Photoreforming of Waste Polymers for Sustainable Hydrogen Fuel and Chemicals Feedstock: Waste to Energy.

Energy from renewable resources is central to environmental sustainability. Among the renewables, sunlight-driven fuel synthesis is a sustainable and economical approach to produce vectors such as hydrogen through water splitting. The photocatalytic water splitting is limited by the water oxidation half-reaction, which is kinetically and energetically demanding and entails designer photocatalysts. Such challenges can be addressed by employing alternative oxidation half-reactions. Photoreforming can drive the breakdown of waste plastics and biomass into valuable organic products for the production of H2. We provide an overview of photoreforming and its underlying mechanisms that convert waste polymers into H2 fuels and fine chemicals. This is of paramount importance from two complementary perspectives: (i) green energy harvesting and (ii) environmental sustainability by decomposing waste polymers into valuables. Competitive results for the generation of H2 fuel without environmental hazards through photoreforming are being generated. The photoreforming process, mechanisms, and critical assessment of the field are scarce. We address such points by focusing on (i) the concept of photoreforming and up-to-date knowledge with key milestones achieved, (ii) uncovering the concepts and challenges in photoreforming, and (iii) the design of photocatalysts with underlying mechanisms and pathways through the use of different polymer wastes as substrates.

Shape-Controlled First-Row Transition Metal Vanadates for Electrochemical and Photoelectrochemical Water Splitting.

Transition metal vanadates (MVs) possess abundant electroactive sites, short ion diffusion pathways, and optical properties that make them suitable for various electrochemical (EC) and photoelectrochemical (PEC) applications. While these materials are commonly used in energy storage devices like batteries and capacitors, their shape-controlled 1D and 2D morphologies have gained equal popularity in water splitting (WS) technology in recent times. This review focuses on recent progress made on various first-row (3d, 4 s) transition metal vanadates (t-MVs) having controlled one-dimensional (fiber, wire, or rod) and two-dimensional (layered or sheet) morphologies with a specific emphasis on copper vanadates (CuV), cobalt vanadates (CoV), iron vanadates (FeV), and nickel vanadates (NiV). The review covers different aspects of shape-controlled 1D and 2D t-MVs including optoelectrical properties, wet chemistry synthesis, and electrochemical (EC-WS) and photoelectrochemical water splitting (PEC-WS) performance in terms of onset potential, overpotential, and long-term stability or high cyclic performance. The review concludes by providing some possible thoughts on how to promote the water-splitting attributes of shape-controlled t-MVs more effectively.

Outcomes of dorsal nasal augmentation using costochondral graft.

Objective: To assess functional and aesthetic outcomes in patients having undergone dorsal nasal augmentation with costochondral graft in a tertiary care setting. METHODS: The single-centre, retrospective, observational study was conducted at Shifa International Hospital, Islamabad, Pakistan, and comprised data of patients who underwent dorsal nasal augmentation using costochondral graft between January 1, 2018, and December 31, 2022. Aesthetic outcomes in terms of patient satisfaction were assessed using Facial Appearance, Health-related Quality of Life and Adverse Effects scores. Data was analysed using SPSS 26. RESULTS: Of the 46 patients, 28(61%) were males and 18(39%) were females. The overall mean age was 28.39±9.13 years. Dorsal nasal deficiency occurred secondary to congenital causes in 12(26.1%) patients, trauma 19(41.3%) and prior surgery 15(32.6%). Postoperative complication rate was 7(15%); 3(6.5%) had recipient site infection and 2(4.3%) had rib graft resorption. Besides, 1(2.2%) patient reported pain 2 months postoperatively and 1(2.2%) had hypertrophic scarring. Patient satisfaction with the outcome was noted in all the 10 parameters analysed. Most commonly reported problem was that the nose was 'looking thick/swollen' by 12(26.1%) patients, but the issue resolved during 1-year follow-up. Conclusion: Costochondral graft was found to be an ideal material for dorsal nasal augmentation, with high patient satisfaction rate.

Nano biomaterials based strategies for enhanced brain targeting in the treatment of neurodegenerative diseases: an up-to-date perspective.

