Creation of a Novel Classification System (PTNM) for Peyronie's Disease and Penile Curvature Using Evidence-Based Criteria.

PURPOSE: Our goal was to identify new Peyronie's disease (PD) subtypes, non-PD penile curvature classifications, and define active (acute) vs stable (chronic) phases of disease using evidence-based analyses. MATERIALS AND METHODS: A retrospective review was performed of 1098 men who presented with penile deformity, including subjective standardized and nonstandardized questionnaires and objective measures. A second cohort of 719 men who were sent a mailed survey was also utilized for the relapsing/remitting subtype. Statistical analyses were performed to identify clusters of disease characteristics representative of distinct PD and non-PD categorizations, including sensitivity/specificity analyses and subtype comparisons. RESULTS: Comparative analyses identified 4 distinct subtypes of PD: (1) classical and nonclassical, (2) calcifying-moderate/severe calcification, (3) progressive-subjective worsening following disease onset, and (4) relapsing/remitting-reactivation following ≥ 6 months of stability. Additional, non-PD categorizations included congenital (lifelong), maturational (developed around puberty), and trauma induced. Statistical analyses demonstrated unique profiles among each category. Penile pain was not found to be a reliable predictor for disease progression or stability. Stable phase disease (historically "chronic") was variably defined by subtype: classical (≥3 months); progressive, calcifying, or trauma induced (≥12 months + ≥3 months stable OR ≥6 months stable). Similarly, PD subtypes may be assigned at ≥ 3 months following disease onset. A PTNM staging system is proposed to help communicate disease states, in which P = PD component (Ca-calcifying, Cl-classical, P-progressive, R-relapsing/remitting, U-undifferentiated), T = trauma component (0-absent, 1-present), N = non-PD component (C-congenital, M-maturational, U-undifferentiated), and M = mode (0-stable, 1-active); for example, PClT1N0M0 = stable classical PD with prior trauma. CONCLUSIONS: The current study provides an evidence-based proposal for the establishment of new PD subtypes and non-PD curvature categorizations as well as a standardized definition for active vs stable phases of disease.

Further evaluation of the shape of atomic Hirshfeld surfaces: M...H contacts and homoatomic bonds.

It is well known that Hirshfeld surfaces provide an easy and straightforward way of analysing intermolecular interactions in the crystal environment. The use of atomic Hirshfeld surfaces has also demonstrated that such surfaces carry information related to chemical bonds which allow a deeper evaluation of the structures. Here we briefly summarize the approach of atomic Hirshfeld surfaces while further evaluating the kind of information that can be retrieved from them. We show that the analysis of the metal-centre Hirshfeld surfaces from structures refined via Hirshfeld Atom Refinement (HAR) allow accurate evaluation of contacts of type M...H, and that such contacts can be related to the overall shape of the surfaces. The compounds analysed were tetraaquabis(3-carboxypropionato)metal(II), [M(C4H3O4)2(H2O)4], for metal(II)/M = manganese/Mn, cobalt/Co, nickel/Ni and zinc/Zn. We also evaluate the sensitivity of the surfaces by an investigation of seemingly flat surfaces through analysis of the curvature functions in the direction of C-C bonds. The obtained values not only demonstrate variations in curvature but also show a correlation with the hybridization of the C atoms involved in the bond.

Valley-Dependent Electronic Properties of Metal Monochalcogenides GaX and Janus Ga2XY (X, Y = S, Se, and Te).

Two-dimensional (2D) materials have shown outstanding potential for new devices based on their interesting electrical properties beyond conventional 3D materials. In recent years, new concepts such as the valley degree of freedom have been studied to develop valleytronics in hexagonal lattice 2D materials. We investigated the valley degree of freedom of GaX and Janus GaXY (X, Y = S, Se, Te). By considering the spin-orbit coupling (SOC) effect in the band structure calculations, we identified the Rashba-type spin splitting in band structures of Janus Ga2SSe and Ga2STe. Further, we confirmed that the Zeeman-type spin splitting at the K and K' valleys of GaX and Janus Ga2XY show opposite spin contributions. We also calculated the Berry curvatures of GaX and Janus GaXY. In this study, we find that GaX and Janus Ga2XY have a similar magnitude of Berry curvatures, while having opposite signs at the K and K' points. In particular, GaTe and Ga2SeTe have relatively larger Berry curvatures of about 3.98 Å2 and 3.41 Å2, respectively, than other GaX and Janus Ga2XY.

