Synergistic action and mechanism of scoparone, a key bioactive component of Artemisia capillaris, and spirodiclofen against spider mites.

BACKGROUND: Plants have numerous defensive secondary metabolites to withstand insect attacks. Scoparone, which is extracted from the medicinal plant Artemisia capillaris, has potent acaricidal effects on Tetranychus cinnabarinus. Spirodiclofen, derived from a tetronic acid derivative, is a potent commercial acaricide that is extensively used globally. However, whether scoparone has synergistic effects when used in conjunction with spirodiclofen and the underlying synergistic mechanism remains unclear. RESULTS: Scoparone exhibited a potent synergistic effect when it was combined with spirodiclofen at a 1:9 ratio. Subsequently, cytochrome P450 monooxygenase (P450) activity, RNA-Seq and qPCR assays indicated that the enzyme activity of P450 and the expression of one P450 gene from T. cinnabarinus, TcCYP388A1, were significantly inhibited by scoparone and spirodiclofen + scoparone; conversely, P450 was activated in spirodiclofen-exposed mites. Importantly, RNAi-mediated silencing of the TcCYP388A1 gene markedly increased the susceptibility of spider mites to spirodiclofen, scoparone and spirodiclofen + scoparone, and in vitro, the recombinant TcCYP388A1 protein could metabolize spirodiclofen. Molecular docking and functional analyses further indicated that R117, which is highly conserved in Arachnoidea species, may be a vital specific binding site for scoparone in the mite TcCYP388A1 protein. This binding site was subsequently confirmed using mutagenesis data, which revealed that this binding site was the sole site selected by scoparone in spider mites over mammalian or fly CYP388A1. CONCLUSIONS: These results indicate that the synergistic effects of scoparone and spirodiclofen on mites occurs through the inhibition of P450 activity, thus reducing spirodiclofen metabolism. The synergistic effect of this potent natural product on the detoxification enzyme-targeted activity of commercial acaricides may offer a sustainable strategy for pest mite resistance management. © 2024 Society of Chemical Industry.

Tensor network methods for extracting conformal field theory data from fixed-point tensors and defect coarse graining.

We present a comprehensive study on extracting conformal field theory data using tensor network methods, especially, from the fixed-point tensor of the linearized tensor renormalization group (lTRG) for the classical two-dimensional Ising model near the critical temperature. Utilizing two different methods, we extract operator scaling dimensions and operator product expansion coefficients by introducing defects on the lattice and by employing the fixed-point tensor. We also explore the effects of pointlike defects in the lattice on the coarse-graining process. We find that there is a correspondence between coarse-grained defect tensors and conformal states obtained from the lTRG fixed-point equation. We also analyze the capabilities and limitations of our proposed coarse-graining scheme for tensor networks with pointlike defects, including graph-independent local truncation (GILT) and higher-order tensor renormalization group (HOTRG). Our results provide a better understanding of the capacity and limitations of the tensor renormalization group scheme in coarse-graining defect tensors, and we show that GILT+HOTRG can be used to give accurate two- and four-point functions under specific conditions. We also find that employing the minimal canonical form further improves the stability of the RG flow.

Serious Mental Illness in Assisted Living Communities: Association with Nursing Home Placement.

OBJECTIVES: Assess prevalence of serious mental illness (SMI) alone, and co-occurring with Alzheimer disease and related dementias (ADRD), among Medicare beneficiaries in assisted living (AL). Examine the association between permanent nursing home (NH) placement and SMI, among residents with and without ADRD. DESIGN: 2018-2019 retrospective cohort of Medicare beneficiaries in AL. Residents were followed for up to 2 years to track their NH placement. We used data from the Medicare Enrollment Database, the Medicare Beneficiary Summary File, Minimum Data Set, and a national directory of state-licensed AL communities. AL residents were identified using a validated, previously reported 9-digit zip code methodology. SETTING AND PARTICIPANTS: A cross-sectional study sample included 289,350 Medicare beneficiaries in 17,265 AL communities across 50 states and in the District of Columbia. METHODS: The outcome was permanent NH placement: a continuous stay for more than 90 days. Key independent variable was presence of SMI-schizophrenia, bipolar disorder, and major depression. Other covariates included sociodemographic factors and presence of other chronic conditions, including ADRD. A linear probability model with robust SEs, and AL-level random effects, was used to test the association between SMI diagnoses, ADRD, and their interactions on NH placement. RESULTS: More than half (55.65%) of AL residents had a diagnosis of SMI, among them 93.2% had major depression, 28.5% schizophrenia, and 22.2% bipolar disorder. Individuals with schizophrenia and bipolar disorder had a significantly lower probability of NH placement, a 32% and a 15% decrease relative to the cohort mean, respectively. Placement risk was significantly greater for residents with ADRD compared to those without, increasing for those who also had schizophrenia or bipolar disorder, 12.9% and 1.5% relative to the sample mean, respectively. CONCLUSION AND IMPLICATIONS: Presence of schizophrenia and bipolar disorder, in conjunction with ADRD, significantly increases the risk of long-term NH placement, suggesting that ALs may not be well prepared to care for these residents.

