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The rise of antimicrobial resistance has positioned ESKAPE pathogens as a serious global health threat, primarily due to the limitations and frequent failures of current treatment options. This growing risk has spurred the scientific community to seek innovative antibiotic therapies and improved oversight strategies. This review aims to provide a comprehensive overview of the origins and resistance mechanisms of ESKAPE pathogens, while also exploring next-generation treatment strategies for these infections. In addition, it will address both traditional and novel approaches to combating antibiotic resistance, offering insights into potential new therapeutic avenues. Emerging research underscores the urgency of developing new antimicrobial agents and strategies to overcome resistance, highlighting the need for novel drug classes and combination therapies. Advances in genomic technologies and a deeper understanding of microbial pathogenesis are crucial in identifying effective treatments. Integrating precision medicine and personalized approaches could enhance therapeutic efficacy. The review also emphasizes the importance of global collaboration in surveillance and stewardship, as well as policy reforms, enhanced diagnostic tools, and public awareness initiatives, to address resistance on a worldwide scale., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The ability to precisely pattern cells and proteins is crucial in various scientific disciplines, including cell biology, bioengineering, and materials chemistry. Current techniques, such as microcontact stamping, 3D bioprinting, and direct photopatterning, have limitations in terms of cost, versatility, and throughput. In this Article, we present an accessible approach that combines the throughput of photomask systems with the versatility of programmable light patterning using a low-cost consumer LCD resin printer. The method involves utilizing a bioinert hydrogel, poly(ethylene glycol) diacrylate (PEGDA), and a 405 nm sensitive photoinitiator (LAP) that are selectively cross-linked to form a hydrogel upon light exposure, creating specific regions that are protein and cell-repellent. Our result highlights that a low-cost LCD resin printer can project virtual photomasks onto the hydrogel, allowing for reasonable resolution and large-area printing at a fraction of the cost of traditional systems. The study demonstrates the calibration of exposure times for optimal resolution and accuracy and shape corrections to overcome the inherent challenges of wide-field resin printing. The potential of this approach is validated through widely studied 2D and 3D stem cell applications, showcasing its biocompatibility and ability to replicate complex tissue engineering patterns. We also validate the method with a cell-adhesive polymer (gelatin methacrylate; GelMA). The combination of low cost, high throughput, and accessibility makes this method broadly applicable across fields for enabling rapid and precise fabrication of cells and tissues in standard laboratory culture vessels., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Acute respiratory distress syndrome (ARDS) is associated with high mortality rates, which are further exacerbated when accompanied by acute kidney injury (AKI). Presently, there is a lack of comprehensive studies thoroughly elucidating the metabolic dysregulation in ARDS patients with AKI leading to poor outcomes. We hypothesized that metabolomics can be a potent tool to highlight the differences in the metabolic profile unraveling unidentified pathophysiological mechanisms of ARDS patients with and without AKI. 1 H nuclear magnetic resonance spectroscopy was used to identify key metabolites in the serum samples of 75 patients. Distinct clusters of both groups were obtained as the study's primary outcome using multivariate analysis. Notable alternations in the levels of nine metabolites were identified. Pathway analysis revealed the dysregulation of five significant cycles, which resulted in various complications, such as hyperammonemia, higher energy requirements, and mitochondrial dysfunction causing oxidative stress. Identified metabolites also showed a significant correlation with clinical scores, indicating severity. This study shows the alterations in the metabolite concentration highlighting the difference in the pathophysiology of both patient groups and its association with outcome, pointing in the direction of a personalized medicine approach and holding significant promise for application in critical care settings to improve clinical outcomes.

In this work, shellac and its crosslinking were studied to produce paper straws for the application of liquid products. Commercial paper straws are not durable for liquid foods due to their hygroscopic nature, and thus, they find it challenging to replace single-use plastics. Shellac is a naturally occurring resin utilized as an adhesive and water-resistant coating over the paper straw. Shellac was cured at 125 °C, 150 °C, 175 °C, and 200 °C, and it was crosslinked in about 210 min, 150 min, 60 min, and 30 min respectively and studied for kinetics. The crosslinking of shellac produced a thermally stable material. Compared to commercial paper straws, these paper shellac straws exhibited high bending stiffness (1356.11 Nmm), tensile strength (13,74 MPa), flexural strength (21.72 MPa), and compression strength (24.99 MPa). Moreover, the paper shellac straws didn't bend in wet conditions under load for up to one day, while the commercial paper straw bends in 8 min. Therefore, paper straws with shellac can replace plastic-based straws for a sustainable future., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arihant Ahuja reports financial support was provided by the Prime Minister Research Fellowship, Ministry of Education, India. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study developed active packaging films of Polylactic acid incorporated with the plant-based essential oils of Trachyspermum ammi, T. ammi and Vanilla to package waffles, where the antimicrobial property was provided by T. ammi and its odor was masked by vanilla essential oil. Compared to conventional solvent-cast films of smaller sizes requiring a huge amount of solvents, bigger-size PLA-oil films with lower solvent demand were prepared by tape casting technique with 10, 30, and 50 wt% essential oil blends. Films were studied for their morphological, chemical, mechanical, barrier, and antimicrobial properties. The presence and time-bound release of volatile oils from the films was confirmed by infrared spectroscopy, with a continuous decrease of oils from the films till day 30. The plasticizing effect of oils in films was evidenced by decreased tensile strength and crystallinity. In contrast, an increase in elongation at break and water vapor permeability of oil films were also measured. Finally, when packed in PLA films containing 50 wt% blend of both oils, waffles shelf-life extended up to 30 days compared to 2 days for the neat PLA film, where Vanilla was found effective in masking the unpleasant odor of T.ammi as confirmed by sensory analysis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The protein-protein interaction (PPI) network of the Mediator complex is very tightly regulated and depends on different developmental and environmental cues. Here, we present an interactive platform for comparative analysis of the Mediator subunits from humans, baker's yeast Saccharomyces cerevisiae, and model plant Arabidopsis thaliana in a user-friendly web-interface database called MediatorWeb. MediatorWeb provides an interface to visualize and analyze the PPI network of Mediator subunits. The database facilitates downloading the untargeted and unweighted network of Mediator complex, its submodules, and individual Mediator subunits to better visualize the importance of individual Mediator subunits or their submodules. Further, MediatorWeb offers network visualization of the Mediator complex and interacting proteins that are functionally annotated. This feature provides clues to understand functions of Mediator subunits in different processes. In an additional tab, MediatorWeb provides quick access to secondary and tertiary structures, as well as residue-level contact information for Mediator subunits in each of the three model organisms. Another useful feature of MediatorWeb is detection of interologs based on orthologous analyses, which can provide clues to understand the functions of Mediator complex in less explored kingdoms. Thus, MediatorWeb and its features can help the user to understand the role of Mediator complex and its subunits in the transcription regulation of gene expression., (© 2024 Federation of European Biochemical Societies.)

Triterpenoids (C30-isoprenoids) represent a major group of natural products with various physiological functions in plants. Triterpenoids and their derivatives have medicinal uses owing to diverse bioactivities. Arjuna (Terminalia arjuna) tree bark accumulates highly oxygenated β-amyrin-derived oleanane triterpenoids (e.g., arjunic acid, arjungenin, and arjunolic acid) with cardioprotective roles. However, biosynthetic routes and enzymes remain poorly understood. We mined the arjuna transcriptome and conducted cytochrome P450 monooxygenase (P450) assays using Saccharomyces cerevisiae and Nicotiana benthamiana to identify six P450s and two P450 reductases for oxidative modifications of oleanane triterpenoids. P450 assays using oleananes revealed a greater substrate promiscuity of C-2α and C-23 hydroxylases/oxidases than C-28 oxidases. CYP716A233 and CYP716A432 catalyzed β-amyrin/erythrodiol C-28 oxidation to produce oleanolic acid. C-2α hydroxylases (CYP716C88 and CYP716C89) converted oleanolic acid and hederagenin to maslinic acid and arjunolic acid. CYP716C89 also hydroxylated erythrodiol and oleanolic aldehyde. However, CYP714E107a and CYP714E107b catalyzed oleanolic acid/maslinic acid/arjunic acid, C-23 hydroxylation to form hederagenin, arjunolic acid and arjungenin, and hederagenin C-23 oxidation to produce gypsogenic acid, but at a lower rate than oleanolic acid C-23 hydroxylation. Overall, P450 substrate selectivity suggested that C-28 oxidation is the first P450-catalyzed oxidative modification in the arjuna triterpenoid pathway. However, the pathway might branch thereafter through C-2α/C-23 hydroxylation of oleanolic acid. Taken together, these results provided new insights into substrate range of P450s and unraveled biosynthetic routes of triterpenoids in arjuna. Moreover, complete elucidation and reconstruction of arjunolic acid pathway in S. cerevisiae and N. benthamiana suggested the utility of arjuna P450s in heterologous production of cardioprotective compounds., (© 2024 Society for Experimental Biology and John Wiley & Sons Ltd.)

