Pattern-Matched Polymer Ligpands Toward Near-Perfect Synergistic Passivation for High-Performance and Stable Br/Cl Mixed Perovskite Light-Emitting Diodes.

Mixed Br/Cl perovskite nanocrystals (PeNCs) exhibit bright pure-blue emission benefiting for fulfilling the Rec. 2100 standard. However, phase segregation remains a significant challenge that severely affects the stability and emission spectrum of perovskite light-emitting diodes (PeLEDs). Here, we demonstrate the optimization of the spacing between polydentate functional groups of polymer ligands to match the surface pattern of CsPbBr1.8Cl1.2 PeNCs, resulting in effective synergistic passivation effect and significant improvements in PeLED performances. The block and alternating copolymers with different inter-functional group spacing are facilely synthesized as ligands for PeNCs. Surprisingly, block copolymers with a higher functional group density do not match PeNCs, while alternating copolymers enable efficient PeNCs with the high photoluminescence intensity, low non-radiative recombination rate and high exciton binding energy. Density functional theory calculations clearly confirm the almost perfect match between alternating copolymers and PeNCs. Finally, pure-blue PeLEDs are achieved with the emission at 467 nm and Commission Internationale de l'Eclairage (CIE) coordinates of (0.131, 0.071), high external quantum efficiency (9.1%) and record spectral and operational stabilities (~ 80 mins) in mixed-halide PeLEDs. Overall, this study contributes to designing the polymer ligands and promoting the development of high-performance and stable pure-color PeLEDs towards display applications.

Bridging ribosomal synthesis to cell growth through the lens of kinetics.

Understanding prokaryotic cell growth requires a multiscale modeling framework from the kinetics perspective. The detailed kinetics pathway of ribosomes exhibits features beyond the scope of the classical Hopfield kinetics model. The complexity of the molecular responses to various nutrient conditions poses additional challenge to elucidate the cell growth. Herein, a kinetics framework is developed to bridge ribosomal synthesis to cell growth. For the ribosomal synthesis kinetics, the competitive binding between cognate and near-cognate tRNAs for ribosomes can be modulated by Mg2+. This results in distinct patterns of the speed - accuracy relation comprising "trade-off" and "competition" regimes. Furthermore, the cell growth rate is optimized by varying the characteristics of ribosomal synthesis through cellular responses to different nutrient conditions. In this scenario, cellular responses to nutrient conditions manifest by two quadratic scaling relations: one for nutrient flux versus cell mass, the other for ribosomal number versus growth rate. Both are in quantitative agreement with experimental measurements.

Clinical manifestations and early effectiveness of methimazole in patients with graves' hyperthyroidism-related severe hepatic dysfunction.

BACKGROUND: Graves' hyperthyroidism (GH) is often accompanied by mild to moderate liver injury, but severe hepatic dysfunction (SHD) is relatively rare. Whether patients with GH-related SHD can be treated with methimazole (MMI) remains controversial. This study aimed to determine the clinical characteristics and to evaluate the role of low-dose MMI for such patients. METHODS: 33 patients with GH-related SHD were selected for this retrospective study in the Fifth Medical Center of Chinese PLA General Hospital from January 2017 to July 2022. The clinical manifestations, therapeutic responses, and effectiveness of MMI were evaluated. RESULTS: Systemic jaundice (100.0%), yellow urine (100.0%), fatigue (87.9%), and goiter (66.7%) were the main symptoms. Total bilirubin (TBIL) had no linear correlation with free triiodothyronine (FT3) (r = -0.023, p = .899), free thyroxine (FT4) (r = 0.111, p = .540), T3 (r = -0.144, p = .425), and T4 (r = 0.037, p = .837). On the 14th day after admission, FT3, FT4, T3, T4, TBIL, direct bilirubin (DBIL), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), and international normalized ratio (INR) decreased compared with the baseline (p < .05). The decrease rates of FT3, FT4, T3, T4, TBIL, and DBIL in the MMI group were higher than those in the non-MMI group (p < .05). The improvement rate of the MMI group (77.8%) was higher than that of the non-MMI group (9.5%, p = .001). MMI treatment is an independent predictor affecting the early improvement of patients (OR = 0.022, p = .010). CONCLUSIONS: The main clinical manifestations of patients with GH-related SHD were symptoms related to liver disease. Low-dose MMI was safe and effective for them.