Hospice providers serving assisted living residents: Association of higher volume with lower quality.

BACKGROUND: Assisted living (AL) community caregivers are known to report lower quality of hospice care. However, little is known about hospice providers serving AL residents and factors that may contribute to, and explain, differences in quality. We examined the association between hospice providers' AL patient-day volume and their quality ratings based on Hospice Item Set (HIS) and Consumer Assessment of Healthcare Providers and Systems (CAHPS) Hospice Surveys. METHODS: This cross-sectional study employed information from the Medicare Compare website and Medicare claims data. Medicare-eligible AL residents were identified using previously validated methods and merged with hospice claims. Linear probability models adjusting for county fixed effects were used to examine the association between hospice provider AL volume, measured as the share of annual hospice patient days from AL residents, and quality measures obtained from HIS and CAHPS. Models controlled for hospice providers' profit status and daily patient census. RESULTS: Higher AL-volume hospice providers were 7 percentage points more likely to have caregivers reporting lower median scores on domains of pain assessment, dyspnea treatment, and emotional support. Their caregivers also reported lower scores in team communications and training family to provide care. Higher AL-volume hospice providers also were 5 percentage points less likely to get higher aggregated scores from all CAHPS domains and 7 percentage points less likely to have higher HIS composite scores. CONCLUSIONS: Hospice providers serving higher volumes of AL patient days had lower quality scores. In order to identify targeted opportunities for quality improvement, research is needed to understand why lower quality providers are concentrated in the AL market.

A novel approach to study multi-domain motions in JAK1's activation mechanism based on energy landscape.

The family of Janus Kinases (JAKs) associated with the JAK-signal transducers and activators of transcription signaling pathway plays a vital role in the regulation of various cellular processes. The conformational change of JAKs is the fundamental steps for activation, affecting multiple intracellular signaling pathways. However, the transitional process from inactive to active kinase is still a mystery. This study is aimed at investigating the electrostatic properties and transitional states of JAK1 to a fully activation to a catalytically active enzyme. To achieve this goal, structures of the inhibited/activated full-length JAK1 were modelled and the energies of JAK1 with Tyrosine Kinase (TK) domain at different positions were calculated, and Dijkstra's method was applied to find the energetically smoothest path. Through a comparison of the energetically smoothest paths of kinase inactivating P733L and S703I mutations, an evaluation of the reasons why these mutations lead to negative or positive regulation of JAK1 are provided. Our energy analysis suggests that activation of JAK1 is thermodynamically spontaneous, with the inhibition resulting from an energy barrier at the initial steps of activation, specifically the release of the TK domain from the inhibited Four-point-one, Ezrin, Radixin, Moesin-PK cavity. Overall, this work provides insights into the potential pathway for TK translocation and the activation mechanism of JAK1.

Influence Mechanism of Interfacial Oxidation of Li3YCl6 Solid Electrolyte on Reduction Potential.

Halide-based solid electrolytes are promising candidates for all solid-state lithium-ion batteries (ASSLBs) due to their high ionic conductivity, wide electrochemical window, and excellent chemical stability with cathode materials. However, when tested in practice, their intrinsic electrochemical stability windows do not well match the conditions for stable operation of ASSBs. Existing literature reports halide-based ASSBs that still operate well outside the electrochemical stability window, while ASSBs that do not operate within the window are not well studied or the studies are based on the cathode material interface. In this study, we aim to elucidate the mechanism behind all-solid-state battery failure by investigating how the reduction potential of Li3YCl6 solid-state electrolyte itself changes under overcharging conditions. Our findings demonstrate that in Li-In|Li3YCl6|Li3YCl6-C half-cells during the first state of charge, Cl ions participate in charge compensation, resulting in a depletion of ligands. This phenomenon significantly affects the reduction potential of Y3+, causing it to be reduced to Y2Cl3 and ultimately to Y0 at conditions far exceeding its actual reduction potential. Furthermore, we analyze the interfacial impedance induced by this process and propose a novel perspective on battery failure.

