Three-dimensional spatial quantitative analysis of cardiac lymphatics in the mouse heart.

OBJECTIVE: Three-dimensional (3D) microscopy and image data analysis are necessary for studying the morphology of cardiac lymphatic vessels (LyVs) and their association with other cell types. We aimed to develop a methodology for 3D multiplexed lightsheet microscopy and highly sensitive and quantitative image analysis to identify pathological remodeling in the 3D morphology of LyVs in young adult mouse hearts with familial hypertrophic cardiomyopathy (HCM). METHODS: We developed a 3D lightsheet microscopy workflow providing a quick turn-around (as few as 5-6 days), multiplex fluorescence detection, and preservation of LyV structure and epitope markers. Hearts from non-transgenic and transgenic (TG) HCM mice were arrested in diastole, retrograde perfused, immunolabeled, optically cleared, and imaged. We built an image-processing pipeline to quantify LyV morphological parameters at the chamber and branch levels. RESULTS: Chamber-specific pathological alterations of LyVs were identified, and significant changes were seen in the right atrium (RA). TG hearts had a higher volume percent of ER-TR7+ fibroblasts and reticular fibers. In the RA, we found associations between ER-TR7+ volume percent and both LyV segment density and median diameter. CONCLUSIONS: This workflow and study enabled multi-scale analysis of pathological changes in cardiac LyVs of young adult mice, inviting ideas for research on LyVs in cardiac disease.

Cutaneous warmth and hotness thresholds to radiation heat exposure at a distance of 10 cm from 17 body regions.

The purpose of the present study was to evaluate body regional differences in cutaneous warmth and hotness thresholds in relation to radiant heat exposure. Fourteen male subjects participated in this study (age: 25 ± 5 y, height: 176.6 ± 5.5 cm, body weight: 70 ± 5.8 kg). Cutaneous warmth and hotness thresholds were measured on the forehead, neck, chest, abdomen, upper back, lower back, upper arm, forearm, palm, back of hand, front thigh, shin, top of foot, buttock, back thigh, calf, and sole. The forehead (34.8 ± 0.2 °C), lower back (34.1 ± 1.2 °C) and palm (34.3 ± 0.7 °C) had the highest warmth thresholds, whereas the foot (29.8 ± 1.9 °C) and sole (28.0 ± 2.1 °C) had the lowest values among the 17 regions (P<0.001). Higher warmth thresholds were related to higher initial skin temperatures (Tsk) (r=0.972, P<0.001). Increases in Tsk for detecting warmth sensation were smaller for the lower back with a rise of 0.2 ± 0.4 °C and the abdomen (0.3 ± 0.3 °C) than for the buttock (0.9 ± 0.8 °C) and sole (0.8 ± 0.6 °C) (P<0.05). Increases in Tsk for detecting hotness sensation ranged from 0.5 to 1.5 °C. Warmth and hotness thresholds on the abdomen or sole had significant relationships with body mass index, indicating that the overweight are less sensitive to detecting radiant heat on the abdomen or sole. Thermal thresholds from radiant heat exposure of 100 cm2 were lower than the values from conductive heat exposure of 6.25 cm2, which might be explained by the effect of spatial summation.

The Ventral Midline Thalamus Mediates Hippocampal Spatial Information Processes upon Spatial Cue Changes.

