Hydroxypropyl-Beta Cyclodextrin Barrier Prevents Respiratory Viral Infections: A Preclinical Study.

The emergence and mutation of pathogenic viruses have been occurring at an unprecedented rate in recent decades. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into a global public health crisis due to extensive viral transmission. In situ RNA mapping has revealed angiotensin-converting enzyme 2 (ACE2) expression to be highest in the nose and lower in the lung, pointing to nasal susceptibility as a predominant route for infection and the cause of subsequent pulmonary effects. By blocking viral attachment and entry at the nasal airway using a cyclodextrin-based formulation, a preventative therapy can be developed to reduce viral infection at the site of entry. Here, we assess the safety and antiviral efficacy of cyclodextrin-based formulations. From these studies, hydroxypropyl beta-cyclodextrin (HPBCD) and hydroxypropyl gamma-cyclodextrin (HPGCD) were then further evaluated for antiviral effects using SARS-CoV-2 pseudotypes. Efficacy findings were confirmed with SARS-CoV-2 Delta variant infection of Calu-3 cells and using a K18-hACE2 murine model. Intranasal pre-treatment with HPBCD-based formulations reduced viral load and inflammatory signaling in the lung. In vitro efficacy studies were further conducted using lentiviruses, murine hepatitis virus (MHV), and influenza A virus subtype H1N1. These findings suggest HPBCD may be used as an agnostic barrier against transmissible pathogens, including but not limited to SARS-CoV-2.

Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats.

Retinitis pigmentosa (RP) is a retinal degenerative disease associated with a diversity of genetic mutations. In a natural progression study (NPS) evaluating the molecular changes in Royal College of Surgeons (RCS) rats using lipidomic profiling, RNA sequencing, and gene expression analyses, changes associated with retinal degeneration from p21 to p60 were evaluated, where reductions in retinal ALOX15 expression corresponded with disease progression. This important enzyme catalyzes the formation of specialized pro-resolving mediators (SPMs) such as lipoxins (LXs), resolvins (RvDs), and docosapentaenoic acid resolvins (DPA RvDs), where reduced ALOX15 corresponded with reduced SPMs. Retinal DPA RvD2 levels were found to correlate with retinal structural and functional decline. Retinal RNA sequencing comparing p21 with p60 showed an upregulation of microglial inflammatory pathways accompanied by impaired damage-associated molecular pattern (DAMP) clearance pathways. This analysis suggests that ALXR/FPR2 activation can ameliorate disease progression, which was supported by treatment with an LXA4 analog, NAP1051, which was able to promote the upregulation of ALOX12 and ALOX15. This study showed that retinal inflammation from activated microglia and dysregulation of lipid metabolism were central to the pathogenesis of retinal degeneration in RP, where ALXR/FPR2 activation was able to preserve retinal structure and function.

Analysis of Contact Allergens in Polyvinyl Chloride Examination Gloves in the United States.

Background: Polyvinyl chloride (PVC) gloves are recommended as a safe alternative for patients with rubber accelerator allergy. However, allergic contact dermatitis to other chemicals in PVC gloves has been reported. Objective: To analyze single-use PVC medical examination gloves in the United States for the presence of potential contact allergens. Methods: Using liquid chromatography-mass spectrometry, 20 unique PVC gloves were analyzed in triplicate for 6 chemicals: benzisothiazolinone, bisphenol A, mono(2-ethylhexyl) maleate, tricresyl phosphate, triphenyl phosphate, and triphenyl phosphite. Results: All 20 PVC gloves contained detectable quantities of benzisothiazolinone (range, 0.001-1.48 parts per million [ppm]), bisphenol A (0.01-0.11 ppm), triphenyl phosphate (0.01-2.11 ppm), and triphenyl phosphite (0.001-0.22 ppm). Eighteen (90%) gloves contained mono(2-ethylhexyl) maleate (0.001-0.14 ppm) and 3 (15%) contained tricresyl phosphate (0.001-0.002 ppm). Conclusions: Known allergens were present in all 20 PVC gloves. However, the detected levels were mostly low and their relationship with sensitization and elicitation thresholds requires further study.

Exploring genetic variability, heritability, and trait correlations in gari and eba quality from diverse cassava varieties in Nigeria.

