MmcA is an electron conduit that facilitates both intracellular and extracellular electron transport in Methanosarcina acetivorans.

Methanogens are a diverse group of Archaea that obligately couple energy conservation to the production of methane. Some methanogens encode alternate pathways for energy conservation, like anaerobic respiration, but the biochemical details of this process are unknown. We show that a multiheme c-type cytochrome called MmcA from Methanosarcina acetivorans is important for intracellular electron transport during methanogenesis and can also reduce extracellular electron acceptors like soluble Fe3+ and anthraquinone-2,6-disulfonate. Consistent with these observations, MmcA displays reversible redox features ranging from -100 to -450 mV versus SHE. Additionally, mutants lacking mmcA have significantly slower Fe3+ reduction rates. The mmcA locus is prevalent in members of the Order Methanosarcinales and is a part of a distinct clade of multiheme cytochromes that are closely related to octaheme tetrathionate reductases. Taken together, MmcA might act as an electron conduit that can potentially support a variety of energy conservation strategies that extend beyond methanogenesis.

Joint Exposure to Multiple Air Pollutants, Genetic Susceptibility, and Incident Dementia: A Prospective Analysis in the UK Biobank Cohort.

Objectives: This study aimed to evaluate the joint effects of multiple air pollutants including PM2.5, PM10, NO2, and NOx with dementia and examined the modifying effects of genetic susceptibility. Methods: This study included 220,963 UK Biobank participants without dementia at baseline. Weighted air pollution score reflecting the joint exposure to multiple air pollutants were constructed by cross-validation analyses, and inverse-variance weighted meta-analyses were performed to create a pooled effect. The modifying effect of genetic susceptibility on air pollution score was assessed by genetic risk score and APOE ε4 genotype. Results: The HR (95% CI) of dementia for per interquartile range increase of air pollution score was 1.13 (1.07∼1.18). Compared with the lowest quartile (Q1) of air pollution score, the HR (95% CI) of Q4 was 1.26 (1.13∼1.40) (P trend = 2.17 × 10-5). Participants with high air pollution score and high genetic susceptibility had higher risk of dementia compared to those with low air pollution score and low genetic susceptibility. Conclusion: Our study provides evidence that joint exposure to multiple air pollutants substantially increases the risk of dementia, especially among individuals with high genetic susceptibility.

Identifying risk loci for obsessive-compulsive disorder and shared genetic component with schizophrenia: A large-scale multi-trait association analysis with summary statistics.

Due to limited samples, no genetic loci have been identified for obsessive-compulsive disorder (OCD) in genome-wide association studies. Additionally, although co-morbidities between OCD and schizophrenia (SCZ) were observed, their common genetic etiology was not completely known. Here, we conducted a comprehensive investigation regarding the genetic architecture of OCD and the common genetic foundation shared by OCD and SCZ using summary statistics data (2688 cases and 7037 controls for OCD; 53,386 cases and 77,258 controls for SCZ). We discovered significant genetic correlation between OCD and SCZ (r̂g=0.296, P = 2.82 × 10-11). We then performed two multi-trait association analyses to detect OCD-associated loci and colocalization analysis to detect causal variants. Parallel gene-level analyses were also implemented. We identified 323 OCD-relevant variants located within 12 loci, with four loci shared the same causal variants between OCD and SCZ. Further, the gene-level analyses discovered 8 OCD-associated genes. Finally, multiple functional analyses at both SNP and gene levels showed that these genetic association signals had significant enrichments in the regions of left ventricle and anterior cingulate cortex, and suggested an important role of pathways involving regulation of telomere maintenance, histone phosphorylation, and GnRH secretion. Overall, this study identified new genetic loci for OCD and provided substantial evidence supporting common genetic foundation underlying OCD and SCZ. The findings advanced our understanding of genetic architecture and pathophysiology of OCD as well as shedding light on shared genetic etiology of the two disorders.

Identifying risk loci for FTD and shared genetic component with ALS: A large-scale multitrait association analysis.

