Asymmetry in Polymer-Solvent Interactions Yields Complex Thermoresponsive Behavior.

We introduce a lattice framework that incorporates elements of Flory-Huggins solution theory and the q-state Potts model to study the phase behavior of polymer solutions and single-chain conformational characteristics. Without empirically introducing temperature-dependent interaction parameters, standard Flory-Huggins theory describes systems that are either homogeneous across temperatures or exhibit upper critical solution temperatures. The proposed Flory-Huggins-Potts framework extends these capabilities by predicting lower critical solution temperatures, miscibility loops, and hourglass-shaped spinodal curves. We particularly show that including orientation-dependent interactions, specifically between monomer segments and solvent particles, is alone sufficient to observe such phase behavior. Signatures of emergent phase behavior are found in single-chain Monte Carlo simulations, which display heating- and cooling-induced coil-globule transitions linked to energy fluctuations. The framework also capably describes a range of experimental systems. Importantly, and by contrast to many prior theoretical approaches, the framework does not employ any temperature- or composition-dependent parameters. This work provides new insights regarding the microscopic physics that underpin complex thermoresponsive behavior in polymers.

EXPRESS: Landmark Publications in Analytical Atomic Spectrometry: Fundamentals and Instrumentation Development.

The almost-two-centuries history of spectrochemical analysis has generated a body of literature so vast that it has become nearly intractable for experts, much less for those wishing to enter the field. Authoritative, focused reviews help to address this problem but become so granular that the overall directions of the field are lost. This broader perspective can be provided partially by general overviews but then the thinking, experimental details, theoretical underpinnings and instrumental innovations of the original work must be sacrificed. In the present compilation, this dilemma is overcome by assembling the most impactful publications in the area of analytical atomic spectrometry. Each entry was proposed by at least one current expert in the field and supported by a narrative that justifies its inclusion. The entries were then assembled into a coherent sequence and returned to contributors for a round-robin review.

Revision of the leafhopper genus Smyga (Hemiptera, Cicadellidae, Typhlocybinae).

The leafhopper genus Smyga Dworakowska (Typhlocybinae, Empoascini) is reviewed and a new species, S.brevipenis Webb & Xu, sp. nov. from Brunei and Malaysia, is described based on specimens previously identified as "aberrant specimens" of Smygadistincta Dworakowska. Images of the types of S.brevipenis and S.distincta are given for the first time. A checklist and key to known species of Smyga are also provided.

Sortase-Modified Cholera Toxoids Show Specific Golgi Localization.

Cholera toxoid is an established tool for use in cellular tracing in neuroscience and cell biology. We use a sortase labeling approach to generate site-specific N-terminally modified variants of both the A2-B5 heterohexamer and B5 pentamer forms of the toxoid. Both forms of the toxoid are endocytosed by GM1-positive mammalian cells, and while the heterohexameric toxoid was principally localized in the ER, the B5 pentamer showed an unexpectedly specific localization in the medial/trans-Golgi. This study suggests a future role for specifically labeled cholera toxoids in live-cell imaging beyond their current applications in neuronal tracing and labeling of lipid rafts in fixed cells.

Three new species of the leafhopper genus Arboridia Zachvatkin (Hemiptera, Cicadellidae, Typhlocybinae), with a key and checklist to known species of China.

Three new species of the leafhopper genus ArboridiaZachvatkin 1946, Arboridia (Arboridia) furcata Han, sp. nov., Arboridia (Arboridia) rubrovittata Han, sp. nov., and Arboridia (Arboridia) robustipenis Han, sp. nov., are described and illustrated from fruit trees in Southwest China. A key and checklist to known species from China are provided.

Management of suicidal risk in the emergency department: A clinical pathway using the computerized adaptive screen for suicidal youth.