Background: Arteriovenous Fistula (AVF) surveillance is required to detect early dysfunction (thrombosis, stenosis) and its timely correction prolongs access-patency. Clinical examination (CE) and doppler have been used as screening/surveillance of AVF, for early detection of AVF dysfunction. Since there was inadequate evidence for KDOQI to make recommendations on AVF surveillance and on secondary failure rate. We compared CE, doppler and fistulogram as surveillance modalities in detecting a secondary failure in matured AVF., Methodology: This prospective-observational, single-center study, was done between December 2019-April 2021. CKD stage 5 patients on dialysis/Not-on-dialysis with matured AVF were included at third month. CE, doppler (blood flow, vein diameter, depth), and fistulogram were done at third and sixth month. Secondary failure was assessed at sixth month classifying AVF to patent/functional and failed group. Diagnostic tests were performed by comparing three methods considering fistulogram as gold-standard. Residual urine output is also monitored to look for any contrast induced residual renal function loss., Results: Of total 407 created AVF, 98 (24%) had primary failure. Twenty-five (6%) had surgical complications including unsuccessful AVF and aneurysm/rupture, 156 lost follow-up at third month, 104 consented patients were enrolled, 16 lost to follow-up subsequently, and 88 patients' data were analyzed at the end. At the sixth month, 76(86.4%) had patent AVF, 8 (9.1%) had secondary failure (Thrombosis-4, Central Venous Stenosis-4), and 4 (4.1%) patients expired. Considering fistulogram as a diagnostic standard, CE showed 87.5% sensitivity, and 93.4% specificity (cohen's kappa value of 0.66). Doppler had sensitivity and specificity of 87% and 96% respectively (cohen's kappa value of 0.75), Combination of clinical examination with doppler showed sensitivity and specificity of 100% and 89% respectively., Conclusion: Although the secondary AVF failure rate is less than the primary, CE is an important and valuable tool in the diagnosis and surveillance of AVF in detecting its dysfunction. Moreover, CE with doppler can be used as a surveillance protocol that can detect early AVF dysfunction at par with Fistulogram., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Rheumatoid arthritis (RA) is a common autoimmune condition and chronic inflammatory disease, mostly affecting synovial joints. The complex pathogenesis of RA is supportive of high morbidity, disability, and mortality rates. Pathological changes a common characteristic in RA synovial tissue is attributed to the inadequacy of apoptotic pathways. In that regard, apoptotic pathways have been the center of attention in RA therapeutic approaches. As the regulators in the complex network of apoptosis, microRNAs (miRNAs) are found to be vital modulators in both intrinsic and extrinsic pathways through altering their regulatory genes. Indeed, miRNA, a member of the family of non-coding RNAs, are found to be an important player in not even apoptosis, but proliferation, gene expression, signaling pathways, and angiogenesis. Aberrant expression of miRNAs is implicated in attenuation and/or intensification of various apoptosis routes, resulting in culmination of human diseases including RA. Considering the need for more studies focused on the underlying mechanisms of RA in order to elevate the unsatisfactory clinical treatments, this study is aimed to delineate the importance of apoptosis in the pathophysiology of this disease. As well, this review is focused on the critical role of miRNAs in inducing or inhibiting apoptosis of RA-synovial fibroblasts and fibroblast-like synoviocytes and how this mechanism can be exerted for therapeutic purposes for RA., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Fahad Alsaikhan reports financial support was provided by Prince Sattam bin Abdulaziz University. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Germacrene D, a sesquiterpenoid compound found mainly in plant essential oils at a low level as (+) and/or (-) enantiomeric forms, is an ingredient for the fragrance industry, but a process for the sustainable supply of enantiopure germacrene D is not yet established. Here, we demonstrate metabolic engineering in yeast (Saccharomyces cerevisiae) achieving biosynthesis of enantiopure germacrene D at a high titer. To boost farnesyl pyrophosphate (FPP) flux for high-level germacrene D biosynthesis, a background yeast chassis (CENses5C) was developed by genomic integration of the expression cassettes for eight ergosterol pathway enzymes that sequentially converted acetyl-CoA to FPP and by replacing squalene synthase promoter with a copper-repressible promoter, which restricted FPP flux to the competing pathway. Galactose-induced expression of codon-optimized plant germacrene D synthases led to 13-30 fold higher titers of (+) or (-)-germacrene D in CENses5C than the parent strain CEN.PK2.1C. Furthermore, genomic integration of germacrene D synthases in GAL80, LPP1 and rDNA loci generated CENses8(+D) and CENses8(-D) strains, which produced 41.36 µg/ml and 728.87 µg/ml of (+) and (-)-germacrene D, respectively, without galactose supplementation. Moreover, coupling of mitochondrial citrate pool to the cytosolic acetyl-CoA, by expressing a codon-optimized ATP-citrate lyase of oleaginous yeast, resulted in 137.71 µg/ml and 815.81 µg/ml of (+) or (-)-germacrene D in CENses8(+D)* and CENses8(-D)* strains, which were 67-120 fold higher titers than in CEN.PK2.1C. In fed-batch fermentation, CENses8(+D)* and CENses8(-D)* produced 290.28 µg/ml and 2519.46 µg/ml (+) and (-)-germacrene D, respectively, the highest titers in shake-flask fermentation achieved so far. KEY POINTS: • Engineered S. cerevisiae produced enantiopure (+) and (-)-germacrene D at high titers • Engineered strain produced up to 120-fold higher germacrene D than the parental strain • Highest titers of enantiopure (+) and (-)-germacrene D achieved so far in shake-flask., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nanometer-scale control over surface functionalization of soft gels is important for a variety of applications including controlling interactions with cells for in vitro cell culture and for regenerative medicine. Recently, we have shown that it is possible to transfer a nanometer-thick precision functional polymer layer to the surface of relatively stiff polyacrylamide gels. Here, we develop a fundamental understanding of the way in which the precision polymer backbone participates in the polyacrylamide radical polymerization and cross-linking process, which enables us to generate high-efficiency transfer to much softer hydrogels (down to 5 kPa) with stiffness similar to that of soft tissue. This approach creates hydrogel surfaces with exposed nanostructured functional arrays that open the door to controlled ligand presentation on soft hydrogel surfaces., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Designing surfaces that enable controlled presentation of multivalent ligand clusters (e.g., for rapid screening of biomolecular binding constants or design of artificial extracellular matrices) is a cross-cutting challenge in materials and interfacial chemistry. Existing approaches frequently rely on complex building blocks or scaffolds and are often specific to individual substrate chemistries. Thus, an interlayer chemistry that enabled efficient nanometer-scale patterning on a transferrable layer and subsequent integration with other classes of materials could substantially broaden the scope of surfaces available for sensors and wearable electronics. Recently, we have shown that it is possible to assemble nanometer-resolution chemical patterns on substrates including graphite, use diacetylene polymerization to lock the molecular pattern together, and then covalently transfer the pattern to amorphous materials (e.g., polydimethylsiloxane, PDMS), which would not natively enable high degrees of control over ligand presentation. Here, we develop a low-viscosity PDMS formulation that generates very thin films (<10 μm) with dense cross-linking, enabling high-efficiency surface functionalization with polydiacetylene arrays displaying carbohydrates and other functional groups (up to 10-fold greater than other soft materials we have used previously) on very thin films that can be integrated with other materials (e.g., glass and soft materials) to enable a highly controlled multivalent ligand display. We use swelling and other characterization methods to relate surface functionalization efficiency to the average distance between cross-links in the PDMS, developing design principles that can be used to create even thinner transfer layers. In the context of this work, we apply this approach using precision glycopolymers presenting structured arrays of N -acetyl glucosamine ligands for lectin binding assays. More broadly, this interlayer approach lays groundwork for designing surface layers for the presentation of ligand clusters on soft materials for applications including wearable electronics and artificial extracellular matrix.

