Serine hydroxymethyltransferase6 is involved in growth and resistance against pathogens via ethylene and lignin production in Arabidopsis.

Photorespiratory serine hydroxymethyltransferases (SHMTs) are important enzymes of cellular one-carbon metabolism. In this study, we investigated the potential role of SHMT6 in Arabidopsis thaliana. We found that SHMT6 is localized in the nucleus and expressed in different tissues during development. Interestingly SHMT6 is inducible in response to avirulent, virulent Pseudomonas syringae and to Fusarium oxysporum infection. Overexpression of SHMT6 leads to larger flowers, siliques, seeds, roots, and consequently an enhanced overall biomass. This enhanced growth was accompanied by increased stomatal conductance and photosynthetic capacity as well as ATP, protein, and chlorophyll levels. By contrast, a shmt6 knockout mutant displayed reduced growth. When challenged with Pseudomonas syringae pv tomato (Pst) DC3000 expressing AvrRpm1, SHMT6 overexpression lines displayed a clear hypersensitive response which was characterized by enhanced electrolyte leakage and reduced bacterial growth. In response to virulent Pst DC3000, the shmt6 mutant developed severe disease symptoms and becomes very susceptible, whereas SHMT6 overexpression lines showed enhanced resistance with increased expression of defense pathway associated genes. In response to Fusarium oxysporum, overexpression lines showed a reduction in symptoms. Moreover, SHMT6 overexpression lead to enhanced production of ethylene and lignin, which are important components of the defense response. Collectively, our data revealed that SHMT6 plays an important role in development and defense against pathogens.

Aberrant Lipid Metabolic Signatures in Acute Myeloid Leukemia.

Leukemogenesis is a complex process that involves multiple stages of mutation in either hematopoietic stem or progenitor cells, leading to cancer development over time. Acute myeloid leukemia (AML) is an aggressive malignancy that affects myeloid cells. The major disease burden is caused by immature blast cells, which are eliminated using conventional chemotherapies. Unfortunately, relapse is a leading cause of death in AML patients, with 30%-80% experiencing it within 2 years of initial treatment. The dominant cause of relapse in leukemia is the presence of therapy-resistant leukemic stem cells (LSCs). These cells express genes related to stemness that are frequently difficult to eradicate and tend to survive standard treatments. Studies have demonstrated that by targeting the metabolic pathways of LSCs, it is possible to improve outcomes and extend the survival of those afflicted by leukemia. The overwhelming evidence suggests that lipid metabolism is reprogrammed in LSCs, leading to an increase in fatty acid uptake and de novo lipogenesis. Genes regulating this process also play a crucial role in therapy evasion. In this concise review, we summarize the lipid metabolism in normal hematopoietic cells, AML blast cells, and AML LSCs. We also compare the lipid metabolic signatures in de novo versus therapy-resistant AML blast and LSCs. We further discuss the metabolic switches, cellular crosstalk, potential targets, and inhibitors of lipid metabolism that could alleviate treatment resistance and relapse.

Genetic architecture of disease resistance and tolerance in Douglas-fir trees.

Understanding the genetic basis of how plants defend against pathogens is important to monitor and maintain resilient tree populations. Swiss needle cast (SNC) and Rhabdocline needle cast (RNC) epidemics are responsible for major damage of forest ecosystems in North America. Here we investigate the genetic architecture of tolerance and resistance to needle cast diseases in Douglas-fir (Pseudotsuga menziesii) caused by two fungal pathogens: SNC caused by Nothophaeocryptopus gaeumannii, and RNC caused by Rhabdocline pseudotsugae. We performed case-control genome-wide association analyses and found disease resistance and tolerance in Douglas-fir to be polygenic and under strong selection. We show that stomatal regulation as well as ethylene and jasmonic acid pathways are important for resisting SNC infection, and secondary metabolite pathways play a role in tolerating SNC once the plant is infected. We identify a major transcriptional regulator of plant defense, ERF1, as the top candidate for RNC resistance. Our findings shed light on the highly polygenic architectures underlying fungal disease resistance and tolerance and have important implications for forestry and conservation as the climate changes.

Gene co-expression patterns in Atlantic salmon adipose tissue provide a molecular link among seasonal changes, energy balance and age at maturity.

