Antimicrobial resistance heterogeneity among multidrug-resistant Gram-negative pathogens: Phenotypic, genotypic, and proteomic analysis.

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.

Copper-independent lysosomal localisation of the Wilson disease protein ATP7B.

In hepatocytes, the Wilson disease protein ATP7B resides on the trans-Golgi network (TGN) and traffics to peripheral lysosomes to export excess intracellular copper through lysosomal exocytosis. We found that in basal copper or even upon copper chelation, a significant amount of ATP7B persists in the endolysosomal compartment of hepatocytes but not in non-hepatic cells. These ATP7B-harbouring lysosomes lie in close proximity of ~10 nm to the TGN. ATP7B constitutively distributes itself between the sub-domain of the TGN with a lower pH and the TGN-proximal lysosomal compartments. The presence of ATP7B on TGN-lysosome colocalising sites upon Golgi disruption suggested a possible exchange of ATP7B directly between the TGN and its proximal lysosomes. Manipulating lysosomal positioning significantly alters the localisation of ATP7B in the cell. Contrary to previous understanding, we found that upon copper chelation in a copper-replete hepatocyte, ATP7B is not retrieved back to TGN from peripheral lysosomes; rather, ATP7B recycles to these TGN-proximal lysosomes to initiate the next cycle of copper transport. We report a hitherto unknown copper-independent lysosomal localisation of ATP7B and the importance of TGN-proximal lysosomes but not TGN as the terminal acceptor organelle of ATP7B in its retrograde pathway.

Study on Effects of Probiotics on Gut Microbiome and Clinical Course in Patients with Critical Care Illnesses.

Ventilator-associated pneumonia (VAP) is a nosocomial infection contracted by ventilator patients in which bacteria colonize the upper digestive tract and contaminated secretions are released into the lower airway. This nosocomial infection increases the morbidity and mortality of the patients as well as the cost of treatment. Probiotic formulations have recently been proposed to prevent the colonization of these pathogenic bacteria. In this prospective observational study, we aimed to investigate the effects of probiotics on gut microbiota and their relation to clinical outcomes in mechanically ventilated patients. For this study, 35 patients were recruited (22 probiotic-treated and 13 without probiotic treatment) from a cohort of 169 patients. Patients in the probiotic group were given a dose of 6 capsules of a commercially available probiotic (VSL#3®:112.5 billion CFU/cap) in three divided doses for 10 days. Sampling was carried out after each dose to monitor the temporal change in the gut microbiota composition. To profile the microbiota, we used a 16S rRNA metagenomic approach, and differences among the groups were computed using multivariate statistical analyses. Differences in gut microbial diversity (Bray Curtis and Jaccard distance, p-value > 0.05) between the probiotic-treated group and the control group were not observed. Furthermore, treatment with probiotics resulted in the enrichment of Lactobacillus and Streptococcus in the gut microbiota of the probiotic-treated groups. Our results demonstrated that probiotics might lead to favorable alterations in gut microbiome characteristics. Future studies should focus on the appropriate dosages and frequency of probiotics, which can lead to improved clinical outcomes.

Polygonal gold nanocrystal induced efficient phase transition in 2D-MoS2for enhancing photo-electrocatalytic hydrogen generation.