BACKGROUND: Gari (especially in Nigeria) is an important West African food product made from cassava. It is an affordable, precooked, dry, easy to prepare and store food product. Eba is a stiff dough produced by reconstituting gari in hot water. Gari and eba quality is an important driver of varietal acceptance by farmers, processors, and consumers. RESULTS: This study characterized the genetic variability, heritability, and correlations among quality-related traits of fresh roots, gari, and eba. Thirty-three diverse genotypes, including landraces and released and advanced breeding genotypes, were used in this study. In total, 40 traits categorized into fresh root quality, colour, functional, and texture properties trait groups were assessed. We observed broad phenotypic variability among the genotypes used in this study. Dry matter content had a positive (P < 0.05) correlation with gari%, bulk density and a negative correlation with eba hardness and gumminess. Broad-sense heritability across all environments varied considerably among the different trait groups: 62% to 79% for fresh root quality, 0% to 96% for colour, 0% to 79% for functional and 0% to 57% for texture properties. CONCLUSIONS: The stable broad-sense heritability found for gari%, gari and eba colour, bulk density, swelling index, and hardness measured using instrumental texture profile analysis coupled with sufficient variability in the population indicate good potential for genetic improvement of these traits through recurrent selection. Also, it is possible to genetically improve gari%, bulk density, and swelling power by simultaneously improving the dry matter content of fresh roots. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Computational optimization of delivery parameters to guide the development of targeted Nasal spray.

Airborne transmission by droplets and aerosols is known to play a critical role in the spread of many viruses amongst which are the common flu and the more recent SARS-CoV-2 viruses. In the case of SARS-CoV-2, the nasal cavity not only constitutes an important viral entry point, but also a primary site of infection (Sungnak W. et al. Nat. Med. 26:681-687. https://doi.org/10.1038/s41591-020-0868-6 , 2020).. Although face masks are a well-established preventive measure, development of novel and easy-to-use prophylactic measures would be highly beneficial in fighting viral spread and the subsequent emergence of variants of concern (Tao K. et al. Nat Rev Genet 22:757-773. https://doi.org/10.1038/s41576-021-00408-x , 2021). Our group has been working on optimizing a nasal spray delivery system that deposits particles inside the susceptible regions of the nasal cavity to act as a mechanical barrier to impede viral entry. Here, we identify computationally the delivery parameters that maximize the protection offered by this barrier. We introduce the computational approach and quantify the protection rate obtained as a function of a broad range of delivery parameters. We also introduce a modified design and demonstrate that it significantly improves deposition, thus constituting a viable approach to protect against nasal infection of airborne viruses. We then discuss our findings and the implications of this novel system on the prevention of respiratory diseases and targeted drug delivery.

Genetic variability and genotype by environment interaction of two major cassava processed products in multi-environments.

Conversion of cassava (Manihot esculenta) roots to processed products such as gari and fufu before consumption is a common practice worldwide by cassava end-user for detoxification, prolonged shelf life or profitability. Fresh root and processed product yield are supposed to be equivalent for each genotype, however, that is not the case. Developing genotypes with high product conversion rate is an important breeding goal in cassava as it drives the adoption rates of new varieties. The objective of this study was to quantify the contribution of genetic and genotype-by-environment interaction (GEI) patterns on cassava root conversion rate to gari and fufu. Sixty-seven advanced breeding genotypes from the International Institute of Tropical Agriculture (IITA) were evaluated across eight environments in Nigeria. Root conversion rate means across trials ranges from 14.72 to 22.76% for gari% and 16.96-24.24% for fufu%. Heritability estimates range from 0.17 to 0.74 for trial bases and 0.71 overall environment for gari% and 0.03-0.65 for trial bases and 0.72 overall environment for fufu% which implies that genetic improvement can be made on these traits. Root conversion rate for both gari and fufu% showed a negative but insignificant correlation with fresh root yield and significant positive correlation to Dry Matter content. For all fitted models, environment and interaction had explained more of the phenotypic variation observed among genotypes for both product conversion rates showing the presence of a strong GEI. Wrickle ecovalence (Wi) stability analysis and Geometric Adaptability index (GAI) identified G40 (TMS14F1285P0006) as part of top 5 genotypes for gari% but no overlapping genotype was identified by both stability analysis for fufu%. This genotypic performance across environments suggests that it is possible to have genotype with dual-purpose for high gari and fufu conversion rate.