Current genome-wide association studies of frontotemporal dementia (FTD) are underpowered due to limited samples. Further, common genetic etiologies between FTD and amyotrophic lateral sclerosis (ALS) remain unknown. Using the largest summary statistics of FTD (3526 cases and 9402 controls) and ALS (27,205 cases and 110,881 controls), we found a significant genetic correlation between them (rˆg = 0.637, P = 0.032) and identified 190 FTD-related variants within 5 loci (3p22.1, 5q35.1, 9p21.2, 19p13.11, and 20q13.13). Among these, ALS and FTD had causal variants in 9p21.2 and 19p13.11. Moreover, MOBP (3p22.1), C9orf72 (9p21.2), MOB3B (9p21.2), UNC13A (19p13.11), SLC9A8 (20q13.13), SNAI1 (20q13.13), and SPATA2 (20q13.13) were discovered by both SNP- and gene-level analyses, which together discovered 15 FTD-associated genes, with 10 not detected before (IFNK, RNF114, SLC9A8, SPATA2, SNAI1, SCFD1, POLDIP2, TMEM97, G2E3, and PIGW). Functional analyses showed these genes were enriched in heart left ventricle, kidney cortex, and some brain regions. Overall, this study provides insights into genetic determinants of FTD and shared genetic etiology underlying FTD and ALS.

Co-exposure to multiple air pollutants, genetic susceptibility, and the risk of myocardial infarction onset: A cohort analysis of the UK Biobank participants.

AIMS: The relationship between the long-term joint exposure to ambient air pollution and incidence of myocardial infarction (MI), and modification by genetic susceptibility remain inconclusive. METHODS: We analyzed 329,189 UK Biobank participants without MI at baseline. Exposure concentrations to particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were obtained. Air pollution score assessing the joint exposure were calculated, and its association with MI was evaluated via Cox model under the P-value aggregation framework. Genetic susceptibility to MI was evaluated by incorporating polygenic risk score (PRS) into models. Risk prediction models were also established. RESULTS: During a median follow-up of 13.4 years, 9,993 participants developed MI. Per interquartile range increase of PM2.5, PM10, NO2, and NOx resulted in 74% (95% confidence intervals [CIs] 69%∼79%), 67% (63%∼72%), 46% (42%∼49%), and 38% (35%∼41%) higher risk of MI. Compared with the lowest quartile (Q1) of air pollution score, the multivariable adjusted hazard ratio (HR) (95%CIs) of Q4 (the highest cumulative air pollution) was 3.50 (3.29∼3.72) for MI. Participants with the highest PRS and air pollution score possessed the highest risk of incident MI (HR=4.88, 95%CIs 4.35∼5.47). Integrating PRS, air pollution exposure and traditional factors substantially improved risk prediction of MI. CONCLUSIONS: Long-term joint exposure to air pollutants including PM2.5, PM10, NO2, and NOx is substantially associated with increased risk of MI. Genetic susceptibility to MI strengthens such adverse joint association. Air pollutions together genetic and traditional factors enhances the accuracy of MI risk prediction.

Our study aimed to analyze the relationship between the long-term joint exposure to four ambient air pollutants and incidence of myocardial infarction (MI), and the modification role of genetic susceptibility. Four air pollutants (PM2.5, PM10, NO2, and NOx) were adversely associated with the incidence of MI as well as with its two subtypes including STEMI and NSTEMI. Air pollution score representing co-exposure to multiple air pollutants was related to increased risk of incident MI, STEMI and NSTEMI. Genetic susceptibility to MI strengthened the adverse association of co-exposure to air pollution with the risk of MI, STEMI and NSTEMI.

Neuronal functional connectivity is impaired in a layer dependent manner near the chronically implanted microelectrodes.