Plasmonic nanocrystals (NCs) assisted phase transition of two-dimensional molybdenum disulfide (2D-MoS2) unlashes numerous opportunities in the fields of energy harvesting via electrocatalysis and photoelectrocatalysis by enhancing electronic conductivity, increasing catalytic active sites, lowering Gibbs free energy for hydrogen adsorption and desorption, etc. Here, we report the synthesis of faceted gold pentagonal bi-pyramidal (Au-PBP) nanocrystals (NC) for efficient plasmon-induced phase transition (from 2 H to 1 T phase) in chemical vapor deposited 2D-MoS2. The as-developed Au-PBP NC with the increased number of corners and edges showed an enhanced multi-modal plasmonic effect under light irradiations. The overpotential of hydrogen evolution reaction (HER) was reduced by 61 mV, whereas the Tafel slope decreased by 23.7 mV/dec on photoexcitation of the Au-PBP@MoS2hybrid catalyst. The enhanced performance can be attributed to the light-induced 2H to 1 T phase transition of 2D-MoS2, increased active sites, reduced Gibbs free energy, efficient charge separation, change in surface potential, and improved electrical conductivity of 2D-MoS2film. From density functional theory (DFT) calculations, we obtain a significant change in the electronic properties of 2D-MoS2(i.e. work function, surface chemical potential, and the density of states), which was primarily due to the plasmonic interactions and exchange-interactions between the Au-PBP nanocrystals and monolayer 2D-MoS2, thereby enhancing the phase transition and improving the surface properties. This work would lay out finding assorted routes to explore more complex nanocrystals-based multipolar plasmonic NC to escalate the HER activity of 2D-MoS2and other 2D transition metal dichalcogenides.

Polarized trafficking and copper transport activity of ATP7B: A mutational approach to establish genotype-phenotype correlation in Wilson disease.

Mutation in ATP7B gene causes Wilson disease (WD) that is characterized by severe hepatic and neurological symptoms. ATP7B localizes at the trans-Golgi Network (TGN) transporting copper to copper-dependent enzymes and traffics in apically targeted vesicles upon intracellular copper elevation. To decode the cellular underpinnings of WD manifestation we investigated copper-responsive polarized trafficking and copper transport activity of 15 WD causing point mutations in ATP7B. Amino-terminal mutations Gly85Val, Leu168Pro, and Gly591Asp displayed TGN and subapical localization whereas, Leu492Ser mislocalized at the basolateral region. The actuator domain mutation Gly875Arg shows retention in the endoplasmic reticulum (ER), Ala874Val and Leu795Phe show partial targeting to TGN and post-Golgi vesicles. The nucleotide-binding domain mutations His1069Gln and Leu1083Phe also display impaired targeting. The C-terminal mutations Leu1373Pro/Arg is arrested at ER but Ser1423Asn shows TGN localization. Transmembrane mutant Arg778Leu resides in ER and TGN while Arg969Gln is exclusively ER localized. Cellular Cu level does not alter the targeting of any of the studied mutations. Mutants that traffic to TGN exhibits biosynthetic function. Finally, we correlated cellular phenotypes with the clinical manifestation of the two most prevalent mutations; the early onset and more aggressive WD caused by Arg778Leu and the milder form of WD caused by mutation His1069Gln.

Retromer retrieves the Wilson disease protein ATP7B from endolysosomes in a copper-dependent manner.

The Wilson disease protein, ATP7B maintains copper (herein referring to the Cu+ ion) homeostasis in the liver. ATP7B traffics from trans-Golgi network to endolysosomes to export excess copper. Regulation of ATP7B trafficking to and from endolysosomes is not well understood. We investigated the fate of ATP7B after copper export. At high copper levels, ATP7B traffics primarily to acidic, active hydrolase (cathepsin-B)-positive endolysosomes and, upon subsequent copper chelation, returns to the trans-Golgi network (TGN). At high copper, ATP7B colocalizes with endolysosomal markers and with a core member of retromer complex, VPS35. Knocking down VPS35 did not abrogate the copper export function of ATP7B or its copper-responsive anterograde trafficking to vesicles; rather upon subsequent copper chelation, ATP7B failed to relocalize to the TGN, which was rescued by overexpressing wild-type VPS35. Overexpressing mutants of the retromer complex-associated proteins Rab7A and COMMD1 yielded a similar non-recycling phenotype of ATP7B. At high copper, VPS35 and ATP7B are juxtaposed on the same endolysosome and form a large complex that is stabilized by in vivo photoamino acid labeling and UV-crosslinking. We demonstrate that retromer regulates endolysosome to TGN trafficking of copper transporter ATP7B in a manner that is dependent upon intracellular copper.

