Single-cell analysis of age-related changes in leukocytes of diabetic mouse hindpaws.

Complications associated with Type 1 and Type 2 diabetes, such as diabetic peripheral neuropathy and diabetic foot ulcers, are a growing health-care concern. In addition, this concern increases as diabetic patients age due to their increased susceptibility to complications. To address this growing problem, it is important to understand fluctuations in physiology which lead to pathological changes associated with the metabolic disturbances of diabetes. Our study explores dysregulation of immune cell populations in the hindpaws of healthy and diabetic mice at 12 and 21 weeks of age using single-cell RNA sequencing to provide insight into immune disruptions occurring in the distal limb during chronic diabetes. In 21-week-old Leprdb/db mice, increases were seen in mast cells/basophils, dermal γδ T cells, heterogeneous T cells, and Type 2 innate lymphoid cells. In addition, macrophages represented the largest cluster of immune cells and showed the greatest increase in genes associated with immune-specific pathways. Sub-clustering of macrophages revealed a bias toward angiogenic Lyve1+MHCIIlo macrophages in the hindpaws of 21-week-old diabetic mice, which corresponded to an increase in Lyve1+ macrophages in the hindpaws of 21-week-old diabetic mice on histology. Our results show that in Type 2 diabetes, the immunological function and phenotype of multiple immune cell types shift not only with metabolic disturbance, but also with duration of disease, which may explain the increased susceptibility to pathologies of the distal limb in patients with more chronic diabetes.

Dynamic electrocardiogram changes are a novel risk marker for sudden cardiac death.

BACKGROUND AND AIMS: Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not been investigated. In this study, the nature and prevalence of dynamic ECG remodelling were studied among individuals who eventually suffered SCD. METHODS: The study population was drawn from two prospective community-based SCD studies in Oregon (2002, discovery cohort) and California, USA (2015, validation cohort). For this present sub-study, 231 discovery cases (2015-17) and 203 validation cases (2015-21) with ≥2 archived pre-SCD ECGs were ascertained and were matched to 234 discovery and 203 validation controls based on age, sex, and duration between the ECGs. Dynamic ECG remodelling was measured as progression of a previously validated cumulative six-variable ECG electrical risk score. RESULTS: Oregon SCD cases displayed greater electrical risk score increase over time vs. controls [+1.06 (95% confidence interval +0.89 to +1.24) vs. -0.05 (-0.21 to +0.11); P < .001]. These findings were successfully replicated in California [+0.87 (+0.7 to +1.04) vs. -0.11 (-0.27 to 0.05); P < .001]. In multivariable models, abnormal dynamic ECG remodelling improved SCD prediction over baseline ECG, demographics, and clinical SCD risk factors in both Oregon [area under the receiver operating characteristic curve 0.770 (95% confidence interval 0.727-0.812) increased to area under the receiver operating characteristic curve 0.869 (95% confidence interval 0.837-0.902)] and California cohorts. CONCLUSIONS: Dynamic ECG remodelling improved SCD risk prediction beyond clinical factors combined with the static ECG, with successful validation in a geographically distinct population. These findings introduce a novel concept of SCD dynamic risk and warrant further detailed investigation.

The effect of HIV and mpox co-infection on clinical outcomes: Systematic review and meta-analysis.