Deciphering principles of nucleosome interactions and impact of cancer-associated mutations from comprehensive interaction network analysis.

Nucleosomes represent hubs in chromatin organization and gene regulation and interact with a plethora of chromatin factors through different modes. In addition, alterations in histone proteins such as cancer mutations and post-translational modifications have profound effects on histone/nucleosome interactions. To elucidate the principles of histone interactions and the effects of those alterations, we developed histone interactomes for comprehensive mapping of histone-histone interactions (HHIs), histone-DNA interactions (HDIs), histone-partner interactions (HPIs) and DNA-partner interactions (DPIs) of 37 organisms, which contains a total of 3808 HPIs from 2544 binding proteins and 339 HHIs, 100 HDIs and 142 DPIs across 110 histone variants. With the developed networks, we explored histone interactions at different levels of granularities (protein-, domain- and residue-level) and performed systematic analysis on histone interactions at a large scale. Our analyses have characterized the preferred binding hotspots on both nucleosomal/linker DNA and histone octamer and unraveled diverse binding modes between nucleosome and different classes of binding partners. Last, to understand the impact of histone cancer-associated mutations on histone/nucleosome interactions, we complied one comprehensive cancer mutation dataset including 7940 cancer-associated histone mutations and further mapped those mutations onto 419,125 histone interactions at the residue level. Our quantitative analyses point to histone cancer-associated mutations' strongly disruptive effects on HHIs, HDIs and HPIs. We have further predicted 57 recurrent histone cancer mutations that have large effects on histone/nucleosome interactions and may have driver status in oncogenesis.

Confinement Engineering of Zinc Single-Atom Triggered Charge Redistribution on Ruthenium Site for Alkaline Hydrogen Production.

Optimizing the interaction between metal and support in the supported metal catalysts effectively refines the electronic structure and boosts the catalytic properties of loaded active components. Herein a method is introduced to confine ultrafine ruthenium (Ru) nanoparticles within atomically dispersed Zn-N4 sites on a N-doped carbon network (Ru/Zn-N-C) through the strong electronic metal-support interaction, achieving superior catalytic activity and stability for alkaline hydrogen evolution. Spectroscopic data and theoretical modeling elucidate that the remarkable catalytic performance of Ru sites stems from their strong electronic coupling with neighboring Zn-N4 moiety and pyridinic N/pyrrolic N. This interaction induces an electron-deficient state of Ru, thereby accelerating the dissociation of H2 O and lowering the energy barriers for the desorption of OH* and H*. This insight provides a deeper understanding of the catalytic mechanisms at play. Furthermore, alkaline water electrolyzer using this catalyst as cathode delivers a mass activity of 3 A mgcat -1 at 2.0 V, much surpassing Ru-C. This research opens a novel pathway for the development of advanced materials , tailored for energy storage and conversion applications.

Bound ion effects: Using machine learning method to study the kinesin Ncd's binding with microtubule.

Drosophila Ncd proteins are motor proteins that play important roles in spindle organization. Ncd and the tubulin dimer are highly charged. Thus, it is crucial to investigate Ncd-tubulin dimer interactions in the presence of ions, especially ions that are bound or restricted at the Ncd-tubulin dimer binding interfaces. To consider the ion effects, widely used implicit solvent models treat ions implicitly in the continuous solvent environment without focusing on the individual ions' effects. But highly charged biomolecules such as the Ncd and tubulin dimer may capture some ions at highly charged regions as bound ions. Such bound ions are restricted to their binding sites; thus, they can be treated as part of the biomolecules. By applying multiscale computational methods, including the machine-learning-based Hybridizing Ions Treatment-2 program, molecular dynamics simulations, DelPhi, and DelPhiForce, we studied the interaction between the Ncd motor domain and the tubulin dimer using a hybrid solvent model, which considers the bound ions explicitly and the other ions implicitly in the solvent environment. To identify the importance of treating bound ions explicitly, we also performed calculations using the implicit solvent model without considering the individual bound ions. We found that the calculations of the electrostatic features differ significantly between those of the hybrid solvent model and the pure implicit solvent model. The analyses show that treating bound ions at highly charged regions explicitly is crucial for electrostatic calculations. This work proposes a machine-learning-based approach to handle the bound ions using the hybrid solvent model. Such an approach is not only capable of handling kinesin-tubulin complexes but is also appropriate for other highly charged biomolecules, such as DNA/RNA, viral capsid proteins, etc.