Uncovering mechanisms of brain inflammation in Alzheimer's disease with APOE4: Application of single cell-type lipidomics.

A chronic state of unresolved inflammation in Alzheimer's disease (AD) is intrinsically involved with the remodeling of brain lipids. This review highlights the effect of carrying the apolipoprotein E ε4 allele (APOE4) on various brain cell types in promoting an unresolved inflammatory state. Among its pleotropic effects on brain lipids, we focus on APOE4's activation of Ca2+ -dependent phospholipase A2 (cPLA2) and its effects on arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid signaling cascades in the brain. During the process of neurodegeneration, various brain cell types, such as astrocytes, microglia, and neurons, together with the neurovascular unit, develop distinct inflammatory phenotypes that impact their functions and have characteristic lipidomic fingerprints. We propose that lipidomic phenotyping of single cell-types harvested from brains differing by age, sex, disease severity stage, and dietary and genetic backgrounds can be employed to probe mechanisms of neurodegeneration. A better understanding of the brain cellular inflammatory/lipidomic response promises to guide the development of nutritional and drug interventions for AD dementia.

Does COVID-19 Fear Induce Employee Innovation Performance Deficiency? Examining the Mediating Role of Psychological Stress and Moderating Role of Organizational Career Support.

With the immense, short/long-term, and multidirectional effects of the coronavirus disease (COVID-19) pandemic on work performance, industry activities, and the national/global economy, it has adversely affected employees' psychological well-being due to its elevated stress and anxiety that have substantially affected employee innovation performance (deficiency) (EIP(D)). The goal of this empirical paper is to identify how COVID-19 induces EIPD by examining the mediating role of psychological stress (PS) on the relationship between fear of infection with COVID-19 (FIC) and EIPD based on affective events theory (AET) and the moderating effect of organizational career support (OCS) on the relationship between PS and EIPD. Based on 865 survey responses provided by mid-level managers from Chinese manufacturing firms and the covariance-based structural equation modeling (SEM) technique using AMOS 25, we identified that FIC has a positive relationship with EIPD while PS can fully mediate the link between FIC and EIPD and OCS weakens the positive relationship between PS and EIPD (that is, in the presence of OCS, EIPD decreases despite the presence of PS among the employees). The findings of our empirical study will theoretically and practically contribute to the pandemic-related existing literature by providing an in-depth understanding of these variables. Furthermore, policymakers can also benefit by boosting their EIP from the outcomes revealed and suggestions provided.

Induced variations of ethyl methane sulfonate mutagenized cowpea (Vigna unguiculata L. walp) plants.

Unique variants are desired in the development of genetically improved crops to meet farmer and market needs hence ethyl methane sulfonate (EMS) was used to induce genetic variability in cowpea (Vigna unguiculata cv. Asontem). The main objective of this research was to characterize induced variations in EMS chemically mutagenized population of cowpea (Vigna unguiculata L. Walp Var. Asontem) in the M1 and M2 generations. The optimum concentration (LD50) of EMS for generating the mutagenized population was determined by treating seeds with different concentrations of EMS (0.0, 0.2, 0.4, 0.6, and 0.8% v/v) and observing the germination count after 5 days of planting the seeds in Petri dishes. Three thousand cowpea seeds were treated with the 0.4% EMS to generate the M1 and M2 populations that were evaluated for agronomic and morphological traits with untreated seeds serving as control. Data analysis involved distribution of qualitative and quantitative traits. Germination was significantly reduced in the mutagenized population (17.8%) and compared with that of the wild type (61.6%). Percentage survival was significantly higher in wild type (98.38%) as compared with the M1 population (78.46%). Percentage germination in the M2 population (74.03%) was lower than the wild type (80%). A wide spectrum of agro-morphological abnormalities was observed in the M2 population. Wide variations and uniquely different phenotypic classes were observed in leaf color, leaf shape, growth habit, plant pigmentation, twining tendency, pod curvature, seed shape, and seed coat color. M2 individuals were widely distributed for days to flowering, number of pods per plant, number of seeds per pod, number of locules per pods, percentage seed set, pod length and number of seeds per plant. In conclusion, the EMS mutagenesis was effective in inducing the unique variations that will be useful for breeding and development of new farmer preferred varieties.