INTRODUCTION: Co-infection with HIV and mpox is a significant issue for public health because of the potential combined impact on clinical outcomes. However, the existing literature lacks a comprehensive synthesis of the available evidence. The purpose of this meta-analysis is to provide insight into the impact of HIV and mpox co-infection on clinical outcomes. METHODS: We systematically searched major electronic databases (PubMed, Embase, Cochrane Central, and Web of Science) for pertinent studies published up to June 2023. Included were studies that described the clinical outcomes of people who had both mpox and HIV. We performed the analysis using OpenMeta and STATA 17 software. RESULTS: With an overall number of participants of 35 207, 21 studies that met the inclusion criteria were considered. The greatest number of the studies (n = 10) were cohort designs, with three being cross-sectional and eight being case series studies. The meta-analysis found that people who had both HIV and mpox had a higher hospitalization rate than those who only had mpox (odds ratio [OR] 1.848; 95% confidence interval [CI] 0.918-3.719, p = 0.085, I2 = 60.19%, p = 0.020). Furthermore, co-infected patients had higher mortality rates than those who did not have HIV co-infection (OR 3.887; 95% CI 2.272-6.650, p < 0.001). Meta-regression analysis showed that CD4 levels can significantly predict the risk of hospitalization (p = 0.016) and death (p = 0.031). DISCUSSION: HIV causes immunosuppression, making it difficult for the body to mount an effective immune response against pathogens such as mpox. Individuals who are co-infected are at a higher risk of severe disease and death, according to our findings. Although hospitalization rates did not differ significantly between the two groups, it is critical to prioritize interventions and improve management strategies tailored specifically for people living with HIV. CONCLUSION: This meta-analysis provides substantial evidence that HIV and mpox co-infection has a negative impact on clinical outcomes. Co-infected individuals had higher hospitalization and significantly higher mortality rates. These findings highlight the significance of early diagnosis, prompt treatment initiation, and effective management strategies for people living with HIV and mpox.

Social Phenotyping for Cardiovascular Risk Stratification in Electronic Health Registries.

PURPOSE OF REVIEW: Evaluation of social influences on cardiovascular care requires a comprehensive analysis encompassing economic, societal, and environmental factors. The increased utilization of electronic health registries provides a foundation for social phenotyping, yet standardization in methodology remains lacking. This review aimed to elucidate the primary approaches to social phenotyping for cardiovascular risk stratification through electronic health registries. RECENT FINDINGS: Social phenotyping in the context of cardiovascular risk stratification within electronic health registries can be separated into four principal approaches: place-based metrics, questionnaires, ICD Z-coding, and natural language processing. These methodologies vary in their complexity, advantages and limitations, and intended outcomes. Place-based metrics often rely on geospatial data to infer socioeconomic influences, while questionnaires may directly gather individual-level behavioral and social factors. Z-coding, a relatively new approach, can capture data directly related to social determinant of health domains in the clinical context. Natural language processing has been increasingly utilized to extract social influences from unstructured clinical narratives-offering nuanced insights for risk prediction models. Each method plays an important role in our understanding and approach to using social determinants data for improving population cardiovascular health. These four principal approaches to social phenotyping contribute to a more structured approach to social determinant of health research via electronic health registries, with a focus on cardiovascular risk stratification. Social phenotyping related research should prioritize refining predictive models for cardiovascular diseases and advancing health equity by integrating applied implementation science into public health strategies.

Sustained pain and macrophage infiltration in a mouse muscle contusion model.

INTRODUCTION/AIMS: Prior studies have emphasized the role of inflammation in the response to injury and muscle regeneration, but little emphasis has been placed on characterizing the relationship between innate inflammation, pain, and functional impairment. The aim of our study was to determine the contribution of innate immunity to prolonged pain following muscle contusion. METHODS: We developed a closed-impact mouse model of muscle contusion and a macrophage-targeted near-infrared fluorescent nanoemulsion. Closed-impact contusions were delivered to the lower left limb. Pain sensitivity, gait dysfunction, and inflammation were assessed in the days and weeks post-contusion. Macrophage accumulation was imaged in vivo by injecting i.v. near-infrared nanoemulsion. RESULTS: Despite hindpaw hypersensitivity persisting for several weeks, disruptions to gait and grip strength typically resolved within 10 days of injury. Using non-invasive imaging and immunohistochemistry, we show that macrophage density peaks in and around the affected muscle 3 day post-injury and quickly subsides. However, macrophage density in the ipsilateral sciatic nerve and dorsal root ganglia (DRG) increases more gradually and persists for at least 14 days. DISCUSSION: In this study, we demonstrate pain sensitivity is influenced by the degree of lower muscle contusion, without significant changes to gait and grip strength. This may be due to modulation of pain signaling by macrophage proliferation in the sciatic nerve, upstream from the site of injury. Our work suggests chronic pain developing from muscle contusion is driven by macrophage-derived neuroinflammation in the peripheral nervous system.

