Identification of stem cell populations in sweat glands and ducts reveals roles in homeostasis and wound repair.

Sweat glands are abundant in the body and essential for thermoregulation. Like mammary glands, they originate from epidermal progenitors. However, they display few signs of cellular turnover, and whether they have stem cells and tissue-regenerative capacity remains largely unexplored. Using lineage tracing, we here identify in sweat ducts multipotent progenitors that transition to unipotency after developing the sweat gland. In characterizing four adult stem cell populations of glandular skin, we show that they display distinct regenerative capabilities and remain unipotent when healing epidermal, myoepithelial-specific, and lumenal-specific injuries. We devise purification schemes and isolate and transcriptionally profile progenitors. Exploiting molecular differences between sweat and mammary glands, we show that only some progenitors regain multipotency to produce de novo ductal and glandular structures, but that these can retain their identity even within certain foreign microenvironments. Our findings provide insight into glandular stem cells and a framework for the further study of sweat gland biology.

Arachidonic acid metabolism regulates the development of retinopathy of prematurity among preterm infants.

Extremely preterm infants are at risk of developing retinopathy of prematurity (ROP), characterized by neovascularization and neuroinflammation leading to blindness. Polyunsaturated fatty acid (PUFA) supplementation is recommended in preterm infants to lower the risk of ROP, however, with no significant improvement in visual acuity. Reasonably, this could be as a result of the non-consideration of PUFA metabolizing enzymes. We hypothesize that abnormal metabolism of the arachidonic acid (AA) pathway may contribute to severe stages of ROP. The present study investigated the AA-metabolizing enzymes in ROP pathogenesis by a targeted gene expression analysis of blood (severe ROP = 70, No/Mild = 56), placenta (preterm placenta = 6, full term placenta = 3), and human primary retinal cell cultures and further confirmed at the protein level by performing IHC in sections of ROP retina. The lipid metabolites were identified by LC-MS in the vitreous humor (VH; severe ROP = 15, control = 15). Prostaglandins D2 (p = 0.02), leukotrienes B5 (p = 0.0001), 11,12-epoxyeicosatrienoic acid (p = 0.01), and lipid-metabolizing enzymes of the AA pathway such as CYP1B1, CYP2C8, COX2, and ALOX15 were significantly upregulated while EPHX2 was significantly (0.04) downregulated in ROP cases. Genes involved in hypoxic stress, angiogenesis, and apoptosis showed increased expression in ROP. An increase in the metabolic intermediates generated from the AA metabolism pathway further confirmed the role of these enzymes in ROP, while metabolites for EPHX2 activity were low in abundance. Inflammatory lipid intermediates were higher compared to anti-inflammatory lipids in VH and showed an association with enzyme activity. Both the placenta of preterm infants who developed ROP and hypoxic retinal cultures showed a reduced expression of EPHX2. These findings suggested a strong involvement of EPHX2 in regulating retinal neovascularization and inflammation. The study results underscore the role of arachidonic acid metabolism in the development of ROP and as a potential target for preventing vision loss among preterm-born infants.

GWAS for identification of genomic regions and candidate genes in vegetable crops.

Genome-wide association Studies (GWAS), initially developed for human genetics, have been highly effective in plant research, particularly for vegetable crops. GWAS is a robust tool for identifying genes associated with key traits such as yield, nutritional value, disease resistance, adaptability, and bioactive compound biosynthesis. Unlike traditional methods, GWAS does not require prior biological knowledge and can accurately pinpoint loci, minimizing false positives. The process involves developing a diverse panel, rigorous phenotyping and genotyping, and sophisticated statistical analysis using various models and software tools. By scanning the entire genome, GWAS identifies specific loci or single nucleotide polymorphisms (SNPs) linked to target traits. When a causal SNP variant is not directly genotyped, GWAS identifies SNPs in linkage disequilibrium (LD) with the causal variant, mapping the genetic interval. The method begins with careful panel selection, phenotyping, and genotyping, controlling for environmental effects and utilizing Best Linear Unbiased Prediction (BLUP). High-correlation, high-heritability traits are prioritized. Various genotyping methods address confounders like population structure and kinship. Bonferroni correction (BC) prevents false positives, and significant associations are shown in Manhattan plots. Candidate genes are identified through LD analysis and fine mapping, followed by functional validation. GWAS offers critical insights for enhancing vegetable crop breeding efficiency and precision, driving breakthroughs through advanced methods.