Time and Space Modulation of Substrate Curvature to Regulate Cell Mechanical Identity.

Recently, a variety of microenvironmental biophysical stimuli have been proved to play a crucial role in regulating cell functions. Among them, morpho-physical cues, like curvature, are emerging as key regulators of cellular behavior. Changes in substrate curvature have been shown to impact the arrangement of Focal Adhesions (FAs), influencing the direction and intensity of cytoskeleton generated forces and resulting in an overall alteration of cell mechanical identity. In their native environment, cells encounter varying degrees of substrate curvature, and in specific organs, they are exposed to dynamic changes of curvature due to periodic tissue deformation. However, the mechanism by which cells perceive substrate curvature remains poorly understood. To this aim, a micro-pneumatic device was designed and implemented. This device enables the controlled application of substrate curvature, both statically and dynamically. Employing a combined experimental and simulative approach, human adipose-derived stem cells were exposed to controlled curvature intensity and frequency. During this exposure, measurements were taken on FAs extension and orientation, cytoskeleton organization and cellular/nuclear alignment. The data clearly indicated a significant influence of the substrate curvature on cell adhesion processes. These findings contribute to a better understanding of the mechanisms through which cells perceive and respond to substrate curvature signals. STATEMENT OF SIGNIFICANCE: This work is our contribution to the comprehension of substrate curvature's function as a crucial regulator of cell adhesion at the scale of focal adhesions and cell mechanical identity. In recent years, a large body of knowledge is continuously growing providing comprehension of the role of various microenvironmental biophysical stimuli in regulating cell functions. Nevertheless, little is known about the role of substrate curvature, in particular, when cells are exposed to this stimulus in a dynamic manner. To address the role of substrate curvature on cellular behavior, a micro-pneumatic device was designed and implemented. This device enables the controlled application of substrate curvature, both statically and dynamically. The experiment data made it abundantly evident that the substrate curvature had a major impact on the mechanisms involved in cell adhesion.

Evaluation of Mis-Selection of End Vertebrae and Its Effect on Measuring Cobb Angle and Curve Length in Adolescent Idiopathic Scoliosis.

Background: The Cobb angle is critical in assessing adolescent idiopathic scoliosis (AIS) patients. This study aimed to evaluate the error in selecting the upper- and lower-end vertebrae on AIS digital X-rays by experienced and novice observers and its correlation with the error in measuring the Cobb angle and determining the length of the scoliotic curves. Methods: Using the TraumaMeter v.873 software, eight raters independently evaluated 68 scoliotic curves. Results: The error percentage in the upper-end vertebra selection was higher than for the lower-end vertebra (44.7%, CI95% 41.05-48.3 compared to 35%, CI95% 29.7-40.4). The mean bias error (MBE) was 0.45 (CI95% 0.38-0.52) for the upper-end vertebra and 0.35 (CI% 0.69-0.91) for the lower-end vertebra. The percentage of errors in the choice of the end vertebrae was lower for the experienced than for the novices. There was a positive correlation (r = 0.673, p = 0.000) between the error in selecting the end vertebrae and determining the length of the scoliotic curves. Conclusions: We can conclude that errors in selecting end vertebrae are common among experienced and novice observers, with a greater error frequency for the upper-end vertebrae. Contrary to the consensus, the accuracy of determining the length of the scoliotic curve is limited by the Cobb method's reliance on the correct selection of the end vertebrae.

Curvature-Assisted Vesicle Explosion Under Light-Induced Asymmetric Oxidation.