The ventral midline thalamus, consisting of the reuniens and rhomboid nuclei (RE/Rh), is a thalamic structure interconnected with the limbic systems including the hippocampus. Recently, many studies have revealed that this structure plays distinctive roles in spatial learning and memory in collaboration with hippocampal functions. However, what aspects of spatial information process are influenced by the RE/Rh is not clearly known. To elucidate the roles of RE/Rh in spatial information processing and its effects on hippocampal activity, specifically with the manipulation of spatial contents, we measured hippocampal-dependent spatial memory performance and hippocampal place cell activities after RE/Rh lesion using male C57BL/6J × 129/SvJae hybrid mice. We found that the lesion altered the behavioral aptitude in recognizing locational changes of an object. Furthermore, CA1 place cells in the lesion group showed different spatial representation patterns in recognizing the environment with cue locational changes compared with the control group. Interestingly, the patterns of CA1 place cells in recognizing the same environment previously visited were not disrupted in the lesion group compared with the control group. These findings demonstrate that the ventral midline thalamus (RE/Rh) is important in recognizing the spatial relationships, especially when spatial rearrangement of cue position was introduced.SIGNIFICANCE STATEMENT The ventral midline thalamic nuclei (reuniens and rhomboid) interact with the hippocampus to influence various cognitive functions requiring spatial memories, yet what aspects of spatial information process are influenced by these nuclei is not clearly known. Here, we reveal that these nuclei play a crucial role in modulating hippocampal properties only with locational rearrangement of cues, not with the familiar arrangement. These nuclei are distinctively involved in cue-dependent spatial information processes of CA1 place cells. In particular, we suggest that these nuclei modulate spatial information processing on discrete components, especially when the spatial cue relationship is modified.

A Super-Oxidized Radical Cationic Icosahedral Boron Cluster.

While the icosahedral closo-[B12H12]2- cluster does not display reversible electrochemical behavior, perfunctionalization of this species via substitution of all 12 B-H vertices with alkoxy or benzyloxy (OR) substituents engenders reversible redox chemistry, providing access to clusters in the dianionic, monoanionic, and neutral forms. Here, we evaluated the electrochemical behavior of the electron-rich B12(O-3-methylbutyl)12 (1) cluster and discovered that a new reversible redox event that gives rise to a fourth electronic state is accessible through one-electron oxidation of the neutral species. Chemical oxidation of 1 with [N(2,4-Br2C6H3)3]•+ afforded the isolable [1]•+ cluster, which is the first example of an open-shell cationic B12 cluster in which the unpaired electron is proposed to be delocalized throughout the boron cluster core. The oxidation of 1 is also chemically reversible, where treatment of [1]•+ with ferrocene resulted in its reduction back to 1. The identity of [1]•+ is supported by EPR, UV-vis, multinuclear NMR (1H, 11B), and X-ray photoelectron spectroscopic characterization.

Publisher Correction: A molecular cross-linking approach for hybrid metal oxides.

In the version of this Article originally published, Liban M. A. Saleh was incorrectly listed as Liban A. M. Saleh due to a technical error. This has now been amended in all online versions of the Article.

A molecular cross-linking approach for hybrid metal oxides.

There is significant interest in the development of methods to create hybrid materials that transform capabilities, in particular for Earth-abundant metal oxides, such as TiO2, to give improved or new properties relevant to a broad spectrum of applications. Here we introduce an approach we refer to as 'molecular cross-linking', whereby a hybrid molecular boron oxide material is formed from polyhedral boron-cluster precursors of the type [B12(OH)12]2-. This new approach is enabled by the inherent robustness of the boron-cluster molecular building block, which is compatible with the harsh thermal and oxidizing conditions that are necessary for the synthesis of many metal oxides. In this work, using a battery of experimental techniques and materials simulation, we show how this material can be interfaced successfully with TiO2 and other metal oxides to give boron-rich hybrid materials with intriguing photophysical and electrochemical properties.

Sonochemical Synthesis of Small Boron Oxide Nanoparticles.

The synthesis of small boron oxide nanoparticles (NPs) is reported. A sonochemical approach in the presence of a capping agent was employed to produce approximately 4-5-nm-sized B2O3 NPs, including the 10B isotopically enriched form. The morphology and composition of the NPs were established using transmission electron microscopy and diffraction, respectively. X-ray photoelectron and Fourier transform infrared spectroscopies provided information about surface functionalization of the B2O3 NPs, which can be further modified through a facile, one-step ligand-exchange process. The toxicity of the synthesized NPs was investigated in Chinese hamster ovarian cells, indicating that these systems were nontoxic up to 1.7 mM concentrations.

Sweating distribution and active sweat glands on the scalp of young males in hot-dry and hot-humid environments.