The Risk of Optic Neuritis following mRNA Coronavirus Disease 2019 Vaccination Compared to Coronavirus Disease 2019 Infection and Other Vaccinations.

PURPOSE: To determine the risk of optic neuritis (ON) after mRNA Coronavirus Disease 2019 (COVID-19) vaccine administration. DESIGN: U.S. National aggregate database retrospective cohort study. PARTICIPANTS: Patients were placed into cohorts based on mRNA COVID-19 vaccination status (no vaccine and positive history of COVID-19 infection, 1 vaccine, or 2 vaccines received) from December 2020 to June 2022. Two control cohorts were created with patients vaccinated against influenza or tetanus, diphtheria, and pertussis (Tdap) from June 2018 to December 2019. Patients with any history of ON or significant risk factors for ON development including infectious, inflammatory, and neoplastic diseases were excluded. METHODS: A large deidentified database was queried for the Common Procedural Technology codes for immunization encounters specific to first dose and second dose of mRNA COVID-19 vaccine, influenza, or Tdap. Cohorts were 1:1 propensity score matched on age, sex, race, and ethnicity. The risk of ON development after vaccination was calculated and compared for all 5 cohorts with 95% confidence intervals (CIs) reported. MAIN OUTCOME MEASURES: Risk ratio (RR) of ON 21 days after vaccination (or COVID-19 infection) and incidence of ON per 100 000 individuals. RESULTS: After matching, the first dose COVID-19 and influenza vaccine cohorts (n = 1 678 598, mean age [standard deviation] at vaccination of 45.5 [23.3] years and 43.2 [25.5] years, 55% female) the RR of developing ON was 0.44 (95% CI, 0.28-0.80). The first dose of COVID-19 and Tdap vaccinations (n = 797 538, mean age 38.9 [20.0] years, 54.2% female) cohort had 10 and 16 patients develop ON (RR, 0.63; 95% CI, 0.28-1.38). Comparison of COVID-19-vaccinated patients (n = 3 698 848, 48.2 [21.5] years, 54.7% female) to unvaccinated and COVID-19-infected patients (n = 3 698 848, 49.6 [22.0] years, 55.2% female) showed 49 and 506 patients developing ON, respectively (RR, 0.09; 95% CI, 0.07-0.12). The incidence per 100 000 for ON was 1 in the first dose COVID-19 vaccine cohort, 2 in the influenza cohort, and 2 in the Tdap cohort, and 14 in the COVID-19-infected and unvaccinated cohorts. CONCLUSIONS: Risk of ON after mRNA COVID-19 vaccination is rare and comparable to Tdap vaccination, decreased compared with influenza vaccination, and decreased compared with COVID-19 infection in the absence of vaccination. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Physiological and molecular insights into the alternate bearing in mango (Mangifera indica L.) using next-generation sequencing approaches.

India's mango productivity is hindered by many factors but more importantly due to limited understanding of the genomic complexities behind regular bearing habit. This study is the first to quantify carbohydrate fractions, protein content, and macro and micronutrient storage pools, their transportation, and contributions to regular 'Totapuri' and alternate bearer 'Bombay Green' mango varieties during the 'off' year. Deep RNA sequencing was used to assess gene expression dynamics between buds and flowers of these varieties. Differential pathway analysis showed the greatest number of differentially expressed genes in metabolic processes (1377), followed by oxido-reductase (879), hormone (80), oxidative stress (77), starvation (39), alternate bearing (8), flowering (3), meristem (3), and cellular component (2) pathways. In silico analysis showed that among 15 genes, twelve genes up-regulated in Totapuri and three in Bombay Green, confirmed by qRT-PCR. Additionally, 202 SNPs were identified in 32 alternate bearing-related genes. The study confirmed the reproductive bud's strong ability to import sugars, protein, and starch in the regular bearer variety, enhancing flowering and fruiting during off years. The mineral nutrients and biochemical constituent of the bud and leaf tissue in contrasting genotypes, showed the potential role for regular bearing in mango.

Comparative metabolome analysis reveals higher potential of haemoperfusion adsorption in providing favourable outcome in ACLF patients.