Exposure of cell membranes to reactive oxygen species can cause oxidation of membrane lipids. Oxidized lipids undergo drastic conformational changes, compromising the mechanical integrity of the membrane and causing cell death. For giant unilamellar vesicles, a classic cell mimetic system, a range of mechanical responses under oxidative assault has been observed including formation of nanopores, transient micron-sized pores, and total sudden catastrophic collapse (i.e., explosion). However, the physical mechanism regarding how lipid oxidation causes vesicles to explode remains elusive. Here, with light-induced asymmetric oxidation experiments, the role of spontaneous curvature on vesicle instability and its link to the conformational changes of oxidized lipid products is systematically investigated. A comprehensive membrane model is proposed for pore-opening dynamics incorporating spontaneous curvature and membrane curling, which captures the experimental observations well. The kinetics of lipid oxidation are further characterized and how light-induced asymmetric oxidation generates spontaneous curvature in a non-monotonic temporal manner is rationalized. Using the framework, a phase diagram with an analytical criterion to predict transient pore formation or catastrophic vesicle collapse is provided. The work can shed light on understanding biomembrane stability under oxidative assault and strategizing release dynamics of vesicle-based drug delivery systems.

Unaided Visual Inspection for Assessment of Penile Curvature in the Clinical Setting of Hypospadias Surgery: Survey of Members of Society of Pediatric Urology (India).

Purpose: To compare the accuracy of unaided visual inspection (UVI) to Software App measurement (SAM) of penile curvature (PC) during hypospadias surgery. Methods: Seven clinical pictures of PC (15°-60°) taken during hypospadias repair were shared with 300 members of the Society of Pediatric Urology (India). The respondents were asked to assess the angles by UVI and indicate their preferred correction method of that PC. For each picture, the angles of curvature estimated by UVI were compared with the objective angle measured using an app (SAM), which was considered an accurate estimation. Statistical analysis was done using software; P<0.05 was considered as statistically significant. Results: Ninety-one of 101 (90%) respondents preferred UVI to measure PC during hypospadias surgery. For 6/7 pictures, <40% of participants estimated the angle correctly by UVI (P < 0.001), with the difference in estimation being 3.6°-14.9°. For pictures with PC >30°, the error in UVI estimation was >10°, with no correlation between the accuracy of UVI estimate and surgeon experience. A significant proportion of surgeons chose the incorrect option for PC correction, which was the lowest (69%) for PC 35.8°. Conclusions: Most surgeons preferred UVI to assess PC; UVI is an erroneous technique to measure PC angle, especially in the PC range 30°-60°, where the error was >10°. Most errors were an underestimation of the PC, irrespective of surgeon experience. There was a significant error in the choice of technique for PC correction for a PC of 35°. These results strongly support the objective assessment of PC using SAM during hypospadias repair.

Nonadditivity in Many-Body Interactions between Membrane-Deforming Spheres Increases Disorder.

Membrane-induced interactions play an important role in organizing membrane proteins. Measurements of the interactions between two and three membrane deforming objects have revealed their nonadditive nature. They are thought to lead to complex many-body effects, however, experimental evidence is lacking. We here present an experimental method to measure many-body effects in membrane-mediated interactions using colloidal spheres placed between a deflated giant unilamellar vesicles and a planar substrate. The confined colloidal particles cause a large deformation of the membrane while not being physicochemically attached to it and interact through it. Two particles attract with a maximum force of 0.2 pN. For three particles, compact equilateral triangles were preferred over linear arrangements. We use numerical energy minimization to establish that the attraction stems from a reduction in the membrane-deformation energy caused by the particles. Confining up to 36 particles, we find a preference for hexagonally close packed clusters. However, with increasing number of particles the order of the confined particles decreases, at the same time, diffusivity of the particles increases. Our experiments show that the nonadditive nature of membrane-mediated interactions affects the interactions and arrangements and ultimately leads to spherical aggregates with liquid-like order of potential importance for cellular processes.