Sexual maturation in many fishes requires a major physiological change that involves a rapid transition between energy storage and usage. In Atlantic salmon, this transition for the initiation of maturation is tightly controlled by seasonality and requires a high-energy status. Lipid metabolism is at the heart of this transition since lipids are the main energy storing molecules. The balance between lipogenesis (lipid accumulation) and lipolysis (lipid use) determines energy status transitions. A genomic region containing a transcription co-factor of the Hippo pathway, vgll3, is the main determinant of maturation timing in Atlantic salmon. Interestingly, vgll3 acts as an inhibitor of adipogenesis in mice and its genotypes are potentially associated with seasonal heterochrony in lipid storage and usage in juvenile Atlantic salmon. Here, we explored changes in expression of more than 300 genes directly involved in the processes of adipogenesis, lipogenesis and lipolysis, as well as the Hippo pathway in the adipose tissue of immature and mature Atlantic salmon with distinct vgll3 genotypes. We found molecular evidence consistent with a scenario in which immature males with different vgll3 genotypes exhibit contrasting seasonal dynamics in their lipid profiles. We also identified components of the Hippo signalling pathway as potential major drivers of vgll3 genotype-specific differences in adipose tissue gene expression. This study demonstrates the importance of adipose gene expression patterns for directly linking environmental changes with energy balance and age at maturity through genetic factors bridging lipid metabolism, seasonality and sexual maturation.

How useful are genomic data for predicting maladaptation to future climate?

Methods using genomic information to forecast potential population maladaptation to climate change or new environments are becoming increasingly common, yet the lack of model validation poses serious hurdles toward their incorporation into management and policy. Here, we compare the validation of maladaptation estimates derived from two methods-Gradient Forests (GFoffset) and the risk of non-adaptedness (RONA)-using exome capture pool-seq data from 35 to 39 populations across three conifer taxa: two Douglas-fir varieties and jack pine. We evaluate sensitivity of these algorithms to the source of input loci (markers selected from genotype-environment associations [GEA] or those selected at random). We validate these methods against 2- and 52-year growth and mortality measured in independent transplant experiments. Overall, we find that both methods often better predict transplant performance than climatic or geographic distances. We also find that GFoffset and RONA models are surprisingly not improved using GEA candidates. Even with promising validation results, variation in model projections to future climates makes it difficult to identify the most maladapted populations using either method. Our work advances understanding of the sensitivity and applicability of these approaches, and we discuss recommendations for their future use.

Microbial degradation of low-density polyethylene, polyethylene terephthalate, and polystyrene by novel isolates from plastic-polluted environment.

Biodegradation is an eco-friendly measure to address plastic pollution. This study screened four bacterial isolates that were capable of degrading recalcitrant polymers, i.e., low-density polyethylene, polyethylene terephthalate, and polystyrene. The unique bacterial isolates were obtained from plastic polluted environment. Dermacoccus sp. MR5 (accession no. OP592184) and Corynebacterium sp. MR10 (accession no. OP536169) from Malaysian mangroves and Bacillus sp. BS5 (accession no. OP536168) and Priestia sp. TL1 (accession no. OP536170) from a sanitary landfill. The four isolates showed a gradual increase in the microbial count and the production of laccase and esterase enzymes after 4 weeks of incubation with the polymers (independent experiment set). Bacillus sp. BS5 produced the highest laccase 15.35 ± 0.19 U/mL and showed the highest weight loss i.e., 4.84 ± 0.6% for PS. Fourier transform infrared spectroscopy analysis confirmed the formation of carbonyl and hydroxyl groups as a result of oxidation reactions by enzymes. Liquid chromatography-mass spectrometry analysis showed the oxidation of the polymers to small molecules (alcohol, ethers, and acids) assimilated by the microbes during the degradation. Field emission scanning electron microscopy showed bacterial colonization, biofilm formation, and surface erosion on the polymer surface. The result provided significant insight into enzyme activities and the potential of isolates to target more than one type of polymer for degradation.

Characterization of a CrPME indicates its possible role in determining vindoline accumulation in Catharanthus roseus leaves.

