Plasma Virome of HIV-infected Subjects on Suppressive Antiretroviral Therapy Reveals Association of Differentially Abundant Viruses with Distinct T-cell Phenotypes and Inflammation.

Background: The plasma virome represents the overall composition of viral sequences present in it. Alteration in plasma virome has been reported in treatment naïve and immunocompromised (CD4 count < 200) people with HIV (PWH). However, the effect of ART on virome composition in PWH on ART with preserved CD4 counts is poorly understood. Objectives: We aimed to assess the alterations in plasma virome in PWH on ART in comparison to HIV-negative uninfected controls and to further investigate possible associations of plasma viruses with inflammation and immune dysfunction, namely, immunosenescence and immune exhaustion. Methods: Plasma viral DNA from PWH on ART and controls was used for sequencing on the Illumina Nextseq500 platform, followed by the identification of viral sequences using an automated pipeline, VIROMATCH. Multiplex cytokine assay was performed to measure the concentrations of various cytokines in plasma. Immunophenotyping was performed on PBMCs to identify T cell markers of immunosenescence and immune exhaustion. Results: In our observational, cross-sectional pilot study, chronically infected PWH on ART had significantly different viral species compositions compared to controls. The plasma virome of PWH showed a significantly high relative abundance of species Human gammaherpesvirus 4, also known as Epstein-Barr virus (EBV). Moreover, EBV emerged as a significant viral taxon differentially enriched in PWH on ART, which further correlated positively with the exhaustion phenotype of T cells and significantly increased TNF-α in PWH on ART. Additionally, a significantly increased proportion of senescent T cells and IL-8 cytokine was detected in PWH on ART. Conclusion: Altered plasma virome influenced the inflammatory response and T-cell phenotype in PWH on ART.

Christie, Atkins, Munch-Peterson (CAMP) Negative Listeria monocytogenes Meningitis in Neonates: Report of Two Cases.

Listeria monocytogenes, a gram-positive bacillus and an intracellular pathogen, is an uncommon cause of illness in the general population. During pregnancy, a perinatal infection can lead to serious complications such as abortion, stillbirth, neonatal sepsis, and meningitis. We present two cases of neonatal meningitis caused by Christie, Atkins, Munch-Peterson (CAMP)-negative Listeria monocytogenes. In the first case, a seven-day-old female term neonate delivered vaginally, presented with high-grade fever and refusal to feed. In view of the suspected late-onset sepsis, a septic workup, including cerebrospinal fluid analysis, was conducted. CSF culture reports obtained showed a growth consistent with Listeria monocytogenes, which was CAMP test negative and susceptible to the penicillin group of drugs, cotrimoxazole, erythromycin, and meropenem. The isolate was identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and confirmed by 16S rRNA sequencing. The blood culture was sterile. At 48 hours of admission, the neonate clinically deteriorated with fluctuation in oxygen saturation below 95% at room air. Thus, she was electively intubated and connected to the mechanical ventilator with appropriate settings. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy. The neonate showed clinical improvement within the next 24 hours of initiating antibiotics according to culture susceptibility and was gradually weaned from the mechanical ventilator to continuous positive airway pressure (CPAP). After 24 hours, she was able to maintain normal saturation at room air. In the second case, an 11-day-old low birth weight neonate, small for gestational age, was presented to the NICU with complaints of loose stools, fever, and refusal to feed for the past two days. In view of the suspected sepsis, relevant investigations were carried out while initiating empirical antibiotics IV piperacillin-tazobactam and IV amikacin for the neonate. Meanwhile, there was a dip in oxygen saturation noted on room air for the neonate and he/she was mechanically ventilated. The CSF culture grew Listeria monocytogenes,which was identified using MALDI-TOF MS and confirmed by 16S rRNA sequencing. The isolate tested negative for the CAMP test and was susceptible to ampicillin, penicillin, cotrimoxazole, erythromycin, and meropenem. The blood culture was sterile. The antibiotics were upgraded to meropenem from the empirical antibiotic therapy, the patient's condition improved, and the baby was eventually discharged.

Short-Chain Fatty Acid (SCFA) as a Connecting Link between Microbiota and Gut-Lung Axis-A Potential Therapeutic Intervention to Improve Lung Health.