Poly C Binding Protein 2 dependent nuclear retention of the utrophin-A mRNA in C2C12 cells.

Upregulation of utrophin, the autosomal homologue of dystrophin, can compensate dystrophin deficiency in Duchenne Muscular Dystrophy (DMD) although the therapeutic success is yet to be achieved. The present study has identified Poly (C) binding protein 2 (PCBP2) as a post-transcriptional suppresser for the expression of utrophin-A, the muscle-specific utrophin isoform. This study confirms nuclear retention of utrophin-A mRNA in C2C12 cells, which is mediated by PCBP2. Further investigation demonstrates PCBP2-dependent nuclear retention of follistatin mRNA as well. Its involvement in nuclear retention of mRNA sheds light on a novel function of PCBP2 that makes utrophin-A mRNA less available in cytosol. PCBP2, therefore, may be a target to de-repress utrophin-A expression in DMD.

Graphene-based dual functional metadevice in the THz gap.

This paper presents a graphene-metal dual functional metadevice to provide two separate applications simultaneously, viz., absorption and cross-polarization conversion (CPC) of the electromagnetic (EM) wave without any structural deformations in the terahertz (THz) gap under two different biasing conditions. The meta-atom of the device bears stacked layers of metallic elliptical-shaped split rings, a thin zinc oxide (ZnO) layer, a slotted graphene layer printed over another ZnO layer backed by a continuous gold plate. It provides more than 70% absorptivity over a bandwidth of 3.40 THz (4.25 THz and 7.65 THz), with 90% absorptivity peak at 6.84 THz when the externally applied static electric field (ξ) on the patterned graphene surface is 8.52 V/nm. The change of the ξ to a value of 0.44 V/nm enables the device to produce a CPC ratio (CPCR) above 90% over a bandwidth of almost 3.87 THz (2.22 THz and 6.09 THz), with near unity polarization conversion ratio peaks occurring at 2.38 THz, 3.80 THz, and 5.82 THz. Both findings have been validated using an exhaustive equivalent circuit analysis. The design possesses ultrathin properties (λ0/12.49), along with compactness (λ0/5), which has been improved significantly compared to their microwave counterparts. The proposed metadevice finds useful applications in THz sensing, stealth technology, THz communication, detection, polarization manipulation of EM waves, etc.

Synthesis and Property of Copper-Impregnated α-MnO2 Semiconductor Quantum Dots.

Because of the superior optical and electrical properties, copper-impregnated size tuneable high-temperature stable manganese dioxide semiconductor quantum dots (SQDs) have been successfully synthesized by a modified chemical synthesis technique. Their size-dependent dielectric properties, semiconducting properties, and current-voltage ( I- V) characteristics have been investigated. X-ray diffraction pattern and Raman spectra confirmed that the required phase is present. Because of the different sintering temperature tuneable size of SQDs has been found and confirmed by high-resolution transmission electron microscopy. The band gap energy of the material is found to be 1.25-1.67 eV, measured from Tauc plot using UV-vis absorbance spectrum and their semiconducting properties have been confirmed by the non linear current-voltage ( I- V) behavior. Most intense green emission peak of photoluminescence (PL) spectroscopy confirms the oxygen vacancy defect state. The stoke shifting of Raman spectra, UV absorption, and PL emission are the footprint of quantum confinement effect. Incorporation of a little amount of Cu in tetragonal hollandite structure of α-MnO2 generates strain within that structure. This leads to create sufficient crystal defect state as well as rise in dielectric constant accompanied with low dielectric loss and higher ac conductivity. All these highly desirable properties make the SQDs a potential candidate for developing multifunctional photo-electronic devices. Owing to the tuneable band gap and electronic transport of the SQDs, we realized that the controllable size paves the way for designing SQDs possessing unique properties for optical and electronic device applications. Using this material as a high dielectric separator, a high-performance supercapacitor has been successfully fabricated which can light up 15 light-emitting diodes for 47 min 23 s after charging them only for 30 s.