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is a serious illness associated with altered metabolome, organ failure and high mortality. Need for therapies to improve the metabolic milieu and support liver regeneration are urgently needed. METHODS: We investigated the ability of haemoperfusion adsorption (HA) and therapeutic plasma exchange (TPE) in improving the metabolic profile and survival in ACLF patients. Altogether, 45 ACLF patients were randomized into three groups: standard medical therapy (SMT), HA and TPE groups. Plasma metabolomics was performed at baseline, post-HA and TPE sessions on days 7 and 14 using high-resolution mass spectrometry. RESULTS: The baseline clinical/metabolic profiles of study groups were comparable. We identified 477 metabolites. Of these, 256 metabolites were significantly altered post 7 days of HA therapy (p < .05, FC > 1.5) and significantly reduced metabolites linked to purine (12 metabolites), tryptophan (7 metabolites), primary bile acid (6 metabolites) and arginine-proline metabolism (6 metabolites) and microbial metabolism respectively (p < .05). Metabolites linked to taurine-hypotaurine and histidine metabolism were reduced and temporal increase in metabolites linked to phenylalanine and tryptophan metabolism was observed post-TPE therapy (p < .05). Finally, weighted metabolite correlation network analysis (WMCNA) along with inter/intragroup analysis confirmed significant reduction in inflammatory (tryptophan, arachidonic acid and bile acid metabolism) and secondary energy metabolic pathways post-HA therapy compared to TPE and SMT (p < .05). Higher baseline plasma level of 11-deoxycorticosterone (C03205; AUROC > 0.90, HR > 3.2) correlated with severity (r2 > 0.5, p < .05) and mortality (log-rank-p < .05). Notably, 51 of the 64 metabolite signatures (ACLF non-survivor) were reversed post-HA treatment compared to TPE and SMT(p < .05). CONCLUSION: HA more potentially (~80%) improves plasma milieu compared to TPE and SMT. High baseline plasma 11-deoxycorticosterone level correlates with early mortality in ACLF patients.

Characterization of ectomycorrhizal fungal community of Abies Pindrow using sporocarp sampling, morphotyping, and metabarcoding through next-generation sequencing.

Abies pindrow, commonly known as the West-Himalayan Fir, holds great ecological importance as a native tree species in the Himalayas. Beyond its value as a fuel and timber source, it serves as a keystone species within the ecosystem. However, over recent years, extensive degradation and deforestation have afflicted A. pindrow forests. Utilizing ectomycorrhizal fungal symbionts of A. pindrow could prove pivotal in restoring these deteriorated forests. This study aimed to evaluate the diversity and composition of the ectomycorrhizal fungal community associated with A. pindrow. We employed ectomycorrhizal root tip morphotyping, sporocarp sampling, and Illumina MiSeq metabarcoding of the ITS region of fungal nrDNA. The ectomycorrhizal root tips were categorized into 10 morphotypes based on their morphological characteristics, exhibiting an average colonization rate of 74%. Sporocarp sampling revealed 22 species across 10 genera, with Russula being the most prevalent. The metabarcoding yielded 285,148 raw sequences, identifying 326 operational taxonomic units (OTUs) belonging to 193 genera, 114 families, 45 orders, 22 classes, and 6 divisions. Of these, 36 OTUs across 20 genera were ectomycorrhizal, constituting 63.1% of the fungal community. Notably, Tuber was the most abundant, representing 37.42% of the fungal population, followed by Russula at 21.06%. This study provides a comprehensive understanding of mycorrhizal symbionts of A. pindrow. The findings hold significant implications for utilizing dominant ectomycorrhizal fungi in reforestation endeavors aimed at restoring this important Himalayan conifer.

Mycorrhizal symbiosis in Taxus: a review.

Taxus, a genus of conifers known for its medicinal significance, faces various conservation challenges with several species classified under different threat categories by the IUCN. The overharvesting of bark and leaves for the well-known chemotherapy drug paclitaxel has resulted in its population decline. Exploring the mycorrhizal relationship in Taxus is of utmost importance, as mycorrhizal fungi play pivotal roles in nutrition, growth, and ecological resilience. Taxus predominantly associates with arbuscular mycorrhizal fungi (AM), and reports suggest ectomycorrhizal (EM) or dual mycorrhizal associations as well. This review consolidates existing literature on mycorrhizal associations in Taxus species, focusing on structural, physiological, and molecular aspects. AM associations are well-documented in Taxus, influencing plant physiology and propagation. Conversely, EM associations remain relatively understudied, with limited evidence suggesting their occurrence. The review highlights the importance of further research to elucidate dual mycorrhizal associations in Taxus, emphasizing the need for detailed structural and physiological examinations to understand their impact on growth and survival.