JAK3 Y841 Autophosphorylation Is Critical for STAT5B Activation, Kinase Domain Stability and Dimer Formation.

Janus tyrosine kinase 3 (JAK3) is primarily expressed in immune cells and is needed for signaling by the common gamma chain (γc) family of cytokines. Abnormal JAK3 signal transduction can manifest as hematological disorders, e.g., leukemia, severe combined immunodeficiency (SCID) and autoimmune disease states. While regulatory JAK3 phosphosites have been well studied, here a functional proteomics approach coupling a JAK3 autokinase assay to mass spectrometry revealed ten previously unreported autophosphorylation sites (Y105, Y190, Y238, Y399, Y633, Y637, Y738, Y762, Y824, and Y841). Of interest, Y841 was determined to be evolutionarily conserved across multiple species and JAK family members, suggesting a broader role for this residue. Phospho-substitution mutants confirmed that Y841 is also required for STAT5 tyrosine phosphorylation. The homologous JAK1 residue Y894 elicited a similar response to mutagenesis, indicating the shared importance for this site in JAK family members. Phospho-specific Y841-JAK3 antibodies recognized activated kinase from various T-cell lines and transforming JAK3 mutants. Computational biophysics analysis linked Y841 phosphorylation to enhanced JAK3 JH1 domain stability across pH environments, as well as to facilitated complementary electrostatic JH1 dimer formation. Interestingly, Y841 is not limited to tyrosine kinases, suggesting it represents a conserved ubiquitous enzymatic function that may hold therapeutic potential across multiple kinase families.

Constructing MIL-53(Fe)@ZIF-67(Co) binary metal-organic framework hierarchical heterostructure electrodes for efficient oxygen evolution.

Improving the efficiency of the anodic oxygen evolution reaction (OER) is important to solve the global energy crisis and greenhouse gas emission problems. In this paper, a preparation method for a MIL-53(Fe)@ZIF-67(Co) composite electrode is proposed. The hierarchical structure formed by the combination of MIL-53(Fe) and ZIF-67(Co) provides a rich channel for the transport of electrons and mass in the OER process. XPS analysis and DFT calculations revealed that Fe electrons in MIL-53(Fe) were transferred to Co in ZIF-67(Co) through O, which confirmed the rapid charge transfer effect of this transport channel. The MIL-53(Fe)@ZIF-67(Co) electrode has significant OER performance. When the current density reaches 10 mA cm-2, the overpotential is only 193 mV. This study inaugurates a new way for the rational design of a multiphase interface and the construction of new MOF channel structures.

Synergistic effect of zero-valent iron and static magnetic field on wastewater purification and bioelectricity generation in electroactive constructed wetlands.

This study investigated the enhancement effect of zero-valent iron and static magnetic field on the pollutant removal and power generation of electroactive constructed wetland. As demonstration, a conventional wetland was systematically modified by introducing zero-valent iron and then a static magnetic field, leading to progressive increases in pollutant (namely NH4+-N and chemical oxygen demand) removal efficiencies. By introducing both zero-valent iron and a static magnetic field, the power density increased four-fold to 9.2 mW/m2 and the internal resistance decreased by 26.7% to 467.4 Ω. Notably, static magnetic field decreased the relative abundance of electrochemically active bacteria (such as Romboutsia), while significantly enhancing species diversity. The permeability of the microbial cell membrane was improved, leading to a reduction in activation loss and internal resistance, thereby enhancing power generation capacity. Results showed that the addition of zero-valent iron and the applied magnetic field were beneficial to the pollutants removal and bioelectricity generation.

Phosphorylation of Tyrosine 841 Plays a Significant Role in JAK3 Activation.