Objective: This study aims to reveal longitudinal changes in functional network connectivity within and across different brain structures near the chronically implanted microelectrode. While it is well established that the foreign-body response (FBR) contributes to the gradual decline of the signals recorded from brain implants over time, how does the FBR impact affect the functional stability of neural circuits near implanted Brain-Computer Interfaces (BCIs) remains unknown. This research aims to illuminate how the chronic FBR can alter local neural circuit function and the implications for BCI decoders. Approach: This study utilized multisite Michigan-style microelectrodes that span all cortical layers and the hippocampal CA1 region to collect spontaneous and visually-evoked electrophysiological activity. Alterations in neuronal activity near the microelectrode were tested assessing cross-frequency synchronization of LFP and spike entrainment to LFP oscillatory activity throughout 16 weeks after microelectrode implantation. Main Results: The study found that cortical layer 4, the input-receiving layer, maintained activity over the implantation time. However, layers 2/3 rapidly experienced severe impairment, leading to a loss of proper intralaminar connectivity in the downstream output layers 5/6. Furthermore, the impairment of interlaminar connectivity near the microelectrode was unidirectional, showing decreased connectivity from Layers 2/3 to Layers 5/6 but not the reverse direction. In the hippocampus, CA1 neurons gradually became unable to properly entrain to the surrounding LFP oscillations. Significance: This study provides a detailed characterization of network connectivity dysfunction over long-term microelectrode implantation periods. This new knowledge could contribute to the development of targeted therapeutic strategies aimed at improving the health of the tissue surrounding brain implants and potentially inform engineering of adaptive decoders as the FBR progresses. Our study's understanding of the dynamic changes in the functional network over time opens the door to developing interventions for improving the long-term stability and performance of intracortical microelectrodes.

Cell-specific alterations in autophagy-lysosomal activity near the chronically implanted microelectrodes.

Intracortical microelectrodes that can record and stimulate brain activity have become a valuable technique for basic science research and clinical applications. However, long-term implantation of these microelectrodes can lead to progressive neurodegeneration in the surrounding microenvironment, characterized by elevation in disease-associated markers. Dysregulation of autophagy-lysosomal degradation, a major intracellular waste removal process, is considered a key factor in the onset and progression of neurodegenerative diseases. It is plausible that similar dysfunctions in autophagy-lysosomal degradation contribute to tissue degeneration following implantation-induced focal brain injury, ultimately impacting recording performance. To understand how the focal, persistent brain injury caused by long-term microelectrode implantation impairs autophagy-lysosomal pathway, we employed two-photon microscopy and immunohistology. This investigation focused on the spatiotemporal characterization of autophagy-lysosomal activity near the chronically implanted microelectrode. We observed an aberrant accumulation of immature autophagy vesicles near the microelectrode over the chronic implantation period. Additionally, we found deficits in autophagy-lysosomal clearance proximal to the chronic implant, which was associated with an accumulation of autophagy cargo and a reduction in lysosomal protease level during the chronic period. Furthermore, our evidence demonstrates reactive astrocytes have myelin-containing lysosomes near the microelectrode, suggesting its role of myelin engulfment during acute implantation period. Together, this study sheds light on the process of brain tissue degeneration caused by long-term microelectrode implantation, with a specific focus on impaired intracellular waste degradation.

Long-term influence of air pollutants on morbidity and all-cause mortality of cardiometabolic multi-morbidity: A cohort analysis of the UK Biobank participants.

BACKGROUND: The effects of air pollutants on cardiometabolic diseases (CMDs) have been widely explored, whereas their influences on cardiometabolic multi-morbidity (CMM) were not clear. METHODS: We employed the UK Biobank cohort (N = 317,160) to study the association between six air pollutants (PM2.5, PM10, PM2.5-10, PM2.5abs, NO2, and NOx) and four CMDs including type II diabetes (T2D), coronary artery disease (CAD), stroke and hypertension. CMM was defined as occurrence of two or more of the four diseases. Multi-state Cox models were performed to estimate hazard ratio (HR) and its 95% confidence interval (95%CI). RESULTS: During a median follow-up of 12.8 years, 52,211 participants developed only one CMD, 15,446 further developed CMM, and 16,861 ultimately died. It was demonstrated that per interquartile range increase (IQR) increases in PM2.5, PM10, PM2.5-10, PM2.5abs, NO2, and NOx would increase 12% (9%-15%), 4% (1%-7%), 3% (1%-6%), 7% (4%-10%), 11% (8%-15%) and 10% (7%-13%) higher risk of developing one CMD from health baseline; 7% (2%-12%), 8% (3%-13%), 6% (2%-11%), 10% (5%-15%), 13% (7%-18%) and 10% (5%-15%) greater risk of occurring CMM from one CMD baseline; and 11% (-2%∼26%), 22% (7%-38%), 17% (3%-32%), 31% (16%-49%), 33% (17%-51%) and 32% (17%-50%) larger risk of causing death from CMM baseline, respectively. CONCLUSIONS: We revealed that people living in areas with high air pollution suffered from higher hazard of CMD, CMM and all-cause mortality; our findings implied keeping clean air was an effective approach to prevent or mitigate initiation, progression, and death from healthy to CMDs and from CMDs to CMM.