Repeated dose toxicity studies of Trichostatin A in Swiss albino mice through oral and intravenous route of administration with special emphasis on genotoxicity.

Intravenous and oral 14 d repeated dose toxicity studies of Trichostatin A (TSA) were carried out in Swiss albino mice using low, intermediate, and high doses. Intravenous doses were 10, 25, and 50 µg/kg b.w while the oral doses were 20, 50, and 100 µg/kg b.w. Respective control groups of mice were administered phosphate buffered saline (vehicle only) for 14 consecutive days. All external morphological, hematological, biochemical, urine, histopathological, food intake in addition to body weight and vital organ weight were recorded. During the study no mortality in any animal was observed in either treatment routes. There were no significant changes in morphology, food intake, hematology, biochemical, urine analysis, organ weight. Animals treated high dose of TSA intravenously (50 µg/kg b.w) and orally (100 µg/kg b.w) had enlarged, congested, and discolored kidneys which were statistically significant. Histopathological studies had shown statistically significant degenerated glomerulus in high dose of intravenous and orally treated animals and degenerated tubule were found in orally treated animals. Genotoxicity was evaluated using micronucleus frequency at 14 and 21 d after treatment and chromosomal aberration at 21 d after treatment. Micronucleaus assay and chromosomal assay however did not show any significant changes at any doses and administration routes. Therefore, this study concludes that dose ∼25 µg/kg and ∼50 µg/kg b.w may be considered as No Observed Adverse Effect Level (NOAEL) for intravenous and oral administration of TSA respectively.

A Pilot Study in Adapting the Chronic Care Model to Address Shortage of Child and Adolescent Psychiatry.

There is a nationwide shortage of child and adolescent psychiatrists. This, combined with the mental health crisis caused by the coronavirus 2019 pandemic has lead to low access to care for many individuals. Child Psychiatry Access Programs have been developed to address this need, but we believe they are not sufficient to care for complex cases. We propose that the Chronic Care Model can address these issues by providing, more longitudinal and and faster access to mental health care for patients. Our pilot study had 50 children and adolescent participants in our clinic model, which included the use of trainees supervised by an attending. We found that the mean wait time to appointment with a child and adolescent psychiatrist was 13.54 ± 14.8 days, which is significantly shorter by that reported by other studies. We believe our model clinic may be helpful in a variety of settings and want to share it with other psychiatrists.

Fruit Quality Assessment of Novel Hybrid Pummelo × Sweet Orange and Its Molecular Characterization Using Acidity Specific Markers.

Research background: There is considerable diversity in newly developed pummelo × sweet orange citrus hybrids. Most hybrids showed lower peel thickness and high juice yield but there is a lack of information on fruit quality parameters and molecular characterization. Therefore, the aim of the current study is to determine the content of antioxidants and properties of the fresh juice of 24 new pummelo × sweet orange citrus hybrids (Citrus maxima [Burm. f.] Osbeck × Citrus sinensis [L.] Osbeck) and the parental genotypes along with molecular characteristics determined using acidity specific markers. Experimental approach: The correlation and estimate of inheritance of the fruit juice properties: ascorbic acid, total phenol, total flavonoid, total antioxidant, total soluble solid and sugar contents, pH, titratable acidity, along with sensory evaluation was performed. Molecular characterization of these hybrids was carried out using de novo generated acidity specific simple sequence repeat (SSR) markers. Results and conclusions: The main constituents of the fruit juice of pummelo × sweet orange hybrids were observed in the range of w(ascorbic acid)=40.00-58.13 mg/100 g, total phenols expressed as gallic acid equivalents w(GAE)=40.67-107.33 mg/100 g, total antioxidants expressed as Trolox equivalents b(Trolox)=2.03-5.49 µmol/g, total flavonoids expressed as quercetin equivalents w(QE)=23.67-59.33 mg/100 g, along with other properties: total soluble solids=7.33-11.33 %, w(total sugar)=2.10-5.76 %, w(reducing sugar)=1.69-2.78 %, w(non-reducing sugar)=0.39-3.17 % and titratable acidity 1.00-2.11 %. The above parameters differed significantly in the fruit juice of the evaluated pummelo × sweet orange hybrids. Considering these parameters, the hybrids SCSH 17-9, SCSH 13-13, SCSH 11-15 and SCSH 3-15 had superior antioxidant properties in terms of these parameters. A higher heritability (≥80 %) was also observed for all juice properties. Molecular characterization of pummelo × sweet orange hybrids showed that >50 % of the hybrids were grouped with medium acidity parents. Both molecular and biochemical parameter-based clustering showed that interspecific hybrids exhibit transgressive segregation with increased antioxidants that help alleviate the health problems. Novelty and scientific contribution: These newly developed pummelo × sweet orange citrus hybrids are a valuable source of high-quality antioxidants for a healthy diet. The identification of trait markers that enable selection at the seedling stage is of great benefit to citrus breeders, as the characteristic features of a mature tree are not yet visible at the juvenile stage.