Objective: Given the critical need for efficient and tailored suicide screening for youth presenting in the emergency department (ED), this study establishes validated screening score thresholds for the Computerized Adaptive Screen for Suicidal Youth (CASSY) and presents an example of a suicide risk classification pathway. Methods: Participants were primarily from the Study One derivation cohort of the Emergency Department Screen for Teens at Risk for Suicide (ED-STARS) enrolled in collaboration with Pediatric Emergency Care Applied Research Networks (PECARN). CASSY scores corresponded to the predicted probabilities of a suicide attempt in the next 3 months and risk thresholds were classified as minimal (<1%), low (1%-5%), moderate (5%-10%), and high (>10%). CASSY scores were compared to risk thresholds derived from clinical consensus and ED complaints and dispositions. CASSY risk thresholds were also examined as predictors of future suicide attempts in the Study Two validation cohort of ED-STARS. Results: A total of 1452 teens were enrolled with a median age of 15.2 years, 59.5% were female, 55.6% were White, 22% were Black, 22.3% were Latinx, and 42.8% received public assistance. The clinical consensus suicide risk groups were strongly associated with the CASSY-predicted risk thresholds. Suicide attempts in the Study Two cohort occurred at a frequency consistent with the CASSY-predicted thresholds. Conclusions: The CASSY can be a valuable tool in providing patient-specific risk probabilities for a suicide attempt at 3 months and tailor the threshold cutoffs based on the availability of local mental health resources. We give an example of a clinical risk pathway, which should include segmentation of the ED population by medical versus psychiatric chief complaint.

Thermodynamic driving forces in contact electrification between polymeric materials.

Contact electrification, or contact charging, refers to the process of static charge accumulation after rubbing, or even simple touching, of two materials. Despite its relevance in static electricity, various natural phenomena, and numerous technologies, contact charging remains poorly understood. For insulating materials, even the species of charge carrier may be unknown, and the direction of charge-transfer lacks firm molecular-level explanation. Here, we use all-atom molecular dynamics simulations to investigate whether thermodynamics can explain contact charging between insulating polymers. Based on prior work suggesting that water-ions, such as hydronium and hydroxide ions, are potential charge carriers, we predict preferred directions of charge-transfer between polymer surfaces according to the free energy of water-ions within water droplets on such surfaces. Broad agreement between our predictions and experimental triboelectric series indicate that thermodynamically driven ion-transfer likely influences contact charging of polymers. Furthermore, simulation analyses reveal how specific interactions of water and water-ions proximate to the polymer-water interface explain observed trends. This study establishes relevance of thermodynamic driving forces in contact charging of insulators with new evidence informed by molecular-level interactions. These insights have direct implications for future mechanistic studies and applications of contact charging involving polymeric materials.

The Mutagenic Plasticity of the Cholera Toxin B-Subunit Surface Residues: Stability and Affinity.

Mastering selective molecule trafficking across human cell membranes poses a formidable challenge in healthcare biotechnology while offering the prospect of breakthroughs in drug delivery, gene therapy, and diagnostic imaging. The cholera toxin B-subunit (CTB) has the potential to be a useful cargo transporter for these applications. CTB is a robust protein that is amenable to reengineering for diverse applications; however, protein redesign has mostly focused on modifications of the N- and C-termini of the protein. Exploiting the full power of rational redesign requires a detailed understanding of the contributions of the surface residues to protein stability and binding activity. Here, we employed Rosetta-based computational saturation scans on 58 surface residues of CTB, including the GM1 binding site, to analyze both ligand-bound and ligand-free structures to decipher mutational effects on protein stability and GM1 affinity. Complimentary experimental results from differential scanning fluorimetry and isothermal titration calorimetry provided melting temperatures and GM1 binding affinities for 40 alanine mutants among these positions. The results showed that CTB can accommodate diverse mutations while maintaining its stability and ligand binding affinity. These mutations could potentially allow modification of the oligosaccharide binding specificity to change its cellular targeting, alter the B-subunit intracellular routing, or impact its shelf-life and in vivo half-life through changes to protein stability. We anticipate that the mutational space maps presented here will serve as a cornerstone for future CTB redesigns, paving the way for the development of innovative biotechnological tools.

Active learning of the thermodynamics-dynamics trade-off in protein condensates.

Phase-separated biomolecular condensates exhibit a wide range of dynamic properties, which depend on the sequences of the constituent proteins and RNAs. However, it is unclear to what extent condensate dynamics can be tuned without also changing the thermodynamic properties that govern phase separation. Using coarse-grained simulations of intrinsically disordered proteins, we show that the dynamics and thermodynamics of homopolymer condensates are strongly correlated, with increased condensate stability being coincident with low mobilities and high viscosities. We then apply an "active learning" strategy to identify heteropolymer sequences that break this correlation. This data-driven approach and accompanying analysis reveal how heterogeneous amino acid compositions and nonuniform sequence patterning map to a range of independently tunable dynamic and thermodynamic properties of biomolecular condensates. Our results highlight key molecular determinants governing the physical properties of biomolecular condensates and establish design rules for the development of stimuli-responsive biomaterials.