Neurons and their connecting axons gradually degenerate in neurodegenerative diseases (NDs), leading to dysfunctionality of the neuronal cells and eventually their death. Drug delivery for the treatment of effected nervous system is notoriously complicated because of the presence of natural barriers, i.e., the blood-brain barrier and the blood cerebrospinal fluid barrier. Palliative care is currently the standard care for many diseases. Therefore, treatment programs that target the disease's origin rather than its symptoms are recommended. Nanotechnology-based drug delivery platforms offer an innovative way to circumvent these obstacles and deliver medications directly to the central nervous system, thereby enabling treatment of several common neurological problems, i.e., Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Interestingly, the combination of nanomedicine and gene therapy enables targeting of selective mutant genes responsible for the progression of NDs, which may provide a much-needed boost in the struggle against these diseases. Herein, we discussed various central nervous system delivery obstacles, followed by a detailed insight into the recently developed techniques to restore neurological function via the differentiation of neural stem cells. Moreover, a comprehensive background on the role of nanomedicine in controlling neurogenesis via differentiation of neural stem cells is explained. Additionally, numerous phytoconstituents with their neuroprotective properties and molecular targets in the identification and management of NDs are also deliberated. Furthermore, a detailed insight of the ongoing clinical trials and currently marketed products for the treatment of NDs is provided in this manuscript.

Characterization of the Seed Biopriming, Plant Growth-Promoting and Salinity-Ameliorating Potential of Halophilic Fungi Isolated from Hypersaline Habitats.

Salinity stress is one of the major abiotic factors limiting crop yield in arid and semi-arid regions. Plant growth-promoting fungi can help plants thrive in stressful conditions. In this study, we isolated and characterized 26 halophilic fungi (endophytic, rhizospheric, and soil) from the coastal region of Muscat, Oman, for plant growth-promoting activities. About 16 out of 26 fungi were found to produce IAA, and about 11 isolates (MGRF1, MGRF2, GREF1, GREF2, TQRF4, TQRF5, TQRF5, TQRF6, TQRF7, TQRF8, TQRF2) out of 26 strains were found to significantly improve seed germination and seedling growth of wheat. To evaluate the effect of the above-selected strains on salt tolerance in wheat, we grew wheat seedlings in 150 mM, 300 mM NaCl and SW (100% seawater) treatments and inoculated them with the above strains. Our findings showed that fungal strains MGRF1, MGRF2, GREF2, and TQRF9 alleviate 150 mM salt stress and increase shoot length compared to their respective control plants. However, in 300 mM stressed plants, GREF1 and TQRF9 were observed to improve shoot length. Two strains, GREF2 and TQRF8, also promoted plant growth and reduced salt stress in SW-treated plants. Like shoot length, an analogous pattern was observed in root length, and different salt stressors such as 150 mM, 300 mM, and SW reduced root length by up to 4%, 7.5%, and 19.5%, respectively. Three strains, GREF1, TQRF7, and MGRF1, had higher catalase (CAT) levels, and similar results were observed in polyphenol oxidase (PPO), and GREF1 inoculation dramatically raised the PPO level in 150 mM salt stress. The fungal strains had varying effects, with some, such as GREF1, GREF2, and TQRF9, showing a significant increase in protein content as compared to their respective control plants. Under salinity stress, the expression of DREB2 and DREB6 genes was reduced. However, the WDREB2 gene, on the other hand, was shown to be highly elevated during salt stress conditions, whereas the opposite was observed in inoculated plants.

The Assessment of Antimicrobial Resistance in Gram-Negative and Gram-Positive Infective Endocarditis: A Multicentric Retrospective Analysis.

Background and Objectives: Multidrug-resistant microorganisms have made treating bacterial infections challenging. Resistance to antibiotics is expected to overcome efforts to produce new, effective antibacterial medication that is lifesaving in many situations. Infective endocarditis (IE) is a life-threatening infection that affects 5-15 per 100,000 patients annually and requires rapid antibiotic therapy to prevent morbidity and mortality. Materials and Methods: The present research assessed IE cases over five years, from a multicentric database, with the main objective of determining the degree of antibiotic resistance in these patients, stratified by Gram-positive and Gram-negative bacteria. Results: Bad oral hygiene was present in 58.6% of patients from the Gram-negative group (vs. 38.7% in the Gram-positive group). Non-valvular heart disease was identified in approximately 40% of all patients, and valvopathies in approximately 20%. It was observed that 37.9% of Gram-negative IE bacteria were resistant to three or more antibiotics, whereas 20.7% were susceptible. Among Gram-positive infections, S. aureus was the most commonly involved pathogen, with a multidrug-resistant pattern in 11.2% of patients, while Acinetobacter baumannii had the highest resistance pattern of all Gram-negative pathogens, with 27.4% of all samples resistant to three or more antibiotics. Patients with Gram-negative IE were 4.2 times more likely to die. The mortality risk was 4 times higher when bacteria resistant to two or more antibiotics was involved and 5.7 times higher with resistance patterns to three or more antibiotics than the reference group with no antibiotic resistance. Peripheral catheters were the most common cause of multi-resistant IE, followed by heart surgery, dental procedures, and ENT interventions. Conclusions: Even though Gram-positive infections were the most frequent (83.0% of all cases), Gram-negative IE infections are substantially more deadly than Gram-positive IE infections. However, it was also observed that patients with Gram-negative infections were more likely to have underlying comorbidities, be institutionalized, and be underweight. Although the Gram-negative infections were more severe, their resistance patterns were similar to Gram-positive bacteria. As resistance patterns increase, more efforts should be made to prevent a healthcare catastrophe. At the same time, careful prophylaxis should be considered in patients at risk, including those with central catheters, undergoing dental procedures, and with poor oral hygiene.