Myo-inositol alters the effects of glucose, leptin and insulin on placental palmitic acid and oleic acid metabolism.

Well-regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo-inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope-labelled 13 C-PA or 13 C-OA for 48 h. Explants were treated with glucose (5, 10 mm) or leptin (13 nm) or insulin (150 nm) in combination with myo-inositol (0.3, 30, 60 µm). Forty-seven 13 C-PA lipids and 37 13 C-OA lipids were measured by liquid chromatography-mass spectrometry (LCMS). Compared with controls (5 mm glucose), glucose (10 mm) increased 19 13 C-OA lipids and nine 13 C-PA lipids, but decreased 13 C-OA phosphatidylethanolamine 38:5 and 13 C-PA phosphatidylethanolamine 36:4. The effects of leptin and insulin were less prominent than glucose, with leptin increasing 13 C-OA acylcarnitine 18:1, and insulin increasing four 13 C-PA triacylglycerides. Most glucose, leptin and insulin-induced alterations in lipids were attenuated by co-incubation with myo-inositol (30 or 60 µm), with attenuation also occurring in all subgroups stratified by GDM status and fetal sex. However, glucose-induced increases in acylcarnitine were not attenuated by myo-inositol and were even exaggerated in some instances. Myo-inositol therefore appears to generally act as a moderator, suppressing the perturbation of lipid metabolic processes by glucose, leptin and insulin in placenta in vitro. Whether myo-inositol protects the fetus and pregnancy from unfavourable outcomes requires further research. KEY POINTS: Incubation of placental explants with additional glucose, or to a lesser extent insulin or leptin, alters the placental production of 13 C-lipids from 13 C-palmitic acid (PA) and 13 C-oleic acid (OA) in vitro compared with untreated controls from the same placenta. Co-incubation with myo-inositol attenuated most alterations induced by glucose, insulin or leptin in 13 C-lipids, but did not affect alterations in 13 C-acylcarnitines. Alterations induced by glucose and leptin in 13 C-PA triacylglycerides and 13 C-PA phospholipids were influenced by fetal sex and gestational diabetes status, but were all still attenuated by myo-inositol co-incubation. Insulin differently affected 13 C-PA triacylglycerides and 13 C-PA phospholipids depending on fetal sex, with alterations also attenuated by myo-inositol co-incubation.

Biomolecular map of albumin identifies signatures of severity and early mortality in acute liver failure.