Graphene-based metasurface for a tunable broadband terahertz cross-polarization converter over a wide angle of incidence.

In this paper, using a graphene-based metasurface, we demonstrate a unique design to develop a highly efficient, broadband, mid-infrared cross-polarization converter. The proposed graphene-based metasurface structure comprises periodical ϕ-shaped graphene on the top surface of a noble-metal-backed dielectric silicon dioxide (SiO2). The reported structure converts the incident linearly polarized wave into cross-polarized components with a peak polarization conversion ratio of more than 0.9 over a large band. Furthermore, the metasurface structure exhibits the full width at half-maximum bandwidth of 41.98% with respect to its center frequency of 5.98 THz. The physical insights behind electromagnetic polarization conversion are supported by field distributions and retrieved electromagnetic parameters. The structure works as a broadband cross-polarization converter up to 40° incident angle for both TE and TM polarizations. In addition, the structure is found to be as thin as ∼λ/6 with respect to lowermost frequency of the polarization conversion. The period of the unit cell is ∼λ/24 to support the fact that the structure can be treated as a metasurface.

Immunotoxicity of copper nanoparticle and copper sulfate in a common Indian earthworm.

Copper oxide nanoparticles and copper sulfate are established contaminants of water and soil. Metaphire posthuma is a common variety of earthworm distributed in moist soil of Indian subcontinent. Comparative toxicity of copper nanoparticles and copper sulfate were investigated with reference to selected immune associated parameters of earthworm. Total count, phagocytic response, generation of cytotoxic molecules (superoxide anion, nitric oxide), activities of enzymes like phenoloxidase, superoxide dismutase, catalase, acid phosphatase, alkaline phosphatase and total protein of coelomocytes were estimated under the exposures of 100, 500, 1000mg of copper oxide nanoparticles and copper sulfate per kg of soil for 7 and 14 d. A significant decrease in the total coelomocyte count were recorded with maximum depletion as 15.45 ± 2.2 and 12.5 ± 2 × 104 cells/ml under the treatment of 1000mg/kg of copper nanoparticles and copper sulfate for 14 d respectively. A significant decrease in generation of nitric oxide and activity of phenoloxidase were recorded upon exposure of both toxins for 7 and 14 d indicating possible decline in cytotoxic status of the organism. A maximum inhibition of superoxide dismutase activity was recorded as 0.083 ± 0.0039 and 0.055 ± 0.0057 unit/mg protein/minute against 1000mg/kg of copper nanoparticles and copper sulfate treatment for 14 d respectively. Activities of catalase and alkaline phosphatase were inhibited by all experimental concentrations of both toxins in the coelomocytes of earthworm. These toxins were recorded to be modifiers of the major immune associated parameters of M. posthuma. Unrestricted contamination of soil by sulfate and oxide nanoparticles of copper may lead to an undesirable shift in the innate immunological status of earthworm leading to a condition of immune compromisation and shrinkage in population density of this species in its natural habitat. This article is the first time report of immunological toxicity of nanoparticles and sulfate salt of copper in M.posthuma inhabiting the soil of India, an agriculture based country.

Interfacial bonding characteristics between graphene and dielectric substrates.

Achieving strong adhesion between graphene and SiO(x)/Si substrates is crucial to make reliable graphene based electronics and electro-optic devices. We report the enhanced adhesion energy by vacuum annealing and the quantification of graphene-SiO(x)/Si substrate adhesion energy by using the nano-scratch technique coupled with Raman spectroscopy and x-ray photoelectron spectroscopy (XPS). We found that the adhesion energy of as-transferred graphene on SiO(x)/Si substrates is ~2.978 J m(-2). By applying different annealing protocols of rapid thermal annealing and vacuum annealing, the adhesion energy of graphene-SiO(x)/Si is increased to 10.09 and 20.64 J m(-2), respectively. The increase in adhesion energy is due to the formation of chemical bonds between the graphene and SiO(x) at high temperatures. The XPS depth profiling confirms that C-O and C=O chemical bond formation occurs at the graphene/SiO(x) interface. These results could be adapted for graphene/Si nanoelectronics device fabrication and they open up a pathway towards producing reliable solid state devices.