Topology induced crossover between Langevin, subdiffusion, and Brownian diffusion regimes in supercooled water.

Despite extensive studies of supercooled water, it remains challenging to understand its peculiar dynamic anomalous properties. In this work, we integrated full atomistic simulations of supercooled water over the temperature range of room temperature to 200 K using a quantum-mechanics-based polarizable force field with the dressed dynamics method that couples fast collision events and slow reorganization dynamics of hydrogen-bond networks. Our analysis unveils the salient multiscale features in the transient relaxation dynamics of supercooled water. A classical Langevin behavior dominates at fast timescales, while long-time relaxations unveil two different activation barriers in two temperature regions: below and above 230 K. The modulation of the entropy spectrum by temperature is elucidated in terms of a three-state model underlined by the complexity of the water dynamics associated with a topological transition of a strong hydrogen-bond network. This state-dependent network topology is quantitatively characterized by power-law exponents of inverse network connectivity from 200 to 298 K. This work provides valuable guidance for further studies on the transient relaxation dynamics of supercooled water.

Incorporating Domain Knowledge and Structure-Based Descriptors for Machine Learning: A Case Study of Pd-Catalyzed Sonogashira Reactions.

Machine learning has revolutionized information processing for large datasets across various fields. However, its limited interpretability poses a significant challenge when applied to chemistry. In this study, we developed a set of simple molecular representations to capture the structural information of ligands in palladium-catalyzed Sonogashira coupling reactions of aryl bromides. Drawing inspiration from human understanding of catalytic cycles, we used a graph neural network to extract structural details of the phosphine ligand, a major contributor to the overall activation energy. We combined these simple molecular representations with an electronic descriptor of aryl bromide as inputs for a fully connected neural network unit. The results allowed us to predict rate constants and gain mechanistic insights into the rate-limiting oxidative addition process using a relatively small dataset. This study highlights the importance of incorporating domain knowledge in machine learning and presents an alternative approach to data analysis.

A Tale of Water Molecules in the Ribosomal Peptidyl Transferase Reaction.

The peptidyl transferase center (PTC) in the large subunit of the ribosome plays a critical role in protein synthesis by catalyzing the formation of peptide bonds with an astounding speed of about 15 to 20 peptide bonds per second. The ribosome coordinates the nucleophilic attack and deprotonation in the rate-limiting step at the PTC. However, the details of peptide bond formation within the ribosome, particularly the precise role of the two water molecules in the PTC, remain unclear. Here, we propose a novel stepwise "proton shuttle" mechanism which corroborates all the reported experimental measurements so far. In this mechanism, a water molecule close to A76 of peptidyl-tRNA 2'- and 3'-O stabilizes the transition state. The other one adjacent to the carbonyl oxygen of peptidyl-tRNA actively participates in the proton shuttle, playing the catalytic role of ribosome-catalyzed peptide bond formation.

Reversibility of acute-on-chronic liver failure syndrome in hepatitis B virus-infected patients with and without prior decompensation.

Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome associated with high short-term mortality and reversibility. This study aimed to compare the characteristics of survival and reversibility in hepatitis B virus (HBV)-related ACLF (HBV-ACLF) patients with and without previous decompensation. Overall, 1044 patients who fulfilled the acute hepatic insult criteria of the APASL-ACLF Research Consortium (AARC) definition were enrolled from a prospectively established cohort of HBV-related liver failure patients. These patients were divided into the AARC ACLF group and the non-AARC ACLF group according to prior decompensation. Mortality, reversibility of ACLF syndrome, and predicted factors associated with reversibility were evaluated. Liver transplantation-free mortality of the AARC ACLF group was significantly lower than that of the non-AARC ACLF group (28 days: 28.2% vs. 40.3%, p = .012; 90 days: 41.7% vs. 65.4%, p < .001). The 5-year cumulative reversal rates of ACLF syndrome were 88.0% (374/425) and 66.0% (31/47) in the AARC and non-AARC ACLF groups, respectively, (p = .039). Following reversibility of ACLF syndrome, 340/374 (90.9%) and 21/31 (67.7%) patients in the AARC and non-AARC ACLF groups, respectively, maintained a stable status within 5 years. Although prior decompensation indicated poor reversibility of ACLF syndrome, HBV-infected patients with prior decompensation who fulfilled the acute hepatic insult criteria of the AARC definition showed favourable reversibility and maintained a stable status after receiving nucleoside analogues. The AARC ACLF definition identified HBV-ACLF as a distinct syndrome with good reversibility. HBV-infected patients with prior decompensation could be included in the AARC ACLF management.

Human Leukocyte Antigen Profile Predicts Severity of Autoimmune Liver Disease in Children of European Ancestry.

BACKGROUND AND AIMS: Genetic predisposition to autoimmune hepatitis (AIH) in adults is associated with possession of human leukocyte antigen (HLA) class I (A*01, B*08) and class II (DRB1*03, -04, -07, or -13) alleles, depending on geographic region. Juvenile autoimmune liver disease (AILD) comprises AIH-1, AIH-2, and autoimmune sclerosing cholangitis (ASC), which are phenotypically different from their adult counterparts. We aimed to define the relationship between HLA profile and disease course, severity, and outcome in juvenile AILD. APPROACH AND RESULTS: We studied 236 children of European ancestry (152 female [64%], median age 11.15 years, range 0.8-17), including 100 with AIH-1, 59 with AIH-2, and 77 with ASC. The follow-up period was from 1977 to June 2019 (median 14.5 years). Class I and II HLA genotyping was performed using PCR/sequence-specific primers. HLA B*08, -DRB1*03, and the A1-B8-DR3 haplotype impart predisposition to all three forms of AILD. Homozygosity for DRB1*03 represented the strongest risk factor (8.8). HLA DRB1*04, which independently confers susceptibility to AIH in adults, was infrequent in AIH-1 and ASC, suggesting protection; and DRB1*15 (DR15) was protective against all forms of AILD. Distinct HLA class II alleles predispose to the different subgroups of juvenile AILD: DRB1*03 to AIH-1, DRB1*13 to ASC, and DRB1*07 to AIH-2. Possession of homozygous DRB1*03 or of DRB1*13 is associated with fibrosis at disease onset, and possession of these two genes in addition to DRB1*07 is associated with a more severe disease in all three subgroups. CONCLUSIONS: Unique HLA profiles are seen in each subgroup of juvenile AILD. HLA genotype might be useful in predicting responsiveness to immunosuppressive treatment and course.

Method to extract multiple states in F1-ATPase rotation experiments from jump distributions.

A method is proposed for analyzing fast (10 µs) single-molecule rotation trajectories in F1 adenosinetriphosphatase ([Formula: see text]-ATPase). This method is based on the distribution of jumps in the rotation angle that occur in the transitions during the steps between subsequent catalytic dwells. The method is complementary to the "stalling" technique devised by H. Noji et al. [Biophys. Rev. 9, 103-118, 2017], and can reveal multiple states not directly detectable as steps. A bimodal distribution of jumps is observed at certain angles, due to the system being in either of 2 states at the same rotation angle. In this method, a multistate theory is used that takes into account a viscoelastic fluctuation of the imaging probe. Using an established sequence of 3 specific states, a theoretical profile of angular jumps is predicted, without adjustable parameters, that agrees with experiment for most of the angular range. Agreement can be achieved at all angles by assuming a fourth state with an ∼10 µs lifetime and a dwell angle about 40° after the adenosine 5'-triphosphate (ATP) binding dwell. The latter result suggests that the ATP binding in one ß subunit and the adenosine 5'-diphosphate (ADP) release from another ß subunit occur via a transient whose lifetime is ∼10 µs and is about 6 orders of magnitude smaller than the lifetime for ADP release from a singly occupied [Formula: see text]-ATPase. An internal consistency test is given by comparing 2 independent ways of obtaining the relaxation time of the probe. They agree and are ∼15 µs.