The leaf-specific Catharanthus roseus alkaloid, vindoline, is the major bottleneck precursor in the production of scarce and costly anticancer bisindoles (vincristine and vinblastine). The final steps of its biosynthesis and storage occur in the laticifers. Earlier, we have shown that vindoline content is directly related to laticifer number. Pectin remodeling enzymes, like pectin methylesterase (PME), are known to be involved in laticifer development. A search in the croFGD yielded a leaf-abundant CrPME isoform that co-expressed with a few vindoline biosynthetic genes. Full-length cloning, tissue-specific expression profiling, and in silico analysis of CrPME were carried out. It was found to possess all the specific characteristics of a typical plant PME. Transient silencing (through VIGS) and overexpression of CrPME in C. roseus indicated a direct relationship between its expression and vindoline content. Comparative analysis of transcript abundance and enzyme activity in three familial C. roseus genotypes differing significantly in their vindoline content and laticifer count (CIM-Sushil > Dhawal > Nirmal) also corroborated the positive relationship of CrPME expression with vindoline content. This study highlights the possible role of CrPME, a cell wall remodeling enzyme, in modulating laticifer-associated secondary metabolism.

Conversion of Metal Pyrazolate/(Hydr)oxide Clusters into Nanojars: Solution vs Solid-State Structure and Magnetism.

Nanojars are a class of anion binding and extraction agents composed of a series of [Cu(µ-OH)(µ-pz)]n (pz = pyrazolate; n = 26-36) supramolecular metal-organic complexes. In contrast to other anion binding agents amenable to liquid-liquid extraction, nanojars only form by self-assembly around the target anion, and guest-free nanojar hosts cannot be isolated. An extraordinary binding strength toward highly hydrophilic anions such as carbonate and sulfate was demonstrated by the inability of Ba2+ ions to precipitate the corresponding insoluble barium salts from nanojars. Herein, we provide an additional proof for the superior robustness of the nanojar framework based on competition experiments with other transition metal pyrazolate/(hydr)oxide complexes. In addition to the mass spectrometric characterization, we present variable-temperature nuclear magnetic resonance studies with an emphasis on the influence of the paramagnetic Cu2+ centers on 1H hyperfine shifts, along with X-ray crystallographic analysis of two polymorphs of (MePh3P)2[CO3⊂{Cu(OH)(pz)}27], including the highest (cubic) symmetry nanojar crystal lattice obtained to date as well as magnetism studies for the first time. Furthermore, we provide evidence for the first molybdate-incarcerating nanojars, [MoO4⊂{Cu(µ-OH)(µ-pz)}n]2- (n = 28, 31-33), formed by rearrangement from [MoVI8O12(µ-O)9(µ-pz)6(pzH)6·3pzH] in the presence of Cu2+ ions.

Advances in the co-production of biosurfactant and other biomolecules: statistical approaches for process optimization.

An efficient microbial conversion for simultaneous synthesis of multiple high-value compounds, such as biosurfactants and enzymes, is one of the most promising aspects for an economical bioprocess leading to a marked reduction in production cost. Although biosurfactant and enzyme production separately have been much explored, there are limited reports on the predictions and optimization studies on simultaneous production of biosurfactants and other industrially important enzymes, including lipase, protease, and amylase. Enzymes are suited for an integrated production process with biosurfactants as multiple common industrial processes and applications are catalysed by these molecules. However, the complexity in microbial metabolism complicates the production process. This study details the work done on biosurfactant and enzyme co-production and explores the application and scope of various statistical tools and methodologies in this area of research. The use of advanced computational tools is yet to be explored for the optimization of downstream strategies in the co-production process. Given the complexity of the co-production process and with various new methodologies based on artificial intelligence (AI) being invented, the scope of AI in shaping the biosurfactant-enzyme co-production process is immense and would lead to not only efficient and rapid optimization, but economical extraction of multiple biomolecules as well.

Regioselective synthesis and molecular docking studies of functionalized imidazo [1,2-a]pyridine derivatives through MCRs.

A efficient protocol has been developed for the synthesis of regioselective imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine derivatives through cascade reaction between 2-aminopyridine, arylelglyoxal, and 4-hydroxypyran via three-component reaction to prepare targeted compounds with good to excellent yields. The advantages of this transformation are a catalyst-free reaction, green solvent, operationally simple, scalable, and eco-friendly. The product collects with simple filtration which avoided tedious and expensive purification techniques. In addition, computational studies like molecular docking were conducted to provide the theoretical possibilities of binding these types of synthesized compounds to the VEGFR2 receptors as potential key inhibitors of tumor cell growth and angiogenesis.

Bridging fungal resistance and plant growth through constitutive overexpression of Thchit42 gene in Pelargonium graveolens.

KEY MESSAGE: Thchit42 constitutive expression for fungal resistance showed synchronisation with leaf augmentation and transcriptome analysis revealed the Longifolia and Zinc finger RICESLEEPER gene is responsible for plant growth and development. Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed ~ 2fold increase in leaf size and ~ 2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, de novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and zinc finger (ZF) RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand.