United States-Mexico Border Disparities in Alcoholic Liver Disease Mortality: A Cross-Sectional Analysis 1999-2020.

BACKGROUND: US-Mexico (US-MX) border regions are impacted by socioeconomic disadvantages. Alcohol use disorder remains widely prevalent in US-MX border regions, which may increase the risk of alcoholic liver disease (ALD). GOALS: We aimed to characterize ALD mortality trends in border regions compared to non-border regions from 1999 to 2020 in the United States (US). METHODS: We performed a cross-sectional analysis using the CDC repository. We queried death certificates to find ALD-related deaths from 1999 to 2020, which included demographic information such as gender, race/ethnicity, and area of residence. We estimated age-adjusted mortality rates (AAMR) per 100,000 population and compared the AAMRs across border and non-border regions. We also explored yearly mortality shifts using log-linear regression models and calculated the average annual percentage change (AAPC) using the Monte Carlo permutation test. RESULTS: In all, 11,779 ALD-related deaths were identified in border regions (AAMR 7.29) compared with 361,523 in non-border regions (AAMR 5.03). Border male (AAMR 11.21) and female (AAMR 3.77) populations were higher compared with non-border male (AAMR 7.42) and female (2.85) populations, respectively. Border non-Hispanic populations (AAMR 7.53) had higher mortality compared with non-border non-Hispanic populations (4.79), while both populations experienced increasing mortality shifts (AAPC +1.7, P<0.001 and +3.1, P<0.001, respectively). Border metropolitan (AAMR 7.35) and non-metropolitan (AAMR 6.76) regions had higher mortality rates compared with non-border metropolitan (AAMR 4.96) and non-metropolitan (AAMR 5.44) regions. CONCLUSIONS: Mortality related to ALD was higher in border regions compared with non-border regions. Border regions face significant health disparities when comparing ALD-related mortality.

Synthesis of a 3D Flower-Like BiOCl/Bi-MOF Heterostructure for High-Performance Removal of Rhodamine B and Tetracycline Hydrochloride.

Semiconductor materials based on bismuth metal have been extensively explored for their potential in photocatalytic applications owing to their distinctive crystal structure. Herein, we present the development of a hybrid photocatalyst, CAU-17/BiOCl, featuring a flower-like nanosheet morphology tailored for the photocatalytic degradation of organic contaminants such as rhodamine B (RhB) and tetracycline hydrochloride (TCH). The composite material is obtained by growing thin CAU-17 layers directly onto the host flower-like BiOCl nanosheets under solvothermal conditions. The optimized CAU-17/BiOCl composite possesses excellent photocatalytic performance, achieving a notable 96.0% removal rate for RhB and 78.4% for TCH after 60 and 90 min of LED light irradiation, respectively. This boosted activity is attributed to the heightened absorption of visible light caused by BiOCl and the provision of additional reaction sites due to the thin CAU-17 layers. Furthermore, the establishment of an S-scheme heterojunction mechanism enables efficient charge separation between CAU-17 and BiOCl, facilitating the separation of photoinduced electrons (e-) and holes (h+). Analysis of the degradation mechanism of RhB and TCH reveals the predominant role of superoxide radicals (•O2-), e-, and h+ in the photocatalytic degradation process. Moreover, the removal efficiency of TCH can reach approximately 64.5% after four cycles of recycling of CAU-17/BiOCl. Our work provides a facile, effective solution and a theoretically explained approach for the effective degradation of pollutants using heterojunction photocatalysts.

Efficacy and safety of fenofibrate in combination with phototherapy for the treatment of neonatal hyperbilirubinemia: a systematic review and meta-analyses.