BACKGROUND & AIMS: Acute liver failure (ALF) is associated with high mortality. Alterations in albumin structure and function have been shown to correlate with outcomes in cirrhosis. We undertook a biomolecular analysis of albumin to determine its correlation with hepatocellular injury and early mortality in ALF. METHODS: Altogether, 225 participants (200 patients with ALF and 25 healthy controls [HC]) were enrolled. Albumin was purified from the baseline plasma of the training cohort (ALF, n = 40; survivors, n = 8; non-survivors, n = 32; and HC, n = 5); analysed for modifications, functionality, and bound multi-omics signatures; and validated in a test cohort (ALF, n = 160; survivors, n = 53; non-survivors, n = 107; and HC, n = 20). RESULTS: In patients with ALF, albumin is more oxidised and glycosylated with a distinct multi-omics profile than that in HC, more so in non-survivors (p <0.05). In non-survivors, albumin was more often bound (p <0.05, false discovery rate <0.01) to proteins associated with inflammation, advanced glycation end product, metabolites linked to arginine, proline metabolism, bile acid, and mitochondrial breakdown products. Increased bacterial taxa (Listeria, Clostridium, etc.) correlated with lipids (triglycerides [4:0/12:0/12:0] and phosphatidylserine [39:0]) and metabolites (porphobilinogen and nicotinic acid) in non-survivors (r2 >0.7). Multi-omics signature-based probability of detection for non-survival was >90% and showed direct correlation with albumin functionality and clinical parameters (r2 >0.85). Probability-of-detection metabolites built on the top five metabolites, namely, nicotinic acid, l-acetyl carnitine, l-carnitine, pregnenolone sulfate, and N-(3-hydroxybutanoyl)-l-homoserine lactone, showed diagnostic accuracy of 98% (AUC 0.98, 95% CI 0.95-1.0) and distinguish patients with ALF predisposed to early mortality (log-rank <0.05). On validation using high-resolution mass spectrometry and five machine learning algorithms in test cohort 1 (plasma and paired one-drop blood), the metabolome panel showed >92% accuracy/sensitivity and specificity for prediction of mortality. CONCLUSIONS: In ALF, albumin is hyperoxidised and substantially dysfunctional. Our study outlines distinct 'albuminome' signatures capable of distinguishing patients with ALF predisposed to early mortality or requiring emergency liver transplantation. IMPACTS AND IMPLICATIONS: Here, we report that the biomolecular map of albumin is distinct and linked to severity and outcome in patients with acute liver failure (ALF). Detailed structural, functional, and albumin-omics analysis in patients with ALF led to the identification and classification of albumin-bound biomolecules, which could segregate patients with ALF predisposed to early mortality. More importantly, we found albumin-bound metabolites indicative of mitochondrial damage and hyperinflammation as a putative indicator of <30-day mortality in patients with ALF. This preclinical study validates the utility of albuminome analysis for understanding the pathophysiology and development of poor outcome indicators in patients with ALF.

Phase II trial of a novel chemotherapy regimen CVEP (cyclophosphamide, vinblastine, etoposide and prednisolone) for acquired immunodeficiency syndrome (AIDS)-associated lymphomas.

Management of acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell (DLBCL) and plasmablastic lymphomas (PBL) poses significant challenges. The evidence supports use of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) with or without rituximab as first-line therapy. The need for central venous access, growth factors and significant toxicities limits its use in resource-constrained settings. To address these challenges, we have developed a novel regimen, CVEP (cyclophosphamide, vinblastine, etoposide, and prednisolone) based on the pharmacodynamic principles of dose-adjusted EPOCH. This single-centre phase II study evaluated the efficacy and safety of CVEP regimen in patients with de novo systemic AIDS-related DLBCL and PBL. The primary objective was complete response (CR) rates as assessed by positron emission tomography-computed tomography. The secondary objectives were incidence of Grade 3/4 toxicities, toxicities requiring hospitalisation, and disease-free survival. From May 2011 to February 2017, 42 patients were enrolled. At the end of therapy the CR rates were 69% (29/42) in the intention-to-treat population and 80.5% (29/36) in evaluable patients. At a median follow-up of 69 months, the 5-year disease-free survival was 65.3%. Out of 217 cycles administered, febrile neutropenia occurred in 19.3% and hospitalisation was required in 18.3% of cycles. There were two treatment-related deaths. The CVEP regimen is an active and safe regimen for AIDS-related DLBCL and PBL.

Toxicity analysis of endocrine disrupting pesticides on non-target organisms: A critical analysis on toxicity mechanisms.