Strategies for Improved Electrochemical CO2 Reduction to Value-Added Products by Highly Anticipated Copper-Based Nanoarchitectures.

Uncontrolled CO2 emission from various industrial and domestic sources is a considerable threat to environmental sustainability. Scientists are trying to develop multiple approaches to not only reduce CO2 emissions but also utilize this potent pollutant to get economically feasible products. The electrochemical reduction of CO2 (ERC) is one way to effectively convert CO2 to more useful products (ranging from C1 to C5). Nevertheless, this process is kinetically hindered and less selective towards a specific product and, consequently, requires an efficient electrocatalyst with characteristics like selectivity, stability, reusability, low cost, and environmentally benign. Owing to specified commercial features, copper (Cu)-based materials are highly anticipated and widely investigated for the last two decades. However, their non-modified polycrystalline Cu forms usually lack selectivity and lower overpotential of CO2 reduction. Therefore, extensive research is in progress to induce various alterations ranging from morphological and surface chemistry tuning to structural and optoelectrical characteristics modifications. This review provides an overview of those strategies to improve the CO2 conversion efficiency through Cu-based ERC into valuable C1, C2, and higher molecular weight hydrocarbons. The thermodynamics and kinetics of CO2 reduction via Cu-based electrocatalysts are discussed in detail with the support of the first principle DFT-based models. In the last portion of the review, the reported mechanisms for various products are summarized, with a short overview of the outlook. This review is expected to provide important basics as well as advanced information for experienced as well as new researchers to develop various strategies for Cu and related materials to achieve improved ERC.

Photocatalytic Water-Splitting by Organic Conjugated Polymers: Opportunities and Challenges.

The future challenges associated with the shortage of fossil fuels and their current environmental impacts intrigued the researchers to look for alternative ways of generating green energy. Solar-driven water splitting into oxygen and hydrogen is one of those advanced strategies. Researchers have studied various semiconductor materials to achieve potential results. However, it encountered multiple challenges such as high cost, low photostability and efficiency, and required multistep modifications. The conjugated polymers (CPs) have emerged as promising alternatives for conventional inorganic semiconductors. The CPs offer low cost, sufficient light absorption efficiency, excellent photo and chemical stability, and molecular optoelectronic tunable characteristics. Furthermore, organic CPs also present higher flexibility to tune the basic framework of the backbone of the polymers, amendments in the sidechain to incorporate desired functionalities, and much-needed porosity to serve better for photocatalytic applications. This review article summarizes the recent advancements made in visible-light-driven water splitting covering the aspects of synthetic strategies and experimental parameters employed for water splitting reactions with special emphasis on conjugated polymers such as linear CPs, planarized CPs, graphitic carbon nitride (g-C3 N4 ), conjugated microporous polymers (CMPs), covalent organic frameworks (COFs), and conjugated polymer-based nanocomposites (CPNCs). The current challenges and future prospects have also been described briefly.

Lupeol Treatment Attenuates Activation of Glial Cells and Oxidative-Stress-Mediated Neuropathology in Mouse Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) signifies a major cause of death and disability. TBI causes central nervous system (CNS) damage under a variety of mechanisms, including protein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. Astrocytes and microglia, cells of the CNS, are considered the key players in initiating an inflammatory response after injury. Several evidence suggests that activation of astrocytes/microglia and ROS/LPO have the potential to cause more harmful effects in the pathological processes following traumatic brain injury (TBI). Previous studies have established that lupeol provides neuroprotection through modulation of inflammation, oxidative stress, and apoptosis in Aß and LPS model and neurodegenerative disease. However, the effects of lupeol on apoptosis caused by inflammation and oxidative stress in TBI have not yet been investigated. Therefore, we explored the role of Lupeol on antiapoptosis, anti-inflammatory, and antioxidative stress and its potential mechanism following TBI. In these experiments, adult male mice were randomly divided into four groups: control, TBI, TBI+ Lupeol, and Sham group. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of lupeol against neuroinflammation, oxidative stress, and apoptosis. Lupeol treatment reversed TBI-induced behavioral and memory disturbances. Lupeol attenuated TBI-induced generation of reactive oxygen species/lipid per oxidation (ROS/LPO) and improved the antioxidant protein level, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and heme-oxygenase 1 (HO-1) in the mouse brain. Similarly, our results indicated that lupeol treatment inhibited glial cell activation, p-NF-κB, and downstream signaling molecules, such as TNF-α, COX-2, and IL-1ß, in the mouse cortex and hippocampus. Moreover, lupeol treatment also inhibited mitochondrial apoptotic signaling molecules, such as caspase-3, Bax, cytochrome-C, and reversed deregulated Bcl2 in TBI-treated mice. Overall, our study demonstrated that lupeol inhibits the activation of astrocytes/microglia and ROS/LPO that lead to oxidative stress, neuroinflammation, and apoptosis followed by TBI.

