showing no apparent sequence similarity, the two IDP targets associate in virtually the same manner. As free chains, both target sequences remain flexible and sample their respective bound, natively [Formula: see text]-helical states to a small extent. Association occurs through an intermediate state in the periphery of the S100B binding pocket, stabilized by nonnative interactions which are either hydrophobic or electrostatic in nature. Our results highlight the importance of overall physical properties of IDP segments, such as net charge or presence of strongly hydrophobic amino acids, for molecular recognition via coupled folding-binding.

Kinetic advantage of intrinsically disordered proteins in coupled folding-binding process: a critical assessment of the "fly-casting" mechanism.

Intrinsically disordered proteins (IDPs) are recognized to play important roles in many biological functions such as transcription and translation regulation, cellular signal transduction, protein phosphorylation, and molecular assemblies. The coupling of folding with binding through a "fly-casting" mechanism has been proposed to account for the fast binding kinetics of IDPs. In this article, experimental data from the literature were collated to verify the kinetic advantages of IDPs, while molecular simulations were performed to clarify the origin of the kinetic advantages. The phosphorylated KID-kinase-inducible domain interacting domain (KIX) complex was used as an example in the simulations. By modifying a coarse-grained model with a native-centric Go-like potential, we were able to continuously tune the degree of disorder of the phosphorylated KID domain and thus investigate the intrinsic role of chain flexibility in binding kinetics. The simulations show that the "fly-casting" effect is not only due to the greater capture radii of IDPs. The coupling of folding with binding of IDPs leads to a significant reduction in binding free-energy barrier. Such a reduction accelerates the binding process. Although the greater capture radius has been regarded as the main factor in promoting the binding rate of IDPs, we found that this parameter will also lead to the slower translational diffusion of IDPs when compared with ordered proteins. As a result, the capture rate of IDPs was found to be slower than that of ordered proteins. The main origin of the faster binding for IDPs are the fewer encounter times required before the formation of the final binding complex. The roles of the interchain native contacts fraction (Q(b)) and the mass-center distance (DeltaR) as reaction coordinates are also discussed.

Efficient chain moves for Monte Carlo simulations of a wormlike DNA model: excluded volume, supercoils, site juxtapositions, knots, and comparisons with random-flight and lattice models.

We develop two classes of Monte Carlo moves for efficient sampling of wormlike DNA chains that can have significant degrees of supercoiling, a conformational feature that is key to many aspects of biological function including replication, transcription, and recombination. One class of moves entails reversing the coordinates of a segment of the chain along one, two, or three axes of an appropriately chosen local frame of reference. These transformations may be viewed as a generalization, to the continuum, of the Madras-Orlitsky-Shepp algorithm for cubic lattices. Another class of moves, termed T+/-2, allows for interconversions between chains with different lengths by adding or subtracting two beads (monomer units) to or from the chain. Length-changing moves are generally useful for conformational sampling with a given site juxtaposition, as has been shown in previous lattice studies. Here, the continuum T+/-2 moves are designed to enhance their acceptance rate in supercoiled conformations. We apply these moves to a wormlike model in which excluded volume is accounted for by a bond-bond repulsion term. The computed autocorrelation functions for the relaxation of bond length, bond angle, writhe, and branch number indicate that the new moves lead to significantly more efficient sampling than conventional bead displacements and crankshaft rotations. A close correspondence is found in the equilibrium ensemble between the map of writhe computed for pair of chain segments and the map of site juxtapositions or self-contacts. To evaluate the more coarse-grained freely jointed chain (random-flight) and cubic lattice models that are commonly used in DNA investigations, twisting (torsional) potentials are introduced into these models. Conformational properties for a given superhelical density sigma may then be sampled by computing the writhe and using White's formula to relate the degree of twisting to writhe and sigma. Extensive comparisons of contact patterns and knot probabilities of the more coarse-grained models with the wormlike model show that the behaviors of the random-flight model are similar to that of DNA molecules in a solution environment with high ionic strengths, whereas the behaviors of the cubic lattice model with excluded volume are akin to that of DNA molecules under low ionic strengths.

Inferring global topology from local juxtaposition geometry: interlinking polymer rings and ramifications for topoisomerase action.

Lattice modeling is applied to investigate how the configurations of local chain juxtapositions may provide information about whether two ring polymers (loops) are topologically linked globally. Given a particular juxtaposition, the conditional probability that the loops are linked is determined by exact enumeration and extensive Monte Carlo sampling of conformations satisfying excluded volume constraints. A discrimination factor fL, defined as the ratio of linked to unlinked probabilities, varies widely depending on which juxtaposition is presumed. /log fL/s that are large for small loop size n tend to decrease, signaling diminishing topological information content of the juxtapositions, with increasing n. However, some juxtaposition geometries can impose sufficient overall conformational biases such that /log fL/ remains significant for large n. Notably, for two loops as large as n=200 in the model, the probability that passing the segments of a hooked juxtaposition would unlink an originally linked configuration is remarkably high, approximately 85%. In contrast, segment-passage of a free juxtaposition would link the loops from an originally unlinked configuration more than 90% of the time. The statistical mechanical principles emerging from these findings suggest that it is physically possible for DNA topoisomerases to decatenate effectively by acting selectively on juxtapositions with specific "hooked" geometries.

Chevron behavior and isostable enthalpic barriers in protein folding: successes and limitations of simple Go-like modeling.

It has been demonstrated that a "near-Levinthal" cooperative mechanism, whereby the common Go interaction scheme is augmented by an extra favorability for the native state as a whole, can lead to apparent two-state folding/unfolding kinetics over a broad range of native stabilities in lattice models of proteins. Here such a mechanism is shown to be generalizable to a simplified continuum (off-lattice) Langevin dynamics model with a Calpha protein chain representation, with the resulting chevron plots exhibiting an extended quasilinear regime reminiscent of that of apparent two-state real proteins. Similarly high degrees of cooperativity are possible in Go-like continuum models with rudimentary pairwise desolvation barriers as well. In these models, cooperativity increases with increasing desolvation barrier height, suggesting strongly that two-state-like folding/unfolding kinetics would be achievable when the pairwise desolvation barrier becomes sufficiently high. Besides cooperativity, another generic folding property of interest that has emerged from published experiments on several apparent two-state proteins is that their folding relaxation under constant native stability (isostability) conditions is essentially Arrhenius, entailing high intrinsic enthalpic folding barriers of approximately 17-30 kcal/mol. Based on a new analysis of published data on barnase, here we propose that a similar property should also apply to a certain class of non-two-state proteins that fold with chevron rollovers. However, several continuum Go-like constructs considered here fail to predict any significant intrinsic enthalpic folding barrier under isostability conditions; thus the physical origin of such barriers in real proteins remains to be elucidated.