Pro-myelinating clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health.

Intracortical microelectrodes have become a useful tool in neuroprosthetic applications in the clinic and to understand neurological disorders in basic neurosciences. Many of these brain-machine interface technology applications require successful long-term implantation with high stability and sensitivity. However, the intrinsic tissue reaction caused by implantation remains a major failure mechanism causing loss of recorded signal quality over time. Oligodendrocytes remain an underappreciated intervention target to improve chronic recording performance. These cells can accelerate action potential propagation and provides direct metabolic support for neuronal health and functionality. However, implantation injury causes oligodendrocyte degeneration and leads to progressive demyelination in surrounding brain tissue. Previous work highlighted that healthy oligodendrocytes are necessary for greater electrophysiological recording performance and the prevention of neuronal silencing around implanted microelectrodes over the chronic implantation period. Thus, we hypothesize that enhancing oligodendrocyte activity with a pharmaceutical drug, Clemastine, will prevent the chronic decline of microelectrode recording performance. Electrophysiological evaluation showed that the promyelination Clemastine treatment significantly elevated the signal detectability and quality, rescued the loss of multi-unit activity, and increased functional interlaminar connectivity over 16-weeks of implantation. Additionally, post-mortem immunohistochemistry showed that increased oligodendrocyte density and myelination coincided with increased survival of both excitatory and inhibitory neurons near the implant. Overall, we showed a positive relationship between enhanced oligodendrocyte activity and neuronal health and functionality near the chronically implanted microelectrode. This study shows that therapeutic strategy that enhance oligodendrocyte activity is effective for integrating the functional device interface with brain tissue over chronic implantation period.

MmcA is an electron conduit that facilitates both intracellular and extracellular electron transport in Methanosarcina acetivorans.

Methanogens are a diverse group of Archaea that couple energy conservation to the production of methane gas. While most methanogens have no alternate mode of energy conservation, strains like Methanosarcina acetivorans are known to also conserve energy by dissimilatory metal reduction (DSMR) in the presence of soluble ferric iron or iron-containing minerals. The ecological ramifications of energy conservation decoupled from methane production in methanogens are substantial, yet the molecular details are poorly understood. In this work, we conducted in vitro and in vivo studies with a multiheme c-type cytochrome (MHC), called MmcA, to establish its role during methanogenesis and DSMR in M. acetivorans. MmcA purified from M. acetivorans can donate electrons to methanophenazine, a membrane-bound electron carrier, to facilitate methanogenesis. In addition, MmcA can also reduce Fe(III) and the humic acid analog anthraquinone-2,6-disulfonate (AQDS) during DSMR. Furthermore, mutants lacking mmcA have slower Fe(III) reduction rates. The redox reactivities of MmcA are consistent with the electrochemical data where MmcA displays reversible redox features ranging from -100 to -450 mV versus SHE. MmcA is prevalent in members of the Order Methanosarcinales but does not belong to a known family of MHCs linked to extracellular electron transfer, bioinformatically, and instead forms a distinct clade that is closely related to octaheme tetrathionate reductases. Taken together, this study shows that MmcA is widespread in methanogens with cytochromes where it acts as an electron conduit to support a variety of energy conservation strategies that extend beyond methanogenesis.

How Does Person-Environment Fit Relate to Career Calling? The Role of Psychological Contracts and Organizational Career Management.

