Search

Manpreet Randhawa,1 Thomas Meyer,2 Mukta Sachdev,3 Ratan K Chaudhuri1 1Sytheon Ltd, Boonton, NJ, USA; 2Meyer Sun & Skin Care Consulting, LLC, Memphis, TN, USA; 3MSCR Pvt Ltd, Bengaluru, IndiaCorrespondence: Manpreet RandhawaSytheon Ltd, 315 Wootton Street, Boonton, NJ, USATel +1 973 947 1109Email manpreet@sytheonltd.comBackground: Identification of long-lasting natural antioxidants to protect against and repair skin damage induced by exposure to environmental pollution is in high demand.Objective: To investigate a standardized Terminalia chebula (TC) fruit extract for its long-lasting antioxidant and anti-inflammatory properties and its ability to reverse the visible signs of pollution-induced skin damage in an 8-week clinical study.Material and Methods: Chemical and cell-based in vitro studies were performed to characterize long-lasting antioxidant and anti-inflammatory properties; a clinical study with subjects with normal to dry skin living in a high-pollution city for the previous 5 years was conducted to assess if a formulation containing 1% standardized TC fruit extract affected significant improvements in skin’s visible condition and appearance compared with its placebo.Results: The standardized TC fruit extract provided longer-lasting and more efficient neutralization of reactive oxygen species (ROS) than tocopherol; treatment of keratinocytes with the fruit extract prior to being stressed with urban dust safeguarded against increases in intracellular ROS, inhibited release of inflammatory cytokines IL-6 and IL-8 and protected membrane lipids against peroxidation. A clinical study yielded statistically significant improvements in dermatologist scores and subject self-assessments for skin texture, hydration, tone, firmness and radiance as compared to its placebo.Conclusion: These studies validate the use of this standardized TC fruit extract not only as a restorative to diminish visible signs of existing damage but also as a preventative to help defend skin against damages caused by chronic exposure to environmental pollution.Keywords: long-lasting antioxidant, pollution, skin hydration, skin radiance, Terminalia chebula

Background: Use of permanent hair dyes causes unintended oxidative damage during the short time frame of the dyeing process that leads to perceivable changes in the feel, manageability and appearance of hair. Moreover, after hair has been dyed, regular exposure to the sun as a key environmental stressor continues to stimulate additional oxidative damage and to induce newly developed hair colours to fade prematurely or undergo changes in colour quality., Objective: To document the utility of acetyl zingerone methyl ether (MAZ) as a newly designed haircare ingredient to afford extra protection against oxidative damage and safeguard the integrity of hair colour., Results: We demonstrate that MAZ is compatible chemically with the high alkaline conditions required for the colouring process and from theoretical calculations preferentially binds Fe and Cu ions relative to Ca or Zn ions. In model Fenton reactions MAZ effectively chelated active redox metals (Fe and Cu ions) in the presence of excess Ca +2 ions to inhibit the production of hydroxyl radicals, and in separate studies, MAZ neutralized singlet oxygen with greater efficiency than α-tocopherol by a factor of 2.5. When mixed into permanent dyes prior to hair tress application, MAZ significantly reduced combing forces, and SEM images led to substantial reductions in visual signs of surface damage. In a 28-day clinical study, relative to controls, mixing MAZ into hair dyes prior to application interfered neither with colour development nor with ability to cover grey hair and led to significant improvements in perceived attributes associated with hair's condition immediately following the dyeing process. Over a 28-day maintenance phase, especially between Day 14 and Day 28, continued use of shampoo and conditioner containing MAZ significantly preserved gloss measurements and hair colour in terms of longevity and colour quality as remaining desired and fresh compared to use of control shampoo and conditioner., Conclusion: This work establishes MAZ as a next-generation hair care ingredient for use in permanent dyes to attenuate oxidative damage and in shampoos and conditioners to promote longevity of hair colour and to maintain overall health and appearance of hair on a daily basis., (© 2024 Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Background: Tetrahexydecyl ascorbate (THDA) is a lipophilic precursor to ascorbic acid that may be stabilized by acetyl zingerone (AZ). Studies have shown that the topical application of THDA may have photoprotective effects. Similarly, AZ has been shown to mitigate oxidative and inflammatory stress, thereby improving the appearance of photoaging., Aims: To examine the effects of THDA and AZ (THDA-AZ) on skin photoaging compared to THDA alone., Patients/methods: In this double-blind, randomized controlled trial, healthy individuals aged 30 to 65 were included and 44 participants were randomized to receive either THDA-AZ (THDA 5% + AZ 1%) or THDA only (THDA 5%) for 8 weeks. Facial photographs were taken at 0, 4, and 8 weeks to analyze wrinkle severity, pigment intensity, and redness intensity. A skin colorimeter was used to assess infraorbital pigmentation and erythema. Self-perception of skin and tolerability were assessed through questionnaires., Results: Average wrinkle severity was significantly decreased in the THDA-AZ group at Weeks 4 and 8 by 0.75% (p = 0.023) and 3.72% (p = 0.048), respectively, compared to the THDA group where wrinkle severity at Weeks 4 and 8 was increased by 7.88% and 4.48%, respectively. Facial pigment intensity was significantly decreased in the THDA-AZ group by 4.10% (p = 0.0002) at Week 8 compared to a 0.69% decrease in the THDA group. Facial redness intensity was decreased in the THDA-AZ group at Weeks 4 and 8 by 3.73% (p = 0.0162) and 14.25% (p = 0.045), respectively, compared to the THDA group where at Weeks 4 and 8 erythema increased by 27.5% and 8.34%, respectively. There were no significant differences in either group for infraorbital pigmentation or erythema., Conclusions: Daily use of combined THDA and AZ may improve facial wrinkle severity, pigment intensity, and erythema to a greater extent than THDA. While THDA alone increases facial wrinkle severity and erythema, the addition of AZ reduces both., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background: Preliminary studies support the use of topical coconut and sunflower seed oil for atopic dermatitis (AD). However, standardized topical formulations of fatty acids from these sources have not been studied. Objective: This study investigates whether coconut oil- and sunflower seed oil-derived isosorbide diesters can be used in conjunction with colloidal oatmeal to improve itch, AD severity, and the need for topical steroids in adults. Methods: This was a single-center, 4-week, randomized, double-blind, and vehicle-controlled study conducted between 2021 and 2022. Thirty-two male and female adults with mild-to-moderate AD were enrolled and completed the study. Participants were randomized to receive either 0.1% colloidal oatmeal (vehicle) or isosorbide diesters (IDEAS, 4% isosorbide dicaprylate and 4% isosorbide disunflowerseedate) along with 0.1% colloidal oatmeal. The main outcomes of the study were changes in the visual analogue rating of itch and 75% improvement in the Eczema Area and Severity Index score (EASI 75) at 4 weeks. Other measures included the use of topical steroids and the relative abundance of skin Staphylococcus aureus . Results: Participants in the IDEAS group had a 65.6% improvement in itch compared with 43.8% in the vehicle group ( P  = 0.013). In total, 56.5% and 25% of the those in the IDEAS and vehicle groups, respectively, achieved EASI 75 at 4 weeks ( P  = 0.07). There was no difference in skin hydration or transepidermal water loss. The relative abundance of S. aureus was decreased in the IDEAS group at week 4 compared with no change in the vehicle group ( P  = 0.044). Topical corticosteroid use increased in the vehicle group compared with a decrease in the IDEAS group at week 1 (292.5% vs 24.8%; P value = 0.039) and week 2 (220% vs 46%; P value = 0.08). Conclusions: Topical application of emollients containing coconut oil- and sunflower seed oil-derived fatty esters may improve itch, reduce topical steroid use, and reduce the relative abundance of S. aureus in mild-to-moderate AD. CTR number: NCT04831892.