The microbiome is an integral part of the human gut, and it plays a crucial role in the development of the immune system and homeostasis. Apart from the gut microbiome, the airway microbial community also forms a distinct and crucial part of the human microbiota. Furthermore, several studies indicate the existence of communication between the gut microbiome and their metabolites with the lung airways, called "gut-lung axis". Perturbations in gut microbiota composition, termed dysbiosis, can have acute and chronic effects on the pathophysiology of lung diseases. Microbes and their metabolites in lung stimulate various innate immune pathways, which modulate the expression of the inflammatory genes in pulmonary leukocytes. For instance, gut microbiota-derived metabolites such as short-chain fatty acids can suppress lung inflammation through the activation of G protein-coupled receptors (free fatty acid receptors) and can also inhibit histone deacetylase, which in turn influences the severity of acute and chronic respiratory diseases. Thus, modulation of the gut microbiome composition through probiotic/prebiotic usage and fecal microbiota transplantation can lead to alterations in lung homeostasis and immunity. The resulting manipulation of immune cells function through microbiota and their key metabolites paves the way for the development of novel therapeutic strategies in improving the lung health of individuals affected with various lung diseases including SARS-CoV-2. This review will shed light upon the mechanistic aspect of immune system programming through gut and lung microbiota and exploration of the relationship between gut-lung microbiome and also highlight the therapeutic potential of gut microbiota-derived metabolites in the management of respiratory diseases.

Transcriptional landscape of long non-coding RNAs (lncRNAs) and its implication in viral diseases.

Long non-coding RNAs (lncRNAs) are RNA transcripts of size >200 bp that do not translate into proteins. Emerging data revealed that viral infection results in systemic changes in the host at transcriptional level. These include alterations in the lncRNA expression levels and triggering of antiviral immune response involving several effector molecules and diverse signalling pathways. Thus, lncRNAs have emerged as an essential mediatory element at distinct phases of the virus infection cycle. The complete eradication of the viral disease requires more precise and novel approach, thus manipulation of the lncRNAs could be one of them. This review shed light upon the existing knowledge of lncRNAs wherein the implication of differentially expressed lncRNAs in blood-borne, air-borne, and vector-borne viral diseases and its promising therapeutic applications under clinical settings has been discussed. It further enhances our understanding of the complex interplay at host-pathogen interface with respect to lncRNA expression and function.

Electrocatalytic quantification of quinol in cosmetic samples using Co-doped graphitic carbon nitride @biomolecule assisted electrochemically reduced graphene nanosheets.

A bio-nanocomposite "Co-doped-g-C3N4@ biomolecule assisted electrochemically reduced graphene nanosheets (Co-g-C3N4@GNbme)" was prepared by electrochemical exfoliation of GO from graphite anode in the presence of amino acid 'l-cysteine' followed by its association with Co-g-C3N4. The preparation of material has been confirmed by characterizations with FTIR, XRD, XPS and Raman spectroscopy. The morphology was investigated with TEM and SEM. Further, Co-g-C3N4@GNbme modified GC electrode was utilized for detecting and quantifying the 'Quinol' (a skin lightning agent) in cosmetic samples electrochemically. Quinol is a fundamental constituent utilized in various industries such as pharmaceuticals, oil refineries, textiles, and dyes. In the realm of cosmetics, it is utilized as a skin-lightning agent to inhibit the production of melanin in the skin. However, prolonged use of this component often results in allergic reactions among individuals. Furthermore, the effluents discharged from its manufacturing units pose a significant threat to the environment and human health due to its slow degradation. The detection limit was calculated to be 2.4 nM (S/N = 3).

Chemotherapy as cause of refractory severe headache in a case of small-cell lung cancer.

Small-cell lung cancer (SCLC) is a very fast growing form of cancer and is characterised by early metastasis. As a result, chemotherapy is the mainstay of treatment. Platinum-containing combination regimens are the current treatment of choice for limited stage-SCLC and extensive stage SCLC. Various adverse effects after cisplatin and etoposide chemotherapy include nausea, nephrotoxicity, cardiotoxicity, hepatotoxicity, neurotoxicity, alopecia, gastrointestinal toxicity and myelosuppression. However, severe headache has not been reported yet. Here, we report one such case of severe refractory headache postcisplatin and etoposide chemotherapy which responded only to change in chemotherapy regime. All pertinent causes of headache were ruled out prior to changing the chemotherapy regimen.