Data-Driven Design of Polymer-Based Biomaterials: High-throughput Simulation, Experimentation, and Machine Learning.

Polymers, with the capacity to tunably alter properties and response based on manipulation of their chemical characteristics, are attractive components in biomaterials. Nevertheless, their potential as functional materials is also inhibited by their complexity, which complicates rational or brute-force design and realization. In recent years, machine learning has emerged as a useful tool for facilitating materials design via efficient modeling of structure-property relationships in the chemical domain of interest. In this Spotlight, we discuss the emergence of data-driven design of polymers that can be deployed in biomaterials with particular emphasis on complex copolymer systems. We outline recent developments, as well as our own contributions and takeaways, related to high-throughput data generation for polymer systems, methods for surrogate modeling by machine learning, and paradigms for property optimization and design. Throughout this discussion, we highlight key aspects of successful strategies and other considerations that will be relevant to the future design of polymer-based biomaterials with target properties.

Quantitative N- or C-Terminal Labelling of Proteins with Unactivated Peptides by Use of Sortases and a d-Aminopeptidase.

Quantitative and selective labelling of proteins is widely used in both academic and industrial laboratories, and catalytic labelling of proteins using transpeptidases, such as sortases, has proved to be a popular strategy for such selective modification. A major challenge for this class of enzymes is that the majority of procedures require an excess of the labelling reagent or, alternatively, activated substrates rather than simple commercially sourced peptides. We report the use of a coupled enzyme strategy which enables quantitative N- and C-terminal labelling of proteins using unactivated labelling peptides. The use of an aminopeptidase in conjunction with a transpeptidase allows sequence-specific degradation of the peptide by-product, shifting the equilibrium to favor product formation, which greatly enhances the reaction efficiency. Subsequent optimisation of the reaction allows N-terminal labelling of proteins using essentially equimolar ratios of peptide label to protein and C-terminal labelling with only a small excess. Minimizing the amount of substrate required for quantitative labelling has the potential to improve industrial processes and facilitate the use of transpeptidation as a method for protein labelling.

The most common types of nontraumatic dental conditions among emergency department visits in North Carolina before and during the COVID-19 pandemic.

BACKGROUND: This study aimed to identify the most common types of nontraumatic dental conditions (NTDCs) before and during the COVID-19 pandemic and assess the variations in the most common NTDCs by patient age groups and rural or urban locations and the impact of COVID-19 on emergency department (ED) visits for NTDCs in North Carolina. METHODS: The authors conducted a retrospective data analysis of ED data from the North Carolina Disease Event Tracking and Epidemiology Collection Tool. The authors estimated the proportions of NTDCs of all ED visits in 2019 and 2021 and ranked the proportions of the major categories of NTDCs by age groups and rural or urban locations. They used a multiple logistic regression model to assess the impact of COVID-19 on NTDCs. RESULTS: By the first diagnosis, the proportion of NTDCs dropped from 1.1% in 2019 to 0.99% in 2021 (P < .001). Caries was specified as the third most common NTDC. Oral infection was the top NTDC among young (≤ 17 years) and older patients (≥ 65 years). No significant differences were found in NTDCs between rural and urban areas (P = .68). Children younger than 2 years (adjusted odds ratio, 4.36) and adults aged 18 through 44 years (adjusted odds ratio, 4.54) were more likely to visit the ED for NTDCs than those 75 years and older. CONCLUSIONS: The proportion of NTDCs seen at the ED was lower during the COVID-19 pandemic in 2021 than in 2019. The common NTDCs varied by age group but were similar in rural and urban areas. The most common NTDCs were related to toothache, oral infection, and caries. PRACTICAL IMPLICATIONS: More efforts are needed to reduce ED visits for NTDCs.

24-Hour warning signs for adolescent suicide attempts.