Phototherapy is the standard treatment for neonatal jaundice. We aimed to review the efficacy and safety of fenofibrate as an adjunct therapy. Twelve databases were searched and a systematic review and meta-analysis were conducted. Mean change (MC), mean difference (MD), and risk ratios (RR) with a 95% confidence interval (CI) were calculated using a random effects model. The GRADE approach was used to evaluate the evidence's certainty. Nine randomized trials were included. The MC of total serum bilirubin (mg/dL) was significant at 12, 24, 36, 48, and 72 h with respective MC (95% CI) values of -0.46 (-0.61, -0.310), -1.10 (-1.68, -0.52), -2.06 (-2.20, -1.91), -2.15 (-2.74, -1.56), and -1.13 (-1.71, -0.55). The FEN + PT group had a shorter duration of phototherapy (MD: -14.36 h; 95% CI: -23.67, -5.06) and a shorter hospital stay (MD: -1.40 days; 95% CI: -2.14, -0.66). There was no significant difference in the risk of complications (RR: 0.89; 95% CI: 0.54, 1.46) or the need for exchange transfusion (RR: 0.58; 95% CI: 0.12, 2.81). The certainty of the evidence was very low for all outcomes. In conclusion, fenofibrate might be a safe adjunct to neonatal phototherapy. Larger randomized controlled trials are needed for the confirmation of these results.

Rural-urban stroke mortality gaps in the United States.

INTRODUCTION: Disparities in stroke outcomes, influenced by the use of systemic thrombolysis, endovascular therapies, and rehabilitation services, have been identified. Our study assesses these disparities in mortality after stroke between rural and urban areas across the United States (US). METHODS: We analyzed the CDC data on deaths attributed to cerebrovascular disease from 1999 to 2020. Data was categorized into rural and urban regions for comparative purposes. Age-adjusted mortality rates (AAMR) were computed using the direct method, allowing us to examine the ratios of rural to urban deaths for the cumulative population and among demographic subpopulations. Linear regression models were used to assess temporal changes in mortality ratios over the study period, yielding beta-coefficients (ß). RESULTS: There was a total of 628,309 stroke deaths in rural regions and 2,556,293 stroke deaths within urban regions. There were 1.13 rural deaths for each one urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.41). The rural-urban mortality ratio in Hispanic populations decreased from 1.32 rural deaths for each urban death per 100,000 population in 1999 to 0.85 in 2020 (ß = -0.011, ptrend < 0.001). For non-Hispanic populations, mortality remained stagnant with 1.12 rural deaths for each urban death per 100,000 population in 1999 and 1.07 in 2020 (ß = -0.001, ptrend = 0.543). Regionally, the Southern US exhibited the highest disparity with a urban-rural mortality ratio of 1.19, followed by the Northeast (1.13), Midwest (1.04), and West (1.01). CONCLUSIONS: Our findings depict marked disparities in stroke mortality between rural and urban regions, emphasizing the importance of targeted interventions to mitigate stroke-related disparities.

Plasma-Enabled Graphene Quantum Dot Hydrogels as Smart Anticancer Drug Nanocarriers.

One of the major challenges on the way to low-cost, simple, and effective cancer treatments is the lack of smart anticancer drug delivery materials with the requisite of site-specific and microenvironment-responsive properties. This work reports the development of plasma-engineered smart drug nanocarriers (SDNCs) containing chitosan and nitrogen-doped graphene quantum dots (NGQDs) for drug delivery in a pH-responsive manner. Through a customized microplasma processing, a highly cross-linked SDNC with only 4.5% of NGQD ratio can exhibit enhanced toughness up to threefold higher than the control chitosan group, avoiding the commonly used high temperatures and toxic chemical cross-linking agents. The SDNCs demonstrate improved loading capability for doxorubicin (DOX) via π-π interactions and stable solid-state photoluminescence to monitor the DOX loading and release through the Förster resonance energy transfer (FRET) mechanism. Moreover, the DOX loaded SDNC exhibits anticancer effects against cancer cells during cytotoxicity tests at minimum concentration. Cellular uptake studies confirm that the DOX loaded SDNC can be successfully internalized into the nucleus after 12 h incubation period. This work provides new insights into the development of smart, environmental-friendly, and biocompatible nanographene hydrogels for the next-generation biomedical applications.

Electric Field-Assisted Nanofiltration for PFOA Removal with Exceptional Flux, Selectivity, and Destruction.