Lipidomics in Understanding Pathophysiology and Pharmacologic Effects in Inflammatory Diseases: Considerations for Drug Development.

The lipidome has a broad range of biological and signaling functions, including serving as a structural scaffold for membranes and initiating and resolving inflammation. To investigate the biological activity of phospholipids and their bioactive metabolites, precise analytical techniques are necessary to identify specific lipids and quantify their levels. Simultaneous quantification of a set of lipids can be achieved using high sensitivity mass spectrometry (MS) techniques, whose technological advancements have significantly improved over the last decade. This has unlocked the power of metabolomics/lipidomics allowing the dynamic characterization of metabolic systems. Lipidomics is a subset of metabolomics for multianalyte identification and quantification of endogenous lipids and their metabolites. Lipidomics-based technology has the potential to drive novel biomarker discovery and therapeutic development programs; however, appropriate standards have not been established for the field. Standardization would improve lipidomic analyses and accelerate the development of innovative therapies. This review aims to summarize considerations for lipidomic study designs including instrumentation, sample stabilization, data validation, and data analysis. In addition, this review highlights how lipidomics can be applied to biomarker discovery and drug mechanism dissection in various inflammatory diseases including cardiovascular disease, neurodegeneration, lung disease, and autoimmune disease.

Prevalence and Risk Factors for Intimate Partner Physical Violence-Related Acquired Brain Injury Among Visitors to Justice Center in New York.

OBJECTIVE: The recent United States Government Accountability Office report highlights the need for improved data on the prevalence of intimate partner violence (IPV)-related acquired brain injury (ABI) to help direct Health & Human Services public efforts. This article identifies the prevalence and risk factors for IPV-related ABI among survivors of IPV at a Justice Center in New York. SETTING: Community Justice Center. PARTICIPANTS: Forty survivors of IPV, aged 17 to 73 years (median 32, interquartile range: 25.25, 42) were assessed within 60 days of sustaining physical violence. DESIGN: Retrospective chart review. MAIN MEASURES: The HELPS and the Danger Assessment-Revised were used at the initial Center visit. RESULTS: Of the 40 physical IPV survivors screened, all (100%) reported a prior history of partner-induced ABI within the past 60 days. Thirty-seven (92.5%) survivors also reported sustaining at least 1 potential hypoxic brain injury from strangulation. However, only 16 (40%) survivors screened positive on the HELPS for a history of IPV-related mild traumatic brain injury. Females (95%) and individuals with low income (67.5%) largely comprised our sample. Compared with the County's average, the proportion of African Americans/Blacks and refugees was 227% higher (42.5% vs 13%) and 650% higher (7.5% vs 1.09%), respectively. Refugee status (P = .017) also correlated with number of previous ABIs. On an exploratory binary logistic regression with stepwise selection, only balance difficulties (P = .023) and difficulty concentrating/remembering (P = .009) predicted a positive screen for mild traumatic brain injury. CONCLUSIONS: Consistent with previous findings, our data indicate a high prevalence of IPV-related ABI among visitors to a New York Justice Center. An overrepresentation of African Americans/Blacks and refugees in our sample relative to the region signified a higher prevalence of IPV in these populations and warrants a provision of more trauma-informed ABI resources to these groups/communities. Intimate partner violence survivors visiting Justice Centers should be screened for motor/neurocognitive symptoms suggestive of mild traumatic brain injury. Further research to identify the prevalence and risk factors of IPV-related ABI statewide and nationwide is urgently needed to improve resource allocation and clinical management.

Development of Moderate Intensity Focused Ultrasound (MIFU) for Ocular Drug Delivery.