BACKGROUND: Little is known about when youth may be at greatest risk for attempting suicide, which is critically important information for the parents, caregivers, and professionals who care for youth at risk. This study used adolescent and parent reports, and a case-crossover, within-subject design to identify 24-hour warning signs (WS) for suicide attempts. METHODS: Adolescents (N = 1094, ages 13 to 18) with one or more suicide risk factors were enrolled and invited to complete bi-weekly, 8-10 item text message surveys for 18 months. Adolescents who reported a suicide attempt (survey item) were invited to participate in an interview regarding their thoughts, feelings/emotions, and behaviors/events during the 24-hours prior to their attempt (case period) and a prior 24-hour period (control period). Their parents participated in an interview regarding the adolescents' behaviors/events during these same periods. Adolescent or adolescent and parent interviews were completed for 105 adolescents (81.9% female; 66.7% White, 19.0% Black, 14.3% other). RESULTS: Both parent and adolescent reports of suicidal communications and withdrawal from social and other activities differentiated case and control periods. Adolescent reports also identified feelings (self-hate, emotional pain, rush of feelings, lower levels of rage toward others), cognitions (suicidal rumination, perceived burdensomeness, anger/hostility), and serious conflict with parents as WS in multi-variable models. CONCLUSIONS: This study identified 24-hour WS in the domains of cognitions, feelings, and behaviors/events, providing an evidence base for the dissemination of information about signs of proximal risk for adolescent suicide attempts.

Finding the best location: Improving the anti-amyloid ability of ruthenium(III) complexes with pyridine ligands.

Alzheimer's disease (AD) is a devastating neurological disorder where one of the primary pathological hallmarks are aggregate deposits of the peptide amyloid-beta (Aß). Although the Food and Drug Administration (FDA) has recently approved therapeutics that specifically target Aß, resulting in the removal of these deposits, the associated costs of such treatments create a need for effective, yet cheaper, alternatives. Metal-based compounds are propitious therapeutic candidates as they exploit the metal-binding properties of Aß, forming stable interactions with the peptide, thereby limiting its aggregation and toxicity. Previously, ruthenium-based complexes have shown a strong ability to modulate the aggregation and cytotoxicity of Aß, where the incorporation of a primary amine on the coordinated heterocyclic ligand gave the greatest activity. To determine the importance of the location of the primary amine on the pyridine ligand, thereby establishing structure-activity relationships (SAR), four complexes (RuP1-4) were prepared and evaluated for their ability to coordinate and subsequently modulate the aggregation and cytotoxicity of Aß. Coordination to Aß was determined using three complementary spectroscopic methods: UV-Vis, 1H NMR, and circular dichroism (CD). Similarly, the impact of the complexes on Aß aggregation was evaluated using three sequential methods of turbidity, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Overall, the location of the primary amine on the pyridine ligand did affect the resultant anti-Aß performance, with the 2-aminopyridine complex (RuP2) being the most active. This SAR will provide another guiding principle in the design of future metal-based anti-Aß complexes.

The Cost of Universal Suicide Risk Screening for Adolescents in Emergency Departments.

Suicide is the second leading cause of death among adolescents. As nearly 20% of adolescents visit emergency departments (EDs) each year, EDs have an opportunity to identify previously unrecognized suicide risk. A novel Computerized Adaptive Screen for Suicidal Youth (CASSY) was shown in a multisite study to be predictive for suicide attempts within 3 months. This study uses site-specific data to estimate the cost of CASSY implementation with adolescents in general EDs. When used universally with all adolescents who are present and able to participate in the screening, the average cost was USD 5.77 per adolescent. For adolescents presenting with non-behavioral complaints, the average cost was USD 2.60 per adolescent. Costs were driven primarily by time and personnel required for the further evaluation of suicide risk for those screening positive. Thus, universal screening using the CASSY, at very low costs relative to the cost of an ED visit, can facilitate services needed for at-risk adolescents.

A Revision of the Genus Argolis (Hemiptera: Reduviidae: Stenopodainae) from Asia.

The assassin bug genus Argolis Stål, 1861 (Hemiptera: Reduviidae: Stenopodainae) has a disjunct distribution in Sub-Saharan Africa and Asia. In the present study, the Asian species of Argolis are revised. Two species are recognized, redescribed, and illustrated, with the following new subjective synonyms and new combination proposed: Argolis Stål, 1861 = Bardesanes Distant, 1909, syn. nov. = Neoklugia Distant, 1919, syn. nov.; A. farinator (Reuter, 1882) = N. typica Distant, 1919, syn. nov. = B. sericenotatus Livingstone & Ravichandran, 1989, syn. nov.; A. signata (Distant, 1909), comb. nov. (transferred from Bardesanes) = Caunus noctulus Hsiao, 1977, syn. nov. Lectotypes for C. farinator, B. signatus, and N. typica are designated. A key to separate the two Asian species of Argolis is provided. The sexual dimorphism, systematic relationships, and distribution of Argolis are discussed. Argolis is newly recorded from Laos, Pakistan, and Vietnam.