Background: Individuals with multiple system atrophy (MSA) often complain about pain, nonetheless this remains a poorly investigated non-motor feature of MSA., Objectives: Here, we aimed at assessing the prevalence, characteristics, and risk factors for pain in individuals with MSA., Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines, we systematically screened the PubMED, Cochrane, and Web of Science databases for papers published in English until September 30, 2022, combining the following keywords: "pain," "multiple system atrophy," "MSA," "olivopontocerebellar atrophy," "OPCA," "striatonigral degeneration," "SND," "Shy Drager," and "atypical parkinsonism.", Results: The search identified 700 records. Sixteen studies provided information on pain prevalence in cohorts of MSA individuals and were included in a qualitative assessment based on the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Thirteen studies (11 cross-sectional, two longitudinal) scored ≥14 points on QUADAS assessment and were included in a quantitative analysis, pooling data from 1236 MSA individuals. The resulting pooled prevalence of pain in MSA was 67% (95% confidence intervals [CI] = 57%-75%), and significantly higher in individuals with MSA of parkinsonian rather than cerebellar type (76% [95% CI = 63%-87%] vs. 45% [95% CI = 33%-57%], P  = 0.001). Pain assessment tools and collected information were highly heterogeneous across studies. Two studies reported pain treatment strategies and found that only every second person with MSA complaining about pain had received targeted treatment., Conclusions: We found that pain is a frequent, but still under-recognized and undertreated feature of MSA. Further research is needed to improve pain detection and treatment in MSA., (© 2023 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Fungal infections are the inevitable limiting factor for productivity of tea. Transcriptome reprogramming recruits multiple regulatory pathways during pathogen infection. A comprehensive meta-analysis was performed utilizing previously reported, well-replicated transcriptomic datasets from seven fungal diseases of tea. The study identified a cumulative set of 18,517 differentially expressed genes (DEGs) in tea, implicated in several functional clusters, including the MAPK signaling pathway, transcriptional regulation, and the biosynthesis of phenylpropanoids. Gene set enrichment analyses under each pathogen stress elucidated that DEGs were involved in ethylene metabolism, secondary metabolism, receptor kinase activity, and various reactive oxygen species detoxification enzyme activities. Expressional fold change of combined datasets highlighting 2258 meta-DEGs shared a common transcriptomic response upon fungal stress in tea. Pervasive duplication events caused biotic stress-responsive core DEGs to appear in multiple copies throughout the tea genome. The co-expression network of meta-DEGs in multiple modules demonstrated the coordination of appropriate pathways, most of which involved cell wall organization. The functional coordination was controlled by a number of hub genes and miRNAs, leading to pathogenic resistance or susceptibility. This first-of-its-kind meta-analysis of host-pathogen interaction generated consensus candidate loci as molecular signatures, which can be associated with future resistance breeding programs in tea., (© 2023. Springer Nature Limited.)

The cumulative damage skin sustains from exposure to environmental stressors throughout life exerts significant effects on skin aging and cancer development. One of the main ways by which environmental stressors mediate their effects within skin is through induction of reactive oxygen species (ROS). In this review, we chronicle the multiple properties by which acetyl zingerone (AZ) as a skincare ingredient can benefit skin (1) by helping manage overproduction of ROS through multiple routes as an antioxidant, physical quencher and selective chelator, (2) by fortifying protection after UV exposure ends to prevent the type of epidermal DNA damage that correlates with development of skin cancer, (3) by modulating matrisome activity and nurturing the integrity of the extracellular matrix (ECM) within the dermis and (4) through its proficient ability to neutralize singlet oxygen, by stabilizing the ascorbic acid precursor tetrahexyldecyl ascorbate (THDC) in the dermal microenvironment. This activity improves THDC bioavailability and may blunt pro-inflammatory effects of THDC, such as activation of type I interferon signaling. Moreover, AZ is photostable and can sustain its properties during UV exposure, in contrast to α-tocopherol. All these properties of AZ translate into measurable clinical benefits to improve the visual appearance of photoaged facial skin and to strengthen the skin's own defenses against sun damage.

Terminalia chebula (TC) is a medicinal plant that exhibits antioxidant, anti-inflammatory, and antibacterial properties and that is widely used in Ayurveda and herbal formulations. However, the skin effects of TC as an oral supplement have not been studied. The objective of this study is to determine if oral TC fruit extract supplementation can modulate the skin's sebum production and reduce the appearance of wrinkles. A prospective double-blind placebo-controlled study was conducted on healthy females aged 25-65. Subjects were supplemented with an oral placebo or Terminalia chebula (250 mg capsule, Synastol TC) capsules twice daily for eight weeks. A facial image collection and analysis system was used to assess the facial appearance of wrinkle severity. Standardized, non-invasive tools were used to measure facial moisture, sebum production, transepidermal water loss, melanin index and erythema index. For those who had a baseline sebum excretion rate >80 ug/cm 2 , TC supplementation produced a significant decrease in forehead sebum excretion rate compared to the placebo at four weeks (-17 decrease vs. 20% increase, p = 0.07) and at eight weeks (-33% decrease vs. 29% increase, p < 0.01). Cheek erythema decreased by 2.2% at eight weeks, while the placebo treatment increased cheek erythema by 1.5% ( p < 0.05). Facial wrinkles decreased by 4.3% in the TC group and increased by 3.9% in the placebo group after eight weeks of supplementation ( p < 0.05). TC supplementation reduces facial sebum and improves the appearance of wrinkles. Future studies should consider evaluating oral TC as adjuvant therapy for acne vulgaris.

Cyclobutane pyrimidine dimers (CPDs) are ultraviolet radiation (UV)-induced carcinogenic DNA photoproducts that lead to UV signature mutations in melanoma. Previously, we discovered that, in addition to their incident formation (iCPDs), UV exposure induces melanin chemiexcitation (MeCh), where UV generates peroxynitrite (ONOO - ), which oxidizes melanin into melanin-carbonyls (MCs) in their excited triplet state. Chronic MeCh and energy transfer by MCs to DNA generates CPDs for several hours after UV exposure ends (dark CPD, dCPDs). We hypothesized that MeCh and the resulting dCPDs can be inhibited using MeCh inhibitors, and MC and ONOO - scavengers. Here, we investigated the efficacy of Acetyl Zingerone (AZ), a plant-based phenolic alkanone, and its chemical analogs in inhibiting iCPDs and dCPDs in skin fibroblasts, keratinocytes, and isogenic pigmented and albino melanocytes. While AZ and its methoxy analog, 3-(4-Methoxy-benzyl)-Pentane-2,4-dione (MBPD) completely inhibited the dCPDs, MBPD also inhibited ~50% of iCPDs. This suggests the inhibition of ~80% of total CPDs at any time point post UV exposure by MBPD, which is markedly significant. MBPD downregulated melanin synthesis, which is indispensable for dCPD generation, but this did not occur with AZ. Meanwhile, AZ and MBPD both upregulated the expression of nucleotide excision repair (NER) pathways genes including Xpa , Xpc , and Mitf . AZ and its analogs were non-toxic to the skin cells and did not act as photosensitizers. We propose that AZ and MBPD represent "next-generation skin care additives" that are safe and effective for use not only in sunscreens but also in other specialized clinical applications owing to their extremely high efficacy in blocking both iCPDs and dCPDs.