Trends, patterns and predictors of high-risk fertility behaviour among Indian women: evidence from National Family Health Survey.

BACKGROUND: Numerous studies have demonstrated that high-risk fertility behaviour (HRFB), which includes maternal age below 18 or above 34 years, short birth intervals (less than 24 months), and high parity (birth order above 4), is associated with adverse maternal and child health outcomes. There is a substantial research gap in the domain of high-risk fertility behaviour in the Indian context. Therefore, this study is designed to investigate the current trends and patterns in the prevalence of high-risk births among Indian women, with a primary focus on identifying contributing factors associated with this prevalence. METHODS: The study utilized data from the nationally representative National Family Health Survey (NFHS), which has been conducted in five rounds since 1992-93. Data from all rounds were used to assess the overall trend. However, data from the most recent round of NFHS, conducted during 2019-21, were employed to evaluate current levels and patterns of HRFB prevalence and to identify socio-economic and demographic predictors of HRFB using binomial and multinomial logistic regression models. RESULTS: The prevalence of HRFB has exhibited a consistent decreasing pattern from 1992 to 93 to 2019-21 in India. However, 29.56% of married women continue to experience high-risk births with notably higher rates in several states (e.g., 49.85% in Meghalaya and 46.41% in Bihar). Furthermore, socio-demographic factors like wealth index, educational level, social group, religion, mass media exposure, family size, age at marriage, type and region of residence, and reproductive factors like birth intention, place and type of delivery, ANC visits and current contraceptive use were identified as significant predictors of high-risk births among women in India. CONCLUSION: Despite a 20.4 percentage point decline in HRFB prevalence over the past three decades, a significant proportion of women in specific regions and demographic subgroups continue to experience high-risk births. Therefore, the present study recommends interventions aimed at preventing high-risk births among women in India, with particular emphasis on states with high HRFB prevalence and women from socioeconomically disadvantaged backgrounds.

Tumor hypoxia and role of hypoxia-inducible factor in oral cancer.

BACKGROUND: Head and neck cancer (HNC) is one of the most frequent malignancies in Asian males with a poor prognosis. Apart from well-known prognostic indicators, markers of tumor hypoxia can help us predict response to treatment and survival. METHODS: A review of the literature on the present evidence and potential clinical importance of tumor hypoxia in head and neck cancer was carried out. The data obtained from the literature search is presented as a narrative review. RESULTS: The literature shows possible associations between prognosis and low tumor oxygenation. Intermediate hypoxia biomarkers like HIF-1, GLUT-1, miRNA, and lactate, can help in predicting the response to therapy and survival as their altered expression is related to prognosis. CONCLUSIONS: Hypoxia is common in HNC and can be detected by use of biomarkers. The tumors that show expression of hypoxia biomarkers have poor prognosis except for patients with human papilloma virus-associated or VHL-associated cancers. Therapeutic targeting of hypoxia is emerging; however, it is still in its nascent stage, with increasing clinical trials hypoxia is set to emerge as an attractive therapeutic target in HNC.

Botrytis fruit rot management: What have we achieved so far?

Botrytis cinerea is a destructive necrotrophic phytopathogen causing overwhelming diseases in more than 1400 plant species, especially fruit crops, resulting in significant economic losses worldwide. The pathogen causes rotting of fruits at both pre-harvest and postharvest stages. Aside from causing gray mold of the mature fruits, the fungus infects leaves, flowers, and seeds, which makes it a notorious phytopathogen. Worldwide, in the majority of fruit crops, B. cinerea causes gray mold. In order to effectively control this pathogen, extensive research has been conducted due to its wide host range and the huge economic losses it causes. It is advantageous to explore detection and diagnosis techniques of B. cinerea to provide the fundamental basis for mitigation strategies. Botrytis cinerea has been identified and quantified in fruit/plant samples at pre- and post-infection levels using various detection techniques including DNA markers, volatile organic compounds, qPCR, chip-digital PCR, and PCR-based nucleic acid sensors. In addition, cultural, physical, chemical, biological, and botanical methods have all been used to combat Botrytis fruit rot. This review discusses research progress made on estimating economic losses, detection and diagnosis, as well as management strategies, including cultural, physical, chemical, and biological studies on B. cinerea along with knowledge gaps and potential areas for future research.

A Comprehensive Metagenome Study Identifies Distinct Biological Pathways in Asthma Patients: An In-Silico Approach.