Parkinson's disease (PD) is one of the most frequent age-associated neurodegenerative disorder. Presence of α-synuclein-containing aggregates in the substantia nigra pars compacta (SNpc) and loss of dopaminergic (DA) neurons are among the characteristic of PD. One of the hallmarks of PD pathophysiology is chronic neuroinflammation. Activation of glial cells and elevated levels of pro-inflammatory factors are confirmed as frequent features of the PD brain. Chronic secretion of pro-inflammatory cytokines by activated astrocytes and microglia exacerbates DA neuron degeneration in the SNpc. MicroRNAs (miRNAs) are among endogenous non-coding small RNA with the ability to perform post-transcriptional regulation in target genes. In that regard, the capability of miRNAs for modulating inflammatory signaling is the center of attention in many investigations. MiRNAs could enhance or limit inflammatory signaling, exacerbating or ameliorating the pathological consequences of extreme neuroinflammation. This review summarizes the importance of inflammation in the pathophysiology of PD. Besides, we discuss the role of miRNAs in promoting or protecting neural cell injury in the PD model by controlling the inflammatory pathway. Modifying the neuroinflammation by miRNAs could be considered a primary therapeutic strategy for PD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Heavy metals are extremely hazardous for human health due to their toxic effects. They are non-biodegradable in nature, thus remain in the environment and enter and accumulate in the human body through biomagnification; hence, there is a serious need of their remediation. Phytoremediation has emerged as a green, sustainable, and effective solution for heavy metal removal and many plant species could be employed for this purpose. Plants are able to sequester substantial quantity of heavy metals, in some cases thousands of ppm, due to their robust physiology enabling high metal tolerance and anatomy supporting metal ion accumulation. Identification and modification of potential target genes involved in heavy metal accumulation have led to improved phytoremediation capacity of plants at the molecular level. The introduction of foreign genes through genetic engineering approaches has further enhanced phytoremediation capacity manifolds. This review gives an insight towards improving the phytoremediation efficiency through a better understanding of molecular mechanisms involved, expression of different proteins, genetic engineering approaches for transgenic production, and genetic modifications. It also comprehends novel omics tools such as genomics, metabolomics, proteomics, transcriptomics, and genome editing technologies for improvement of phytoremediation ability of plants., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Aim: Currently, we have limited armamentarium of antifungal agents against Mucorales. There is an urgent need to discover novel antifungal agents that are effective, safe and affordable. Materials & methods: In this study, the anti-Mucorale action of native lactoferrin (LF) and its functional fragments CLF, RR6 and LFcin against three common Mucorale species are reported. The synergistic action of LF with antifungal agents like amphotericin B, isavuconazole and posaconazole was analyzed using checkerboard technique. Results: All the three mucor species showed inhibition when treated with fragments. The checkerboard assay confirmed that native LF showed the best synergistic action against Mucorales in combination with Amphotericin B. Conclusion: These results highlight the potential therapeutic value of native LF against Mucorales.

Mucormycosis, a rare but deadly fungal infection, was an epidemic during the COVID-19 pandemic. The rise in cases (COVID-19-associated mucormycosis, CAM) is attributed to excessive steroid and antibiotic use, poor hospital hygiene, and crowded settings. Major contributing factors include diabetes and weakened immune systems. The main manifesting forms of CAM─cutaneous, pulmonary, and the deadliest, rhinocerebral─and disseminated infections elevated mortality rates to 85%. Recent focus lies on small-molecule inhibitors due to their advantages over standard treatments like surgery and liposomal amphotericin B (which carry several long-term adverse effects), offering potential central nervous system penetration, diverse targets, and simpler dosing owing to their small size, rendering the ability to traverse the blood-brain barrier via passive diffusion facilitated by the phospholipid membrane. Adaptation and versatility in mucormycosis are facilitated by a multitude of virulence factors, enabling the pathogen to dynamically respond to various environmental stressors. A comprehensive understanding of these virulence mechanisms is imperative for devising effective therapeutic interventions against this highly opportunistic pathogen that thrives in immunocompromised individuals through its angio-invasive nature. Hence, this Review delineates the principal virulence factors of mucormycosis, the mechanisms it employs to persist in challenging host environments, and the current progress in developing small-molecule inhibitors against them.

Mucormycosis is a fungal infection of the sinuses, brain and lungs that is the cause of approximately 50% mortality rate despite the available first-line therapy. Glucose-Regulated Protein 78 (GRP78) is already reported to be a novel host receptor that mediates invasion and damage of human endothelial cells by Rhizopus oryzae and Rhizopus delemar , the most common etiologic species of Mucorales. The expression of GRP78 is also regulated by the levels of iron and glucose in the blood. There are several antifungal drugs in the market but they pose a serious side effect to the vital organs of the body. Therefore, there is an immediate need to discover effective drug molecules having increased efficacy with no side effects. With the help of various computational tools, the current study was attempted to determine potential antimucor agents against GRP78. The receptor molecule GRP78 was screened against 8820 known drugs deposited in DrugBank library using high-throughput virtual screening method. Total top 10 compounds were selected based on the binding energies greater than the reference co-crystal molecule. Furthermore, molecular dynamic (MD) simulations using AMBER were performed to calculate the stability of the top-ranked compounds in the active site of GRP78. After extensive computational studies, we propose that two compounds (CID439153 and CID5289104) have inhibitory potency against mucormycosis and can serve as potential drugs that can form the basis of treating mucormycosis disease.Communicated by Ramaswamy H. Sarma.

The reactivation of ubiquitously present Epstein-Barr virus (EBV) is known to be involved with numerous diseases, including neurological ailments. A recent in vitro study from our group unveiled the association of EBV and its 12-amino acid peptide glycoprotein M 146-157 (gM 146-157 ) with neurodegenerative diseases, viz., Alzheimer's disease (AD) and multiple sclerosis. In this study, we have further validated this association at the in vivo level. The exposure of EBV/gM 146-157 to mice causes a decline in the cognitive ability with a concomitant increase in anxiety-like symptoms through behavioral assays. Disorganization of hippocampal neurons, cell shrinkage, pyknosis, and apoptotic appendages were observed in the brains of infected mice. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were found to be elevated in infected mouse brain tissue samples, whereas TNF-α exhibited a decline in the serum of these mice. Further, the altered levels of nuclear factor-kappa B (NF-kB) and neurotensin receptor 2 affirmed neuroinflammation in infected mouse brain samples. Similarly, the risk factor of AD, apolipoprotein E4 (ApoE4), was also found to be elevated at the protein level in EBV/gM 146-157 challenged mice. Furthermore, we also observed an increased level of myelin basic protein in the brain cortex. Altogether, our results suggested an integral connection of EBV and its gM 146-157 peptide to the neuropathologies.

Background: Activated platelets secrete platelet factor 4 (PF4), which contributes to viral pathogenesis. Recently, we reported the proviral role of PF4 in replication of closely related flaviviruses, Japanese encephalitis virus (JEV) and dengue virus (DENV)., Objectives: This study aimed to investigate the detailed mechanism of PF4-mediated virus replication., Methods: PF4 -/- or wild-type (WT) mice were infected with JEV, and host defense mechanisms, including autophagic/interferon (IFN) responses, were assessed. WT mice were pretreated with the CXCR3 antagonist AMG487 that inhibits PF4:CXCR3 pathway. This pathway was tested in PF4 -/- monocytes infected with DENV or in monocytes isolated from patients with DENV infection., Results: PF4 -/- mice infected with JEV showed reduced viral load and improved brain inflammation and survival. PF4 -/- mice synthesized more IFN-α/β with higher expression of phosphorylated IRF3 in the brain. PF4 treatment decreased IRF-3/7/9 and IFN-α/β expression and suppressed autophagic LC3-II flux and lysosomal degradation of viral proteins in JEV-infected cells. PF4 increased the expression of P-mTOR, P-p38, and P-ULK1 Ser757 and decreased expression of LC3-II. Decreased autophagosome-lysosome fusion in turn promoted DENV2 replication. The above processes were reversed by AMG487. Uninfected PF4 -/- monocytes showed elevated LC3-II and autophagosome-lysosome fusion. Microglia of JEV-infected PF4 -/- mice exhibited elevated LC3-II inversely related to viral load. Similarly, monocytes from PF4 -/- mice showed reduced infection by DENV2. In patients with DENV infection, higher plasma PF4 and viral load were inversely correlated with LC3-II, LAMP-1, and lysosomal degradation of DENV-NS1 in monocytes during the febrile phase., Conclusion: These studies suggest that PF4 deficiency or inhibition of the PF4:CXCR3 pathway prevents JEV and DENV infection. The studies also highlight the PF4:CXCR3 axis as a potential target to develop treatment regimens against flaviviruses., Competing Interests: Declaration of competing interests All authors have no competing interests to disclose., (Copyright © 2023 International Society on Thrombosis and Haemostasis. All rights reserved.)