The endocannabinoid (eCB) system plays an active role in epidermal homeostasis. Phytocannabinoids such as cannabidiol modulate this system but also act through eCB-independent mechanisms. This study evaluated the effects of cannabidiol, bakuchiol (BAK), and ethyl (linoleate/oleate) (ELN) in keratinocytes and reconstituted human epidermis. Molecular docking simulations showed that each compound binds the active site of the eCB carrier FABP5. However, BAK and ethyl linoleate bound this site with the highest affinity when combined 1:1 (w/w), and in vitro assays showed that BAK + ELN most effectively inhibited FABP5 and fatty acid amide hydrolase. In TNF-stimulated keratinocytes, BAK + ELN reversed TNF-induced expression shifts and uniquely downregulated type I IFN genes and PTGS2 ( COX2 ). BAK + ELN also repressed expression of genes linked to keratinocyte differentiation but upregulated those associated with proliferation. Finally, BAK + ELN inhibited cortisol secretion in reconstituted human epidermis skin (not observed with cannabidiol). These results support a model in which BAK and ELN synergistically interact to inhibit eCB degradation, favoring eCB mobilization and inhibition of downstream inflammatory mediators (e.g., TNF, COX-2, type I IFN). A topical combination of these ingredients may thus enhance cutaneous eCB tone or potentiate other modulators, suggesting novel ways to modulate the eCB system for innovative skincare product development., (© 2022 The Authors.)

Atopic dermatitis (AD) is a chronic disease in which epidermal barrier disruption triggers Th2-mediated eruption of eczematous lesions. Topical emollients are a cornerstone of chronic management. This study evaluated efficacy of two plant-derived oil derivatives, isosorbide di-(linoleate/oleate) (IDL) and isosorbide dicaprylate (IDC), using AD-like tissue culture models. Treatment of reconstituted human epidermis with cytokine cocktail (IL-4 + IL-13 + TNF-α + IL-31) compromised the epidermal barrier, but this was prevented by co-treatment with IDL and IDC. Cytokine stimulation also dysregulated expression of keratinocyte (KC) differentiation genes whereas treatment with IDC or IDL + IDC up-regulated genes associated with early (but not late) KC differentiation. Although neither IDL nor IDC inhibited Th2 cytokine responses, both compounds repressed TNF-α-induced genes and IDL + IDC led to synergistic down-regulation of inflammatory ( IL1B , ITGA5 ) and neurogenic pruritus ( TRPA1 ) mediators. Treatment of cytokine-stimulated skin explants with IDC decreased lactate dehydrogenase (LDH) secretion by more than 50% (more than observed with cyclosporine) and in vitro LDH activity was inhibited by IDL and IDC. These results demonstrate anti-inflammatory mechanisms of isosorbide fatty acid diesters in AD-like skin models. Our findings highlight the multifunctional potential of plant oil derivatives as topical ingredients and support studies of IDL and IDC as therapeutic candidates.

Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Dimethyl fumarate (DMF) has emerged as a first-line therapy for relapsing-remitting multiple sclerosis (RRMS). This treatment, however, has been limited by adverse effects, which has prompted development of novel derivatives with improved tolerability. We compared the effects of fumarates on gene expression in astrocytes. Our analysis included diroximel fumarate (DRF) and its metabolite monomethyl fumarate (MMF), along with a novel compound isosorbide di-(methyl fumarate) (IDMF). Treatment with IDMF resulted in the largest number of differentially expressed genes. The effects of DRF and MMF were consistent with NRF2 activation and NF-κB inhibition, respectively. IDMF responses, however, were concordant with both NRF2 activation and NF-κB inhibition, and we confirmed IDMF-mediated NF-κB inhibition using a reporter assay. IDMF also down-regulated IRF1 expression and IDMF-decreased gene promoters were enriched with IRF1 recognition sequences. Genes altered by each fumarate overlapped significantly with those near loci from MS genetic association studies, but IDMF had the strongest overall effect on MS-associated genes. These results show that next-generation fumarates, such as DRF and IDMF, have effects differing from those of the MMF metabolite. Our findings support a model in which IDMF attenuates oxidative stress via NRF2 activation, with suppression of NF-κB and IRF1 contributing to mitigation of inflammation and pyroptosis.

The most crucial yield constraint of pigeon pea is susceptibility to the pod borer Helicoverpa armigera, which causes extensive damage and severe economic losses every year. The Agrobacterium-mediated plumular meristem transformation technique was applied for the development of cry1Ac transgenic pigeon pea. Bioactivity of the cry1Ac gene was compared based on integration and expression driven by two promoters, the constitutive CaMV35S promoter and the green-tissue-specific ats1A promoter, in those transgenic events. The transgenic events also contained the selectable marker gene nptII flanked by loxP sites. Independent transgenic events expressing the Cre recombinase gene along with a linked bar selection marker were also developed. Integration and expression patterns of both cry1Ac and cre were confirmed through Southern and western blot analysis of T 1 events. The constitutive expression of the Cry1Ac protein was found to be more effective for conferring resistant activity against H. armigera larvae in comparison to green-tissue-specific expression. Constitutively expressing Cry1Ac T 1 events were crossed with Cre recombinase expressing T 1 events. The crossing-based Cre/lox-mediated marker gene elimination strategy was demonstrated to generate nptII-free Cry1Ac-expressing T 2 events. These events were subsequently analyzed in the T 3 generation for the segregation of cre and bar genes. Five Cry1Ac-expressing T 3 transgenic pigeon pea events were devoid of the nptII marker as well as cre-bar genes. H. armigera larval mortality in those marker-free T 3 events was found to be 80-100%. The development of such nptII selectable marker-free Cry1Ac-expressing pigeon pea transgenics for the first time would greatly support the sustainable biotechnological breeding program for pod borer resistance in pigeon pea. KEY POINTS: • Constitutive expression of Cry1Ac conferred complete resistance against Helicoverpa armigera • Green-tissue-specific expression of Cry1Ac conferred partial pest resistance • Cre/lox-mediated nptII elimination was successful in constitutively expressing Cry1Ac transgenic pigeon pea events., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Vascular wilt caused by Fusarium udum Butler is the most important disease of pigeonpea throughout the world. F. udum isolate MTCC 2204 (M1) inoculated pigeonpea plants of susceptible (ICP 2376) and resistant (ICP 8863) cultivars were taken at invasion stage of pathogenesis process for transcriptomic profiling to understand defense signaling reactions that interplay at early stage of this plant-pathogen encounter. Differential transcriptomic profiles were generated through cDNA-AFLP from M1 inoculated resistant and susceptible pigeonpea root tissues. Twenty five percent of transcript derived fragments (TDFs) were found to be pathogen induced. Among them 73 TDFs were re-amplified and sequenced. Homology search of the TDFs in available databases and thorough study of scientific literature identified several pathways, which could play crucial role in defense responses of the F. udum inoculated resistant plants. Some of the defense responsive pathways identified to be active during this interaction are, jasmonic acid and salicylic acid mediated defense responses, cell wall remodeling, vascular development and pattering, abscisic acid mediated responses, effector triggered immunity, and reactive oxygen species mediated signaling. This study identified important wilt responsive regulatory pathways in pigeonpea which will be helpful for further exploration of these resistant components for pigeonpea improvement., (© 2021. The Author(s).)