Effect of varying the TD-lc-DFTB range-separation parameter on charge and energy transfer in a model pentacene/buckminsterfullerene heterojunction.

Atomistic modeling of energy and charge transfer at the heterojunction of organic solar cells is an active field with many remaining outstanding questions owing, in part, to the difficulties in performing reliable photodynamics calculations on very large systems. One approach to being able to overcome these difficulties is to design and apply an appropriate simplified method. Density-functional tight binding (DFTB) has become a popular form of approximate density-functional theory based on a minimal valence basis set and neglect of all but two center integrals. We report the results of our tests of a recent long-range correction (lc) [A. Humeniuk and R. Mitric, J. Chem. Phys. 143, 134120 (2015)] for time-dependent (TD) lc-DFTB by carrying out TD-lc-DFTB fewest switches surface hopping calculations of energy and charge transfer times using the relatively new DFTBABY [A. Humeniuk and R. Mitric, Comput. Phys. Commun. 221, 174 (2017)] program. An advantage of this method is the ability to run enough trajectories to get meaningful ensemble averages. Our interest in the present work is less in determining exact energy and charge transfer rates than in understanding how the results of these calculations vary with the value of the range-separation parameter (Rlc = 1/µ) for a model organic solar cell heterojunction consisting of a gas-phase van der Waals complex P/F made up of a single pentacene (P) molecule together with a single buckminsterfullerene (F) molecule. The default value of Rlc = 3.03 a0 is found to be much too small as neither energy nor charge transfer is observed until Rlc ≈ 10 a0. Tests at a single geometry show that the best agreement with high-quality ab initio spectra is obtained in the limit of no lc (i.e., very large Rlc). A plot of energy and charge transfer rates as a function of Rlc is provided, which suggests that a value of Rlc ≈ 15 a0 yields the typical literature (condensed-phase) charge transfer time of about 100 fs. However, energy and charge transfer times become as high as ∼300 fs for Rlc ≈ 25 a0. A closer examination of the charge transfer process P*/F → P+/F- shows that the initial electron transfer is accompanied by a partial delocalization of the P hole onto F, which then relocalizes back onto P, consistent with a polaron-like picture in which the nuclei relax to stabilize the resultant redistribution of charges.

Molecular Insights into Small-Molecule Drug Discovery for SARS-CoV-2.

The mainstream approach to antiviral drugs against COVID-19 is to focus on key stages of the SARS-CoV-2 life cycle. The vast majority of candidates under investigation are repurposed from agents of other indications. Understanding protein-inhibitor interactions at the molecular scale will provide crucial insights for drug discovery to stop this pandemic. In this article, we summarize and analyze the most recent structural data on several viral targets in the presence of promising inhibitors for COVID-19 in the context of the perspective of modes of action (MOA) to unravel insightful mechanistic features with atomistic resolution. The targets include spike glycoprotein and various host proteases mediating the entry of the virus into the cells, viral chymotrypsin- and papain-like proteases, and RNA-dependent RNA polymerase. The main purpose of this review is to present detailed MOA analysis to inspire fresh ideas for both de novo drug design and optimization of known scaffolds to combat COVID-19.

Infection deteriorating hepatitis B virus related acute-on-chronic liver failure: a retrospective cohort study.

BACKGROUND: Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China. METHODS: We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated. RESULTS: A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection. CONCLUSIONS: Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.

Generalization of Langevin Dynamics from Spatio-Temporal Dressed Dynamics Perspective.