Nanometer-scale control over surface functionality is important in applications ranging from nanoscale electronics to regenerative medicine. However, approaches that provide precise control over surface chemistry at the nanometer scale are often challenging to use with higher throughput and in more heterogeneous environments (e.g., complex solutions, porous interfaces) common for many applications. Here, we demonstrate a scalable inkjet-based method to generate 1 nm-wide functional patterns on 2D materials such as graphite, which can then be transferred to soft materials such as hydrogels. We examine fluid dynamics associated with the inkjet printing process for low-viscosity amphiphile inks designed to maximize ordering with limited residue and show that microscale droplet fluid dynamics influence nanoscale molecular ordering. Additionally, we show that scalable patterns generated in this way can be transferred to hydrogel materials and used to create surface chemical patterns that induce adsorption of charged particles, with effects strong enough to overcome electrostatic repulsion between a charged hydrogel and a like-charged nanoparticle.

The primary goal of this experiment is to examine the effectiveness of Pseudomonas aeruginosa strain PAR as a rhizobacterium that promotes plant growth in mitigating the negative effects of fluoride-induced stress in tomato ( Lycopersicon esculentum Mill.) plants. A total of 16 rhizobacterial strains were tested for plant growth-promoting (PGP) attributes, with isolates S1, S2, and S3 exhibiting different characteristics. Furthermore, growth kinetics studies revealed that these isolates were resilient to fluoride stress (10, 20, 40, and 80 ppm), with isolate S2 exhibiting notable resilience compared to the other two strains. Phylogenetic analysis revealed isolate S2 as P. aeruginosa strain PAR. Physiological analyses demonstrated that P. aeruginosa strain PAR had a beneficial impact on plant properties under fluoride stress, comprising seed germination, root length, shoot height, relative water content, and leaf area, the strain also impacted the buildup of glycine betaine, soluble sugar, and proline, demonstrating its significance in enhancing plant stress tolerance. In P. aeruginosa strain PAR-treated plants, chlorophyll content increased while malondialdehyde (MDA) levels decreased, indicating enhanced photosynthetic efficiency and less oxidative stress. The strain modified antioxidant enzyme action (catalase, ascorbate, glutathione reductase, peroxidase, and superoxide dismutase), which contributed to improved stress resilience. Mineral analysis revealed a decrease in sodium and fluoride concentrations while increasing magnesium, potassium, phosphorus, and iron levels, emphasizing the strain's significance in nutrient management. Correlation and principal component analysis revealed extensive correlations between physiological and biochemical parameters, underscoring P. aeruginosa strain PAR's multifaceted impact on plant growth and stress response. This study offers valuable information on effectively utilizing PGPR, particularly P. aeruginosa strain PAR, in fluoride-contaminated soils for sustainable agriculture. It presents a promising biological strategy to enhance crop resilience and productivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Singh, Patani, Patel, Vyas, Verma, Amari, Osman, Rathod, Elboughdiri, Yadav, Sahoo, Chundawat and Patel.)

Importance: Severe dengue manifestations caused by the dengue virus are a global health problem. Studies suggest that severe dengue disease depends on uncontrolled immune cell activation, and excessive inflammation adds to the pathogenesis of severe dengue disease. Therefore, it is important to understand the process that triggers the uncontrolled activation of the immune cells. The change in immune response in mild to severe dengue may be due to direct virus-to-cell interaction or it could be a contact-independent process through the extracellular vesicles (EVs) released from infected cells. The importance of circulating EVs in the context of dengue virus infection and pathogenesis remains unexplored. Therefore, understanding the possible biological function of circulating EVs may help to delineate the role of EVs in the progression of disease. Our present study highlights that EVs from plasma of severe dengue patients can have immunosuppressive properties on CD4+ T cells which may contribute to T cell suppression and may contribute to dengue disease progression., Competing Interests: The authors declare no conflict of interest.

The endoplasmic reticulum (ER) is crucial for maintaining cellular homeostasis, and synthesis and folding of proteins and lipids. The ER is sensitive to stresses including viral infection that perturb the intracellular energy level and redox state, and accumulating unfolded/misfolded proteins. Viruses including Japanese encephalitis virus (JEV) activates unfolded protein response (UPR) causing ER stress in host immune cells and promotes inflammation and apoptotic cell death. The chemokine receptor CXCR3 has been reported to play important role in the accumulation of inflammatory immune cells and neuronal cell death in several disease conditions. Recently we described the involvement of CXCR3 in regulating inflammation and JEV infection in mice brain. Supplementation with a CXCR3 antagonist AMG487 significantly reduced JEV infection in the mice brain in conjunction with the downregulation of UPR pathway via PERK:eIF2α:CHOP, and decreased mitochondrial ROS generation, inflammation and apoptotic cell death. Alongside, AMG487 treatment improved interferon (IFN)-α/β synthesis in JEV-infected mice brain. Thus, suggesting a potential therapeutic role of CXCR3 antagonist against JEV infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Sterile fecal filtrate (SFF) is being considered a safer alternative to fecal microbiota transplantation (FMT) therapy; however, its bioactive potency is very little understood. The present study thus assessed the age-dependent immunostimulatory and immunomodulatory attributes of murine SFF in vitro., Methods: SFF from young (Y-SFF) and old (O-SFF) Swiss albino mice were prepared. Immunostimulatory and immunomodulatory effects of SFF were evaluated in resting and lipopolysaccharide (LPS) stimulated macrophage cells by measuring intracellular reactive oxygen species (ROS), nitric oxide (NO) production, inflammatory cytokines profile, as well as gene expression of oxidative and inflammatory transcription factors. SFF were also evaluated for native antioxidant capacity by measuring DPPH and ABTS free radical scavenging activity. Bioactive components present in SFF were also determined by GC/MS analysis., Results: Both Y-SFF and O-SFF induced potent immunostimulatory effects characterized by changes in cell morphology, a significant increase in NO production, ROS levels, and an increased ratio of pro-inflammatory (IL-6, TNF-α, IL-1β) to anti-inflammatory (IL-10) secretory proteins although no significant aggravation in the transcription of NF-κB and Nrf-2 could be observed. Application of LPS to cells significantly augmented a pro-oxidative and pro-inflammatory response which was much higher in comparison to Y-SFF or O-SFF application alone and mediated by strong suppression of Nrf-2 gene expression. Pre-treatment of macrophages with both Y-SFF and O-SFF robustly attenuated cellular hyperresponsiveness to LPS characterized by significantly decreased levels of NO, ROS, and inflammatory cytokines while a concomitant increase in anti-inflammatory protein (IL-10) was observed. Further, both Y-SFF and O-SFF strongly resisted LPS-induced downregulation of Nrf-2 expression although O-SFF appeared to protect cells slightly better from the overall LPS threat. Neat SFF samples exhibited moderate antioxidant capacity and GC/MS analysis of SFF revealed diverse volatile organic compounds characterized by alkanes, organosulphur compounds, furans, amides, amino acids, and antimicrobial elements., Conclusion: Our results indicate that SFF is a potent stimulant of macrophages and confers strong anti-inflammatory effects regardless of donor age thereby suggesting its therapeutic efficacy in lieu of FMT therapy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