The most consumed and economically important beverage plant, tea (Camellia sinensis), and its pests have coevolved so as to maintain the plant-insect interaction. In this review, findings of different research groups on pest responsive tolerance mechanisms that exist in tea manifested through the production of secondary metabolites and their inducers are presented. The phytochemicals of C. sinensis have been categorized into volatiles, nonvolatiles, enzymes, and phytohormones for convenience. Two types of pests, namely the piercing-sucking pests and chewing pests, are associated with tea. Both the insect groups can trigger the production of those metabolites and inducers through several primary and secondary biosynthetic pathways. These induced biomolecules can act as insect repellents and most of them are associated with lowering the nutrient quality of plant tissue and increasing the indigestibility in the pest's gut. Moreover, some of them also act as predator attractants of particular pests. The herbivore-induced plant volatiles secreted from tea plants during pest infestation were (E)-nerolidol, α-farnesene, (Z)-3-hexenol, (E)-4,8-dimethyl-1,3,7-nonatriene, indole, benzyl nitrile (BN), linalool, and ocimenes. The nonvolatiles like theaflavin and L-theanine were increased in response to the herbivore attack. Simultaneously, S-adenosyl-L-methionine synthase, caffeine synthase activities were affected, whereas flavonoid synthesis and wax formation were elevated. Defense responsive enzymes like peroxidase, polyphenol oxidase, phenylalanine ammonia-lyase, ascorbate peroxidase, and catalase are involved in pest prevention mechanisms. Phytohormones like jasmonic acid, salicylic acid, abscisic acid, and ethylene act as the modulator of the defense system. The objective of this review is to discuss the defensive roles of these metabolites and their inducers against pest infestation in tea with an aim to develop environmentally sustainable pesticides in the future.Key points• Herbivore-induced volatile signals and their effects on neighboring tea plant protection• Stereochemical conversion of volatiles, effects of nonvolatiles, expression of defense-responsive enzymes, and phytohormones due to pest attack• Improved understanding of metabolites for bio-sustainable pesticide development., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Tetrahexyldecyl Ascorbate (THDC) is an L-ascorbic acid precursor with improved stability and ability to penetrate the epidermis. The stability and transdermal penetration of THDC, however, may be compromised by the oxidant-rich environment of human skin. In this study, we show that THDC is a poor antioxidant that degrades rapidly when exposed to singlet oxygen. This degradation, however, was prevented by combination with acetyl zingerone (AZ) as a stabilizing antioxidant. As a standalone ingredient, THDC led to unexpected activation of type I interferon signaling, but this pro-inflammatory effect was blunted in the presence of AZ. Moreover, the combination of THDC and AZ increased expression of genes associated with phospholipid homeostasis and keratinocyte differentiation, along with repression of MMP1 and MMP7 expression, inhibition of MMP enzyme activity, and increased production of collagen proteins by dermal fibroblasts. Lastly, whereas THDC alone reduced viability of keratinocytes exposed to oxidative stress, this effect was completely abrogated by the addition of AZ to THDC. These results show that AZ is an effective antioxidant stabilizer of THDC and that combination of these products may improve ascorbic acid delivery. This provides a step towards reaching the full potential of ascorbate as an active ingredient in topical preparations.

Dimethyl fumarate (DMF) is an effective oral treatment for psoriasis administered in Europe for nearly 60 years. However, its potential has been limited by contact dermatitis that prohibits topical application. This paper characterizes a DMF derivative, isosorbide DMF (IDMF), which was designed to have antipsoriatic effects without skin-sensitizing properties. We show that IDMF exhibits neither genotoxicity nor radiation sensitivity in skin fibroblasts and is nonirritating and nonsensitizing in animal models (rat, rabbit, guinea pig). Microarray analysis of cytokine-stimulated keratinocytes showed that IDMF represses the expression of genes specifically upregulated in psoriatic skin lesions but not those of other skin diseases. IDMF also downregulated genes induced by IL-17A and TNF in keratinocytes as well as predicted targets of NF-κB and the antidifferentiation noncoding RNA (i.e., ANCR ). IDMF further stimulated the transcription of oxidative stress response genes ( NQO1 , GPX2 , GSR ) with stronger NRF2/ARE activation compared to DMF. Finally, IDMF reduced erythema and scaling while repressing the expression of immune response genes in psoriasiform lesions elicited by topical application of imiquimod in mice. These data show that IDMF exhibits antipsoriatic activity that is similar or improved compared with that exhibited by DMF, without the harsh skin-sensitizing effects that have prevented topical delivery of the parent molecule., (© 2021 The Authors.)

The breakdown of the epidermal barrier and consequent loss of skin hydration is a feature of skin aging and eczematous dermatitis. Few treatments, however, resolve these underlying processes to provide full symptomatic relief. In this study, we evaluated isosorbide di-(linoleate/oleate) (IDL), which was generated by esterifying isosorbide with sunflower fatty acids. Topical effects of IDL in skin were compared with those of ethyl linoleate/oleate, which has previously been shown to improve skin barrier function. Both IDL and ethyl linoleate/oleate downregulated inflammatory gene expression, but IDL more effectively upregulated the expression of genes associated with keratinocyte differentiation (e.g., KRT1, GRHL2, SPRR4). Consistent with this, IDL increased the abundance of epidermal barrier proteins (FLG and involucrin) and prevented cytokine-mediated stratum corneum degradation. IDL also downregulated the expression of unhealthy skin signature genes linked to the loss of epidermal homeostasis and uniquely repressed an IFN-inducible coexpression module activated in multiple skin diseases, including psoriasis. In a double-blind, placebo-controlled trial enrolling females with dry skin, 2% IDL lotion applied over 2 weeks significantly improved skin hydration and decreased transepidermal water loss (NCT04253704). These results demonstrate mechanisms by which IDL improves skin hydration and epidermal barrier function, supporting IDL as an effective intervention for the treatment of xerotic pruritic skin., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Sequential formation of a poly-cyclic aromatic hydrocarbon (PAH) dication in the H I regions of the interstellar medium (ISM) is proposed to be a function of internal energy of the doubly ionized PAHs, which, in turn, is dependent on the single- and double-ionization potentials of the system. This sets a limit on the single- and double-ionization energies of the system(s) that can further undergo sequential absorption of two photons, leading to a dication (PAH +2 ). Here, we report the single-ionization (I +1 ) and double-ionization (I +2 ) energies and the I +2 /I +1 ratio for some selected PAHs and conjugated polyenes obtained using the Fock space coupled cluster technique, enabling simultaneous consideration of several electronic states of different characters. The I +2 to I +1 ratio bears a constant ratio, giving allowance to determine I +2 from the knowledge of single-ionization (I +1 ) and vice versa. Our observations are in good agreement with the established literature findings, confirming the reliability of our estimates. The measured single- and double-ionization energies further demonstrate that the sequential formation and fragmentation of a PAH dication in the H I regions of the ISM for systems such as benzene and conjugated polyenes such as ethylene and butadiene are quite unlikely because I +2 -I +1 for such system(s) is higher than the available photon energy in the H I regions of the ISM. Present findings may be useful to understand the formation and underlying decay mechanisms of multiply charged ions from PAHs and related compounds that may accentuate the exploration of the phenomenon of high-temperature superconductivity.