The purpose of this study is to develop a method for delivering antiinflammatory agents of high molecular weight (e.g., Avastin) into the posterior segment that does not require injections into the eye (i.e., intravitreal injections; IVT). Diseases affecting the posterior segment of the eye are currently treated with monthly to bimonthly intravitreal injections, which can predispose patients to severe albeit rare complications like endophthalmitis, retinal detachment, traumatic cataract, and/or increased intraocular. In this study, we show that one time moderate intensity focused ultrasound (MIFU) treatment can facilitate the penetration of large molecules across the scleral barrier, showing promising evidence that this is a viable method to deliver high molecular weight medications not invasively. To validate the efficacy of the drug delivery system, IVT injections of vascular endothelial growth factor (VEGF) were used to create an animal model of retinopathy. The creation of this model allowed us to test anti-VEGF medications and evaluate the efficacy of the treatment. In vivo testing showed that animals treated with our MIFU device improved on the retinal tortuosity and clinical dilation compared to the control group while evaluating fluorescein angiogram (FA) Images.

Alterations in Renin-Angiotensin System (RAS) Peptide Levels in Patients with HIV.

Chronic HIV infection has long been associated with an increased risk for cardiovascular diseases. The metabolites of the renin−angiotensin system (RAS) such as angiotensin II (AngII) play an important role in regulating blood pressure and fluid dynamics. Cross-sectional analysis of HIV-positive individuals (n = 71, age > 40 years, stable ART > 3 months with HIV viral load < 50 copies/mL) were compared to a similar HIV seronegative group (n = 72). High-resolution B-mode ultrasound images of the right carotid bifurcation (RBIF) and right common carotid artery (RCCA) were conducted to measure the extent of carotid atherosclerotic vascular disease. Plasma RAS peptide levels were quantified using a liquid chromatography-mass spectrometry-based metabolomics assay. RAS peptide concentrations were compared between persons with HIV and persons without HIV, correlating their association with clinical and cardiac measures. Median precursor peptides (Ang(1-12) and AngI) were significantly higher in the HIV-positive group compared to the HIV-negative. Analyses of the patient subgroup not on antihypertensive medication revealed circulating levels of AngII to be four-fold higher in the HIV-positive subgroup. AngII and TNF-alpha levels were found to have a positive association with RCCA, and AngI/Ang(1-12) ratio and TNF-alpha levels were found to have a positive association with RBIF. In both predictive models, AngIII had a negative association with either RCCA or RBIF, which may be attributed to its ability to bind onto AT2R and thus oppose pro-inflammatory events. These results reveal systemic alterations in RAS as a result of chronic HIV infection, which may lead to the activation of inflammatory pathways associated with carotid thickening. RAS peptide levels and cytokine markers were associated with RCCA and RBIF measurements.

NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment.

Resolving tumor-associated inflammation in the tumor microenvironment (TME) may promote antitumor effects. Lipoxin A4 (LXA4) is a short-lived endogenous bioactive lipid with potent anti-inflammatory and pro-resolving properties. Here, a biomimetic of LXA4, NAP1051, was shown to have LXA4-like in vitro properties and antitumor activity in colorectal cancer xenograft models. NAP1051 inhibited neutrophil chemotaxis toward fMLP and dose-dependently promoted dTHP-1 efferocytosis which was equipotent to aspirin-triggered lipoxin A4 (ATLA). In dTHP-1 cells, NAP1051 induced strong phosphorylation on ERK1/2 and AKT similar to formyl peptide receptor 2 (FPR2/ALX) agonists. In two mouse xenograft colorectal cancer models, NAP1051 significantly inhibited tumor growth when given orally at 4.8 to 5 mg/kg/day. Flow cytometric analyses showed that NAP1051 reduced splenic and intratumoral neutrophil and myeloid-derived suppressor cell populations, which correlated to the antitumor effect. In addition, NAP1051 reduced NETosis in the TME while stimulating T-cell recruitment. Overall, these results show that NAP1051 possesses key lipoxin-like properties and has antitumor activity against colorectal cancer via modulation of neutrophils and NETosis in the TME.

Genomic and Phenotypic Diversity of Cultivated and Wild Tomatoes with Varying Levels of Heat Tolerance.

