Generation and Application of Aryl Radicals Under Photoinduced Conditions.

Photoinduced aryl radical generation is a powerful strategy in organic synthesis that facilitates the formation of diverse carbon-carbon and carbon-heteroatom bonds. The synthetic applications of photoinduced aryl radical formation in the synthesis of complex organic compounds, including natural products, physiologically significant molecules, and functional materials, have received immense attention. An overview of current developments in photoinduced aryl radical production methods and their uses in organic synthesis is given in this article. A generalized idea of how to choose the reagents and approach for the generation of aryl radicals is described, along with photoinduced techniques and associated mechanistic insights. Overall, this article offers a critical assessment of the mechanistic results as well as the selection of reaction parameters for specific reagents in the context of radical cascades, cross-coupling reactions, aryl radical functionalization, and selective C-H functionalization of aryl substrates.

Confocal Surface-Enhanced Raman Imaging of the Intestinal Barrier Crossing Behavior of Model Nanoplastics in Daphnia Magna.

Nanoplastics (nP) pose hazards to aquatic animals once they are ingested. Significant knowledge gaps exist regarding the nP translocation across the animal intestine, which is the first barrier between the ingested nP and the animal body. We examined the intestinal barrier crossing behavior of nP in an aquatic animal model (Daphnia magna) and determined the translocation mechanism with the help of model "core-shell" polystyrene nanoplastics (nPS) and confocal surface-enhanced Raman spectroscopy (SERS). The Raman reporter (4-mercaptobenzoic acid)-tagged gold "core" of the model nPS enables sensitive and reliable particle imaging by confocal SERS. This method detected SERS signals of model nPS concentration as low as 4.1 × 109 particles/L (equivalent to 0.27 µg/L PS "shell" concentration). The translocation was observed with the help of multilayer stacked Raman maps of SERS signals of the model nPS. With a higher concentration or longer exposure time of the model nPS, uptake and translocation of the plastic particles increased. In addition, we demonstrated that clathrin-dependent endocytosis and macropinocytosis were two major mechanisms underlying the translocation. This study contributes to a mechanistic understanding of nP translocation by using the pioneering model nPS and an analytical toolkit, which undergird further investigations into nP behavior and health effects in aquatic species.

Identification of primary metabolites in fungal species of Trichophyton mentagrophyte and Trichophyton rubrum by NMR spectroscopy.

BACKGROUND: Superficial mycoses are fungal infections limited to the outermost layers of the skin and its appendages. The chief causative agents of these mycoses are dermatophytes and yeasts. The diagnosis of dermatophytosis can be made by direct mycological examination with potassium hydroxide (10%-30%) of biological material obtained from patients with suspected mycosis, providing results more rapid than fungal cultures, which may take days or weeks. This information, together with clinical history and laboratory diagnosis, ensures that the appropriate treatment is initiated promptly. However, false negative results are obtained in 5%-15%, by conventional methods of diagnosis of dermatophytosis. OBJECTIVES: To study the metabolic profiles of the commonly occurring dermatophytes by NMR spectroscopy. PATIENTS/MATERIALS: We have used 1D and 2D Nuclear Magnetic Resonance (NMR) experiments along with Human Metabolome Database (HMDB) and Chenomx database search for identification of primary metabolites in the methanol extract of two fungal species: Trichophyton mentagrophyte (T. mentagrophyte) and Trichophyton rubrum (T. rubrum). Both standard strains and representative number of clinical isolates of these two species were investigated. Further, metabolic profiles obtained were analysed using multivariate analysis. RESULTS: We have identified 23 metabolites in the T. mentagrophyte and another 23 metabolites in T. rubrum. Many important metabolites like trehalose, proline, mannitol, acetate, GABA and several other amino acids were detected, which provide the necessary components for fungal growth and metabolism. Altered metabolites were defined between Trichophyton mentagrophyte and T. rubrum strains. CONCLUSION: We have detected many metabolites in the two fungal species T. mentagrophyte and T. rubrum by using NMR spectroscopy. NMR spectroscopy provides a holistic snapshot of the metabolome of an organism. Key metabolic differences were identified between the two fungal strains. We need to perform more studies on metabolite profiling of the samples from these species for their rapid diagnosis and prompt treatment.