The ground and low-lying excited state electronic structural properties (such as equilibrium geometries, harmonic frequencies, excitation energies, barrier energy, and so on) of the methylene amidogene radical (H 2 CN) and its anion (H 2 CN - ) have been studied using the CASCI (complete active space configuration interaction) and SSMRPT (state-specific multireference Møller-Plesset perturbation theory) methods with density function theory (DFT) orbitals. Here, the span of the active orbitals have been obtained from Kohn-Sham DFT using B3LYP exchange-correlation functionals in the CASCI (DFT-CASCI) approximation to describe nondynamic correlation associated with electronic degeneracies. The DFT-SSMRPT protocol provides an attractive way to deal with both dynamical and nondynamical correlation effects in strongly correlated systems such as H 2 CN and H 2 CN - . The present work clearly indicates that the electronic absorption band near 35,050 cm -1 corresponds to the B̃ 2 A 1 ← X̃ 2 B 2 transition. DFT-SSMRPT findings are in close agreement with high-level theoretical estimates. It is concluded that the transition at 1725 cm -1 could be due to the CN stretching of the trans -HCNH isomer which is originally assigned to the CN stretch of H 2 CN in the experiment. The present results confirm most of the previous vibrational assignments. It is not possible to definitively assign a transition to the 35,600 cm -1 band with the present estimations, suggesting further experiment is urgently called for.

Human-Computer Interaction (HCI) and games set a new domain in understanding people's motivations in gaming, behavioral implications of game play, game adaptation to player preferences and needs for increased engaging experiences in the context of HCI serious games (HCI-SGs). When the latter relate with people's health status, they can become a part of their daily life as assistive health status monitoring/enhancement systems. Co-designing HCI-SGs can be seen as a combination of art and science that involves a meticulous collaborative process. The design elements in assistive HCI-SGs for Parkinson's Disease (PD) patients, in particular, are explored in the present work. Within this context, the Game-Based Learning (GBL) design framework is adopted here and its main game-design parameters are explored for the Exergames, Dietarygames, Emotional games, Handwriting games, and Voice games design, drawn from the PD-related i-PROGNOSIS Personalized Game Suite (PGS) (www.i-prognosis.eu) holistic approach. Two main data sources were involved in the study. In particular, the first one includes qualitative data from semi-structured interviews, involving 10 PD patients and four clinicians in the co-creation process of the game design, whereas the second one relates with data from an online questionnaire addressed by 104 participants spanning the whole related spectrum, i.e., PD patients, physicians, software/game developers. Linear regression analysis was employed to identify an adapted GBL framework with the most significant game-design parameters, which efficiently predict the transferability of the PGS beneficial effect to real-life, addressing functional PD symptoms. The findings of this work can assist HCI-SG designers for designing PD-related HCI-SGs, as the most significant game-design factors were identified, in terms of adding value to the role of HCI-SGs in increasing PD patients' quality of life, optimizing the interaction with personalized HCI-SGs and, hence, fostering a collaborative human-computer symbiosis., Competing Interests: Authors Hugo Silva and Gonçalo Telo were employed by the company PLUX, Wireless Biosignals. Moreover, Konstantinos Filis, Elina Theodoropoulou, and George Lyberopoulos were employed by the company COSMOTE Kinites Tilepekoinonies AE. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dias, Diniz, Konstantinidis, Savvidis, Zilidou, Bamidis, Grammatikopoulou, Dimitropoulos, Grammalidis, Jaeger, Stadtschnitzer, Silva, Telo, Ioakeimidis, Ntakakis, Karayiannis, Huchet, Hoermann, Filis, Theodoropoulou, Lyberopoulos, Kyritsis, Papadopoulos, Depoulos, Trivedi, Chaudhuri, Klingelhoefer, Reichmann, Bostantzopoulou, Katsarou, Iakovakis, Hadjidimitriou, Charisis, Apostolidis and Hadjileontiadis.)

Dimethyl fumarate (DMF) has emerged as a first-line treatment for the relapsing-remitting multiple sclerosis (RRMS) subtype. It is hypothesized that DMF has anti-inflammatory and antioxidant effects although mechanisms are not fully understood. This study used RNA-seq to profile gene expression responses to DMF in cultured astrocytes. Responses were compared with those of isosorbide di-(methyl fumarate) (IDMF), a newly designed fumarate that may partially replicate DMF activity with fewer adverse effects. Both compounds altered the expression of MS-associated genes, including those near MS susceptibility loci and genes dysregulated in MS patient astrocytes. The shared DMF/IDMF transcriptome response involved altered expression of antioxidant genes (e.g., HMOX1) and genes linked to extracellular matrix integrity (TIMP3, MMP9) and migration of pro-inflammatory cells into CNS (CCL2). IDMF-specific transcriptome responses included down-regulation of mitotic genes associated with a proliferative reactive astrocyte phenotype (ICAM1) and repression of genes encoding NF-kappaB subunits (NFKB2, RELA, RELB) and NF-kappaB targets (NCAPG, CXCL1, OAS3). Overall, these results identify astrocyte-centered mechanisms that may contribute to the established efficacy of DMF as an RRMS treatment. Furthermore, our findings support a rationale for further studies of IDMF as a novel fumarate, which may have unique suppressive effects on astrocyte reactivity and glial scar formation. [200 words]., Competing Interests: Declaration of competing interest IDMF was developed and patented by Sytheon Ltd (Boonton, NJ). RKC is president and CEO of Sytheon with ownership interest. KB is chief executive officer of Sunny BioDiscovery, Inc. (Santa Paula, CA). WRS and KB have received consulting reimbursement from Sytheon., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Terminalia chebula (TC) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage, skin aging, and wound healing. However, molecular and cellular mechanisms underlying these benefits remain unclear., Objective: To profile dermal expression responses to a standardized tannin-enriched TC fruit extract (Synastol ® TC)., Materials and Methods: Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures., Results: Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress, solar-simulated UV radiation, and wounding, with increased expression of genes associated with water homeostasis, skin barrier establishment, blood vessel development, and circadian rhythms. TC also increased expression of extracellular matrix components, such as collagens (COL1A1, COL1A2) and proteoglycans (PRELP, OGN), and in separate assays, we showed that TC inhibits MMP enzymes (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12) and microbial activity (S. aureus, P. acnes). Unexpectedly, mRNA and protein levels of late keratinocyte (KC) differentiation markers (FLG, LOR) were increased by TC, and expression responses in skin cultures broadly resembled those that occur with KC differentiation. Consistent with these results, TC increased expression of transcription factors regulating KC differentiation (FOS, GHRL3, PPARG) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes., Conclusion: These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer. Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder with the non-motor symptoms preceding the motor impairment that is needed for clinical diagnosis. In the current study, an angle-based analysis that processes activity data during sleep from a smartwatch for quantification of sleep quality, when applied on controls and PD patients, is proposed. Initially, changes in their arm angle due to activity are captured from the smartwatch triaxial accelerometry data and used for the estimation of the corresponding binary state (awake/sleep). Then, sleep metrics (i.e., sleep efficiency index, total sleep time, sleep fragmentation index, sleep onset latency, and wake after sleep onset) are computed and used for the discrimination between controls and PD patients. A process of validation of the proposed approach when compared with the PSG-based ground truth in an in-the-clinic setting, resulted in comparable state estimation. Moreover, data from 15 early PD patients and 11 healthy controls were used as a test set, including 1,376 valid sleep recordings in-the-wild setting. The univariate analysis of the extracted sleep metrics achieved up to 0.77 AUC in early PD patients vs. healthy controls classification and exhibited a statistically significant correlation (up to 0.46) with the clinical PD Sleep Scale 2 counterpart Items. The findings of the proposed method show the potentiality to capture non-motor behavior from users' nocturnal activity to detect PD in the early stage.