A wide variety of bacteria are present in soil but in rhizospheric area, the majority of microbes helps plant in defending diseases and facilitate nutrient uptake. These microorganisms are supported by plants and they are known as plant growth-promoting rhizobacteria (PGPR). The PGPRs have the potential to replace chemical fertilizers in a way that is more advantageous for the environment. Fluoride (F) is one of the highly escalating, naturally present contaminants that can be hazardous for PGPRs because of its antibacterial capacity. The interactions of F with different bacterial species in groundwater systems are still not well understood. However, the interaction of PGPR with plants in the rhizosphere region reduces the detrimental effects of pollutants and increases plants' ability to endure abiotic stress. Many studies reveal that PGPRs have developed F defense mechanisms, which include efflux pumps, Intracellular sequestration, enzyme modifications, enhanced DNA repair mechanism, detoxification enzymes, ion transporter/antiporters, F riboswitches, and genetic mutations. These resistance characteristics are frequently discovered by isolating PGPRs from high F-contaminated areas or by exposing cells to fluoride in laboratory conditions. Numerous studies have identified F-resistant microorganisms that possess additional F transporters and duplicates of the well-known targets of F. Plants are prone to F accumulation despite the soil's low F content, which may negatively affect their growth and development. PGPRs can be used as efficient F bioremediators for the soil environment. Environmental biotechnology focuses on creating genetically modified rhizobacteria that can degrade F contaminants over time. The present review focuses on a thorough systemic analysis of contemporary biotechnological techniques, such as gene editing and manipulation methods, for improving plant-microbe interactions for F remediation and suggests the importance of PGPRs in improving soil health and reducing the detrimental effects of F toxicity. The most recent developments in the realm of microbial assistance in the treatment of F-contaminated environments are also highlighted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Singh, Yadav, Gautam, Rathod, Chundawat, Singh, Verma, Sahoo and Patel.)

Plant-associated microbes include taxonomically diverse communities of bacteria, archaebacteria, fungi, and viruses, which establish integral ecological relationships with the host plant and constitute the phyto-microbiome. The phyto-microbiome not only contributes in normal growth and development of plants but also plays a vital role in the maintenance of plant homeostasis during abiotic stress conditions. Owing to its immense metabolic potential, the phyto-microbiome provides the host plant with the capability to mitigate the abiotic stress through various mechanisms like production of antioxidants, plant growth hormones, bioactive compounds, detoxification of harmful chemicals and toxins, sequestration of reactive oxygen species and other free radicals. A deeper understanding of the structure and functions of the phyto-microbiome and the complex mechanisms of phyto-microbiome mediated abiotic stress mitigation would enable its utilization for abiotic stress alleviation of crop plants and development of stress-resistant crops. This review aims at exploring the potential of phyto-microbiome to alleviate drought, heat, salinity and heavy metal stress in crop plants and finding sustainable solutions to enhance the agricultural productivity. The mechanistic insights into the role of phytomicrobiome in imparting abiotic stress tolerance to plants have been summarized, that would be helpful in the development of novel bioinoculants. The high-throughput modern approaches involving candidate gene identification and target gene modification such as genomics, metagenomics, transcriptomics, metabolomics, and phyto-microbiome based genetic engineering have been discussed in wake of the ever-increasing demand of climate resilient crop plants., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Singh, Mazahar, Chapadgaonkar, Giri and Shourie.)

Background: The complex life cycle of geohelminth parasites make it difficult to manage repeated infections that occur in endemic areas, that requires the development of new therapeutic strategies. Human hookworm Ancylostoma sp . and Necator sp . are a serious problem in many areas of the world where the old age anti-helminthics are ineffective. To address this, we have tried a non-traditional therapeutic approach for a sustainable solution to manage parasite infections., Aims and Objectives: In this study, we attempted to develop a new type of therapy using value-added probiotics-producing antiparasitic RNA interference (RNAi) molecules against a vital hookworm ( Ancylostoma sp.) enzyme, astacin-like metalloprotease Ac -MTP-1. A new gut delivery RNAi vector was designed to produce double-stranded RNA (dsRNA) against the target to be delivered by feeding with a probiotic Lactococcus lactis that when administered in endemic areas can potentially be used to control the spread of infection by interrupting the life cycle of hookworm., Results: The engineered probiotics colonizing the gut, when consumed by the parasite released the dsRNA that which knocked down the target by RNAi interfering with their moulting and tissue migration. The initial penetration of the larvae into the gut lining was reduced by 70%, followed by a reduction of up to 50% in migration to the critical organs. The damage caused to the liver (30%-40%) and the kidneys (50%-60%) by the hookworm in mouse models as quantitated by enzymes released in the blood was totally reversed when the worms were pre fed with the engineered L. lactis before the parasite challenge., Conclusions: We believe that this is the first demonstrated knockdown of a target gene in hookworms using probiotics genetically engineered to stimulate RNAi (RNAi food), administered through the oral route. This novel method of parasite control when extended to other hookworms, A. duodenalis and A. ceylanicum can augment the efficacy of the existing anthelminthics if combined with them., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Tropical Parasitology.)

Bacterioferritin comigratory protein family 1 Cys peroxiredoxin from Candidatus Liberibacter asiaticus (CLaBCP) is an important antioxidant defense protein that participates in the reduction of ROS, free radicals, and peroxides. In the present study, we report the biochemical studies and in silico screening of potent antibacterial molecules against CLaBCP. The CLaBCP showed enzymatic activity with the Km value 54.43, 94.34, 120.6 µM, and Vmax of 59.37, 69.37, 70.0 µM min -1 for H 2 O 2 , TBHP, CHP respectively. The residual peroxidase activity of CLaBCP was analyzed at different ranges of pH and temperatures. The CLaBCP showed structural changes and unfolding in the presence of its substrates and guanidinium chloride by CD and fluorescence. The structure-based drug design method was employed to screen and identify the more efficient molecule against CLaBCP. The validated CLaBCP model was used for the virtual screening of potent antibacterial molecules. The docking was performed at CLaBCP active site to evaluate the binding energy of the top five molecules (LAS 34150849, BDE 33184869, LAS 51497689, BDE 33672484, and LAS 34150966). All identified molecule has a higher binding affinity than adenanthin analyzed by molecular docking. Molecular dynamics studies such as RMSD, Rg, SASA, and PCA results showed that the CLaBCP inhibitor(s) complex is more stable than the CLaBCP-adenanthin complex. MMPBSA results suggested that the identified molecule could form a lower energy CLaBCP-inhibiter(s) complex than the CLaBCP-adenanthin complex. The screened molecules may pave the route for the development of potent antibacterial molecules against CLa.Communicated by Ramaswamy H. Sarma.

Introduction: Probiotic lactobacilli are generally recognized as safe (GRAS) and are being used in several food and pharma formulations. However, growing concern of antibiotic resistance in bacterial strains of food origin and its possible transmission via functional foods is increasingly being emphasized., Objectives: This study screened potential probiotic lactic acid bacteria (LAB) strains for their phenotypic and genotypic antibiotic resistance profiles., Methods: Susceptibility to different antibiotics was assayed by the Kirby Bauer standard disc diffusion protocol. Both conventional and SYBR-RTq-PCR were used for detection of resistance coding genes., Results: A variable susceptibility pattern was documented against different antibiotic classes. LAB strains irrespective of origin displayed marked phenotypic resistance against cephalosporins, aminoglycosides, quinolones, glycopeptides; and methicillin among beta-lactams with few exceptions. In contrast, high sensitivity was recorded against macrolides, sulphonamides and carbapenems sub-group of beta-lactams with some variations. parC, associated with ciprofloxacin resistance was detected in 76.5% of the strains. Other prevalent resistant determinants observed were aac(6?)Ii (42.1%), ermB, ermC (29.4%), and tetM (20.5%). Six (?17.6%) of the isolates were free from genetic resistance determinants screened in this study., Conclusion: Study revealed presence of antibiotic resistance determinants among lactobacilli from both fermented foods and human sources., (© 2023. The Author(s).)