Per- and polyfluoroalkyl substances (PFAS) pose significant environmental and human health risks and thus require solutions for their removal and destruction. However, PFAS cannot be destroyed by widely used removal processes like nanofiltration (NF). A few scarcely implemented advanced oxidation processes can degrade PFAS. In this study, we apply an electric field to a membrane system by placing a nanofiltration membrane between reactive electrodes in a crossflow configuration. The performance of perfluorooctanoic acid (PFOA) rejection, water flux, and energy consumption were evaluated. The reactive and robust SnO2-Sb porous anode was created via a sintering and sol-gel process. The characterization and analysis techniques included field emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), ion chromatography, mass spectroscopy, porosimeter, and pH meter. The PFOA rejection increased from 45% (0 V) to 97% (30 V) when the electric field and filtration were in the same direction, while rejection capabilities worsened in opposite directions. With saline solutions (1 mM Na2SO4) present, the induced electro-oxidation process could effectively mineralize PFOA, although this led to unstable removal and water fluxes. The design achieved an exceptional performance in the nonsaline feed of 97% PFOA rejection and water flux of 68.4 L/m2 hr while requiring only 7.31 × 10-5 kWh/m3/order of electrical energy. The approach's success is attributed to the proximity of the electrodes and membrane, which causes a stronger electric field, weakened concentration polarization, and reduced mass transfer distances of PFOA near the membrane. The proposed electric field-assisted nanofiltration design provides a practical membrane separation method for PFAS removal from water.

Experimental Investigation of Relative Localization Estimation in a Coordinated Formation Control of Low-Cost Underwater Drones.

This study presents a relative localization estimation method for a group of low-cost underwater drones (l-UD), which only uses visual feedback provided by an on-board camera and IMU data. It aims to design a distributed controller for a group of robots to reach a specific shape. This controller is based on a leader-follower architecture. The main contribution is to determine the relative position between the l-UD without using digital communication and sonar positioning methods. In addition, the proposed implementation of the EKF to fuse the vision data and the IMU data improves the prediction capability in cases where the robot is out of view of the camera. This approach allows the study and testing of distributed control algorithms for low-cost underwater drones. Finally, three robot operating system (ROS) platform-based BlueROVs are used in an experiment in a near-realistic environment. The experimental validation of the approach has been obtained by investigating different scenarios.

Efflux Pump Inhibitors in Controlling Antibiotic Resistance: Outlook under a Heavy Metal Contamination Context.

Multi-drug resistance to antibiotics represents a growing challenge in treating infectious diseases. Outside the hospital, bacteria with the multi-drug resistance (MDR) phenotype have an increased prevalence in anthropized environments, thus implying that chemical stresses, such as metals, hydrocarbons, organic compounds, etc., are the source of such resistance. There is a developing hypothesis regarding the role of metal contamination in terrestrial and aquatic environments as a selective agent in the proliferation of antibiotic resistance caused by the co-selection of antibiotic and metal resistance genes carried by transmissible plasmids and/or associated with transposons. Efflux pumps are also known to be involved in either antibiotic or metal resistance. In order to deal with these situations, microorganisms use an effective strategy that includes a range of expressions based on biochemical and genetic mechanisms. The data from numerous studies suggest that heavy metal contamination could affect the dissemination of antibiotic-resistant genes. Environmental pollution caused by anthropogenic activities could lead to mutagenesis based on the synergy between antibiotic efficacy and the acquired resistance mechanism under stressors. Moreover, the acquired resistance includes plasmid-encoded specific efflux pumps. Soil microbiomes have been reported as reservoirs of resistance genes that are available for exchange with pathogenic bacteria. Importantly, metal-contaminated soil is a selective agent that proliferates antibiotic resistance through efflux pumps. Thus, the use of multi-drug efflux pump inhibitors (EPIs) originating from natural plants or synthetic compounds is a promising approach for restoring the efficacy of existing antibiotics, even though they face a lot of challenges.

Sensory neuron dysfunction in orthotopic mouse models of colon cancer.