To compute the electronic excitation energies, a state-specific multireference Møller-Plesset perturbation theory (SSMRPT) with a complete active space configuration interaction reference function constructed using the orbitals obtained by the density functional theory (DFT) is presented as an accurate, as well as computationally affordable, and efficient protocol at the level of second order. The global hybrid B3LYP (Becke, 3-parameter, Lee-Yang-Parr) functional has been used to generate orbitals. The present method, called DFT-SSMRPT, uses perturbers that are individual Slater determinants and accounts for the coupling between the nondynamical and dynamical correlation effects. We have applied the new method to compute excitation energies in conjugated systems of π-electrons such as trans-1,3-butadiene, trans,trans-1,3,5-hexatriene, and all-trans-1,3,5,7-octatetraene. The ordering of the excited states is correctly reproduced by the DFT-SSMRPT calculations. The relative ordering of low-lying excited 1 B u and 1 A g states alters when the length of the polyene changes. The results match reasonably well with the literature including experimental and best theoretical findings. The accuracy of the method is sufficient to discern the energy gap between the close low-lying singlet and triplet states. The DFT-SSMRPT appears as an affordable computational ab initio avenue for a qualitatively correct description of excitation energies.

Zingerone (Z) is a phenolic alkanone derived from natural sources with anti-inflammatory and antioxidant effects. Acetyl zingerone (AZ) is a recently designed molecule that shares structural features with Z but is expected to have improved stability and antioxidant function. This study utilized microarrays to compare the effects of Z and AZ on gene expression in reconstituted human epidermis. Both Z and AZ increased Notch pathway gene expression (NOTCH1 and MAML3) and decreased expression of genes linked to extracellular matrix disassembly (MMP3 and CTSV) and reactive oxygen species metabolism (PMAIP1 and ARG2). Although Z and AZ each inhibited in vitro matrix metallopeptidase (MMP)-1, MMP-3, and MMP-12 activity, inhibition of MMP-3 and MMP-12 was greater with AZ. Moreover, AZ led to more consistent increases in the expression of genes encoding collagens (COL11A2), proteoglycans (VCAN), and extracellular matrix glycoproteins (SPARC). Finally, AZ opposed gene expression patterns associated with fibroblast senescence, keratinocyte differentiation, and IL-17A stimulation. These effects were AZ-specific and not replicated by Z. These results show that AZ improves extracellular matrix integrity with retinoid-like effects on differentiation and inflammation. Our findings provide a rationale for clinical studies to understand the benefits of AZ in the treatment or prevention of skin aging, or potentially, as a treatment for other human skin diseases., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Recent research has shown that significant levels of cyclobutane pyrimidine dimers (CPDs) in DNA continue to form in melanocytes for several hours in the dark after exposure to ultraviolet radiation (UVR) ends. We document the utility of a new multifunctional ingredient, 3-(4-hydroxy, 3-methoxybenzyl)-pentane-2,4-dione (INCI acetyl zingerone (AZ)), to protect melanocytes against CPD formation after UVR exposure ends., Methods: The use of AZ as an intervention to reduce CPD formation after irradiation was assessed in vitro by comparing kinetic profiles of CPD formation for several hours after irradiation in cells that were untreated or treated with AZ immediately after irradiation. Multifunctional performance of AZ as an antioxidant, quencher and scavenger was established using industry-standard in vitro chemical assays, and then, its efficacy in a more biological assay was confirmed by its in vitro ability to reduce intracellular levels of reactive oxygen species (ROS) in keratinocytes exposed to UVA radiation. Molecular photostability was assessed in solution during exposure to solar-simulated UVR and compared with the conventional antioxidant α-tocopherol., Results: Even when added immediately after irradiation, AZ significantly inhibited ongoing formation of CPDs in melanocytes after exposure to UVA. Incubation with AZ before irradiation decreased intracellular levels of UVA-induced ROS formation in keratinocytes. Compared with α-tocopherol, the molecular structure of AZ endows it with significantly better photostability and efficacy to neutralize free radicals (∙OH, ∙OOH), physically quench singlet oxygen ( 1 O 2 ) and scavenge peroxynitrite (ONOO - )., Conclusion: These results designate AZ as a new type of multifunctional ingredient with strong potential to extend photoprotection of traditional sunscreens and daily skincare products over the first few hours after sun exposure ends., (© 2019 The Authors. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Société Française de Cosmétologie.)

A reliable pigeon pea transformation system can assist the rapid improvement of this important grain legume through transgenic development. Here we describe two methods of Agrobacterium tumefaciens-mediated pigeon pea transformation. In the tissue culture based embryonic explant transformation method, microshoot grafting was included to obtain rapid root induction, while the other method was culture independent and designated as plumular meristem transformation. Both methods drastically enhanced the transformation frequency and have the potential to provide reasonable solutions for maximum transgenic recovery in biotechnological breeding programs.

We report the Auger and Coster-Kronig transition energies (related to double ionization potentials) of noble gas elements obtained using the Fock-space multireference coupled cluster (FSMRCC) method with relativistic spinors. The resulting Auger and Coster-Kronig lines are found to be in agreement with the experimental data and with other reference theoretical estimates. To the best of our knowledge, no prior report of relativistic calculations is available for Auger transition energies at the FSMRCC level of theory. The ionization potentials resulted from this method with no extra cost are also found to be in agreement with experiment, particularly the outer-valence ones. Interestingly, the FSMRCC and the multiconfiguration Dirac-Fock calculations exhibit an inversion in the 3 P energy levels of the xenon atom for N 4,5 -O 23 O 23 Auger transitions, where the 3 P j state energies appear in the order J = 1, 0, 2, a feature which can be verified experimentally.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder worldwide, causing both motor and non-motor symptoms. In the early stages, symptoms are mild and patients may ignore their existence. As a result, they do not undergo any related clinical examination; hence delaying their PD diagnosis. In an effort to remedy such delay, analysis of data passively captured from user's interaction with consumer technologies has been recently explored towards remote screening of early PD motor signs. In the current study, a smartphone-based method analyzing subjects' finger interaction with the smartphone screen is developed for the quantification of fine-motor skills decline in early PD using Convolutional Neural Networks. Experimental results from the analysis of keystroke typing in-the-clinic data from 18 early PD patients and 15 healthy controls have shown a classification performance of 0.89 Area Under the Curve (AUC) with 0.79/0.79 sensitivity/specificity, respectively. Evaluation of the generalization ability of the proposed approach was made by its application on typing data arising from a separate self-reported cohort of 27 PD patients' and 84 healthy controls' daily usage with their personal smartphones (data in-the-wild), achieving 0.79 AUC with 0.74/0.78 sensitivity/specificity, respectively. The results show the potentiality of the proposed approach to process keystroke dynamics arising from users' natural typing activity to detect PD, which contributes to the development of digital tools for remote pathological symptom screening.