Background: The physiology and pathology of AVF maturation depends on the vessels characteristics and its ability to remodel. Outcome of AVF using flow mediated dilatation (FMD), AVF blood flow and diameter has been studied., Methodology: Present observational study included single stage AVF (both Radiocephalic and Brachiocephalic) in consecutive CKD five patients ( n  = 158) prospectively over 1 year. Demographic and Doppler ultrasound parameters of upper limb (for vessel diameter and FMD) at baseline were recorded. Blood flow, diameter and depth of AVF were studied at 2, 6 and 12 weeks and their association with clinical maturation (usage of fistula with two needles for 75% of dialysis sessions during 15 day period) was studied ( n  = 129, after excluding lost to followup and expired patients; accordingly cohort was divided in matured ( M ) or non-matured (NM) groups. Clinical and radiological parameters between both groups were compared; receiver operator curve (ROC) and correlation of Doppler parameters were analysed., Results: Of 129 AVF, 67.4% were matured and 32.5% non-matured. Mean age was 40 years with male predominance75% in both the groups. The mean arterial diameter for distal (NM = 1.96 ± 0.58 and M  = 2.02 ± 0.41) and proximal AVF (NM = 3.37 ± 0.82 and M = 3.36 ± 0.75) was not statistically different in both the groups. The matured fistula group had a mean FMD of 11.67 ± 4.09 as against FMD value of 9.365 ± 3.55 in the failed fistula group ( p value 0.01). For maturation prediction, sensitivity and specificity of blood flow at 2 weeks were 86.2% and 59.5% and at 6 weeks 96.6% and 64.3%, respectively. In multivariate analysis predictors for AVF maturation were FMD (adjusted odds ratio (AOR) = 1.15) and blood flow (AOR = 1.67)., Conclusion: Second and Sixth week AVF blood flow was found to be predicting AVF maturation. Higher baseline FMD correlated with the AVF maturation, but not with vessel diameter.

The expression of recombinant proteins by the AOX1 promoter of Komagataella phaffii is typically induced by adding methanol to the cultivation medium. Since growth on methanol imposes a high oxygen demand, the medium is often supplemented with an additional secondary carbon source which serves to reduce the consumption of methanol, and hence, oxygen. Early research recommended the use of glycerol as the secondary carbon source, but more recent studies recommend the use of sorbitol because glycerol represses P AOX1 expression. To assess the validity of this recommendation, we measured the steady state concentrations of biomass, residual methanol, and LacZ expressed from P AOX1 over a wide range of dilution rates (0.02-0.20 h -1 ) in continuous cultures of the Mut + strain fed with methanol + glycerol (repressing) and methanol + sorbitol (non-repressing). We find that under these conditions, the specific P AOX1 expression rate (measured as either specific LacZ productivity or specific AOX productivity) is completely determined by the specific methanol consumption rate regardless of the type (repressing/non-repressing) of the secondary carbon source. In both cultures, the specific P AOX1 expression rate is proportional to the specific methanol consumption rate, provided that the latter is below 0.15 g/(gdw-h); beyond this threshold consumption rate, the specific P AOX1 expression rate of both cultures saturates to the same value. Analysis of the data in the literature shows that the same phenomenon also occurs in continuous cultures of Escherichia coli fed with mixtures of lactose plus repressing/non-repressing carbon sources. The specific P lac expression rate is completely determined by the specific lactose consumption rate, regardless of the type of secondary carbon source, glycerol or glucose., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Singh and Narang.)

Plant Growth Promoting Rhizobacteria (PGPR) has gained immense importance in the last decade due to its in-depth study and the role of the rhizosphere as an ecological unit in the biosphere. A putative PGPR is considered PGPR only when it may have a positive impact on the plant after inoculation. From the various pieces of literature, it has been found that these bacteria improve the growth of plants and their products through their plant growth-promoting activities. A microbial consortium has a positive effect on plant growth-promoting (PGP) activities evident by the literature. In the natural ecosystem, rhizobacteria interact synergistically and antagonistically with each other in the form of a consortium, but in a natural consortium, there are various oscillating environmental conditions that affect the potential mechanism of the consortium. For the sustainable development of our ecological environment, it is our utmost necessity to maintain the stability of the rhizobacterial consortium in fluctuating environmental conditions. In the last decade, various studies have been conducted to design synthetic rhizobacterial consortium that helps to integrate cross-feeding over microbial strains and reveal their social interactions. In this review, the authors have emphasized covering all the studies on designing synthetic rhizobacterial consortiums, their strategies, mechanism, and their application in the field of environmental ecology and biotechnology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Singh, Yadav, Chundawat, Soltane, Awwad, Ibrahium, Yadav and Vicas.)

The growing consumer awareness towards healthy and safe food has reformed food processing strategies. Nowadays, food processors are aiming at natural, effective, safe, and low-cost substitutes for enhancing the shelf life of food products. Milk, besides being a rich source of nutrition for infants and adults, serves as a readily available source of precious functional peptides. Due to the existence of high genetic variability in milk proteins, there is a great possibility to get bioactive peptides with varied properties. Among other bioactive agents, milk-originated antimicrobial peptides (AMPs) are gaining interest as attractive and safe additive conferring extended shelf life to minimally processed foods. These peptides display broad-spectrum antagonistic activity against bacteria, fungi, viruses, and protozoans. Microbial proteolytic activity, extracellular peptidases, food-grade enzymes, and recombinant DNA technology application are among few strategies to tailor specific peptides from milk and enhance their production. These bioprotective agents have a promising future in addressing the global concern of food safety along with the possibility to be incorporated into the food matrix without compromising overall consumer acceptance. Additionally, in conformity to the current consumer demands, these AMPs also possess functional properties needed for value addition. This review attempts to present the basic properties, synthesis approaches, action mechanism, current status, and prospects of antimicrobial peptide application in food, dairy, and pharma industry along with their role in ensuring the safety and health of consumers., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Multivalent interactions between carbohydrates and proteins enable a broad range of selective chemical processes of critical biological importance. Such interactions can extend from the macromolecular scale (1-10 nm) up to much larger scales across a cell or tissue, placing substantial demands on chemically patterned materials aiming to leverage similar interactions in vitro. Here, we show that diyne amphiphiles with carbohydrate headgroups can be assembled on highly oriented pyrolytic graphite (HOPG) to generate nanometer-resolution carbohydrate patterns, with individual linear carbohydrate assemblies up to nearly 1 μm, and microscale geometric patterns. These are then photopolymerized and covalently transferred to the surfaces of hydrogels. This strategy suspends carbohydrate patterns on a relatively rigid polydiacetylene (persistence length ∼ 16 nm), exposed at the top surface of the hydrogel above the bulk pore structure. Transferred patterns of appropriate carbohydrates (e.g., N -acetyl-d-glucosamine, GlcNAc) enable selective, multivalent interactions ( K D ∼ 40 nM) with wheat germ agglutinin (WGA), a model lectin that exhibits multivalent binding with appropriately spaced GlcNAc moieties. WGA binding affinity can be further improved ( K D ∼ 10 nM) using diacetylenes that shift the polymer backbone closer to the displayed carbohydrate, suggesting that this strategy can be used to modulate carbohydrate presentation at interfaces. Conversely, GlcNAc-patterned surfaces do not induce specific binding of concanavalin A, and surfaces patterned with glucuronic acid, or with simple carboxylic acid or hydroxyl groups, do not induce WGA binding. More broadly, this approach may have utility in designing synthetic glycan-mimetic interfaces with features from molecular to mesoscopic scales, including soft scaffolds for cells.

Lateral root (LR) formation is a vital organogenetic process that determines the root architecture in plants. The number of root branches governs the degree of anchorage, efficiency of nutrients acquisition, and water uptake. The molecular pathways involved in LR formation have been extensively studied in Arabidopsis thaliana ( At ). A plant hormone, Auxin, is a key regulator of root development and promotes LR formation in plants. A plethora of Arabidopsis genes have been identified to regulate LR initiation, patterning, and emergence processes. Recently, the involvement of flowering time control pathways and circadian clock pathways in LR development has come to light, but the connecting link between these processes is still missing. We have established that GIGANTEA (GI), a key component of photoperiodic flowering, can regulate the formation of LRs in Arabidopsis . GI is known to be involved in red light signaling and circadian clock signaling pathways. Here, we report that over-expression of GI enhances LR formation in red light in At . Real-time PCR analysis shows that GI positively regulates the transcription of TRANSPORT INHIBITOR RESPONSE 1 ( TIR1 ) which is an upstream component of auxin signaling. Furthermore, gi-100 mutant downregulates the LR initiation signaling gene, AUXIN RESPONSE FACTOR 7 ( ARF7 ), and its downstream target gene, LATERAL ORGAN BOUNDARIES-DOMAIN 16 ( LBD16 ). Hence, GI acts as a positive regulator of IAA14-ARF7-LBD16 modules during LR initiation. We have also checked the effect of GI on the expression of NAC1 and AIR3 genes which are controlled by TIR1 during LR formation. Our results show that GI induces the NAC1 transcription and its downstream gene, AIR3 expression, which leads to the enhancement of LR initiation. Taken together, our results suggest that GI controls the expression of TIR1 to govern auxin signaling during LR formation in presence of red light and GI can act as a link between circadian clock signaling, flowering time control pathways, light signaling, and lateral root development pathways.