Selenium - An environmentally friendly micronutrient in agroecosystem in the modern era: An overview of 50-year findings.

Agricultural productivity is constantly being forced to maintain yield stability to feed the enormously growing world population. However, shrinking arable and nutrient-deprived soil and abiotic and biotic stressor (s) in different magnitudes put additional challenges to achieving global food security. Though well-defined, the concept of macro, micronutrients, and beneficial elements is from a plant nutritional perspective. Among various micronutrients, selenium (Se) is essential in small amounts for the life cycle of organisms, including crops. Selenium has the potential to improve soil health, leading to the improvement of productivity and crop quality. However, Se possesses an immense encouraging phenomenon when supplied within the threshold limit, also having wide variations. The supplementation of Se has exhibited promising outcomes in lessening biotic and abiotic stress in various crops. Besides, bulk form, nano-Se, and biogenic-Se also revealed some merits and limitations. Literature suggests that the possibilities of biogenic-Se in stress alleviation and fortifying foods are encouraging. In this article, apart from adopting a combination of a conventional extensive review of the literature and bibliometric analysis, the authors have assessed the journey of Se in the "soil to spoon" perspective in a diverse agroecosystem to highlight the research gap area. There is no doubt that the time has come to seriously consider the tag of beneficial elements associated with Se, especially in the drastic global climate change era.

Urinary Metabolomics Identified Metabolic Perturbations Associated with Gutka, a Smokeless Form of Tobacco.

Gutka, a form of smokeless tobacco, is widely used in the Indian subcontinent and in other regions of South Asia. Smokeless tobacco exposure is most likely to increase the incidence of oral cancer in the Indian population, and metabolic changes are a hallmark of cancer. The development of biomarkers for early detection and better prevention measures for smokeless tobacco users at risk of oral cancer can be aided by studying urinary metabolomics and offering insight into altered metabolic profiles. This study aimed to investigate urine metabolic alterations among smokeless tobacco users using targeted LC-ESI-MS/MS metabolomics approaches to better understand the effects of smokeless tobacco on human metabolism. Smokeless tobacco users' specific urinary metabolomics signatures were extracted using univariate, multivariate analysis and machine learning methods. Statistical analysis identified 30 urine metabolites significantly associated with metabolomic alterations in humans who chew smokeless tobacco. Receiver operator characteristic (ROC) curve analysis evidenced the 5 most discriminatory metabolites from each approach that could differentiate between smokeless tobacco users and controls with higher sensitivity and specificity. An analysis of multiple-metabolite machine learning models and single-metabolite ROC curves revealed discriminatory metabolites capable of distinguishing smokeless tobacco users from nonusers more effectively with higher sensitivity and specificity. Furthermore, metabolic pathway analysis depicted several dysregulated pathways in smokeless tobacco users, including arginine biosynthesis, beta-alanine metabolism, TCA cycle, etc. This study devised a novel strategy to identify exposure biomarkers among smokeless tobacco users by combining metabolomics and machine learning algorithms.

Donor-Acceptor Covalent Organic Frameworks as a Heterogeneous Photoredox Catalyst for Scissoring Alkenes to Carbonyl Constituents.

The conversion of alkenes to carbonyl constituents via the cleavage of the C═C bond is unique due to its biological and pharmacological significance. Though a number of oxidative C═C cleavage protocols have been demonstrated for terminal and electron-rich alkene systems, none of them were optimized for electron-deficient and conjugated alkenes. In this work, a covalent organic framework containing triphenylamine and triazine units was revealed to cleave the C═C bond of alkenes under very mild conditions involving visible light irradiation due to its photoredox property. The alkenes can be conveniently broken across the double bond to their constituent carbonyl derivatives on light irradiation in the presence of air and the covalent organic framework photocatalyst. This protocol is applicable for a wide range of alkenes in an aqueous acetonitrile medium with high functional group tolerance and regioselectivity. Though the electron-deficient alkenes required tetramethylethylene diamine as a sacrificial donor, the electron-rich alkenes do not demand any additives.