Purpose: The formation of one's career calling involves endowing work with meaning and realizing oneself in work, and it has become a focus of organizational behavior research in the past decade. Although there are many studies on the outcome variables of career calling, research on the antecedents of career calling formation is relatively scarce, and its mechanisms are unclear. Based on fit theory and social exchange theory, we analyzed the data of 373 employees and explored the relationship between person-environment fit (focusing on person-organization fit and person-job fit), psychological contract, career calling and organizational career management. Methods: We adopted a multi-timepoint data collection method to analyze data from 373 employees from an internet technology company. A mediated moderation model and hypotheses were tested using Mplus 8.3 software. Results: The results showed that person-organization fit and person-job fit were positively related to career calling, and the psychological contract played a partial mediating role. The moderating effect of organizational career management on person-organization fit, person-job fit and the psychological contract was also confirmed. Moreover, the mediating effect of the psychological contract was stronger when organizational career management was higher. Conclusion: We examined the important influence of individual-level and organizational-level factors on the formation of career calling. The findings highlight the important role and mechanism of person-environment fit in the formation of career calling through psychological factors, which has managerial implications for how to develop employees' career calling.

Preparation of fat replacer utilizing gluten and barley ß-glucan and the interaction between them.

BACKGROUND: Fat replacers prepared from polysaccharides and proteins possess functional properties of both polysaccharides and proteins. In this study, an aqueous system of barley ß-glucan (BBG) and gluten was prepared. The interactions between BBG and gluten (with/without extrusion modification) were studied. Triple analysis methods, including differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and low-field nuclear magnetic resonance (LF-NMR), were utilized to analyze the freezing-thawing and thermal evaporation process, as well as the distribution state of water. Meanwhile, fluorescence microscopic analysis, dynamic rheological analysis and electrophoresis analysis were used to study the structure and rheological properties of the system. RESULTS: The results showed that BBG significantly increased the water-holding capacity of gluten, regardless of extrusion treatment, with the water absorption reaching about 4.8 to 6.4 times of its weight, which was 1 to 2.5 times higher than that without BBG. The triple analysis results suggested that BBG increased the binding capacity of the system to weakly bound water, hindered the aggregation of gluten and reduced the thermal decomposition temperature of the BBG and gluten composite system. After the gluten was extruded and homogenized with the BBG solution, the appearance of the composite system was more uniform and delicate. CONCLUSIONS: In conclusion, BBG increased the water-holding capacity of the BBG and gluten composite system. With these changes, the composite system presented great potential for the preparation of polysaccharide-gluten fat replacer. © 2023 Society of Chemical Industry.

Pro-myelinating Clemastine administration improves recording performance of chronically implanted microelectrodes and nearby neuronal health.

Intracortical microelectrodes have become a useful tool in neuroprosthetic applications in the clinic and to understand neurological disorders in basic neurosciences. Many of these brain-machine interface technology applications require successful long-term implantation with high stability and sensitivity. However, the intrinsic tissue reaction caused by implantation remains a major failure mechanism causing loss of recorded signal quality over time. Oligodendrocytes remain an underappreciated intervention target to improve chronic recording performance. These cells can accelerate action potential propagation and provides direct metabolic support for neuronal health and functionality. However, implantation injury causes oligodendrocyte degeneration and leads to progressive demyelination in surrounding brain tissue. Previous work highlighted that healthy oligodendrocytes are necessary for greater electrophysiological recording performance and the prevention of neuronal silencing around implanted microelectrodes over chronic implantation. Thus, we hypothesize that enhancing oligodendrocyte activity with a pharmaceutical drug, Clemastine, will prevent the chronic decline of microelectrode recording performance. Electrophysiological evaluation showed that the promyelination Clemastine treatment significantly elevated the signal detectability and quality, rescued the loss of multi-unit activity, and increased functional interlaminar connectivity over 16-weeks of implantation. Additionally, post-mortem immunohistochemistry showed that increased oligodendrocyte density and myelination coincided with increased survival of both excitatory and inhibitory neurons near the implant. Overall, we showed a positive relationship between enhanced oligodendrocyte activity and neuronal health and functionality near the chronically implanted microelectrode. This study shows that therapeutic strategy that enhance oligodendrocyte activity is effective for integrating the functional device interface with brain tissue over chronic implantation period.

The amino acid transporter SLC7A11-mediated crosstalk implicated in cancer therapy and the tumor microenvironment.