Endocrine disrupting compounds are the chemicals which mimics the natural endocrine hormones and bind to the receptors made for the hormones. Upon binding they activate the cascade of reaction which leads to permanent activating of the signalling cycle and ultimately leads to uncontrolled growth. Pesticides are one of the endocrine disrupting chemicals which cause cancer, congenital birth defects, and reproductive defects in non-target organisms. Non-target organisms are keen on exposing to these pesticides. Although several studies have reported about the pesticide toxicity. But a critical analysis of pesticide toxicity and its role as endocrine disruptor is lacking. Therefore, the presented review literature is an endeavour to understand the role of the pesticides as endocrine disruptors. In addition, it discusses about the endocrine disruption, neurological disruption, genotoxicity, and ROS induced pesticide toxicity. Moreover, biochemical mechanisms of pesticide toxicity on non-target organisms have been presented. An insight on the chlorpyrifos toxicity on non-target organisms along with species names have been presented.

Optimizing silver nanowire dimensions by the modification of polyol synthesis for the fabrication of transparent conducting films.

Transparent conducting films (TCFs) made by the assembly/deposition of silver nanowires (Ag NWs) are widely used to manufacture flexible electronics such as touch screens, heaters, displays, and organic light-emitting diodes. Controlling the dimensions (length and diameter) of the nanowires is key in obtaining TCFs with the desired optoelectronic properties, namely sheet resistance and optical transparency. This work describes a combined experimental and theoretical investigation on the optimization of the NW dimensions to fabricate high-quality TCFs. Ag NWs of different dimensions are synthesized by the modified polyol method and the average diameter and length of the wires are tailored over a wide range, 35-150 nm and 12-130µm respectively, by controlling the synthesis parameters such as reaction conditions, stabilizing agents, and growth promoters. The synthesized NWs are spin coated on glass substrates to form TCFs. Comparing the films with different lengths, but identical diameters, enabled the quantification of the effect of length on the optoelectronic properties of the TCFs. Similarly, the effect of NW diameter is also studied. A non-uniformity factor is defined to evaluate the uniformity of the TCF and the transmittance of the NW network is shown to be inversely proportional to its area coverage. The sheet conductance versus the normalized number density is plotted for the different concentrations of NWs to extract a conductivity exponent that agrees well with the theoretical predictions. For thin film networks, the relation between the transmittance and sheet resistance provides the percolative figure of merit (FoM) as a fitting parameter. A large FoM is desirable for a good-performing TCF and the synthesis conditions to achieve this are optimized.

Conformational effects in the vibrational and electronic spectra of propionaldehyde: Experimental and theoretical studies.

We report here investigations on conformational effects in the vibrational and electronic spectra of the propionaldehyde (propanal) molecule using FTIR (600-3200 cm-1) and vacuum ultraviolet (VUV) synchrotron radiation photoabsorption (52 500-85 000 cm-1) spectroscopy respectively. Detailed theoretical calculations (using DFT and TDDFT methodologies) on ground and excited states of the cis and gauche conformers of propanal are performed; a comprehensive spectral analysis of the IR and VUV spectra is presented. A reinvestigation of the IR spectrum reveals several new bands assigned to the gauche conformer based on theoretical calculations. The VUV spectrum exhibits rich Rydberg series structure assigned to ns, np and nd series converging to the first ionization potentials of the two conformers. Earlier assignments of the 3s cis and gauche origins are revised in addition to extending Rydberg series analysis to several higher members. Vibronic bands accompanying the 3s, 4s and 4p Rydberg states are assigned using estimated vibrational frequencies of cis and gauche conformers in the cationic ground state. Simulated potential energy curves of the first few excited states (singlets and triplets) of cis and gauche conformers of propanal help in gaining insights into photodissociation mechanisms and possible conformational effects therein.

Myo-inositol: a potential prophylaxis against premature onset of labour and preterm birth.

The incidence of preterm birth (PTB), delivery before 37 completed weeks of gestation, is rising in most countries. Several recent small clinical trials of myo-inositol supplementation in pregnancy, which were primarily aimed at preventing gestational diabetes, have suggested an effect on reducing the incidence of PTB as a secondary outcome, highlighting the potential role of myo-inositol as a preventive agent. However, the underlying molecular mechanisms by which myo-inositol might be able to do so remain unknown; these may occur through directly influencing the onset and progress of labour, or by suppressing stimuli that trigger or promote labour. This paper presents hypotheses outlining the potential role of uteroplacental myo-inositol in human parturition and explains possible underlying molecular mechanisms by which myo-inositol might modulate the uteroplacental environment and inhibit preterm labour onset. We suggest that a physiological decline in uteroplacental inositol levels to a critical threshold with advancing gestation, in concert with an increasingly pro-inflammatory uteroplacental environment, permits spontaneous membrane rupture and labour onset. A higher uteroplacental inositol level, potentially promoted by maternal myo-inositol supplementation, might affect lipid metabolism, eicosanoid production and secretion of pro-inflammatory chemocytokines that overall dampen the pro-labour uteroplacental environment responsible for labour onset and progress, thus reducing the risk of PTB. Understanding how and when inositol may act to reduce PTB risk would facilitate the design of future clinical trials of maternal myo-inositol supplementation and definitively address the efficacy of myo-inositol prophylaxis against PTB.