Metal-free C-H Activation over Graphene Oxide toward Direct Syntheses of Structurally Different Amines and Amides in Water.

Unprecedented metal-free synthesis of a variety of amines and amides is reported via amination of C(sp3)-H and C(sp2)-H bonds. The strategy involves graphene-oxide/I2-catalyzed nitrene insertion using PhINTs as a nitrene (NT) source in water at room temperature. A wide range of structurally different substrates, viz., cyclohexane, cyclic ethers, arenes, alkyl aromatic systems, and aldehydes/ketones, having an α-phenyl ring have been employed successfully to afford the corresponding nitrene insertion product in good yield, albeit low in few cases. The envisaged method has superiority over others in terms of its operational simplicity, metal-free catalysis, use of water as a solvent, ambient reaction conditions, and reusability of the catalyst.

Cu(I)-Induced Activation of Furan for Inverse Electron Demand ADAR with Alkenes toward Regioselective Synthesis of Tetrahydropyridine.

The aza-Diels-Alder reaction of various alkenes and in situ formed 1-aza-1,3-dienes from the reaction of furan/pyrrole/thiophene and PhINTs for the regioselective synthesis of tetrahydropyridine (THP) derivatives was realized. The reaction was catalyzed by TpMe2Cu as a catalyst under very mild reaction conditions. Structurally different alkenes, along with an alkyne, have been utilized as dienophiles to afford a wide range of different THP derivatives up to 70% yield. The potential application of the envisaged method was also investigated by a gram-scale synthesis.

Bio-reduction of Graphene Oxide: Catalytic Applications of (Reduced) GO in Organic Synthesis.

This work is based on various bio-reduction of graphene oxide into reduced graphene oxide and their applications in organic synthesis and group transformations. Graphene oxide, with abundant oxygencontaining functional groups on its basal plane, provides potential advantages, including excellent dispersibility in solvents and the good heterogeneous catalyst. This manuscript reviews various methods of synthesis of graphene and graphene oxide and a comparative study on their advantages and disadvantages, how to overcome disadvantages and covers extensive relevant literature review. In the last few years, investigation based on replacing the chemical reduction methods by some bio-compatible, chemical/impurity-free rGO including flash photo reductions, hydrothermal dehydration, solvothermal reduction, electrochemical approach, microwave-assisted reductions, light and radiation-induced reductions has been reported. Particularly, plant extracts have been applied significantly as an efficient reducing agent due to their huge bioavailability and low cost for bio-reduction of graphene oxide. These plant extracts mainly contain polyphenolic compounds, which readily get oxidized to the corresponding unreactive quinone form, which are the driving force for choosing them as bio-compatible catalyst. Currently, efforts are being made to develop biocompatible methods for the reduction of graphene oxide. The reduction abilities of such phytochemicals have been reported in the synthesis and stabilization of various nanoparticles viz. Ag, Au, Fe and Pd. Various part of plant extract has been applied for the green reduction of graphene oxide. Furthermore, the manuscript describes the catalytic applications of graphene oxide and reduced graphene oxide nanosheets as efficient carbo-catalysts for valuable organic transformations. Herein, important works dedicated to exploring graphene-based materials as carbocatalysts, including GO and rGO for organic synthesis including various functional group transformations, oxidation, reduction, coupling reaction and a wide number of multicomponent reactions have been highlighted. Finally, the aim of this study is to provide an outlook on future trends and perspectives for graphene-based materials in metal-free carbo-catalysis in green synthesis of various pharmaceutically important moieties.

Occurrence and toxicity of a fusarium mycotoxin, zearalenone.