Inverse transitions and disappearance of the λ-line in the asymmetric random-field Ising and Blume-Capel models.

We report on reentrance in the random-field Ising and Blume-Capel models, induced by an asymmetric bimodal random-field distribution. The conventional continuous line of transitions between the paramagnetic and ferromagnetic phases, the λ-line, is wiped away by the asymmetry. The phase diagram, then, consists of only first-order transition lines that always end at ordered critical points. We find that, while for symmetric random-field distributions there is no reentrance, the asymmetry in the random-field results in a range of temperatures for which magnetization shows reentrance. While this does not give rise to an inverse transition in the Ising model, for the Blume-Capel model, however, there is a line of first-order inverse phase transitions that ends at an inverse-ordered critical point. We show that the location of the inverse transitions can be inferred from the ground-state phase diagram of the model.

Investigating the muti-scaling properties and connectedness of the sovereign bond yields: Hurst exponent and network analysis approach.

Using daily yield data of 14 sovereign bond markets from emerging and developed economies from July 10, 2000, to July 10, 2022, we examine their scaling properties using generalized Hurst exponent and spectral density analysis and investigate the connectedness based on a network analysis approach. We consider the yields of 2-year and 10-year bond yields to investigate the scaling properties for short- and long-term sovereign bonds. This selection also allows us to examine sovereign bond spreads with respect to the USA. We also use regularized partial correlation network analysis to connect different countries in communities based on yields. We find that the scaling behavior of the bond yields for both terms fits well using the Hurst exponent and spectral analysis confirms this finding. Moreover, we also find that even though bonds in both cohorts show anti-persistent behavior except that of the USA, the developed economies' bond yields are relatively less anti-persistent as compared to those of emerging economies. The networks of both the 2-year and 10-year yields indicate community formation in various countries which provides diversification benefits to the investors. Most of the emerging countries are classified into one community in the long-tenure bonds as well but this concentration is more evident in the short-tenure bonds.

Wilson disease-causing mutations in the carboxyl terminus of ATP7B regulates its localization and Golgi exit selectively in the unpolarized cells.

Mutational inactivation of the P-type Cu-ATPase ATP7B interferes with its cellular functions to varying extent leading to varied cellular phenotypes. Wilson's disease (WD) primarily affects organs composed of polarized/differentiated epithelial cells. Therefore, phenotypic variability might differ depending on the polarization/differentiation of the cells. The present study investigates the intracellular stability and localization of ATP7B harboring WD mutations in both unpolarized/undifferentiated and polarized/differentiated cell-based models. Green fluorescent protein (GFP)-ATP7B harboring the WD causing mutations, N41S, S653Y, R778Q, G1061E, H1069Q, S1423N, S1426I, and T1434M, are included for investigation. The C-terminal WD mutations (S1423N, S1426I, and T1434M), exhibit distinct localization and Cu(I) responsive anterograde and retrograde trafficking in undifferentiated/unpolarized vs. differentiated/polarized cells. While basal localization of the S1423N mutant gets corrected in the differentiated glia, its Cu(I) responsive anterograde and retrograde trafficking behavior is not identical to the wild-type. But localization and trafficking properties are completely rescued for the S1426I and T1434M mutants in the differentiated cells. Comprehensive meta-analysis on the effect of the reported C-terminal mutations on patient phenotype and cultured cells demonstrate discrete regions having distinct effects. While mutations in the proximal C-terminus affect ATP7B stability, the present study shows that the distal region dictates cell-specific Trans Golgi Network (TGN) localization and exit. The localization and export properties are corrected in the differentiated cells, which is a plausible mechanism for the milder phenotype exhibited by these mutations. It highlights the critical role of the C-terminus in cell-specific TGN retention and exit of ATP7B.