Methanolic fraction of Cassia fistula L. bark exhibits potential to combat oxidative stress and possess antiproliferative activity.

Cassia fistula L. is well known for its traditional medicinal properties as an anti-inflammatory, hepatoprotective, antifungal, antibacterial, antimutagenic, and wound healing agent. The aim of the present study was to determine antioxidant, genoprotective, and cytotoxic potential of different fractions of C. fistula bark including hexane (CaMH), chloroform (CaMC), ethyl acetate (CaME), and methanol (CaMM). Among all the fractions studied, CaMM exhibited maximal radical scavenging activity in antioxidant DPPH assay, Superoxide anion radical scavenging assay and nitric oxide radical scavenging assay displayed an IC50 value of 18.95, 29.41, and 13.38 µg/ml, respectively. CaMM fraction possessed the highest phenolic (130.37 mg gallic acid equivalent/g dry weight of extract) and flavonoid (36.96 mg rutin equivalent/g dry weight of fraction) content. Data demonstrated significant positive correlation between polyphenol levels and radical scavenging activity. Single cell gel electrophoresis (Comet assay) exhibited genoprotective potential of C. fistula bark fractions against DNA damage induced by hydrogen peroxide (H2O2) in human lymphocytes. CaMM fraction displayed highest protective ability against H2O2 induced-toxicity as evidenced by significant decrease in % tail DNA content from 30 to 7% at highest concentration (200 µg/ml). CaMM was found to be rich in catechin, gallic acid, chlorogenic acid, and kaempferol. The phenolic content and antioxidant ability of the fractions was markedly negatively correlated with H2O2- induced DNA damage in human lymphocytes. Cytotoxic potential was evaluated against dermal epidermoid carcinoma (A431), pancreatic (MIA PaCa-2) and brain glioblastoma (LN-18) cancer cell lines using MTT assay. Results showed that C. fistula bark fractions possessed highest toxicity against the skin carcinoma cells. CaMM fraction reduced over 50% cell growth at the concentration of 76.72 µg/ml in A431 cells. These findings suggest that fractions of C. fistula bark exhibit potential to be considered as therapeutic agents in various carcinomas.

Enhanced Oil Recovery Using Indigenous Microbiome of High Temperature Oil Reservoirs.

Crude oil is a primary energy source used for economic expansion across the world. Secondary recovery processes employed by industries to recover oil from oil wells leave behind 70% of the oil trapped in marginal and deleted zones of reservoirs. To recover the oil from depleted zones, microbial enhanced oil recovery (MEOR) tertiary processes were introduced, which involve the production of metabolites from the indigenous microbiome. In this study, the indigenous microbiota was identified as Marinobacterium sp., Silvanigrella sp., Petrothermobacter sp., Pseudomonas sp., Bacillus sp., Nitrincola sp., Halomonas sp., Uncultured Roseovarius sp., and Phaeobacter. Further, the secondary metabolites such as volatile fatty acids (ethanol, acetone, and acetate), biomass, gases (CO2, CH4), and biosurfactants were estimated through gas chromatography and FTIR spectroscopy. Once stable microbial growth was attained in the baltch media, it was optimized through response surface methodology (RSM) to minimize the process cost. The optimized media with 9 g/L of molasses, 1.75 g/L of sodium bicarbonate, and 1.25 g/L of ammonium chloride showed a significant impact on metabolite production. Additionally, core flood studies to simulate field studies were performed that represented that TeriK-1 brought a significant increment of 18.9%, which makes it suitable for MEOR field implementation. This study is one of its kind where the indigenous thermophilic sp. was successfully established and is capable of producing the secondary metabolites that aid in the MEOR process.