Asthma is a multifactorial disease with phenotypes and several clinical and pathophysiological characteristics. Besides innate and adaptive immune responses, the gut microbiome generates Treg cells, mediating the allergic response to environmental factors and exposure to allergens. Because of the complexity of asthma, microbiome analysis and other precision medicine methods are now widely regarded as essential elements of efficient disease therapy. An in-silico pipeline enables the comparative taxonomic profiling of 16S rRNA metagenomic profiles of 20 asthmatic patients and 15 healthy controls utilizing QIIME2. Further, PICRUSt supports downstream gene enrichment and pathway analysis, inferring the enriched pathways in a diseased state. A significant abundance of the phylum Proteobacteria, Sutterella, and Megamonas is identified in asthma patients and a diminished genus Akkermansia. Nasal samples reveal a high relative abundance of Mycoplasma in the nasal samples. Further, differential functional profiling identifies the metabolic pathways related to cofactors and amino acids, secondary metabolism, and signaling pathways. These findings support that a combination of bacterial communities is involved in mediating the responses involved in chronic respiratory conditions like asthma by exerting their influence on various metabolic pathways.

Zinc nitride quantum dots as an efficient probe for simultaneous fluorescence detection of Cu2+ and Mn2+ ions in water samples.

The exceptional ascending heights of graphene (carbon) and boron nitride nanostructures have invited scientists to explore metal nitride nanomaterials. Herein, Zn3N2 quantum dots (QDs) were prepared via a simple hydrothermal route from the reaction between zinc nitrate hexahydrate and ammonia solution that possess efficient strength towards sensing applications of metal ions (Cu2+ and Mn2+). The as-prepared Zn3N2 QDs show bright fluorescence, displaying an emission peak at 408 nm upon excitation at 320 nm, with a quantum yield (QY) of 29.56%. It was noticed that the fluorescence intensity of Zn3N2 QDs linearly decreases with the independent addition of Cu2+ and Mn2+ ions, displaying good linearity in the ranges 2.5-50 µM and 0.05-5 µM with detection limits of 21.77 nM and of 63.82 nM for Cu2+ and Mn2+ ions, respectively. The probe was successfully tested for quantifying Cu2+ and Mn2+ in real samples including river, canal, and tap water, providing good recoveries with a relative standard deviation < 2%. Furthermore, the masking proposition can successfully eliminate the interference if the two metal ions exist together. It was found that thiourea is efficiently able to mask Cu2+ and selectively quenches Mn2+, and L-cysteine is able to halt the quenching potential of Mn2+ and is selectively able to sense Cu2+. The Zn3N2 QDs provide a simple way for the simultaneous detection of both Cu2+ and Mn2+ ions in environmental samples at low sample preparations requirements.

Exploring the abundance of microplastics in Indian landfill leachate: An analytical study.

Landfills are a major source of many emerging pollutants, including microplastics (MPs). This makes them a potential threat to human and environmental health and calls for a more detailed analysis of their hazard potential. India is a developing country with multiple unscientific waste dumping sites. In spite of their hazardous nature, detailed studies on the abundance of microplastics in landfills in India are scanty. Current work investigates the abundance and diversity of MPs in two landfills of India, Uruli Devachi in Pune (S1) and Deonar in Mumbai (S2). MPs collected from landfill leachate using multiple filters were analyzed using an optical microscope and categorized on the basis of shape, color and size to give information on their distribution. MP abundance in S1 was 1473 ± 273.01 items/L while 2067 ± 593.75 items/L were found in leachate from S2. Film and fragment were the dominant shape and black was the dominant color of MP found in both the landfills. Maximum number of MPs were in the size range below 100 µm in both the landfills necessitating the study of small sized particles. Chemical characterization revealed the prevalence of four types of MPs (polyethylene terephthalate, polypropylene, cellulose acetate and polyvinyl chloride). This study sheds light on the prevalence, characteristics, abundance and distribution of MPs in landfill leachate in Western India, sparking more research into the processes followed for capturing the factual small sized microplastic abundance data. This study is vital for a detailed management of landfill leachate enabling a sustainable waste management and targeted actions for ecosystem preservation.

Modulating cultivation regimes of Messastrum gracile SVMIICT7 for biomass productivity integrated with resource recovery via hydrothermal liquefaction.