Curved Structure Regulated Single Metal Sites for Advanced Electrocatalytic Reactions.

Curved surface with defined local electronic structures and regulated surface microenvironments is significant for advanced catalytic engineering. Since single-atom catalysts are highly efficient and active, they have attracted much attention in recent years. The curvature carrier has a significant effect on the electronic structure regulation of single-atom sites, which effectively promote the catalytic efficiency. Here, the effect of the curvature structure with exposed metal atoms for catalysis is comprehensively summarized. First, the substrates with curvature features are reviewed. Second, the applications of single-atom catalysts containing curvature in a variety of different electrocatalytic reactions are discussed in depth. The impact of curvature effects in catalytic reactions is further analyzed. Finally, prospects and suggestions for their application and future development are presented. This review paves the way for the construction of high curvature-containing surface carriers, which is of great significance for single-atom catalysts development.

Exploration of Curvature and Stiffness Dual-Regulated Breast Cancer Cell Motility by a Motor-Clutch Model and Cell Traction Force Characterization.

The migration of breast cancer cells is the main cause of death and significantly regulated by physical factors of the extracellular matrix (ECM). To be specific, the curvature and stiffness of the ECM were discovered to effectively guide cell migration in velocity and direction. However, it is not clear what the extent of effect is when these dual-physical factors regulate cell migration. Moreover, the mechanobiology mechanism of breast cancer cell migration in the molecular level and analysis of cell traction force (CTF) are also important, but there is a lack of systematic investigation. Therefore, we employed a microfluidic platform to construct hydrogel microspheres with an independently adjustable curvature and stiffness as a three-dimensional substrate for breast cancer cell migration. We found that the cell migration velocity was negatively correlated to curvature and positively correlated to stiffness. In addition, curvature was investigated to influence the focal adhesion expression as well as the assignment of F-actin at the molecular level. Further, with the help of a motor-clutch mathematical model and hydrogel microsphere stress sensors, it was concluded that cells perceived physical factors (curvature and stiffness) to cause changes in CTF, which ultimately regulated cell motility. In summary, we employed a theoretical model (motor-clutch) and experimental strategy (stress sensors) to understand the mechanism of curvature and stiffness regulating breast cancer cell motility. These results provide evidence of force driven cancer cell migration by ECM physical factors and explain the mechanism from the perspective of mechanobiology.

A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs.

Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.

Visual and refractive outcomes of opposite clear corneal incision combined with rotationally asymmetric multifocal intraocular lens implantation.

Purpose: To evaluate the visual and refractive outcomes of astigmatic cataract patients following opposite clear corneal incision (OCCI) combined with rotationally asymmetric multifocal intraocular lens (IOL) implantation. Setting: Department of Ophthalmology, Zhongshan Hospital (Xiamen), Fudan University, People's Republic of China. Design: Retrospective cohort study. Methods: This study comprised 58 cataract eyes of 54 patients with corneal astigmatism who underwent phacoemulsification and rotationally asymmetric multifocal IOL implantation which received either OCCI (OCCI group) or a single clear corneal incision (SCCI group). The follow-up period was 3 months after surgery. Distance, intermediate and near visual acuity, refractive outcomes, and corneal anterior keratometry were compared between the two groups. Vector analysis was used to evaluate astigmatism correction. Results: Three months after surgery, the distance, intermediate and near visual acuity, and sphere remained comparable between the two groups, but a significant difference was detected in residual astigmatism and anterior corneal keratometric astigmatism. In the OCCI group, the residual astigmatism and keratometric astigmatism were -0.60 ± 0.29 D and 0.59 ± 0.28 D, respectively, which were lower than those in SCCI groups (-1.18 ± 0.47 D and 1.15 ± 0.45 D, both p < 0.05). In vector analysis, the difference vector (DV), angle of error (AoE), absolute AoE, index of success (IoS) and correction index (CI) were statistically significantly different between the two groups (p < 0.05). Conclusion: OCCI combined with rotationally asymmetric multifocal intraocular lens implantation showed predictable and desirable efficacy in treating cataract patients with astigmatism.