Understanding multiscale dynamics characteristics has been the holy grail in a broad range of scientific disciplines from physics, chemistry, to biology, and beyond. The seminal Langevin equation successfully unravels remarkable details of Brownian motion dynamics involving stochastic collisions from the fluidic medium. However, extraordinary phenomena beyond the scope of Langevin dynamics were observed to exhibit a series of multiscale dynamic features in recent years. Here, an explicit spatio-temporal coupled kernel is developed to provide the microscopic account for delicate dynamic coupling between particle and medium in the dressed dynamics perspective. This methodology is applied to investigate an aqueous solvation shell model with an explicit spatial boundary to illustrate the significance of spatial and temporal coupling, leading to a general temporal profile of dressed dynamics over 12 orders of magnitude in time In particular, the time-resolved viscosity is formulated to address the remarkable enhancement of viscosity measured by the liquid cell electron microscopy. The understanding of dressed dynamics processes will be greatly enriched by further studies on the detailed dynamics that manifests the microscopic inhomogeneity of medium.

Unraveling Dynamic Transitions in Time-Resolved Biomolecular Motions by A Dressed Diffusion Model.

Recent experimental data reveal the complexity of diffusion dynamics beyond the scope of classical Brownian dynamics. The particles exhibit diverse diffusive motions from the anomalous toward classical diffusion over a wide range of temporal scales. Here a dressed diffusion model is developed to account for non-Brownian phenomena. By coupling the particle dynamics with a local field, the dressed diffusion model generalizes the Langevin equation through coupled damping kernels and generates the salient feature of time-dependent diffusion dynamics reported in the experimental measurements of biomolecules. The dressed diffusion model provides one quantitative aspect for future endeavors in this rapid-growing field.

Systematic characterisation of the structure and radical scavenging potency of Pu'Er tea () polyphenol theaflavin.

The structure, energetics and radical scavenging potency of theaflavin (TF), a natural polyphenolic antioxidant found in oxidised tea, have been characterised by a series of density functional theory (DFT) determinations. Exploratory conformational searches yielded 153 distinct neutral structures. Results showed TF's structural preferences to be regulated by its unique fused double ring benzotropolone moiety, and its degree of planarity, with structural diversity, principally arising from variations of its nine -OH groups. The distinct 3D conformational 'poses' are shown to be stabilised by a complex network of intra-system interactions, damping overall structural floppiness. This rigidification, together with stability, is shown to be coupled with radical scavenging potency in the TF system. Radical scavenging via hydrogen atom abstraction (HAB) in H2O solution was determined to be spontaneous with very low reaction barriers (ΔGrel ∼ 4 kJ mol-1).

Comparison of satellite reflectance algorithms for estimating turbidity and cyanobacterial concentrations in productive freshwaters using hyperspectral aircraft imagery and dense coincident surface observations.

We analyzed 37 satellite reflectance algorithms and 321 variants for five satellites for estimating turbidity in a freshwater inland lake in Ohio using coincident real hyperspectral aircraft imagery converted to relative reflectance and dense coincident surface observations. This study is part of an effort to develop simple proxies for turbidity and algal blooms and to evaluate their performance and portability between satellite imagers for regional operational turbidity and algal bloom monitoring. Turbidity algorithms were then applied to synthetic satellite images and compared to in situ measurements of turbidity, chlorophyll-a (Chl-a), total suspended solids (TSS) and phycocyanin as an indicator of cyanobacterial/blue green algal (BGA) abundance. Several turbidity algorithms worked well with real Compact Airborne Spectrographic Imager (CASI) and synthetic WorldView-2, Sentinel-2 and Sentinel-3/MERIS/OLCI imagery. A simple red band algorithm for MODIS imagery and a new fluorescence line height algorithm for Landsat-8 imagery had limited performance with regard to turbidity estimation. Blue-Green Algae/Phycocyanin (BGA/PC) and Chl-a algorithms were the most widely applicable algorithms for turbidity estimation because strong co-variance of turbidity, TSS, Chl-a, and BGA made them mutual proxies in this experiment.