Reports of neurological sequelae related to colon cancer are largely restricted to rare instances of paraneoplastic syndromes, due to autoimmune reactions. Systemic inflammation associated with tumor development influences sensory neuron function in other disease models, though the extent to which this occurs in colorectal cancer is unknown. We induced orthotopic colorectal cancer via orthotopic injection of two colorectal cancer cell lines (MC38 and CT26) in two different mouse strains (C57BL/6 and Balb/c, respectively). Behavioral tests of pain sensitivity and activity did not detect significant alterations in sensory sensitivity or diminished well-being throughout tumor development. However, immunohistochemistry revealed widespread reductions in intraepidermal nerve fiber density in the skin of tumor-bearing mice. Though loss of nerve fiber density was not associated with increased expression of cell injury markers in dorsal root ganglia, lumbar dorsal root ganglia neurons of tumor-bearing animals showed deficits in mitochondrial function. These neurons also had reduced cytosolic calcium levels in live-cell imaging and reduced spontaneous activity in multi-electrode array analysis. Bulk RNA sequencing of DRGs from tumor-bearing mice detected activation of gene expression pathways associated with elevated cytokine and chemokine signaling, including CXCL10. This is consistent with the detection of CXCL10 (and numerous other cytokines, chemokines and growth factors) in MC38 and CT26 cell-conditioned media, and the serum of tumor-bearing mice. Our study demonstrates in a pre-clinical setting that colon cancer is associated with latent sensory neuron dysfunction and implicates cytokine/chemokine signaling in this process. These findings may have implications for determining risk factors and treatment responsiveness related to neuropathy in colorectal cancer.

Physiological effects of inactivation and the roles of Elovl3/ELOVL3 in maintaining ocular homeostasis.

Recently, elongase of very long chain fatty acids-3 (ELOVL3) was demonstrated to play a pivotal role in physiology and biochemistry of the ocular surface by maintaining a proper balance in the lipid composition of meibum. The goal of this study was to further investigate the effects of ELOVL3 ablation in homozygous Elovl3-knockout mice (E3hom) in comparison with age and sex matched wild-type controls (E3wt). Slit lamp examination of the ocular surface of mice, and histological examination of their ocular tissues, highlighted a severe negative impact of Elovl3 inactivating mutation on the Meibomian glands (MG) and conjunctiva of mice. MG transcriptomes of the E3hom and E3wt mice were assessed and revealed a range of up- and downregulated genes related to lipid biosynthesis, inflammation, and stress response, compared with E3wt mice. Heat stage polarized light microscopy was used to assess melting characteristics of normal and abnormal meibum. The loss of Elovl3 led to a 8°C drop in the melting temperature of meibum in E3hom mice, and increased its fluidity. Also noted were the excessive accumulation of lipid material and tears around the eye and severe ocular inflammation, among other abnormalities.

Clinical evaluation of a novel subcutaneous lactate monitor.

Lactate levels are commonly used as an indirect measure to assess metabolic stress in clinical conditions like sepsis. Dynamic lactate measurements are recommended to assess and guide treatment in patients with shock and other critical care conditions. A minimally invasive, continuous lactate monitor has potential to improve clinical decisions and patient care. The purpose of the study was to evaluate continuous lactate measurements of a novel enzymatic Continuous Lactate Monitor (CLM) developed in our laboratory. Lactate levels were monitored during incremental cycling exercise challenges as a tool for hyperlactatemia. Six healthy individuals 18-45 y/o (4 males, 2 females) participated in the study. CLM devices were inserted subcutaneously in the postero-lateral trunk below the renal angle, one hour before the exercise challenge. Each exercise challenge consisted of a 3 to 12-min warm up period, followed by up to 7, 4-min incremental workload bouts separated by rest intervals. Continuous lactate measurements obtained from CLM were compared with commercial lactate analyzer (Abbott iSTAT) measurements of venous blood (plasma) drawn from the antecubital vein. Blood was drawn at up to 25 time points spanning the duration of before exercise, during exercise, and up to 120 min post exercise. Area under the curve (AUC), and delay time were calculated to compare the CLM readings with plasma lactate concentration. Average plasma lactate concentration increased from 1.02 to 16.21 mM. Ratio of AUC derived from CLM to plasma lactate was 1.025 (0.990-1.058). Average dynamic delay time of CLM to venous plasma lactate was 5.22 min (2.87-10.35). Insertion sites examined 48 h after CLM removal did not show signs of side effects and none required medical attention upon examination. The newly developed CLM has shown to be a promising tool to continuously measure lactate concentration in a minimally invasive fashion. Results indicate the CLM can provide needed trends in lactate over time. Such a device may be used in the future to improve treatment in clinical conditions such as sepsis.