A single dietary factor, daily consumption of a fermented beverage, can modulate the gut bacteria and fecal metabolites within the same ethnic community.

IMPORTANCE: Our study investigated how a traditional drink called Apong, made from fermented rice, affects the gut and health of the Mishing community in India. We compared two groups of people who drink Apong to a group of people who do not drink it. To accomplish this, we studied the gut bacteria, fecal metabolites, and blood samples of the participants. It was found that the people who drank Apong had higher blood pressure but lower blood sugar and protein levels than people who did not drink it. We also found that the gut microbiome composition of people who drank Apong was different from those who did not drink it. Moreover, people who drank Apong had lower levels of isovaleric acid in their feces. Overall, this study shows that a traditional drink like Apong can affect the gut bacteria of a community.

Biofunctionalized CdS Quantum Dots: A Case Study on Nanomaterial Toxicity in the Photocatalytic Wastewater Treatment Process.

The toxic nature of inorganic nanostructured materials as photocatalysts is often not accounted for in traditional wastewater treatment reactions. Particularly, some inorganic nanomaterials employed as photocatalysts may release secondary pollutants in the form of ionic species that leach out due to photocorrosion. In this context, this work is a proof-of-concept study for exploring the environmental toxicity effect of extremely small-sized nanoparticles (<10 nm) like quantum dots (QDs) that are employed as photocatalysts, and in this study, cadmium sulfide (CdS) QDs are chosen. Typically, CdS is an excellent semiconductor with suitable bandgap and band-edge positions that is attractive for applications in solar cells, photocatalysis, and bioimaging. However, the leaching of toxic cadmium (Cd2+) metal ions due to the poor photocorrosion stability of CdS is a matter of serious concern. Therefore, in this report, a cost-effective strategy is devised for biofunctionalizing the active surface of CdS QDs by employing tea leaf extract, which is expected to hinder photocorrosion and prevent the leaching of toxic Cd2+ ions. The coating of tea leaf moieties (chlorophyll and polyphenol) over the CdS QDs (referred to hereafter as G-CdS QDs) was confirmed through structural, morphological, and chemical analysis. Moreover, the enhanced visible-light absorption and emission intensity of G-CdS QDs in comparison to that of C-CdS QDs synthesized through a conventional chemical synthesis approach confirmed the presence of chlorophyll/polyphenol coating. Interestingly, the polyphenol/chlorophyll molecules formed a heterojunction with CdS QDs and enabled the G-CdS QDs to exhibit enhanced photocatalytic activity in the degradation of methylene blue dye molecules over C-CdS QDs while effectively preventing photocorrosion as confirmed from cyclic photodegradation studies. Furthermore, detailed toxicity studies were conducted by exposing zebrafish embryos to the as-synthesized CdS QDs for 72 h. Surprisingly, the survival rate of the zebrafish embryos exposed to G-CdS QDs was equal to that of the control, indicating a significant reduction in the leaching of Cd2+ ions from G-CdS QDs in comparison to C-CdS QDs. The chemical environment of C-CdS and G-CdS before and after the photocatalysis reaction was examined by X-ray photoelectron spectroscopy. These experimental findings prove that biocompatibility and toxicity could be controlled by simply adding tea leaf extract during the synthesis of nanostructured materials, and revisiting green synthesis techniques can be beneficial. Furthermore, repurposing the discarded tea leaves may not only facilitate the control of toxicity of inorganic nanostructured materials but can also help in enhancing global environmental sustainability.