Zearalenone (ZEA) is a mycotoxin produced by the fungi of Fusarium genera, which contaminates the cereals and food stuffs worldwide. Fusarium mycotoxins are considered as important metabolites related to animal and human health. Evidences indicate that ZEA has been found to be present in different food stuffs from developed countries like USA, Canada, France, Germany, Japan, etc. and developing nations like Egypt, Thailand, Iran, Croatia, Philippines, etc. The toxicokinetic studies reveal that following oral exposure of ZEA, the compound is absorbed through gastrointestinal tract (GIT), gets metabolized and distributed to different body parts. ZEA has been shown to cause reproductive disorders in laboratory animals. Although the toxicity of ZEA in humans have not been conclusively established nonetheless, limited evidences indicate that ZEA can cause hyper estrogenic syndrome. Though, ZEA causes low acute toxicity, but reports are available confirming the systemic toxicity caused by ZEA. There is no review available that addresses the occurrence, systemic toxicity and the probable mechanisms of ZEA toxicity. This review shall address the world-wide occurrence and in vivo & in vitro toxicity studies of ZEA over the past 20 years. The review shall also discuss the toxicokinetics of ZEA and metabolites; illustrates the systemic toxicity and probable mechanisms of action leading to the risk associated with ZEA.

Presence of Zearalenone in Cereal Grains and Its Exposure Risk Assessment in Indian Population.

Zearalenone (ZEA) is a toxic metabolite of Fusarium genera that frequently contaminates cereal grains. India being a tropical country provides suitable conditions for fungal invasion to the cereals. In the absence of any regulatory limits for ZEA in India, the present study was carried out to analyze the contamination levels of ZEA in different cereal samples consumed by Indian population and its exposure assessment through intake. Out of 117 cereal samples comprising of wheat, rice, corn, and oats, 70 (84%) were found to be positive for ZEA contamination, among which 24 (33%) samples exceeded the permissible limits proposed by European Union when analyzed by high-performance liquid chromatography. The positive samples were further validated by Liquid Chromatography-Mass Spectroscopy (LC-MS) analysis. Based on the quantitative estimation of ZEA contamination in cereals and their daily consumption values, the probable daily intake of ZEA was found to be 16.9- and 7.9-fold higher in rice and wheat samples, respectively, than the tolerable daily intake prescribed by European Food Safety Authority. The presence of ZEA at high levels indicates a higher exposure risk for Indian population as wheat and rice are staple foods in India. Thus, there is an immediate need to set the permissible levels of ZEA in India to safeguard the health of 1.34 billion people. PRACTICAL APPLICATION: High levels of ZEA contaminated wheat and rice samples suggest that the consumers are at a greater exposure risk. The study will help the Indian regulatory bodies to set the permissible level of ZEA in different cereal grains so as to safeguard the health of common masses. This can happen by simply adopting to European Food Safety Authority standards or depending on the consumption pattern of food and its occurrence, the new safe limit can be prescribed in India like in other Asian countries.

NHC-catalysed diastereoselective synthesis of multifunctionalised piperidines via cascade reaction of enals with azalactones.

NHC-catalysed azalactone ring-opening and piperidine ring-closing cascade with α,ß-unsaturated aldehydes (enals) in a one-pot operation is reported. The present reaction cascade offers a convenient method for a highly diastereoselective synthesis of multifunctionalised piperidines in excellent yields under mild conditions.

Strategic applications of Baylis-Hillman adducts to general syntheses of 3-nitroazetidines.

A novel one-pot highly diastereoselective synthesis of substituted 3-nitroazetidines via an anionic domino process is described. The synthesis involves a high yielding annulation of Baylis-Hillman alcohols and their aldehydes with either N-aryl/tosylphosphoramidates or N-aryl/tosylphosphoramidates in combination with a task-specific ionic liquid [bmim][X-Y] to afford the corresponding 1,2,3-tri- and 1,2,3,4-tetrasubstituted azetidines, respectively. Plausible mechanisms for the formation of various 3-nitroazetidines have been suggested.

A novel multicomponent synthesis of polyfunctionalized bicyclic tetrahydropyrimidinone derivatives via mercaptoacetylative ring transformations.

A novel K-10 clay (nanoclay)-catalyzed expeditious synthesis of polyfunctionalized bicyclic pyrimidines using unprotected aldoses, 2-methyl-2-phenyl-1,3-oxathiolan-5-one and amidines/guanidine is reported. These polyfunctionalized bicyclic pyrimidines were obtained in excellent yields (72-93%) with high cis diastereoselectivity (>94%) at the ring junction via tandem condensation, mercaptoacetylative ring transformation and cyclization reactions. The process presents an excellent illustration of use of carbohydrates as renewable resources for the formation of pharmaceutically relevant fine chemicals employing solvent-free microwave irradiation conditions in a one-pot procedure.