The present study was designed to assess Messastrum gracile SVMIICT7 potential in treating dairy wastewater (autoclaved (ADWW) and raw (DWW)) with relation to nutrient removal, in-vivo Chl-a-based biomass, and bio-oil synthesis. Chlorophyll a fluorescence kinetics revealed improved photochemical efficiency (0.639, Fv/Fm) in M. gracile when grown with DWW. This may be owing to enhanced electron transport being mediated by an effective water-splitting complex at photosystem (PSII) of thylakoids. The increase in ABS/RC observed in DWW can be attributed to the elevated chlorophyll content and reduced light dissipation, as evident by higher values of ETo/RC and a decrease in non-photochemical quenching (NPQ). M. gracile inoculated in DWW had the highest Chl-a-biomass yield (1.8 g L-1) and biomolecules while maximum nutrient removal efficiency was observed in ADWW (83.7% TN and 60.07% TP). M. gracile exhibited substantial bio-oil yield of 29.6% and high calorific value of 37.19 MJ kg-1, predominantly composed of hydrocarbons along with nitrogen and oxygen cyclic compounds. This research offers a thorough investigation into wastewater treatment, illustrating the conversion of algal biomass into valuable energy sources and chemical intermediates within the framework of a biorefinery.

Neuroprotective effect of taxifolin against aluminum chloride-induced dementia and pathological alterations in the brain of rats: possible involvement of toll-like receptor 4.

Aluminum (Al) overexposure damages various organ systems, especially the nervous system. Regularly administered aluminum chloride (AlCl3) to rats causes dementia and pathophysiological alterations linked to Alzheimer's disease (AD). Taxifolin's neuroprotective effects against AlCl3-induced neurotoxicity in vitro and in vivo studies were studied. Taxifolin (0.1, 0.3, 1, 3, and 10 µM) was tested against AlCl3 (5 mM)-induced neurotoxicity in C6 and SH-SY5Y cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. Additionally, neural morphology was examined by confocal microscopy. Additionally, taxifolin's mode of binding with the co-receptor of toll-like receptor 4 (TLR4), human myeloid differentiation-2 (hMD-2) was investigated. AlCl3 (25 mg/kg/d, i.p.) was administered to rats for 14 d, and from the eighth day, taxifolin (1, 2, and 5 mg/kg/d, i.p.) was given along with AlCl3. This study assessed memory impairment using the Morris water maze, plus maze, and pole tests. This study also performed measurement of oxidant (malondialdehyde [MDA] and nitrite), antioxidant (reduced glutathione), and inflammatory (myeloperoxidase [MPO] activity, TLR4 expression) parameters in rats' brain in addition to histopathology. The docking score for taxifolin with hMD-2 was found to be -4.38 kcal/mol. Taxifolin treatment reduced the neurotoxicity brought on by AlCl3 in both C6 and SH-SY5Y cells. Treatment with 10 µM taxifolin restored AlCl3-induced altered cell morphology. AlCl3 administration caused memory loss, oxidative stress, inflammation (increased MPO activity and TLR4 expression), and brain atrophy. Taxifolin treatment significantly improved the AlCl3-induced memory impairment. Taxifolin treatment also mitigated the histopathological and neurochemical consequences of repeated AlCl3 administration in rats. Thus, taxifolin may protect the brain against AD.

Cutaneous Exposure to Arsenicals Is Associated with Development of Constrictive Bronchiolitis in Mice.

Organoarsenicals, such as lewisite and related chloroarsine, diphenylchloroarsine (DPCA), are chemical warfare agents developed during World War I. Stockpiles in Eastern Europe remain a threat to humans. The well-documented effects of cutaneous exposure to these organoarsenicals include skin blisters, painful burns, and life-threatening conditions such as acute respiratory distress syndrome. In survivors, long-term effects such as the development of respiratory ailments are reported for the organoarsenical sulfur mustard; however, no long-term pulmonary effects are documented for lewisite and DPCA. No animal models exist to explore the relationship between skin exposure to vesicants and constrictive bronchiolitis. We developed and characterized a mouse model to study the long-term effects of cutaneous exposure on the lungs after exposure to a sublethal dose of organoarsenicals. We exposed mice to lewisite, DPCA, or a less toxic surrogate organoarsenic chemical, phenyl arsine oxide, on the skin. The surviving mice were followed for 20 weeks after skin exposure to arsenicals. Lung microcomputed tomography, lung function, and histology demonstrated increased airway resistance, increased thickness of the smooth muscle layer, increased collagen deposition in the subepithelium, and peribronchial lymphocyte infiltration in mice exposed to arsenical on skin.