Methyl Internal Rotation in Fruit Esters: Chain-Length Effect Observed in the Microwave Spectrum of Methyl Hexanoate.

The gas-phase structures of the fruit ester methyl hexanoate, CH3-O-(C=O)-C5H11, have been determined using a combination of molecular jet Fourier-transform microwave spectroscopy and quantum chemistry. The microwave spectrum was measured in the frequency range of 3 to 23 GHz. Two conformers were assigned, one with Cs symmetry and the other with C1 symmetry where the γ-carbon atom of the hexyl chain is in a gauche orientation in relation to the carbonyl bond. Splittings of all rotational lines into doublets were observed due to internal rotation of the methoxy methyl group CH3-O, from which torsional barriers of 417 cm-1 and 415 cm-1, respectively, could be deduced. Rotational constants obtained from geometry optimizations at various levels of theory were compared to the experimental values, confirming the soft degree of freedom of the (C=O)-C bond observed for the C1 conformer of shorter methyl alkynoates like methyl butyrate and methyl valerate. Comparison of the barriers to methyl internal rotation of methyl hexanoate to those of other CH3-O-(C=O)-R molecules leads to the conclusion that though the barrier height is relatively constant at about 420 cm-1, it decreases in molecules with longer R.

Tracking macrophages in diabetic neuropathy with two-color nanoemulsions for near-infrared fluorescent imaging and microscopy.

BACKGROUND: The incidence of diabetes and diabetic peripheral neuropathy continues to rise, and studies have shown that macrophages play an important role in their pathogenesis. To date, macrophage tracking has largely been achieved using genetically-encoded fluorescent proteins. Here we present a novel two-color fluorescently labeled perfluorocarbon nanoemulsion (PFC-NE) designed to monitor phagocytic macrophages in diabetic neuropathy in vitro and in vivo using non-invasive near-infrared fluorescent (NIRF) imaging and fluorescence microscopy. METHODS: Presented PFC-NEs were formulated with perfluorocarbon oil surrounded by hydrocarbon shell carrying two fluorescent dyes and stabilized with non-ionic surfactants. In vitro assessment of nanoemulsions was performed by measuring fluorescent signal stability, colloidal stability, and macrophage uptake and subsequent viability. The two-color PFC-NE was administered to Leprdb/db and wild-type mice by tail vein injection, and in vivo tracking of the nanoemulsion was performed using both NIRF imaging and confocal microscopy to assess its biodistribution within phagocytic macrophages along the peripheral sensory apparatus of the hindlimb. RESULTS: In vitro experiments show two-color PFC-NE demonstrated high fluorescent and colloidal stability, and that it was readily incorporated into RAW 264.7 macrophages. In vivo tracking revealed distribution of the two-color nanoemulsion to macrophages within most tissues of Leprdb/db and wild-type mice which persisted for several weeks, however it did not cross the blood brain barrier. Reduced fluorescence was seen in sciatic nerves of both Leprdb/db and wild-type mice, implying that the nanoemulsion may also have difficulty crossing an intact blood nerve barrier. Additionally, distribution of the nanoemulsion in Leprdb/db mice was reduced in several tissues as compared to wild-type mice. This reduction in biodistribution appears to be caused by the increased number of adipose tissue macrophages in Leprdb/db mice. CONCLUSIONS: The nanoemulsion in this study has the ability to identify phagocytic macrophages in the Leprdb/db model using both NIRF imaging and fluorescence microscopy. Presented nanoemulsions have the potential for carrying lipophilic drugs and/or fluorescent dyes, and target inflammatory macrophages in diabetes. Therefore, we foresee these agents becoming a useful tool in both imaging inflammation and providing potential treatment in diabetic peripheral neuropathy.