Blue light and skin: what is the intriguing link?

Blue light has garnered attention because of its ability to penetrate more deeply into the skin layers, and induce cellular dysfunction and DNA damage. Photoageing, hyperpigmentation and melasma are some of the cutaneous changes that develop on exposure to blue light. To date, the therapeutic roles of blue light have been evaluated in dermatological conditions like psoriasis, eczema, acne vulgaris, actinic keratosis and cutaneous malignancies, among others. In this review, we have attempted to present an evidence-based compilation of the effects of blue light on the skin.

Dermatological adverse drug reactions to tyrosine kinase inhibitors: a narrative review.

Tyrosine kinase inhibitors (TKIs) target the signal transduction pathways of protein kinases by several modes of inhibition. Adverse effects are generally dose dependent, with certain side-effects unique to each drug. However, due to similarities in target sites, different classes of TKIs may have identical or overlapping side-effect profiles. This narrative review is an attempt to summarize the common and uncommon adverse effects of different classes of TKIs.

The economic burden of topical corticosteroid use in dermatophytosis: a cost-of-illness analysis of steroid-modified vs. steroid-naive dermatophytosis.

Dermatophytosis is one of the leading causes of visits to the dermatology department, especially in India, where the hot and humid climate favours fungal acquisition and perpetuation. Usual modalities of treatment include the use of either oral or topical antifungals or a combination of both, depending on the severity and extent of infection as well as the type of causative organism. But recently, steroid-modified dermatophytosis, an iatrogenically perpetuated dermatophytosis caused by the indiscriminate use of topical corticosteroids has emerged as a troublesome epidemic. We planned a cost-of-illness analysis of superficial dermatophytosis comparing the direct healthcare costs in steroid-naive and steroid-modified dermatophytosis. In our study, the average total cost of treatment for steroid-naive and steroid-modified dermatophytosis was found to be rupees (Rs) 2172.42 and Rs 3770.61 respectively, meaning that the cost for patients who used topical steroids is an additional 40% on average for treatment, when compared with the cost for patients who are steroid naive. The need for more consultations, investigations (relating to atypical presentation) and extended duration of treatment with higher-grade antifungals were found to contribute to the increased financial burden in steroid-modified dermatophytosis.

Obesity and hidradenitis suppurativa: targeting meta-inflammation for therapeutic gain.

Hidradenitis suppurativa (HS) is a chronic, inflammatory condition of the pilosebaceous unit. The typical patient with HS is characterized as someone with obesity, who smokes and who has nodules, abscesses and/or draining tunnels predominantly distributed in intertriginous skin. It has been established that lifestyle and genetic factors are the main pathophysiological drivers of HS. In this critical review, we explore the interrelatedness of meta-inflammation, obesity and HS and discuss if and how this relationship may be manipulated for a therapeutic end.

Glycolysis is integral to histamine-induced endothelial hyperpermeability.

Histamine-induced vascular leakage is a core process of allergic pathologies, including anaphylaxis. Here, we show that glycolysis is integral to histamine-induced endothelial barrier disruption and hyperpermeability. Histamine rapidly enhanced glycolysis in endothelial cells via a pathway that involved histamine receptor 1 and phospholipase C beta signaling. Consistently, partial inhibition of glycolysis with 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) prevented histamine-induced hyperpermeability in human microvascular endothelial cells, by abolishing the histamine-induced actomyosin contraction, focal adherens junction formation, and endothelial barrier disruption. Pharmacologic blockade of glycolysis with 3PO in mice reduced histamine-induced vascular hyperpermeability, prevented vascular leakage in passive cutaneous anaphylaxis and protected from systemic anaphylaxis. In conclusion, we elucidated the role of glycolysis in histamine-induced disruption of endothelial barrier integrity. Our data thereby point to endothelial glycolysis as a novel therapeutic target for human pathologies related to excessive vascular leakage, such as systemic anaphylaxis.