Janus Kinase 3 (JAK3) plays a key role in the development, proliferation, and differentiation of various immune cells. It regulates gene expression by phosphorylation of Signal Transducers and Activators of Transcriptions (STATs) via the JAK/STAT pathway. Recently, we found a new JAK3 phosphorylation site, tyrosine 841 (Y841). The results showed that pY841 helps the kinase domain flip around the pseudo kinase domain, which may cause JAK3 conformational changes. It also reduces the size of the cleft between the N-lobe and the C-lobe of the JAK3 kinase domain. However, pY841 was found to enlarge the cleft when ATP/ADP was bound to the kinase. The increase in the cleft size suggested that pY841 enhanced the elasticity of the kinase domain. For unphosphorylated JAK3 (JAK3-Y841), the binding forces between the kinase domain and ATP or ADP were similar. After phosphorylation of Y841, JAK3-pY841 exhibited more salt bridges and hydrogen bonds between ATP and the kinase than between ADP and the kinase. Consequently, the electrostatic binding force between ATP and the kinase was higher than that between ADP and the kinase. The result was that compared to ADP, ATP was more attractive to JAK3 when Y841 was phosphorylated. Therefore, JAK3-pY841 tended to bind ATP rather than ADP. This work provides new insights into the role of phosphorylation in kinase activation and ATP hydrolysis and sheds light on the importance of understanding the molecular mechanisms that regulate the kinase function.

End-of-Life Care Transitions in Assisted Living: Associations With State Staffing and Training Regulations.

OBJECTIVE: We examined the frequency and categories of end-of-life care transitions among assisted living community decedents and their associations with state staffing and training regulations. DESIGN: Cohort study. SETTING AND PARTICIPANTS: Medicare beneficiaries who resided in assisted living facilities and had validated death dates in 2018-2019 (N = 113,662). METHODS: We used Medicare claims and assessment data for a cohort of assisted living decedents. Generalized linear models were used to examine the associations between state staffing and training requirements and end-of-life care transitions. The frequency of end-of-life care transitions was the outcome of interest. State staffing and training regulations were the key covariates. We controlled for individual, assisted living, and area-level characteristics. RESULTS: End-of-life care transitions were observed among 34.89% of our study sample in the last 30 days before death, and among 17.25% in the last 7 days. Higher frequency of care transitions in the last 7 days of life was associated with higher regulatory specificity of licensed [incidence risk ratio (IRR) = 1.08; P = .002] and direct care worker staffing (IRR = 1.22; P < .0001). Greater regulatory specificity of direct care worker training (IRR = 0.75; P < .0001) was associated with fewer transitions. Similar associations were found for direct care worker staffing (IRR = 1.15; P < .0001) and training (IRR = 0.79; P < .001) and transitions within 30 days of death. CONCLUSIONS AND IMPLICATIONS: There were significant variations in the number of care transitions across states. The frequency of end-of-life care transitions among assisted living decedents during the last 7 or 30 days of life was associated with state regulatory specificity for staffing and staff training. State governments and assisted living administrators may wish to set more explicit guidelines for assisted living staffing and training to help improve end-of-life quality of care.

HIT-2: Implementing machine learning algorithms to treat bound ions in biomolecules.

Electrostatic features are fundamental to protein functions and protein-protein interactions. Studying highly charged biomolecules is challenging given the heterogeneous distribution of the ionic cloud around such biomolecules. Here we report a new computational method, Hybridizing Ions Treatment-2 (HIT-2), which is used to model biomolecule-bound ions using the implicit solvation model. By modeling ions, HIT-2 allows the user to calculate important electrostatic features of the biomolecules. HIT-2 applies an efficient algorithm to calculate the position of bound ions from molecular dynamics simulations. Modeling parameters were optimized by machine learning methods from thousands of datasets. The optimized parameters produced results with errors lower than 0.2 Å. The testing results on bound Ca2+ and Zn2+ in NAMD simulations also proved that HIT-2 can effectively identify bound ion types, numbers, and positions. Also, multiple tests performed on HIT-2 suggest the method can handle biomolecules that undergo remarkable conformational changes. HIT-2 can significantly improve electrostatic calculations for many problems in computational biophysics.

A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules.

Microtubules are key players in several stages of the cell cycle and are also involved in the transportation of cellular organelles. Microtubules are polymerized by α/ß tubulin dimers with a highly dynamic feature, especially at the plus ends of the microtubules. Therefore, understanding the interactions among tubulins is crucial for characterizing microtubule dynamics. Studying microtubule dynamics can help researchers make advances in the treatment of neurodegenerative diseases and cancer. In this study, we utilize a series of computational approaches to study the electrostatic interactions at the binding interfaces of tubulin monomers. Our study revealed that among all the four types of tubulin-tubulin binding modes, the electrostatic attractive interactions in the α/ß tubulin binding are the strongest while the interactions of α/α tubulin binding in the longitudinal direction are the weakest. Our calculations explained that due to the electrostatic interactions, the tubulins always preferred to form α/ß tubulin dimers. The interactions between two protofilaments are the weakest. Thus, the protofilaments are easily separated from each other. Furthermore, the important residues involved in the salt bridges at the binding interfaces of the tubulins are identified, which illustrates the details of the interactions in the microtubule. This study elucidates some mechanistic details of microtubule dynamics and also identifies important residues at the binding interfaces as potential drug targets for the inhibition of cancer cells.