Opto-impedance spectroscopy and equivalent circuit analyses of AC powder electroluminescent devices.

High energy photons can affect the dielectric response of AC powder electroluminescent devices (ACPELDs). In this paper, electroluminescent (EL), phosphor and dielectric films are photo-excited at peak wavelengths of 399 nm, 520 nm and 625 nm to identify the dielectric relaxation processes occurring in ACPELDs. The 399 nm illumination changes the frequency-dependent dielectric responses of both EL and phosphor films due to the photo-induced excitation of ZnS:Cu,Al phosphor particles. A higher illumination intensity increases the dipolar polarization in the resin matrix and enhances the Maxwell-Wagner-Sillars (MWS) effect at the particle/resin interfaces. Equivalent circuits relating to the relaxation processes present in the EL and phosphor films are derived. From the analyses of the circuit component values, a charge generation and accumulation process is proposed to explain these opto-impedance behaviors.

Squid Suckerin Biomimetic Peptides Form Amyloid-like Crystals with Robust Mechanical Properties.

We present the self-assembly of fibers formed from a peptide sequence (A1H1) derived from suckerin proteins of squid sucker ring teeth (SRT). SRT are protein-only biopolymers with an unconventional set of physicochemical and mechanical properties including high elastic modulus coupled with thermoplastic behavior. We have identified a conserved peptide building block from suckerins that possess the ability to assemble into materials with similar mechanical properties as the native SRT. A1H1 displays amphiphilic characteristics and self-assembles from the bottom-up into mm-scale fibers initiated by the addition of a polar aprotic solvent. A1H1 fibers are thermally resistant up to 239 °C, coupled with an elastic modulus of ∼7.7 GPa, which can be explained by the tight packing of ß-sheet-enriched crystalline building blocks as identified by wide-angle X-ray scattering (WAXS), with intersheet and interstrand distances of 5.37 and 4.38 Å, respectively. A compact packing of the peptides at their Ala-rich terminals within the fibers was confirmed from molecular dynamics simulations, and we propose a hierarchical model of fiber assembly of the mature peptide fiber.

Nanodroplet-Mediated Assembly of Platinum Nanoparticle Rings in Solution.

Soft fluidlike nanoscale objects can drive nanoparticle assembly by serving as a scaffold for nanoparticle organization. The intermediate steps in these template-directed nanoscale assemblies are important but remain unresolved. We used real-time in situ transmission electron microscopy to follow the assembly dynamics of platinum nanoparticles into flexible ringlike chains around ethylenediaminetetraacetic acid nanodroplets dispersed in solution. In solution, these nanoring assemblies form via sequential attachment of the nanoparticles to binding sites located along the circumference of the nanodroplets, followed by the rearrangement and reorientation of the attached nanoparticles. Additionally, larger nanoparticle ring assemblies form via the coalescence of smaller ring assemblies. The intermediate steps of assembly reported here reveal how fluidlike nanotemplates drive nanoparticle organization, which can aid the future design of new nanomaterials.

Ultrafast Killing and Self-Gelling Antimicrobial Imidazolium Oligomers.

Infectious diseases and the increasing threat of worldwide pandemics have underscored the importance of antibiotics and hygiene. Intensive efforts have been devoted to developing new antibiotics to meet the rapidly growing demand. In particular, advancing the knowledge of the structure-property-activity relationship is critical to expedite the design and development of novel antimicrobial with the needed potential and efficacy. Herein, a series of new antimicrobial imidazolium oligomers are developed with the rational manipulation of terminal group's hydrophobicity. These materials exhibit superior activity, excellent selectivity, ultrafast killing (>99.7% killing within 30 s), and desirable self-gelling properties. Molecular dynamic simulations reveal the delicate effect of structural changes on the translocation motion across the microbial cell membrane. The energy barrier of the translocation process analyzed by free energy calculations provides clear kinetic information to suggest that the spontaneous penetration requires a very short timescale of seconds to minutes for the new imidazolium oligomers.