Assessment of genetic variability in heat-tolerant tomato germplasm is a pre-requisite to improve yield and fruit quality under heat stress. We assessed the population structure and diversity in a panel of three Solanum pimpinellifolium (wild tomatoes) and 42 S. lycopersicum (cultivated tomatoes) lines and accessions with varying heat tolerance levels. The DArTseq marker was used for the sequencing and 5270 informative single nucleotide polymorphism (SNP) markers were retained for the genomic analysis. The germplasm was evaluated under two heat stress environments for five yield and flower related traits. The phenotypic evaluation revealed moderate broad-sense heritabilities for fruit weight per plant and high broad-sense heritabilities for fruit weight, number of inflorescences per plant, and number of flowers per inflorescence. The hierarchical clustering based on identity by state dissimilarity matrix and UPGMA grouped the germplasm into three clusters. The cluster analysis based on heat-tolerance traits separated the germplasm collection into five clusters. The correlation between the phenotypic and genomic-based distance matrices was low (r = 0.2, p < 0.05). The joint phenotypic and genomic-based clustering grouped the germplasm collection into five clusters well defined for their response to heat stress ranging from highly sensitive to highly tolerant groups. The heat-sensitive and heat-tolerant clusters of S. lycopersicum lines were differentiated by a specific pattern of minor allele frequency distribution on chromosome 11. The joint phenotypic and genomic analysis revealed important diversity within the germplasm collection. This study provides the basis for efficient selection of parental lines to breed heat-tolerant varieties.

Genotype by Environment Interaction on Resistance to Cassava Green Mite Associated Traits and Effects on Yield Performance of Cassava Genotypes in Nigeria.

Cassava is the main source of carbohydrate for over 70% of the people in Nigeria, the world's largest producer and consumer of the crop. The yields of cassava are, however, relatively low in Nigeria largely due to pests and disease infections that significantly lead to inconsistencies in productivity of cassava genotypes in various environments. Fifty-eight F1 hybrid cassava genotypes plus their two parents which served as check varieties were evaluated in three locations for two years (that is six environments). The objectives of the study were to evaluate genotype by environment interactions (GEI) on resistance to cassava green mite [CGM, Mononychellus tanajoa (Bondar)] associated traits and effects on yield performance of cassava genotypes in Nigeria and to identify superior genotypes that exhibit high stability which combine CGM resistance and high fresh root yield with general and specific environmental adaptation using additive main effects and multiplicative interaction (AMMI) and genotype stability index (GSI). The combined analysis of variance based on AMMI revealed significant genotype, environment, and genotype by environment interactions (GEI) for all traits. The percentage variation due to environment was higher than the percentage variation due to genotype for cassava green mite severity (CGMS), leaf retention (LR), root dry matter content (RDMC), and fresh root yield (FRY) indicating that environment greatly influenced the expression of these traits. The percentage variation due to GEI accounted for higher percentage variation than that of genotype and environment separately for all traits, indicating the influence of genotype by environment interaction on expression of the traits. These findings reveal that screening/evaluating for these traits needs multi-environment trials. According to GSI ranking, genotypes G31 (IBA131794), G19 (IBA131762), the check variety G52 (TMEB778), and G11 (IBA131748) were identified as the most stable and most resistant to CGM which also combine high FRY and other useful agronomic traits, implying that these traits in cassava can even be incorporated as preferred by farmers. These genotypes can be tested in more environments to determine their adaptability and potential recommendation for release to farmers for growing.

Cyanine Nanocages Activated by Near-Infrared Light for the Targeted Treatment of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a common and prevalent condition that affects large numbers of people across a range of ages. Individuals engaging in physical activities and victims of accidents are at a higher risk for TBI. There is a lack of available treatment specifically for TBI. Given the difficulty to determine its precise location in the brain, TBI remains difficult to fully diagnose or treat. Herein, we disclose a novel strategy for directing therapeutic agents to TBI sites, without the need to determine the precise location of the TBI activity in the brain. This novel approach is based on the use of a cyanine dye nanocage carrying Gabapentin, a known TBI therapeutic agent. Upon exposure of the cyanine nanocage to near-infrared light, the local release of Gabapentin is triggered, selectively at the TBI-affected site.

Cyanine Nanocage Activated by Near-IR Light for the Targeted Delivery of Cyclosporine A to Traumatic Brain Injury Sites.