Using a comprehensive approach to investigate the interaction between Kinesin-5/Eg5 and the microtubule.

Kinesins are microtubule-based motor proteins that play important roles ranging from intracellular transport to cell division. Human Kinesin-5 (Eg5) is essential for mitotic spindle assembly during cell division. By combining molecular dynamics (MD) simulations with other multi-scale computational approaches, we systematically studied the interaction between Eg5 and the microtubule. We find the electrostatic feature on the motor domains of Eg5 provides attractive interactions to the microtubule. Additionally, the folding and binding energy analysis reveals that the Eg5 motor domain performs its functions best when in a weak acidic environment. Molecular dynamics analyses of hydrogen bonds and salt bridges demonstrate that, on the binding interfaces of Eg5 and the tubulin heterodimer, salt bridges play the most significant role in holding the complex. The salt bridge residues on the binding interface of Eg5 are mostly positive, while salt bridge residues on the binding interface of tubulin heterodimer are mostly negative. Such salt bridge residue distribution is consistent with electrostatic potential calculations. In contrast, the interface between α and ß-tubulins is dominated by hydrogen bonds rather than salt bridges. Compared to the Eg5/α-tubulin interface, the Eg5/ß-tubulin interface has a greater number of salt bridges and higher occupancy for salt bridges. This asymmetric salt bridge distribution may play a significant role in Eg5's directionality. The residues involved in hydrogen bonds and salt bridges are identified in this work and may be helpful for anticancer drug design.

Pressure-Induced Hydrogen Transfer in 2-Butyne via a Double CH···π Aromatic Transition State.

Hydrogen transfer (H-transfer) is an important elementary reaction in chemistry and bioscience. It is often facilitated by the hydrogen bonds between the H-donor and acceptor. Here, at room temperature and high pressure, we found that solid 2-butyne experienced a concerted two-in-two-out intermolecular CH···π H-transfer, which initiated the subsequent polymerization. Such double H-transfer goes through an aromatic Hückel six-membered ring intermediate state via intermolecular CH···π interactions enhanced by external pressure. Our work shows that H-transfer can occur via the CH···π route in appropriate conformations under high pressure, which gives important insights into the H-transfer in solid-state hydrocarbons.

End-Of-Life Care In Assisted Living Communities: Race And Ethnicity, Dual Enrollment Status, And State Regulations.

Assisted living communities are the final home for many of their residents, most of whom are older, frail, and cognitively or functionally impaired. Yet little is known about end-of-life care in this setting. We examined associations of both death at home and home hospice care with individual characteristics, such as race or ethnicity and dual Medicare-Medicaid enrollment; community characteristics; and the stringency of state-level assisted living regulations. Of the 100,783 fee-for-service Medicare beneficiaries residing in 16,560 assisted living communities who died in 2018-19, almost 60 percent died at home, 84 percent of them with home hospice. In predicting the likelihood of death at home, dual Medicare-Medicaid enrollment was more important than race or ethnicity; in contrast, race was a stronger predictor than dual enrollment for hospice care at death. Residents were less likely to die at home or with home hospice in states with lower regulatory stringency regarding assisted living communities. These findings may help inform efforts to ensure equitable access to desired end-of-life care in this setting and suggest an important role for state-level regulation.

HIT web server: A hybrid method to improve electrostatic calculations for biomolecules.

The electrostatic features of highly charged biomolecules are crucial and challenging tasks in computational biophysics. The electrostatic calculations by traditional implicit solvent methods are efficient but have difficulties on highly charged biomolecules. We have developed a Hybridizing Ion Treatment (HIT) tool, which successfully hybridizes the explicit ions and implicit solvation model to accurately calculate the electrostatic potential for highly charged biomolecules. Here we implemented the HIT tool into a web server. In this study, a training set was prepared to optimize the number of frames for the HIT web server. The results on tubulins, DNAs, and RNAs, reveal the mechanisms for the motor proteins, DNA of HIV, and tRNA. This HIT web server can be widely used to study highly charged biomolecules, including DNAs, RNAs, molecular motors, and other highly charged biomolecules.