Plasmon-Free Polymeric Nanowrinkled Substrates for Surface-Enhanced Raman Spectroscopy of Two-Dimensional Materials.

We report plasmon-free polymeric nanowrinkled substrates for surface-enhanced Raman spectroscopy (SERS). Our simple, rapid, and cost-effective fabrication method involves depositing a poly(ethylene glycol)diacrylate (PEGDA) prepolymer solution droplet on a fully polymerized, flat PEGDA substrate, followed by drying the droplet at room conditions and plasma treatment, which polymerizes the deposited layer. The thin polymer layer buckles under axial stress during plasma treatment due to its different mechanical properties from the underlying soft substrate, creating hierarchical wrinkled patterns. We demonstrate the variation of the wrinkling wavelength with the drying polymer molecular weight and concentration (direct relations are observed). A transition between micron to nanosized wrinkles is observed at 5 v % concentration of the lower molecular-weight polymer solution (PEGDA Mn 250). The wrinkled substrates are observed to be reproducible, stable (at room conditions), and, especially, homogeneous at and below the transition regime, where nanowrinkles dominate, making them suitable candidates for SERS. As a proof-of-concept, the enhanced SERS performance of micro/nanowrinkled surfaces in detecting graphene and hexagonal boron nitride (h-BN) is illustrated. Compared to the SiO2/Si surfaces, the wrinkled PEGDA substrates significantly enhanced the signature Raman band intensities of graphene and h-BN by a factor of 8 and 50, respectively.

Oxidizing Cerium(IV) Alkoxide Complexes Supported by the Kläui Ligand [Co(η5-C5H5){P(O)(OEt)2}3]-: Synthesis, Structure, and Redox Reactivity.

Tetravalent cerium alkoxide complexes supported by the Kläui tripodal ligand [Co(η5-C5H5){P(O)(OEt)2}3]- (LOEt-) have been synthesized, and their nucleophilic and redox reactivity have been studied. Treatment of the Ce(IV) oxo complex [CeIV(LOEt)2(O)(H2O)]·MeCONH2 (1) with iPrOH or reaction of [CeIV(LOEt)2Cl2] (2) with Ag2O in iPrOH afforded the Ce(IV) dialkoxide complex [CeIV(LOEt)2(OiPr)2] (3-iPr). The methoxide and ethoxide analogues [CeIV(LOEt)2(OR)2] (R = Me (3-Me), Et (3-Et)) have been prepared similarly from 2 and Ag2O in ROH. Reaction of 3-iPr with an equimolar amount of 2 yielded a new Ce(IV) complex that was formulated as the chloro-alkoxide complex [CeIV(LOEt)2(OiPr)Cl] (4). Treatment of 3-iPr with HX and methyl triflate (MeOTf) afforded [Ce(LOEt)2X2] (X- = Cl-, NO3-, PhO-) and [CeIV(LOEt)2(OTf)2], respectively, whereas treatment with excess CO2 in hexane led to isolation of the Ce(IV) carbonate [CeIV(LOEt)2(CO3)]. 3-iPr reacted with water in hexane to give a Ce(III) complex and a Ce(IV) species, presumably the reported tetranuclear oxo cluster [CeIV4(LOEt)4(O)5(OH)2]. The Ce(IV) alkoxide complexes are capable of oxidizing substituted phenols, possibly via a proton-coupled electron transfer pathway. Treatment of 3-iPr with ArOH afforded the Ce(III) aryloxide complexes [CeIII(LOEt)2(OAr)] (Ar = 2,4,6-tri-tert-butylphenyl (5), 2,6-diphenylphenyl (6)). On the other hand, a Ce(III) complex containing a monodeprotonated 2,2'-biphenol ligand, [CeIII(LOEt)2(tBu4C12H4O2H)] (7) (tBu4C12H4O2H2 = 4,4',6,6'-tetra-tert-butyl-2,2'-biphenol), was isolated from the reaction of 3-iPr with 2,4-di-tert-butylphenol. The crystal structures of complexes 3-iPr, 3-Me, 3-Et, and 5-7 have been determined.