Free energy calculations for membrane morphological transformations and insights to physical biology and oncology.

In this chapter, we aim to bridge basic molecular and cellular principles surrounding membrane curvature generation with rewiring of cellular signals in cancer through multiscale models. We describe a general framework that integrates signaling with other cellular functions like trafficking, cell-cell and cell-matrix adhesion, and motility. The guiding question in our approach is: how does a physical change in cell membrane configuration caused by external stimuli (including those by the extracellular microenvironment) alter trafficking, signaling and subsequent cell fate? We answer this question by constructing a modeling framework based on stochastic spatial continuum models of cell membrane deformations. We apply this framework to explore the link between trafficking, signaling in the tumor microenvironment, and cell fate. At each stage, we aim to connect the results of our predictions with cellular experiments.

The WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.

Cells generate a wide range of actin-based membrane protrusions for various cell behaviors. These protrusions are organized by different actin nucleation promoting factors. For example, N-WASP controls finger-like filopodia, whereas the WAVE complex controls sheet-like lamellipodia. These different membrane morphologies likely reflect different patterns of nucleator self-organization. N-WASP phase separation has been successfully studied through biochemical reconstitutions, but how the WAVE complex self-organizes to instruct lamellipodia is unknown. Because WAVE complex self-organization has proven refractory to cell-free studies, we leverage in vivo biochemical approaches to investigate WAVE complex organization within its native cellular context. With single molecule tracking and molecular counting, we show that the WAVE complex forms highly regular multilayered linear arrays at the plasma membrane that are reminiscent of a microtubule-like organization. Similar to the organization of microtubule protofilaments in a curved array, membrane curvature is both necessary and sufficient for formation of these WAVE complex linear arrays, though actin polymerization is not. This dependency on negative membrane curvature could explain both the templating of lamellipodia and their emergent behaviors, including barrier avoidance. Our data uncover the key biophysical properties of mesoscale WAVE complex patterning and highlight an integral relationship between NPF self-organization and cell morphogenesis.

Phenylboronic acid interacts with pectic rhamnogalacturonan-II and displays anti-auxinic effects during Arabidopsis thaliana root growth and development.

Boron dimerizes RG-II in the plant cell wall and is crucial for plant cell elongation. However, studying RG-II dimerization in plants is challenging because of the severe phenotypes or lethality of RG-II mutants. Boron deprivation abrogates both RG-II dimerization and plant growth, but whether or how these phenotypes are functionally linked has remained unclear. Boric acid analogues can serve as experimental tools to interfere with RG-II cross-linking. Here, we investigated RG-II dimerization and developmental phenotypes in Arabidopsis thaliana seedlings treated with a boric acid analogue, phenylboronic acid (PBA), to test whether the observed developmental phenotypes are attributable to alteration of RG-II dimerization or to other putative functions of boron in plants. We found that PBA treatment altered root development in seedlings while RG-II dimerization and distribution were not affected. Surprisingly, under low boron conditions, PBA treatment i) had no effect on root size but still prevented lateral root development and ii) restored RG-II dimerization. PBA treatment also disrupted auxin levels, potentially explaining the absence of lateral roots in seedlings treated with this analogue. We conclude that PBA interacts both with RG-II and other cellular targets such as auxin signaling components, and that the phenotypes caused by PBA arise from interference with multiple functions of boron.

Comparison of egg-shape equations using relative curvature measures of nonlinearity.