Parkinson's Disease (PD) is a neurodegenerative disorder that manifests through slowly progressing symptoms, such as tremor, voice degradation and bradykinesia. Automated detection of such symptoms has recently received much attention by the research community, owing to the clinical benefits associated with the early diagnosis of the disease. Unfortunately, most of the approaches proposed so far, operate under a strictly laboratory setting, thus limiting their potential applicability in real world conditions. In this work, we present a method for automatically detecting tremorous episodes related to PD, based on acceleration signals. We propose to address the problem at hand, as a case of Multiple-Instance Learning, wherein a subject is represented as an unordered bag of signal segments and a single, expert-provided, ground-truth. We employ a deep learning approach that combines feature learning and a learnable pooling stage and is trainable end-to-end. Results on a newly introduced dataset of accelerometer signals collected in-the-wild confirm the validity of the proposed approach.

Objective: The study involved the synthesis of a novel derivative of caprylic acid - isosorbide dicaprylate (IDC) - and the evaluation of its potential in improving water homoeostasis and epidermal barrier function in human skin., Methods: The effect of IDC on gene expression was assayed in skin organotypic cultures by DNA microarrays. The results were then confirmed for a few key genes by quantitative PCR, immuno- and cytochemistry. Final validation of skin hydration properties was obtained by four separate clinical studies. Level of hydration was measured by corneometer either by using 2% IDC lotion alone vs placebo or in combination with 2% glycerol lotion vs 2% glycerol only. A direct comparison in skin hydration between 2% IDC and 2% glycerol lotions was also carried out. The epidermal barrier function improvement was assessed by determining changes in transepidermal water loss (TEWL) on the arms before and after treatment with 2% IDC lotion versus placebo., Results: IDC was found to upregulate the expression of AQP3, CD44 and proteins involved in keratinocyte differentiation as well as the formation and function of stratum corneum. A direct comparison between 2% IDC versus 2% glycerol lotions revealed a three-fold advantage of IDC in providing skin hydration. Severely dry skin treated with 2% IDC in combination with 2% glycerol showed 133% improvement, whereas 35% improvement was observed with moderately dry human skin., Conclusion: Topical isosorbide dicaprylate favourably modulates genes involved in the maintenance of skin structure and function, resulting in superior clinical outcomes. By improving skin hydration and epidermal permeability barrier, it offers therapeutic applications in skin ageing., (© 2017 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

The present investigation reports on the prospect of using state specific multireference perturbation theory (SSMRPT) with an improved virtual orbital complete active space configuration interaction (IVO-CASCI) reference function (IVO-SSMRPT) to generate potential energy surfaces (PESs) for molecular systems [such as CH 4 , C 2 H 6 , C 2 H 4 , H 2 O 2 , LiH, and KN] by stretching and breaking of suitable bonds with modest basis sets. We have also revisited the dissociation energy profile of triplet ketene which exhibits a step-like structure in the observed rate. The application of the method has also been made to the ionization energies of H 2 O. Although the perturbative corrections are obtained by the diagonalization of the effective Hamiltonian, in IVO-SSMRPT, only one physically relevant solution is achievable. It is parameter free and does not require any threshold to avoid the intruder problem. It is strictly size-extensive and size-consistent provided that local orbitals are used. The PESs obtained with our approach are smooth all along the reaction path. Our estimates are in close agreement with the available reference data indicating that IVO-SSMRPT is a robust paradigm for the accurate computation of ground, excited and ionized states as it captures the mutual inter-play of different flavors of correlation effects in a balanced and accurate way.

A relativistic study of spectroscopic properties of the endohedral fullerenes Ng@C 60 q (where Ng = He, Ne and q=0,±1,±2 are the charges) associated with the C 60 molecule has been done using the equation of motion coupled cluster (EOM-CC) methodology. Specific properties estimated are the transition energies, dipole oscillator strengths, and transition probabilities for the low-lying excitations 1s 2 ( 1 S 0 ) → 1snp ( 1 P 1 ) (n = 2, 3, 4) for He@C 60 q and 1s 2 2s 2 2p 6 ( 1 S 0 ) → 1s 2 2s 2 2p 5 ns∕nd ( 1 P 1 ) (n = 3, 4) for Ne@C 60 q , which have been compared with those for the isolated atom to depict the confinement effect of the host molecule on the encapsulated atom. This is accomplished by introducing an effective potential to the atomic Hamiltonian induced by the fullerene moiety and its charge. The EOM-CC results have been compared with those estimated with the random phase approximation (and configuration interaction singles) to understand the effect of electron correlation under such confinement. The systematic and interesting behavior of the properties is highlighted indicating the effect of fullerene cage potential on the redistribution of electron density of the guest atom.

Background: Parkinson's disease (PD) has been associated with peripheral neuropathy (PN). PN has been demonstrated in some rare genetic forms of PD (e.g. PARK2 mutations) but has also been linked to levodopa exposure., Objective: The aim of this systematic review is to clarify any evidence of peripheral nervous system involvement in idiopathic PD., Methods: A systematic computer-based literature search was conducted on PubMed database., Findings: The pooled estimate of the prevalence of large fiber PN in PD was 16.3% (based on 1376 patients). The pooled estimate of the prevalence of biopsy-proven small fiber neuropathy was 56.9% (based on 72 patients). Large fiber PN in PD is in the majority of cases distal, symmetrical, axonal and predominantly sensory. There are, however, few reports of chronic idiopathic demyelinating polyneuropathy and very occasional cases of acute neuropathies. Although nerve conduction studies have been performed in the majority of the studies, they included only a limited number of nerves, mainly in the lower limbs. There is little evidence to support a direct link between levodopa treatment and the development of PN in idiopathic PD. In the majority of the cases PN has been linked to abnormalities in vitamin B12, methylmalonic acid or fasting homocysteine levels. Additional aetiological risk factors for PN may be responsible for any apparent link between PD and PN., Conclusions: Large-scale prospective studies with long-term follow-up with detailed baseline assessments are needed in order to understand the natural history of PN in PD, both on clinical and neurophysiological parameters., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Key Message: Independent transgenic pigeonpea events were developed using two cry genes. Transgenic Cry2Aa-pigeonpea was established for the first time. Selected transgenic events demonstrated 100% mortality of Helicoverpa armigera in successive generations. Lepidopteran insect Helicoverpa armigera is the major yield constraint of food legume pigeonpea. The present study was aimed to develop H. armigera-resistant transgenic pigeonpea, selected on the basis of transgene expression and phenotyping. Agrobacterium tumefaciens-mediated transformation of embryonic axis explants of pigeonpea cv UPAS 120 was performed using two separate binary vectors carrying synthetic Bacillus thuringiensis insecticidal crystal protein genes, cry1Ac and cry2Aa. T 0 transformants were selected on the basis of PCR and protein expression profile. T 1 events were exclusively selected on the basis of expression and monogenic character for cry, validated through Western and Southern blot analyses, respectively. Independently transformed 12 Cry1Ac and 11 Cry2Aa single-copy events were developed. The level of Cry-protein expression in T 1 transgenic events was 0.140-0.175% of total soluble protein. Expressed Cry1Ac and Cry2Aa proteins in transgenic pigeonpea exhibited significant weight loss of second-fourth instar larvae of H. armigera and ultimately 80-100% mortality in detached leaf bioassay. Selected Cry-transgenic pigeonpea events, established at T 2 generation, inherited insect-resistant phenotype. Immunohistofluorescence localization in T 3 plants demonstrated constitutive accumulation of Cry1Ac and Cry2Aa in leaf tissues of respective transgenic events. This study is the first report of transgenic pigeonpea development, where stable integration, effective expression and biological activity of two Cry proteins were demonstrated in subsequent three generations (T 0 , T 1, and T 2 ). These studies will contribute to biotechnological breeding programmes of pigeonpea for its genetic improvement.