The solute carrier family 7 member 11 (SLC7A11), an amino acid transporter protein is frequently overexpressed in human malignancies. The expression and activity of SLC7A11 is finely regulated by oncogenes and tumor suppressors in tumor cells through various mechanisms and is highly specific for cystine and glutamate. Cystine is mainly transported intracellularly by SLC7A11 in the tumor microenvironment (TME) and is involved in GSH synthesis, which leads to ferroptosis resistance in tumor cells and promotes tumorigenesis and progression. The downregulation of SLC7A11 presents a unique drug discovery opportunity for ferroptosis-related diseases. Experimental work has shown that the combination of targeting SLC7A11 and tumor immunotherapy triggers ferroptosis more potently. Moreover, immunotargeting of SLC7A11 increases the chemosensitivity of cancer stem cells to doxorubicin, suggesting that it may act as an adjuvant to chemotherapy. Thus, SLC7A11 could be a promising target to overcome resistance mechanisms in conventional cancer treatments. This review provides an overview of the regulatory network of SLC7A11 in the TME and progress in the development of SLC7A11 inhibitors. In addition, we summarize the cytotoxic effects of blocking SLC7A11 in cancer cells, cancer stem cells and immune cells.

In vivo spatiotemporal dynamics of astrocyte reactivity following neural electrode implantation.

Brain computer interfaces (BCIs), including penetrating microelectrode arrays, enable both recording and stimulation of neural cells. However, device implantation inevitably causes injury to brain tissue and induces a foreign body response, leading to reduced recording performance and stimulation efficacy. Astrocytes in the healthy brain play multiple roles including regulating energy metabolism, homeostatic balance, transmission of neural signals, and neurovascular coupling. Following an insult to the brain, they are activated and gather around the site of injury. These reactive astrocytes have been regarded as one of the main contributors to the formation of a glial scar which affects the performance of microelectrode arrays. This study investigates the dynamics of astrocytes within the first 2 weeks after implantation of an intracortical microelectrode into the mouse brain using two-photon microscopy. From our observation astrocytes are highly dynamic during this period, exhibiting patterns of process extension, soma migration, morphological activation, and device encapsulation that are spatiotemporally distinct from other glial cells, such as microglia or oligodendrocyte precursor cells. This detailed characterization of astrocyte reactivity will help to better understand the tissue response to intracortical devices and lead to the development of more effective intervention strategies to improve the functional performance of neural interfacing technology.

Bovine serum albumin-gold nanoclusters protein corona stabilized polystyrene nanoparticles as dual-color fluorescent nanoprobes for breast cancer detection.

Breast cancer is the most prevalent malignancy and the first leading cause of cancer-related mortality among the female population worldwide. Approaches for precise and reliable detection of breast cancer cells, particularly in the nascent state, are desperately needed for elevating the survival rate of patients bearing the breast tumor. In this work, we successfully performed the sensitive, precise, and reliable breast cancer cell detection using facilely fabricated bovine serum albumin-gold nanocluster (BSA-AuNCs) protein corona stabilized, epithelial cell adhesion molecule (EpCAM) aptamer linked fluorescent polystyrene nanoparticle (PS NP), termed as PS-BSA-AuNCs-Apt. The rapidly adsorbed BSA-AuNCs hard protein corona without complicated covalent conjugation not only imparted excellent colloidal stability to the PS nanoparticles, but also offered numerous active anchors for the targeted EpCAM aptamers to locate. With the remarkable aid of the aptamers specifically targeting the EpCAM-positive breast cancer cells, the PS-BSA-AuNCs-Apt emitted strong and photostable dual-color fluorescent signals for precise and reliable cancer cell detection by overcoming the false signals. The specific identification potency of the PS-BSA-AuNCs-Apt system was further verified by successfully detecting the xenografted breast tumor tissue. Notably, to the best of our knowledge, the protein corona formed nanoprobes was exploited for direct tumor cell and tissue detection with high efficacy for the first time, demonstrating their promising potential in clinical tumor detection.

Investigation of the Feasibility of Ventricular Delivery of Resveratrol to the Microelectrode Tissue Interface.