PURPOSE: We investigated the effects of humidity on regional sweating secretion and active sweat gland density on the scalp during passive heating in hot environments. METHODS: Eight male subjects shaved their heads prior to expose to dry (30%RH; H30%) and humid (85%RH; H85%) conditions at an air temperature of 32 °C. Total sweat rate, local sweat rates (frontal, vertex, temporal, and occipital regions), active sweat glands on the scalp (2 frontal, 2 parietal, 2 temporal, 1 occipital, and 1 vertex), and rectal and skin temperatures were measured during leg immersion in 42 °C water for 60 min. RESULTS: (1) Total sweat rates were greater for H30% (179.4 ± 35.6 g h-1) than for H85% (148.1 ± 27.2 g h-1) (P < 0.05). (2) Scalp sweat secretion tended to be greater in the H85% than the H30%. (3) Head sweat rates were greater on the frontal than on the vertex for both humidity conditions (P < 0.05). (4) Active sweat gland density on the scalp was greater for H85% (82 ± 13 glands cm-2) than for H30% (62 ± 17 glands cm-2) (P < 0.05). (5) No significant difference was found in rectal temperature between H30% and H85%, whereas mean skin temperature was significantly lower for H30% (34.8 ± 0.7 °C) than for the H85% condition (36.0 ± 0.3 °C) (P < 0.05). CONCLUSIONS: These results indicate that the thermoregulatory sweating responses for the scalp region were significantly increased in the hot-humid condition compared to the hot-dry condition. Among the regions on the scalp surface, the vertex was the least sensitive to the change in humidity.

Comparisons between Shikoro-type helmet with no hood and typical fire protective helmets with hood in a hot and humid environment.

The purpose of this study was to evaluate physiological and subjective responses while wearing the Shikoro-type helmet for firefighters when compared to typical helmets. Eight firefighters conducted a 30-min exercise at a 5 km h-1 in three helmet conditions at an air temperature of 32 °C with 70%RH. The results showed that no significant differences in rectal, mean skin temperature and physiological strain index among the three conditions were found during exercise and recovery. Skin temperatures on the cheek, ear and neck during exercise were significantly lower for the Shikoro-type condition (p < 0.05), but forehead temperature was greater for the Shikoro-type helmet when compared to the other conditions (p < 0.05). Statistical differences in thermal sensation and thermal comfort for overall and local body regions were not found among the three conditions. These results imply that the Shikoro-type helmet had local advantages in reducing skin temperatures on the face and neck. Practitioner Summary: Firefighters wear their helmet with its hood to protect the head and neck but a Shikoro type helmet has no fire protective hood. This study aimed to evaluate the comfort function of Shikoro helmet along with typical helmets. The results demonstrated thermal benefits of the Shikoro helmet on the head.

Sensitivity to cutaneous warm stimuli varies greatly in the human head.

The head has been known as the most sensitive area to temperature changes but the values are limited to the face. The purpose of this study was to examine cutaneous warm thresholds on the scalp and face of young males. Eight males participated in this study (24 ± 3 yrs in age, 178.2 ± 5.3cm in height, and 90.0 ± 15.4kg in body mass). All measurements were conducted in an environmental chamber (27 ± 1°C air temperature and 53 ± 1% relative humidity). Cutaneous warm thresholds were measured on nine areas of the following regions: the frontal (two points on the right), parietal (a point on the right and the vertex, respectively), temporal (two points on the right), and occipital region (on the right) along with the forehead using a thermal stimulator (rate of temperature increase 0.1°Cs-1). Skin temperatures on the nine head regions were monitored during the threshold test. The results showed that 1) no significant differences were found in initial skin temperatures among the nine head regions; 2) cutaneous warm detecting temperatures were significantly greater on the vertex (38.2 ± 3.5°C) than on the forehead (34.8 ± 1.4°C) and the other seven scalp regions (P < 0.05); 3) subjects detected the increase of 1.2 ± 1.0°C on the forehead and 1.5 ± 1.2°C on the occipital region as the first warmth while the vertex was the most insensitive to the increase of temperature (4.0 ± 3.2°C) (P < 0.05). In summary, the scalp region of young males was less sensitive to the temperature change when compared to the forehead, and the vertex was the most insensitive among the eight scalp regions to the temperature increase. We conclude that the entire head should be considered as a binary topography with the face and the scalp in terms of cutaneous thermal sensitivity.