Targeted metagenome sequencing reveals the abundance of Planctomycetes and Bacteroidetes in the rhizosphere of pomegranate.

Agricultural productivity of pomegranate can be enhanced by identifying the crop-associated microbial diversity in the rhizosphere region with respect to plant growth promoters and other beneficial organisms. Traditional culture methods have limitations in microbial screening as only 1-2% of these organisms can be cultured. In the present study, 16S rRNA amplicon-based metagenomics approach using MinION Oxford Nanopore platform was employed to explore the microbial diversity in the rhizosphere of pomegranate Bhagwa variety, across variable soil depths from 0 to 5 cms (R2), 5-10 cms (R4) and 10-15 cms (R6), using bulk soil as the control. Across all the three layers, significant variations in pH, nitrogen content and total fungal count were observed. 16S rRNA analysis showed the abundance of planctomycetes, Pirellula staleyi, followed by bacteroidetes, Flavisolibacter LC59 and Niastella koreensis across the various soil depths in the rhizospheric soil samples. Pathway prediction analysis indicated arginine and proline metabolism (gamma-glutamyl putrescine oxidase) and hydrogen sulfide biosynthesis as the most abundant pathway hits. Comparative abundance analysis across layers showed the R6 layer with the maximum microbial diversity in terms of highest dimension of variation (79.2%) followed by R4 and R2 layers (p < 0.01). Our analysis shows the significant influence of root zone in shaping microbial diversity. This study has reported the presence of Planctomycetes, Pirellula staleyi for the first time in the pomegranate field.

Physical, Electrochemical, and Solvent Permeation Properties of Amphiphilic Conetwork Membranes Formed through Interlinking of Poly(vinylidene fluoride)-Graft-Poly[(2-dimethylamino)ethyl Methacrylate] with Telechelic Poly(ethylene glycol) and Small Molecular Weight Cross-Linkers.

We report the preparation of dense and porous amphiphilic conetwork (APCN) membranes through the covalent interconnection of poly(vinylidene fluoride)-graft-poly[(2-dimethylamino)ethyl methacrylate] (PVDF-g-PDMAEMA) copolymers with telechelic poly(ethylene glycol) (PEG) or α,α-dichloro-p-xylene (XDC). The dense APCN membranes exhibit varying solvent swelling and mechanical properties depending on the compositions and overall crystallinity. The crystallinity of both PVDF (20-47%) and PEG (9-17%) is significantly suppressed in the dense APCNs prepared through the interconnection of PVDF-g-PDMAEMA with reactive PEG as compared to the APCN membranes (48-53%) prepared with XDC as well as mechanical blend of PVDF-g-PDMAEMA plus nonreactive PEG. The dense APCN membranes exhibit a good transport number of monovalent ions and ionic conductivity. The APCN membrane interconnected with PEG and containing binary ionic liquids exhibits a room-temperature lithium ion conductivity of 0.52 mS/cm. On the other hand, APCN ultrafiltration (UF) membranes exhibit organic solvent-resistant behavior. The UF membrane obtained by interconnecting PVDF-g-PDMAEMA with telechelic PEG shows low protein fouling propensity, higher hydrophilicity, and water flux as compared to membranes prepared using XDC as the interconnecting agent. The significant effect of the covalent interconnection of the amphiphilic graft copolymers with telechelic PEG or XDC on the overall properties provides a good opportunity to modulate the properties and performance of APCN membranes.

Newly designed acrylamide derivative-based pH-responsive hydrogel-urease bioconjugates: synthesis and catalytic urea hydrolysis.

Jack bean urease, the first nickel metalloenzyme, and crystallized enzymes have historical significance due to their several applications in the biomedical and other fields. For the first time, cross-linker free pH-responsive hydrogel-urease bioconjugates have been reported. Without the use of divinyl benzene or divinyl acrylamide derivatives, urease was immobilized inside the hydrogel matrix and various grades of bioconjugates were synthesized. The hydrogel-urease bioconjugate exhibits excellent swelling-deswelling and pH-responsive characteristics without affecting the urease enzyme. The pH-responsive bioconjugates were characterized by FT-IR, powder XRD, SEM, TGA, and UV-vis spectroscopy. Urea hydrolysis and enzyme affinity have been investigated at pH 4, pH 7, and pH 11 using bioconjugates and free urease. At basic pH, BCs showed excellent enzyme activity. In summary, this technique is effective for stabilizing biomacromolecules at different pHs for a variety of real applications.