The relativistic multireference (MR) perturbative approach is one of the most successful tools for the description of computationally demanding molecular systems of heavy elements. We present here the ground state dissociation energy surfaces, equilibrium bond lengths, harmonic frequencies, and dissociation energies of Ag 2 , Cu 2 , Au 2 , and I 2 computed using the four-component (4c) relativistic spinors based state-specific MR perturbation theory (SSMRPT) with improved virtual orbital complete active space configuration interaction (IVO-CASCI) functions. The IVO-CASCI method is a simple, robust, useful and lower cost alternative to the complete active space self-consistent field approach for treating quasidegenerate situations. The redeeming features of the resulting method, termed as 4c-IVO-SSMRPT, lies in (i) manifestly size-extensivity, (ii) exemption from intruder problems, (iii) the freedom of convenient multipartitionings of the Hamiltonian, (iv) flexibility of the relaxed and unrelaxed descriptions of the reference coefficients, and (v) manageable cost/accuracy ratio. The present method delivers accurate descriptions of dissociation processes of heavy element systems. Close agreement with reference values has been found for the calculated molecular constants indicating that our 4c-IVOSSMRPT provides a robust and economic protocol for determining the structural properties for the ground state of heavy element molecules with eloquent MR character as it treats correlation and relativity on equal footing.

The state-specific multireference perturbation theory (SSMRPT) with an improved virtual orbital complete active space configuration interaction (IVO-CASCI) reference function [called as IVO-SSMRPT] is used to investigate the energy surface, geometrical parameters, molecular properties of spectroscopic interest for the systems/situations [such as BeH 2 , BeCH 2 , MgCH 2 , Si 2 H 4 , unimolecular dissociation of H 2 CO, and intramolecular reaction pathways of 1,3-butadiene] where the effect of quasidegeneracy cannot be neglected. The merit of using the IVO-CASCI rather than complete active space self-consistent field (CASSCF) is that it is free from iterations beyond those in the initial SCF calculation and the convergence difficulties that plague CASSCF calculations with increasing size of the CAS. While IVO-CASCI describes the non-dynamical correlation, the SSMRPT scheme is a good second-order perturbative approximation to account for the rest of the correlation energy. Our IVO-SSMRPT method is instrumental in avoiding intruder states in an size-extensive manner and allows the revision of the content of wave function in the model space. It can treat model as well as real systems with predictive accuracy, as is evident from the fairly nice accordance between our estimates, and high-level theoretical results. Our estimates also corroborate well with some experimental findings.

Objective: The study concerned the synthesis of a novel photostabilizer based on benzylidenepentanedione chemistry and the evaluation of its potential in developing a broad-spectrum sunscreen formulation containing avobenzone., Methods: 3-(3,4,5-Trimethoxybenzylidene)-2-4-pentanedione (TMBP) was synthesized through a condensation reaction and incorporated into a sunscreen formulation containing, inter alia, avobenzone. The SPF, critical wavelength and in vitro photostability of the product were measured. The photostability was compared with that afforded by current avobenzone photostabilizers, namely octocrylene, ethylhexylmethoxycrylene and diethylhexylsyringylidenemalonate. The photostability of TMBP either alone or in the presence of avobenzone in a methanolic solution was also evaluated by UV spectrophotometric and HPLC analyses. The optical properties of TMBP were estimated experimentally and supported by time-dependent density functional theory (TD-DFT) calculations., Results: The ability of TMBP to stabilize avobenzone under ultraviolet (UV) light exposure was shown both in formulated products and in solution. A comparative stability study incorporating various combinations of avobenzone, TMBP (vs. three commercial photostabilizers) and UVB sunscreens clearly showed TMBP to be a very effective stabilizer. The photostabilizing effect of TMBP arises from triplet-state energy transfer from avobenzone to TMBP and through light-induced reactions that preserve the main chromophores. Interestingly, a 50% in vivo SPF boosting was observed when TMBP was used with organic and inorganic sunscreens when alone it has no contribution to SPF. TMBP-containing sunscreen formulations clearly showed a critical wavelength of well over 370 nm and can thus be categorized as broad-spectrum sunscreens., Conclusion: We were able to design a very effective photostabilizer, trimethoxybenzylidene pentanedione (INCI name), based on benzylidenepentanedione chemistry. TMBP is very efficient in stabilizing avobenzone in formulated products and boosts in vivo SPF by >50% for organic and inorganic sunscreens, and the formulations have critical wavelengths of >370 nm. These efficacious properties make it a promising additive for inclusion in broad-spectrum photoprotective products., (© 2016 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Highly accurate electronic structure calculations are often needed to supplement scant experimental data. We report the ground 3 D 3 and some selected low lying excited/ionized states of Pt and its ions obtained using the Fock space multireference coupled cluster method with four-component relativistic spinors. The present work establishes the stability of the 2 S 1/2 state of its negative ion and reproduces the binding energy of this state within 10 cm -1 . The first ionization potential (cm -1 ) is estimated to be 72 005, deviating from the experiment by just 200 (0.3%). We also report the magnetic hyperfine coupling constants (A) of Pt and its ions. The present calculation provides the A value (GHz) of the 3 D 3 state of Pt to be 5.78 exhibiting very good agreement with the experimental data of 5.70. To our knowledge, this is the first relativistic ab initio calculation of the ionization potential and magnetic hyperfine coupling constant for the neutral and ionic states of Pt at a high level of correlation treatment.

A four-component (4c) relativistic state specific multireference coupled cluster (4c-SSMRCC) method has been developed and applied to compute the ground state spectroscopic constants of Ag 2 , Cu 2 , Au 2 , and I 2 . The reference functions used in these calculations are obtained using computationally inexpensive improved virtual orbital-complete active space configuration interaction scheme. Rigorous size-extensivity and insensitivity towards the intruder state problem make our method an interesting choice for the calculation of the dissociation energy surface. To the best of our knowledge, this study is the first implementation of the SSMRCC within the relativistic framework. The overall agreement of our results, employing the smallest model space, with both theoretical and experimental reference values indicates that the 4c-SSMRCC method can be fruitfully used to describe electronic structures and associated properties of systems containing heavy elements. We observe a relativistic bond stabilization for the coinage metal dimers while the I-I bond is weakened by the relativistic effects.

Recently a state-specific multireference perturbation theory (SSMRPT) with an improved virtual orbitals complete active space configuration interaction (IVO-CASCI) reference function has been proposed for treating electronic structures of radicals such as methylene, m-benzyne, pyridyne, and pyridynium cation. This new development in MRPT, termed as IVO-SSMRPT, ensures that it is able to describe the structure of radicaloids with reasonable accuracy even with small reference spaces. IVO-SSMRPT is also capable of predicting the correct ordering of the lowest singlet-triplet gaps. Investigation of the first three electronic states of the oxygen molecule has also been used for rating our method. The agreement of our estimates with the available far more expensive benchmark state-of-the-art ab initio calculations is creditable. The IVO-SSMRPT method provides an effective avenue with manageable cost/accuracy ratio for accurately dealing with radicaloid systems possessing varying degrees of quasidegeneracy.