Blue Phosphorescent Zwitterionic Iridium(III) Complexes Featuring Weakly Coordinating nido-Carborane-Based Ligands.

We report the development of a new class of phosphorescent zwitterionic bis(heteroleptic) Ir(III) compounds containing pyridyl ligands with weakly coordinating nido-carboranyl substituents. Treatment of phenylpyridine-based Ir(III) precursors with C-substituted ortho-carboranylpyridines in 2-ethoxyethanol results in a facile carborane deboronation and the formation of robust and highly luminescent metal complexes. The resulting nido-carboranyl fragments associate with the cationic Ir(III) center through primarily electrostatic interactions. These compounds phosphoresce at blue wavelengths (450-470 nm) both in a poly(methyl methacrylate) (PMMA) matrix and in solution at 77 K. These complexes display structural stability at temperatures beyond 300 °C and quantum yields greater than 40%. Importantly, the observed quantum yields correspond to a dramatic 10-fold enhancement over the previously reported Ir(III) congeners featuring carboranyl-containing ligands in which the boron cluster is covalently attached to the metal. Ultimately, this work suggests that the use of a ligand framework containing a weakly coordinating anionic component can provide a new avenue for designing efficient Ir(III)-based phosphorescent emitters.

Stochastic characterization of navigation strategies in an automated variant of the Barnes maze.

Animals can use a repertoire of strategies to navigate in an environment, and it remains an intriguing question how these strategies are selected based on the nature and familiarity of environments. To investigate this question, we developed a fully automated variant of the Barnes maze, characterized by 24 vestibules distributed along the periphery of a circular arena, and monitored the trajectories of mice over 15 days as they learned to navigate towards a goal vestibule from a random start vestibule. We show that the patterns of vestibule visits can be reproduced by the combination of three stochastic processes reminiscent of random, serial, and spatial strategies. The processes randomly selected vestibules based on either uniform (random) or biased (serial and spatial) probability distributions. They closely matched experimental data across a range of statistical distributions characterizing the length, distribution, step size, direction, and stereotypy of vestibule sequences, revealing a shift from random to spatial and serial strategies over time, with a strategy switch occurring approximately every six vestibule visits. Our study provides a novel apparatus and analysis toolset for tracking the repertoire of navigation strategies and demonstrates that a set of stochastic processes can largely account for exploration patterns in the Barnes maze.

Three-dimensional spatial quantitative analysis of cardiac lymphatics in the mouse heart.

Objective: 3D microscopy and image data analysis are necessary for studying the morphology of cardiac lymphatic vessels (LyVs) and association with other cell types. We aimed to develop a methodology for 3D multiplexed lightsheet microscopy and highly sensitive and quantitative image analysis to identify pathological remodeling in the 3D morphology of LyVs in young adult mouse hearts with familial hypertrophic cardiomyopathy (HCM). Methods: We developed a 3D lightsheet microscopy workflow providing a quick turn-around (as few as 5-6 days), multiplex fluorescence detection, and preservation of LyV structure and epitope markers. Hearts from non-transgenic (NTG) and transgenic (TG) HCM mice were arrested in diastole, retrograde perfused, immunolabeled, optically cleared, and imaged. We built an image processing pipeline to quantify LyV morphological parameters at the chamber and branch levels. Results: Chamber-specific pathological alterations of LyVs were identified, but most significantly in the right atrium (RA). TG hearts had a higher volume fraction of ER-TR7 + fibroblasts and reticular fibers. In the RA, we found associations between ER-TR7 + volume fraction and both LyV segment density and median diameter. Conclusions: This workflow and study enabled multi-scale analysis of pathological changes in cardiac LyVs of young adult mice, inviting ideas for research on LyVs in cardiac disease.

A Catalytically Accessible Polyoxometalate in a Porous Fiber for Degradation of a Mustard Gas Simulant.