Plants have evolved a network of complex signaling pathways that allow them to cope with the fluctuations of internal and external environmental cues. GIGANTEA (GI), a well-known, highly conserved plant nuclear protein, has been shown to regulate multiple biological functions in plants such as circadian rhythm, light signaling, cold tolerance, hormone signaling, and photoperiodic flowering. Recently, the role of GI in disease tolerance against different pathogens has come to light; however, a detailed mechanism to understand the role of GI in pathogen defense remains largely unexplained. Here, we report that GIGANTEA is upregulated upon infection with a virulent oomycete pathogen, Hyaloperonospora arabidopsidis ( Hpa ), in Arabidopsis thaliana accession Col-0. To investigate the role of GI in Arabidopsis defense, we examined the pathogen infection phenotype of gi mutant plants and found that gi-100 mutant was highly susceptible to Hpa Noco2 infection. Notably, the quantitative real-time PCR showed that PHYTOALEXIN DEFICIENT4 ( PAD4 ) and several PAD4-regulated downstream genes were downregulated upon Noco2 infection in gi-100 mutant as compared to Col-0 plants. Furthermore, the chromatin immunoprecipitation results show that GI can directly bind to the intronic region of the PAD4 gene, which might explain the mechanism of GI function in regulating disease resistance in plants. Taken together, our results suggest that GI expression is induced upon Hpa pathogen infection and GI can regulate the expression of PAD4 to promote resistance against the oomycete pathogen Hyaloperonospora arabidopsidis in Arabidopsis thaliana .

Many areas of modern materials chemistry, from nanoscale electronics to regenerative medicine, require design of precisely-controlled chemical environments at near-molecular scales. Most work on high-resolution interface patterning to date has focused on hard surfaces, such as those for electronics. However, design of interfaces for biological environments increasingly requires precise control over interfaces of soft materials, which is in many cases complicated by nano-to-microscale heterogeneity in the substrate material. In this Feature Article, we describe historical approaches to nanoscale patterning on hard surfaces, challenges in extension to soft interfaces, and an approach to molecular-scale hard and soft interface design based on self-assembled molecular networks, which can be assembled noncovalently on hard surfaces to generate nanometer-scale patterns, then covalently transferred to soft materials including PDMS and hydrogels.

Lactoperoxidase (LPO) is a glycosylated antimicrobial protein present in milk with a molecular mass of 78 kDa. LPO is included in many biological processes and is well-known to have biocidal actions, acting as an active antibiotic and antiviral agent. The wide spectrum biocidal activity of LPO is mediated via a definite inhibitory system named lactoperoxidase system which plays a potent role in the innate immune response. With the current advancement in nanotechnology, nanoformulations can be developed for stabilizing and potentiating the activity of LPO for several applications. In the research described in this Research Communication, fresh LPO purified from bovine mammary gland secretions was used for nanoparticle synthesis using a simple thermal process at different pH and temperatures. The round-shaped nanoparticles (average size 229 nm) were successfully synthesized at pH 7.0 and a temperature of 75°C. These nanoparticles were tested against four different bacterial species namely S. flexineri, P. aeruginosa, S. aureus, and E. coli. The prepared nanoparticles exhibited strong inhibition of the growth against all four bacterial species as stated by their MIC and ZOI values. These results may help in increasing the efficiency of lactoperoxidase system and will assist in identifying novel avenues to enhance the stability and antimicrobial function of LPO in drug discovery and industrial processes.

Background: A successful transition from the NICU to home is fundamental for the long-term health and well-being of preterm infants. Post-NICU discharge, parents may experience a lack of support and resources during the transition to home. The purpose of this scoping review was to identify post-NICU discharge interventions that may reduce parental stress and provide support to families with preterm infants., Method: Systematic searches of databases, i.e., PubMed, Web of Science, and CINAHL. Inclusion criteria were data-based articles: 1) published in English between 2011 and 2021, 2) published in peer-reviewed journals, (3) focused on families with preterm infants, and (4) focused on interventions to reduce parental stress and provide support to families with preterm infants post-NICU discharge., Results: 26 articles were included and synthesized. We identified the following face-to-face and remote communication interventions: in-person home visits, phone/video calls, text messages, periodic email questionnaires, mobile/website apps, and online social networking sites., Discussion: Families may highly benefit from a comprehensive family-focused post-NICU discharge follow-up intervention that includes face-to-face and remote communication and support. Post-NICU discharge interventions are imperative to provide education related to infant care and health, increase parental confidence and competency, increase parent-infant relationship, promote emotional and social support, reduce unplanned hospital visits, parental stress, and maternal post-partum depression., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective  Traumatic brain injury leads to the activation of sympathetic nervous system and elevation in serum catecholamine levels. The aim of this study was to determine whether catecholamine level obtained within 24 hours of traumatic brain injury provides a reliable prognostic marker for outcome. Materials and Methods  This study was a prospective observational cohort study on 36 moderate-to-severe traumatic brain injury. Plasma epinephrine (E), norepinephrine (NE), and dopamine (DA) levels were measured by using computed tomography enzyme-linked immunosorbent assay test and compared with Glasgow coma scale (GCS) that was obtained concurrently. Neurological outcome was determined by GCS at day 7 of treatment and by Glasgow outcome scale at mean follow-up of 9.73 ± 2.26 months. Results  Patients with GCS 3 to 4 had markedly increase in baseline mean E (771.5 ± 126.0), NE (2,225.0 ± 215.4), and DA (590.2 ± 38.8) levels as compared with control, while patients with better GCS (11-12) had mildly elevated levels. Patients with GCS 5 to 10 had intermediate values. Cases with markedly elevated baseline E, NE, and DA level were either died or remained in poor GCS (3 or 4) at day 7 of treatment and remained in persistent vegetative state at mean follow-up of 9.73 ± 2.26 months. Cases with only mildly elevated E, NE, and DA level were improved to better GCS on treatment and had good recovery on follow-up. Conclusion  These data indicate that a markedly elevated catecholamine level was an excellent endogenous and readily quantifiable marker that appears to reflect the extent of brain injury and predict the likelihood of recovery., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Hydrogels are broadly used in applications where polymer materials must interface with biology. The hydrogel network is amorphous, with substantial heterogeneity on length scales up to hundreds of nanometers, in some cases raising challenges for applications that would benefit from highly structured interactions with biomolecules. Here, we show that it is possible to generate ordered patterns of functional groups on polyacrylamide hydrogel surfaces. We demonstrate that, when linear patterns of amines are transferred to polyacrylamide, they pattern interactions with DNA at the interface, a capability of potential importance for preconcentration in chromatographic applications, as well as for the development of nanostructured hybrid materials and supports for cell culture.

Context: Maternal mortality is considered a key health indicator of Maternal and Child Health. Considering the fact that complications are preventable and most of them are modifiable, the study has been planned to analyse maternal deaths in order to suggest recommendations for preventing it. There are various delays according to the three-delay model at primary and secondary level; therefore, interventions are needed at those levels to prevent maternal deaths., Aims: To determine the various direct and indirect causes of maternal deaths, analyse the association of medical and social factors with maternal deaths and ^to determine the predictors of maternal deaths., Settings and Design: Hospital-based retrospective cross-sectional study of all the maternal deaths occurring in the last 4 years at a tertiary health care facility., Methods and Material: Data were collected from the Facility Based Maternal Death Review forms., Statistical Analysis Used: Data were entered and analysed by IBM SPSS version 25.0 software., Results: For maternal deaths, direct obstetric causes were responsible in 128 (74.4%) and indirect causes in 45 (26.2%) cases followed by unspecified causes in 78 (45.3%) and 1 (0.6%) coincidental cause. Statistically significant associations were observed between maternal death and period of gestation, mode of delivery and outcome of delivery ( P = 0.12, P = 0.04 and P < 0.001, respectively)., Conclusions: The health professionals of primary and secondary level should be well equipped to diagnose the complications and to manage it as early as possible. Thus, maternal mortality rates can be decreased to significant level., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