Does weight loss lead to improvement of dermatological conditions: what is the evidence?

Obese and overweight individuals may have a wide spectrum of cutaneous features and can have more severe manifestations of multiple dermatological conditions. There have been multiple expert opinions on the role of weight loss, in the improvement of skin conditions. There have been few studies over the past decade evaluating the effects of exercise and other modes of weight reduction on various dermatoses such as psoriasis, acne vulgaris, hidradenitis suppurativa and acanthosis nigricans. In this review, we have attempted to provide a summary of the beneficial effects of weight loss on various dermatological conditions.

Bitten by the travelling bug: a review of toponymous contributions in dermatology.

The diverse world of dermatology has a wealth of protracted and at times tenuous names encompassing disease conditions, characteristic clinical descriptions and signs, among others. Many dermatological entities are identified by toponyms or place names. Although some sound irrelevant and archaic (with only historical importance reminding us of the lively history of the subject), other terminologies aid in easy recollection. In this review, we have succinctly summarized various toponymous description in dermatology covering diseases, signs, scales, criteria and treatments.

Mucocutaneous manifestations of COVID-19-related multisystem inflammatory syndrome in adults: an update.

Multisystem inflammatory syndrome in adults (MIS-A) is an inflammatory condition that affects multiple extrapulmonary organ systems (cardiac, gastrointestinal tract, dermatological and/or neurological), attributed to a postinfectious and atypical complication occurring weeks to months after infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The diagnosis is primarily based on findings encompassing persistent fever, elevated inflammatory markers, multiorgan involvement and a temporal relationship with COVID-19 infection. The existing literature on MIS-A, although growing, is limited to case reports and small case series. It is imperative that dermatologists be aware of this entity and aid the critical care team to ensure timely diagnosis and early therapeutic intervention. In this review, we concisely highlight the varied presentations, pathogenesis and treatment options in MIS-A.

Vaccines against sexually transmitted infections: an update.

Sexually transmitted infections (STI) constitute a major share of the diseases encountered by physicians. Although science has made considerable progress in terms of diagnosing and treating such infections, development of effective and safe vaccines is still needed. Syphilis, viral warts, gonorrhoea, genital herpes, chlamydia and trichomoniasis are the most common infections that are transmitted sexually. In this review, we have attempted to summarize the current status, lacunae and avenues for future research, with reference to the development of STI vaccines.

Chronic venous disease. Part 2: diagnosis and treatment.

Chronic venous disease (CVD) is a common medical condition that results from venous hypertension of the limbs, leading to significant morbidity. The diagnosis is quite straightforward from patient history and obvious clinical manifestations. In the recent past, the availability of various invasive and noninvasive treatments has assisted in evaluation of such cases. Although compression therapy is the mainstay of management, newer surgical and other interventional techniques are now being considered for patients who do not respond to conventional medical management. The second part of this two-part review article will outline a diagnostic approach in cases of CVD and discuss the management principles encompassing conservative, pharmacological and interventional options.

Tofacitinib in paediatric dermatoses: a narrative review.

Tofacitinib has revolutionized the treatment of numerous dermatological conditions in different age groups. However, evidence for its effectiveness, safety and tolerability in the paediatric population is limited. We performed a literature search, which showed that oral tofacitinib is a reliable option in refractory juvenile dermatomyositis, severe alopecia areata, atopic dermatitis and psoriasis. Topical tofacitinib is an effective option in vitiligo and halo naevus. The risk-benefit ratio should be assessed prior to consideration of this molecule. In this narrative review, we have attempted to present a summary of the evidence of using tofacitinib (oral and topical) in paediatric dermatoses.