Polyoxometalates (POMs) are versatile materials for chemical catalysis due to their tunable acidity and rich redox properties. While POMs have attracted significant attention in homogeneous catalysis, challenges regarding aggregation and instability in solvents often prevent the wide implementation of POMs as heterogeneous catalysts. Therefore, the successful incorporation of a POM into a solid support, such as a polymer, is desirable for practical applications where unique functionalities of the POM combine with the advantages of the polymer. In this work, we showcase how polymers of intrinsic microporosity (PIMs) can serve as matrices for anchoring a pure inorganic Keggin-type POM (H3PW12O40) to fabricate PIM-based composite materials. Specifically, we found that PIMs installed with amidoxime functionalities could successfully attach POMs (PW12@PIM-1-AO) without self-segregation. Furthermore, we fabricated porous fibrous mats via electrospinning of the PIM-POM composites. Comprehensive characterization confirmed the integrity of the POM in the composite material. Following this, we demonstrated that the incorporated POMs in the composite fibers maintained their innate catalytic activity for the oxidative degradation of 2-chloroethyl ethyl sulfide, a sulfur mustard simulant, in the presence of hydrogen peroxide as the oxidant. Ultimately, our work highlights that PIM-based hybrid materials provide a potential route for implementing these reactive fiber mats into protective equipment.

BODIPY-Based Polymers of Intrinsic Microporosity for the Photocatalytic Detoxification of a Chemical Threat.

Effective heterogeneous photocatalysts capable of detoxifying chemical threats in practical settings must exhibit outstanding device integrity. We report a copolymerization that yields robust, porous, processible, chromophoric BODIPY (BDP; boron-dipyrromethene)-containing polymers of intrinsic microporosity (BDP-PIMs). Installation of a pentafluorophenyl at the meso position of a BDP produced reactive monomer that when combined with 5,5,6,6-tetrahydroxy-3,3,3,3-tetramethyl-1,1-spirobisindane (TTSBI) and tetrafluoroterephthalonitrile (TFTPN) yields PIM-1. Postsynthetic modification of these polymers yields Br-BDP-PIM-1a and -1b─polymers containing bromine at the 2,6-positions. Remarkably, the brominated polymers display porosity and processability features similar to those of H-BDP-PIMs. Gas adsorption reveals molecular-scale porosity and Brunette-Emmet-Teller surface areas as high as 680 m2 g-1. Electronic absorption spectra reveal charge-transfer (CT) bands centered at 660 nm, while bands arising from local excitations, LE, of BDP and TFTPN units are at 530 and 430 nm, respectively. Fluorescence spectra of the polymers reveal a Förster resonance energy-transfer (FRET) pathway to BDP units when TFTPN units are excited at 430 nm; weak phosphorescence at room temperature indicates a singlet-to-triplet intersystem crossing. The low-lying triplet state is well positioned energetically to sensitize the conversion of ground-state (triplet) molecular oxygen to electronically excited singlet oxygen. Photosensitization capabilities of these polymers toward singlet-oxygen-driven detoxification of a sulfur-mustard simulant 2-chloroethyl ethyl sulfide (CEES) have been examined. While excitation of CT and LEBDP bands yields weak catalytic activity (t1/2 > 15 min), excitation to higher energy states of TFTPN induces significant increases in photoactivity (t1/2 ≅ 5 min). The increase is attributable to (i) enhanced light collection, (ii) FRET between TFTPN and BDP, (iii) the presence of heavy atoms (bromine) having large spin-orbit coupling energies that can facilitate intersystem crossing from donor-acceptor CT-, FRET-, or LE-generated BDP singlet states to BDP-related triplet states, and (iv) polymer triplet excited-state sensitization of the formation of CEES-reactive, singlet oxygen.

Synthesis and structural properties of a 2D Zn(II) dodecahydroxy-closo-dodecaborate coordination polymer.