A 2-dimensional (2D) egg-shape equation can be used to construct a 3D egg geometry based on the hypothesis that an egg is a solid of revolution, which helps to calculate egg volume and surface area. The parameters in the 2D egg-shape equation are potentially valuable for providing a clue to the ecology and evolution of avian eggs. In this study, the 5-parameter Preston equation (PE), the 4-parameter Troscianko equation (TE), and another 2 egg-shape equations, were compared in describing real 2D egg-shape data of 300 Gallus gallus domesticus eggs and additional 50 eggs that represented the variation in avian egg geometries. Adjusted root-mean-square error was used to quantify each equation's prediction error. Given that the 4 equations are nonlinear, relative curvature measures of nonlinearity were used to assess the extent of nonlinearity in each equation. PE was found to be the best among the 4 equations in terms of adjusted root-mean-square error and minimizing nonlinearity. The empirically determined egg volumes using a graduated cylinder were compared with the predicted egg volumes using the formula for a solid of revolution based on 2D predictions from the 4 egg-shape equations. There were negligible differences in the predicted egg volumes and surface areas among the 4 equations, indicating that these equations are all valid in calculating egg volume and surface area. In addition, we proposed a 5-parameter TE and found that it outperformed the above 4 equations in describing the 2D egg shape of G. gallus, but was less general than PE for other egg shapes. This work provides statistical evidence to show which equation is the best for describing the geometry of avian eggs and nondestructively calculating their volume and surface area, helping to classify poultry eggs into different grades according to the morphological characteristics of the eggs.

Early-onset and uncontrolled diabetes mellitus factors correlate with complications of Peyronie's disease.

BACKGROUND: Peyronie's disease (PD) is a connective tissue disorder that affects the penis and is characterized by abnormal collagen structure in the penile tunica albuginea, resulting in plaque formation and penile deformity. PD's overall prevalence is estimated at 3.2% to 8.9%, with rates as high as 20.3% among men with type 2 diabetes mellitus (DM). However, the characteristics of DM associated with PD complications remain unclear. AIM: To explore clinical associations between DM characteristics and PD complications. METHODS: We conducted a retrospective analysis of patients with DM and PD who presented at our institution between 2007 and 2022. We examined patients' clinical histories, DM- and PD-related clinical parameters, and complications. Penile deformities were assessed through physical examination, photographs, and penile Doppler ultrasound. Patients were categorized into subgroups based on age of DM onset: early (<45 years), average (45-65 years), and late (>65 years). OUTCOMES: Outcomes included effects of DM characteristics on PD development, progression, and severity. RESULTS: In total, 197 patients were included in the evaluation. Early-onset diabetes and elevated hemoglobin A1c (HbA1c) levels exhibited significant correlations with the early development of PD (ρ = 0.66, P < .001, and ρ = -0.24, P < .001, respectively). Furthermore, having DM at an early age was associated with the occurrence of penile plaque (ρ = -0.18, P = .03), and there were no significant differences in plaque dimensions (ρ = -0.29, P = .053). A rise in HbA1c levels after the initial PD diagnosis displayed positive correlations with the formation of penile plaque (ρ = 0.22, P < .006). CLINICAL IMPLICATIONS: These findings emphasize the need for comprehensive assessments and personalized treatment strategies for individuals with DM and PD. Enhanced management approaches can improve outcomes for those facing both challenges. STRENGTHS AND LIMITATIONS: Limitations include the single-site retrospective design with potential selection bias, inaccuracies in medical record data, and challenges in controlling confounding variables. CONCLUSIONS: This study highlights that early-onset diabetes and poor diabetes control, as indicated by a subsequent rise in HbA1c levels following PD diagnosis, are significantly correlated with the onset and severity of PD. Revealing the mechanisms behind these findings will help us develop better management strategies for individuals with DM and PD.

Nonlinear Electrical Transport Unveils Fermi Surface Malleability in a Moiré Heterostructure.