More than 2.8 million annually in the United States are afflicted with some form of traumatic brain injury (TBI), where 75% of victims have a mild form of TBI (MTBI). TBI risk is higher for individuals engaging in physical activities or involved in accidents. Although MTBI may not be initially life-threatening, a large number of these victims can develop cognitive and physical dysfunctions. These late clinical sequelae have been attributed to the development of secondary injuries that can occur minutes to days after the initial impact. To minimize brain damage from TBI, it is critical to diagnose and treat patients within the first or "golden" hour after TBI. Although it would be very helpful to quickly determine the TBI locations in the brain and direct the treatment selectively to the affected sites, this remains a challenge. Herein, we disclose our novel strategy to target cyclosporine A (CsA) into TBI sites, without the need to locate the exact location of the TBI lesion. Our approach is based on TBI treatment with a cyanine dye nanocage attached to CsA, a known therapeutic agent for TBI that is associated with unacceptable toxicities. In its caged form, CsA remains inactive, while after near-IR light photoactivation, the resulting fragmentation of the cyanine nanocage leads to the selective release of CsA at the TBI sites.

Optimizing pollencounter for high throughput phenotyping of pollen quality in tomatoes.

The macro "PollenCounter" in ImageJ was initially developed to assess pollen viability in grapevine. We set out to see if PollenCounter could be used to assess pollen number and viability in tomatoes.•We tested different optimization scenarios by adjusting the pollen size (100-900, 200-900 pixel2) and circularity of pollen grains (0.4-1, 0.5-1, and 0.6-1) on 31 microscopic images of stained tomato pollen. Both total pollen number and proportion of viable pollen were positively and significantly correlated with the outputs from manual counting. The scenario with 100-900 pixel2 pollen size and 0.4-1 circularity had the highest association for pollen number (r = 0.99) and pollen viability (r = 0.86). PollenCounter is 32-fold faster than manual counting.•We added a command to the macro to automatically save the outputs containing the number of total and viable pollen, avoiding transcription errors inherent to manual counting.•We successfully applied the optimized PollenCounter to discriminate tomato genotypes based on pollen number and pollen viability under heat stress. Our results show that PollenCounter, as an open-access macro, can be customized and improved to meet users' needs. The use of PollenCounter can save time and money in pollen quality assessment. We outline the steps to optimize the macro for other samples or crop species. The optimized macro could allow efficient screening of a large germplasm collection for pollen thermo-tolerance and selection of best thermo-tolerant individuals in breeding programs.

Genetic Studies on the Inheritance of Storage-Induced Cooking Time in Cowpeas [Vigna unguiculata (L.) Walp].

Cowpeas provide food and income for many small-holder farmers in Africa. Cowpea grains contain substantial quantities of protein, carbohydrates, vitamins, and fiber. In areas where subsistence farming is practiced, cowpea's protein is cheaper than that obtained from other sources such as fish, meat, poultry or dairy products and combines well with cereal grains in diets. However, long-cooking times, typical of many grain legumes, is a major limitation to the utilization of cowpeas especially among the low-income and growing middle-income population of Africa. Long periods of cooking cowpeas lead to loss of nutrients, loss of useful time and increased greenhouse gas emission through increased burning of firewood. Fast-cooking cowpeas has the potential to deliver highly nutritious food to the hungry within shorter periods, encourage less use of firewood, improve gender equity, increase the consumption of cowpeas, trigger an increase in demand for cowpeas and thus incentivize cowpea production by smallholder farmers in Sub-Saharan Africa. In this study, the inheritance of storage-induced cooking time in cowpeas was investigated. Two sets of bi-parental crosses were conducted involving three cowpea genotypes: CRI-11(1)-1, C9P(B) and TVu7687. Generation means from six generations were used to determine the phenotypic and genotypic variances and coefficients of variation. Broad and narrow sense heritabilities and genetic advance percentage of mean were estimated. Generation mean analysis showed that additive, dominant, additive-additive, additive-dominant, and dominant-dominant gene actions were significant (p < 0.001). Fast-cooking trait was dominant over the long-cooking trait. Broad sense heritability for crosses C9P(B) × CRI-11(1)-1 and TVu7687 × CRI-11(1)-1 were 0.94 and 0.99 respectively while narrow sense heritabilities were 0.84 and 0.88 respectively. Genetic advances were 27.09 and 40.40 respectively. High narrow-sense heritabilities and moderate genetic advance for the fast-cooking trait indicated the presence of additive genes in the trait and the possibility of introgressing the trait into farmer-preferred varieties using conventional selection methods. However, due to significant epistatic gene effects observed, effective selection for fast-cooking trait would be appropriate at advanced generations.