Aims: Fibrosis is associated with all forms of adult cardiac diseases including myocardial infarction (MI). In response to MI, the heart undergoes ventricular remodelling that leads to fibrotic scar due to excessive deposition of extracellular matrix mostly produced by myofibroblasts. The structural and mechanical properties of the fibrotic scar are critical determinants of heart function. Yes-associated protein (Yap) and transcriptional coactivator with PDZ-binding motif (Taz) are the key effectors of the Hippo signalling pathway and are crucial for cardiomyocyte proliferation during cardiac development and regeneration. However, their role in cardiac fibroblasts, regulating post-MI fibrotic and fibroinflammatory response, is not well established., Methods and Results: Using mouse model, we demonstrate that Yap/Taz are activated in cardiac fibroblasts after MI and fibroblasts-specific deletion of Yap/Taz using Col1a2Cre(ER)T mice reduces post-MI fibrotic and fibroinflammatory response and improves cardiac function. Consistently, Yap overexpression elevated post-MI fibrotic response. Gene expression profiling shows significant downregulation of several cytokines involved in post-MI cardiac remodelling. Furthermore, Yap/Taz directly regulate the promoter activity of pro-fibrotic cytokine interleukin-33 (IL33) in cardiac fibroblasts. Blocking of IL33 receptor ST2 using the neutralizing antibody abrogates the Yap-induced pro-fibrotic response in cardiac fibroblasts. We demonstrate that the altered fibroinflammatory programme not only affects the nature of cardiac fibroblasts but also the polarization as well as infiltration of macrophages in the infarcted hearts. Furthermore, we demonstrate that Yap/Taz act downstream of both Wnt and TGFβ signalling pathways in regulating cardiac fibroblasts activation and fibroinflammatory response., Conclusion: We demonstrate that Yap/Taz play an important role in controlling MI-induced cardiac fibrosis by modulating fibroblasts proliferation, transdifferentiation into myofibroblasts, and fibroinflammatory programme., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Most high-resolution interfacial patterning approaches are restricted to crystalline inorganic interfaces. Recently, we have shown that it is possible to generate 1 nm resolution functional patterns on soft materials, such as polydimethylsiloxane (PDMS), by creating highly structured striped patterns of functional alkyldiacetylenes on a hard crystalline surface, photopolymerizing to set the molecular pattern as a striped-phase polydiacetylene (sPDA), and then covalently transferring the sPDAs to PDMS. Transfer depends on the diacetylene polymerization, making it important to understand design principles for efficient sPDA polymerization and cross-linking to PDMS. Here, we combine single-molecule and fluorescence-based metrics for sPDA polymerization and transfer, first to characterize sPDA polymerization of amine striped phases, and then to develop a probabilistic model that describes the transfer process in terms of sPDA-PDMS cross-linking reaction efficiency and number of reactions required for transfer. We illustrate that transferred patterns of alkylamines can be used to direct both adsorption of CdSe nanocrystals with alkyl ligand shells and covalent reactions with fluorescent dyes, highlighting the utility of functional patterning of the PDMS surface.

Abnormal coagulation dynamics, including disseminated intravascular coagulopathy, pulmonary embolism, venous thromboembolism and risk of thrombosis are often associated with the severity of COVID-19. However, very little is known about the contribution of platelets in above pathogenesis. In order to decipher the pathophysiology of thrombophilia in COVID-19, we recruited severely ill patients from ICU, based on the above symptoms and higher D-dimer levels, and compared these parameters with their asymptomatic counterparts. Elevated levels of platelet-derived microparticles and platelet-leukocyte aggregates suggested the hyperactivation of platelets in ICU patients. Strikingly, platelet transcriptome analysis showed a greater association of IL-6 and TNF signalling pathways in ICU patients along with higher plasma levels of IL-6 and TNFα. In addition, upregulation of pathways like blood coagulation and hemostasis, as well as inflammation coexisted in platelets of these patients. Further, the increment of necrotic pathway and ROS-metabolic processes in platelets was suggestive of its procoagulant phenotype in ICU patients. This study suggests that higher plasma IL-6 and TNFα may trigger platelet activation and coagulation, and in turn aggravate thrombosis and hypercoagulation in severe COVID-19 patients. Therefore, the elevated IL-6 and TNFα, may serve as potential risk factors for platelet activation and thrombophilia in these patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The present study evaluated polluted river water as a medium for the growth of oleaginous microalgae under mixotrophic conditions. Microalgae grow in the medium and produce biomass, pigments, and lipids with the removal of pollution loads from wastewater. Selenastrum sp. SL7 produced maximum biomass and lipids of 660 mg L -1 and 194.5 mg L -1 , respectively. Fatty acid profiling data showed that elevated saturated fatty acid production and major fatty acids found in lipid from these algae were palmitic acids, oleic acid, stearic acid, linolenic acid, and linoleic acid. The low percentage of polyunsaturated fatty acids of EPA was also detected. Water quality in terms of pH, DO, TDS, COD, and BOD was significantly improved. The use of this medium for microalgae cultivation not only improves the biomass and lipid yields but also serves as an excellent means of phycoremediation of pollutants in waste streams with value addition and environmental benefits., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Acinetobacter baumannii is a multidrug-resistant, opportunistic, nosocomial pathogen for which a new line of treatments is desperately needed. We have targeted the enzyme of the first step of the histidine biosynthesis pathway, viz., ATP-phosphoribosyltransferase (ATP-PRT). The three-dimensional structure of ATP-PRT was predicted on the template of the known three-dimensional structure of ATP-PRT from Psychrobacter arcticus ( Pa ATPPRT) using a homology modeling approach. High-throughput virtual screening (HTVS) of the antibacterial library of Life Chemicals Inc., Ontario, Canada was carried out followed by molecular dynamics simulations of the top hit compounds. In silico results were then biochemically validated using surface plasmon resonance spectroscopy. We found that two compounds, namely, F0843-0019 and F0608-0626, were binding with micromolar affinities to the ATP-phosphoribosyltransferase from Acinetobacter baumannii ( Ab ATPPRT). Both of these compounds were binding in the same way as AMP in Pa ATPPRT, and the important residues of the active site, viz., Val4, Ser72, Thr76, Tyr77, Glu95, Lys134, Val136, and Tyr156, were also interacting via hydrogen bonds. The calculated binding energies of these compounds were -10.5 kcal/mol and -11.1 kcal/mol, respectively. These two compounds can be used as the potential lead molecules for designing antibacterial compounds in the future, and this information will help in drug discovery programs against Acinetobacter worldwide.

SARS-CoV-2 is the etiological agent COVID-19, one of the most impactful health crises afflicting humanity in recent decades. While research advances have yielded several treatment and prevention options, the pandemic is slow to abate, necessitating an expansion of our treatment arsenal. As a member of the coronaviridae, SARS-CoV-2 contains several ion channels, of which E and 3a are the best characterized. Since ion channels as a family are excellent drug targets, we sought to inhibit both viroporins as a means to curb infectivity. In a previous targeted study, we identified several blockers to each channel from an extensive drug repurposing library. Herein, we examined the ability of said compounds on the whole virus in cellulo. Gratifyingly, many of the blockers exhibited antiviral activity in a stringent assay examining protection from viral-driven death. In particular, darapladib and flumatinib, both 3a blockers, displayed potent antiviral activity. Furthermore, appreciable synergism between flumatinib and several E blockers was identified in a concentration regime in which the compounds are present in human plasma following oral administration. Taken together, targeting ion channels represents a promising approach to both augment and complement our antiviral arsenal against COVID-19.

Genus Flavivirus contains several important human pathogens. Among these, the Zika virus is an emerging etiological agent that merits concern. One of its structural proteins, prM, plays an essential role in viral maturation and assembly, making it an attractive drug and vaccine development target. Herein, we have characterized ZikV-M as a potential viroporin candidate using three different bacteria-based assays. These assays were subsequently employed to screen a library of repurposed drugs from which ten compounds were identified as ZikV-M blockers. Mutational analyses of conserved amino acids in the transmembrane domain of other flaviviruses, including West Nile and Dengue virus, were performed to study their role in ion channel activity. In conclusion, our data show that ZikV-M is a potential ion channel that can be used as a drug target for high throughput screening and drug repurposing.