Association of gut microbial dysbiosis with disease severity, response to therapy and disease outcomes in Indian patients with COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is associated with systemic hyper-inflammation. An adaptive interaction between gut microbiota and host immune systems is important for intestinal homeostasis and systemic immune regulation. The association of gut microbial composition and functions with COVID-19 disease severity is sparse, especially in India. We analysed faecal microbial diversity and abundances in a cohort of Indian COVID-19 patients to identify key signatures in the gut microbial ecology in patients with severe COVID-19 disease as well as in response to different therapies. The composition of the gut microbiome was characterized using 16Sr RNA gene sequences of genomic DNA extracted from faecal samples of 52 COVID-19 patients. Metabolic pathways across the groups were predicted using PICRUSt2. All statistical analyses were done using Vegan in the R environment. Plasma cytokine abundance at recruitment was measured in a multiplex assay. RESULTS: The gut microbiome composition of mild and severe patients was found to be significantly different. Immunomodulatory commensals, viz. Lachnospiraceae family members and Bifidobacteria producing butyrate and short-chain fatty acids (SCFAs), were under represented in patients with severe COVID-19, with an increased abundance of opportunistic pathogens like Eggerthella. The higher abundance of Lachnoclostridium in severe disease was reduced in response to convalescent plasma therapy. Specific microbial genera showed distinctive trends in enriched metabolic pathways, strong correlations with blood plasma cytokine levels, and associative link to disease outcomes. CONCLUSION: Our study indicates that, along with SARS-CoV-2, a dysbiotic gut microbial community may also play an important role in COVID-19 severity through modulation of host immune responses.

Poly(N-acryloylglycine-acrylamide) Hydrogel Mimics the Cellular Microenvironment and Promotes Neurite Growth with Protection from Oxidative Stress.

In this work, the glycine-based acryloyl monomer is polymerized to obtain a neurogenic polymeric hydrogel for regenerative applications. The synthesized poly(N-acryloylglycine-acrylamide) [poly(NAG-b-A)] nanohydrogel exhibits high swelling (∼1500%) and is mechanically very stable, biocompatible, and proliferative in nature. The poly(NAG-b-A) nanohydrogel provides a stable 3D extracellular mimetic environment and promotes healthy neurite growth for primary cortical neurons by facilitating cellular adhesion, proliferation, actin filament stabilization, and neuronal differentiation. Furthermore, the protective role of the poly(NAG-b-A) hydrogel for the neurons in oxidative stress conditions is revealed and it is found that it is a clinically relevant material for neuronal regenerative applications, such as for promoting nerve regeneration via GSK3ß inhibition. This hydrogel additionally plays an important role in modulating the biological microenvironment, either as an agonist and antagonist or as an antioxidant. Furthermore, it favors the physiological responses and eases the neurite growth efficiency. Additionally, we found out that the conversion of glycine-based acryloyl monomers into their corresponding polymer modulates the mechanical performance, mimics the cellular microenvironment, and accelerates the self-healing capability due to the responsive behavior towards reactive oxygen species (ROS). Thus, the p(NAG-b-A) hydrogel could be a potential candidate to induce neuronal regeneration since it provides a physical cue and significantly boosts neurite outgrowth and also maintains the microtubule integrity in neuronal cells.

Multiple transitions in an infinite range p-spin random crystal field Blume-Capel model.

We study a p-spin model with ferromagnetic coupling and quenched random crystal fields for p≥3 for spin-1 systems. We find that the model has lines of first-order transitions at finite temperature (T) for all p≥3. For bimodal distribution of the random crystal field these lines meet at a triple point for weak strength of the crystal field (Δ). Beyond a critical strength of Δ, they do not meet and one of the lines ends at a critical point (T_{c}). Interestingly, we find that on increasing T from T_{c}, keeping other parameters fixed, the system undergoes one more transition which is first order in its character. The system thus exhibits a Gardner-like transition for a range of parameters for all finite p≥3. For p→∞ the model behaves differently and there is only one random first-order transition at T=0.