(1) Background: Intracortical microelectrodes (IMEs) are essential to basic brain research and clinical brain-machine interfacing applications. However, the foreign body response to IMEs results in chronic inflammation and an increase in levels of reactive oxygen and nitrogen species (ROS/RNS). The current study builds on our previous work, by testing a new delivery method of a promising antioxidant as a means of extending intracortical microelectrodes performance. While resveratrol has shown efficacy in improving tissue response, chronic delivery has proven difficult because of its low solubility in water and low bioavailability due to extensive first pass metabolism. (2) Methods: Investigation of an intraventricular delivery of resveratrol in rats was performed herein to circumvent bioavailability hurdles of resveratrol delivery to the brain. (3) Results: Intraventricular delivery of resveratrol in rats delivered resveratrol to the electrode interface. However, intraventricular delivery did not have a significant impact on electrophysiological recordings over the six-week study. Histological findings indicated that rats receiving intraventricular delivery of resveratrol had a decrease of oxidative stress, yet other biomarkers of inflammation were found to be not significantly different from control groups. However, investigation of the bioavailability of resveratrol indicated a decrease in resveratrol accumulation in the brain with time coupled with inconsistent drug elution from the cannulas. Further inspection showed that there may be tissue or cellular debris clogging the cannulas, resulting in variable elution, which may have impacted the results of the study. (4) Conclusions: These results indicate that the intraventricular delivery approach described herein needs further optimization, or may not be well suited for this application.

Antifungal Activities and Mode of Action of Cymbopogon citratus, Thymus vulgraris, and Origanum heracleoticum Essential Oil Vapors against Botrytis cinerea and Their Potential Application to Control Postharvest Strawberry Gray Mold.

Gray mold caused by Botrytis cinerea is one of the most destructive postharvest decay of strawberry fruit. The present study aims to identify essential oils with antifungal activity against B. cinerea and the underlying mechanisms and their potential application in controlling postharvest decay. In the screening test, essential oils from Cymbopogon citratus (Cc), Thymus vulgraris (Tv), and Origanum heracleoticum (Oh) exhibited maximum inhibition of B. cinerea mycelial growth. The three essential oils altered the hyphal morphology and ultrastructure and resulted in many blebs around the hyphae. The essential oils damaged the plasma membrane of B. cinerea cells and resulted in the leakage of intercellular nucleic acids, proteins and soluble sugars. The exposure of strawberries to the vapors of these three essential oils in commercial package reduced gray mold, with Tv and Oh exhibiting strong efficiency and disease index reduction by 53.85% and 57.69%, respectively. Oh also inhibited postharvest decay and maintained fruit quality, preventing weight loss and soluble solid degradation. The study proposes using plant essential oils as an alternative to chemical fungicides in controlling the gray mold of strawberries.

Hydrogen Evolving Activity of Dithiolene-Based Metal-Organic Frameworks with Mixed Cobalt and Iron Centers.

Electrocatalytic systems based on metal-organic frameworks (MOFs) have attracted great attention due to their potential application in commercially viable renewable energy-converting devices. We have recently shown that the cobalt 2,3,6,7,10,11-triphenylenehexathiolate (CoTHT) framework can catalyze the hydrogen evolution reaction (HER) in fully aqueous media with Tafel slopes as low as 71 mV/dec and near-unity Faradaic efficiency (FE). Taking advantage of the high synthetic tunability of MOFs, here, we synthesize a series of iron and mixed iron/cobalt THT-based MOFs. The incorporation of the iron and cobalt dithiolene moieties is verified by various spectroscopic techniques, and the integrity of the crystalline structure is maintained regardless of the stoichiometries of the two metals. The hydrogen evolving activity of the materials was explored in pH 1.3 aqueous electrolyte solutions. Unlike CoTHT, the FeTHT framework exhibits minimal activity due to a late catalytic onset [-0.440 V versus reversible hydrogen electrode (RHE)] and a large Tafel slope (210 mV/dec). The performance of the mixed-metal MOFs is adversely affected by the incorporation of Fe, where increasing Fe content results in MOFs with lower HER activity and diminished long-term stability and FE for H2 production. It is proposed that the FeTHT domains undergo alternative Faradaic processes under catalytic conditions, which alter its local structure and electrochemical behavior, eventually resulting in a material with diminished HER performance.