Van Hove singularities enhance many-body interactions and induce collective states of matter ranging from superconductivity to magnetism. In magic-angle twisted bilayer graphene, van Hove singularities appear at low energies and are malleable with density, leading to a sequence of Lifshitz transitions and resets observable in Hall measurements. However, without a magnetic field, linear transport measurements have limited sensitivity to the band's topology. Here, we utilize nonlinear longitudinal and transverse transport measurements to probe these unique features in twisted bilayer graphene at zero magnetic field. We demonstrate that the nonlinear responses, induced by the Berry curvature dipole and extrinsic scattering processes, intricately map the Fermi surface reconstructions at various fillings. Importantly, our experiments highlight the intrinsic connection of these features with the moiré bands. Beyond corroborating the insights from linear Hall measurements, our findings establish nonlinear transport as a pivotal tool for probing band topology and correlated phenomena.

Nonalternant B,N-Embedded Helical Nanographenes Containing Azepines: Programmable Synthesis, Responsive Chiroptical Properties and Spontaneous Resolution into a Single-Handed Helix.

Heteroatom-embedded helical nanographenes (NGs) constitute an important and appealing class of intrinsically chiral materials. In this work, a series of B,N-embedded helical NGs bearing azepines was synthesized via stepwise regioselective cyclodehydrogenation. First, the phenyl- or nitrogen-bridged dimers were efficiently clipped into highly congested model compounds 1 and 2. Later, the controllable Scholl reactions of the tetraphenyl-tethered precursor generated 1, 7 or 8 new C‒C bonds, thereby establishing a robust method for the preparation of nonalternant BN-HNGs with up to 31 fused rings. The helical bilayer nature was unambiguously verified by X-ray diffraction analysis. The helical chirality was transferred to the stereogenic boron centers upon fluoride coordination, with a concave-concave structure to comply with the bilayer skeleton. Notably, the largest nonalternant BN-HNG (6) spontaneously resolved into a homochiral 41 helix structure as a molecular spiral staircase during crystallization via conglomerate formation at the single-crystal scale. The large twisted C2-symmetric pi-surface and the dynamic chiral skeleton induced by curved azepines might have synergistic effects on self-recognition of enantiomers of 6 to achieve the intriguing spontaneous resolution behavior. The chiroptical properties of the enantiomer of 6 were further investigated, revealing that 6 had a strong chiroptical response in the visible range (400-700 nm).

Disconjugacies of saccade duration and trajectories in strabismus.

Introduction: For decades, the saccadic system has been a favorite target of neurophysiologists seeking to elucidate the neural control of eye movements, partly because saccades are characterized by a set of highly stereotyped relationships between amplitude, duration, and peak velocity. There is a large literature describing the dynamics and trajectories of these movements in normal primates, but there are no similarly detailed analyses for subjects with infantile strabismus syndrome. Previous studies have shown the amplitudes and directions of saccades often differ for the two eyes in this disorder, but it is unknown whether a similar disconjugacy exists for duration. The present study was designed to determine whether or not saccade duration differs for the two eyes in strabismus, and whether there are abnormalities involving the trajectories of these movements. Methods: Dynamic analyses of saccade trajectories and durations were performed for two normal monkeys, two with esotropia and two with exotropia. The amount of curvature was compared for the two eyes. For each monkey with strabismus, the amount of curvature was compared to normal controls. Saccades were placed into 12 bins, based on direction; for each bin, the mean saccade duration was compared for the two eyes (duration disconjugacy). The duration disconjugacy for each bin was then compared for monkeys with strabismus, versus normal control animals. Results: Surprisingly, the amount of curvature was not consistently greater in subjects with pattern strabismus. However, saccade curvature differed for the two eyes by a significantly greater amount for all monkeys with strabismus, compared to normal controls. In addition, for a subset of saccades in subjects with strabismus, saccade duration differed for the two eyes by more than 10 ms, even when the animal was fully alert. Discussion: To the best of the author's knowledge, this is the first study to show that, in strabismus, saccade durations can differ for the two eyes by an abnormally large amount. These data also suggest that, in monkeys with pattern strabismus, abnormal horizontal-vertical crosstalk in brainstem can lead to directional disconjugacy without significantly impairing component stretching. These results place important constraints on future attempts to model the neural mechanisms that contribute to directional disconjugacy in pattern strabismus.