In this work, we discuss the synthesis and characterization of a 2D coordination polymer composed of a dianionic perhydroxylated boron cluster, [B12(OH)122-], coordinated to Zn(II)-the first example of a transition metal-coordinated [B12(OH)12]2- compound. This material was synthesized via cation exchange from the starting cesium salt and then subjected to rigorous characterization prior to and after thermal activation. Numerous techniques, including XRD, FTIR, SEM, TGA, and solid-state NMR revealed a 2D coordination polymer composed of sheets of Zn(II) ions intercalated between planes of boron clusters. The as-synthesized material was then evacuated of solvent via thermal treatment, and atomic-level changes from this transformation were elucidated through a combination of 1D and 2D solid-state NMR analyses of 11B and 1H nuclei, suggesting the full removal of coordinated solvent molecules. Evidence also suggested that [B12(OH)122-] can adjust its coordination to Zn(II) in the solid-state through hemilability of its numerous -OH ligands.

Postsynthetically Modified Polymers of Intrinsic Microporosity (PIMs) for Capturing Toxic Gases.

Polymers of intrinsic microporosity (PIMs) are promising materials for gas adsorption because of their high surface area, processability, and tailorable backbone. Specifically, nitrile groups on the backbone of PIM-1, an archetypal PIM, can be converted to other functional groups to selectively capture targeted gas molecules. Despite these appealing features of PIMs, their potential has mainly only been realized for the separation of nontoxic gases. Here, we prepared PIM-1 materials modified with carboxylic acid and amidoxime functional groups and investigated their performance as adsorbents for the capture of ammonia (NH3) and sulfur dioxide (SO2) gases. After determining the Brønsted acidity or basicity of the PIMs from potentiometric acid-base titrations, which can be correlated with affinity for acidic or basic toxic gases, we explored the uptake capacity toward NH3 and SO2, respectively. Gas sorption studies revealed that the carboxylated PIM showed higher affinity toward NH3 through the incorporation of Brønsted acid sites, while the amidoxime functionalized PIM exhibited affinity toward SO2 through the installed of slightly basic functional groups. Overall, this study highlights new insight into PIMs as solid sorbent materials for capturing toxic gases, which can be transferred to their potential use in practical applications, such as personal protective equipment or air filtration.

Perfunctionalized Dodecaborate Clusters as Stable Metal-Free Active Materials for Charge Storage.

We report a class of perfunctionalized dodecaborate clusters that exhibit high stability towards high concentration electrochemical cycling. These boron clusters afford several degrees of freedom in material design to tailor properties including solubility and redox potential. The exceptional stability of these clusters was demonstrated using a symmetric flow cell setup for electrochemical cycling between two oxidation states for 45 days, with post-run analysis showing negligible decomposition of the active species (<0.1%). To further probe the limits of this system, a prototype redox flow battery with two different cluster materials was used to determine mutual compatibility. This work effectively illustrates the potential of bespoke boron clusters as robust material platform for electrochemical energy conversion and storage.

Cross-linked porous polyurethane materials featuring dodecaborate clusters as inorganic polyol equivalents.

We report the discovery that a perhydroxylated dodecaborate cluster ([B12(OH)12]2-) can act as an inorganic polyol, serving as a molecular cross-linker in the synthesis of polyurethane-based materials. We further demonstrate how the inherent robustness of the utilized boron cluster can effectively enhance the thermal stability of the produced polyurethane materials incorporating [B12(OH)12]2- building blocks compared to analogous polymers made from carbon-based polyols. Ultimately, this approach provides a potential route to tune the chemical and physical properties of soft materials through incorporation of polyhedral boron-rich clusters into the polymer network.

Sterically Unprotected Nucleophilic Boron Cluster Reagents.

A cornerstone of modern synthetic chemistry rests on the ability to manipulate the reactivity of a carbon center by rendering it either electrophilic or nucleophilic. However, accessing a similar reactivity spectrum with boron-based reagents has been significantly more challenging. While classical nucleophilic carbon-based reagents normally do not require steric protection, readily accessible, unprotected boron-based nucleophiles have not yet been realized. Herein, we demonstrate that the bench stable closo-hexaborate cluster anion can engage in a nucleophilic substitution reaction with a wide array of organic and main group electrophiles. The resulting molecules containing B‒C bonds can be further converted to tricoordinate boron species widely used in organic synthesis.