Genome and Transcriptome-Wide Analysis of OsWRKY and OsNAC Gene Families in Oryza sativa and Their Response to White-Backed Planthopper Infestation.

Plants are threatened by a wide variety of herbivorous insect assaults, and display a variety of inherent and induced defenses that shield them against herbivore attacks. Looking at the massive damage caused by the white-backed planthopper (WBPH), Sogatella furcifera, we undertook a study to identify and functionally annotate OsWRKY and OsNAC transcription factors (TFs) in rice, especially their involvement in WBPH stress. OsWRKY and OsNAC TFs are involved in various developmental processes and responses to biotic and abiotic stresses. However, no comprehensive reports are available on the specific phycological functions of most of the OsWRKY and OsNAC genes in rice during WBPH infestation. The current study aimed to comprehensively explore the OsWRKY and OsNAC genes by analyzing their phylogenetic relationships, subcellular localizations, exon-intron arrangements, conserved motif identities, chromosomal allocations, interaction networks and differential gene expressions during stress conditions. Comparative phylogenetic trees of 101 OsWRKY with 72 AtWRKY genes, and 121 OsNAC with 110 AtNAC genes were constructed to study relationships among these TFs across species. Phylogenetic relationships classified OsWRKY and OsNAC into eight and nine clades, respectively. Most TFs in the same clade had similar genomic features that represented similar functions, and had a high degree of co-expression. Some OsWRKYs (Os09g0417800 (OsWRKY62), Os11g0117600 (OsWRKY50), Os11g0117400 (OsWRKY104) and OsNACs (Os05g0442700, Os12g0630800, Os01g0862800 and Os12g0156100)) showed significantly higher expressions under WBPH infestation, based on transcriptome datasets. This study provides valuable information and clues about predicting the potential roles of OsWRKYs and OsNACs in rice, by combining their genome-wide characterization, expression profiling, protein-protein interactions and gene expressions under WBPH stress. These findings may require additional investigation to understand their metabolic and expression processes, and to develop rice cultivars that are resistant to WBPH.

The effect of ivermectin on non-severe and severe COVID-19 disease and gender-based difference of its effectiveness.

The COVID-19 pandemic has led to mortality and morbidity since December 2019. Many possible treatment options have been advised till date. The role of ivermectin in the treatment of COVID-19 disease remains controversial. The aim of our study was to evaluate the effect of ivermectin in hospitalized patients with non-severe and severe COVID-19 disease. We conducted a retrospective cohort study that compared outcomes in 2 groups of COVID-19 patients hospitalized at the largest tertiary care center of Pakistan. The study group was given ivermectin along with standard treatment of covid-19 disease; the comparison group was not. Data on mortality, inflammatory markers such as C-reactive protein (CRP) and ferritin, length of hospital stay and baseline characteristics were collected from Aga Khan University's database from October 2020 till February 2021. Statistical analysis was done to determine the effectiveness of ivermectin in non-severe and severe COVID-19. Comparison of effectiveness of Ivermectin in both the genders was also conducted. The cohort included 188 patients out of which 90 were treated with ivermectin. Mortality and length of hospitalization was not found to be significantly different in the study group compared with the control group (5.6% vs 5.1%; p=0.87 and 5 days vs 4 days; p=0.27). Analysis of secondary outcomes did not yield statistically significant results, apart from ferritin levels which were significantly less in patients treated with ivermectin (547.1 vs 756.7; p=0.03). The ferritin and CRP levels in affected males were higher than in females on admission and discharge. Our findings suggest ivermectin does not significantly affect all-cause mortality, length of hospitalization and CRP levels in hospitalized COVID-19 patients. Large scale randomized controlled trials (RCTs) are required to further evaluate the role of ivermectin in covid-19 disease.

Genome-wide analysis and functional characterization of the Dof transcription factor family in rice (Oryza sativa L.).

MAIN CONCLUSION: Exhaustive searches of the rice genome have revealed 30 different potential OsDof (Oryza sativa DNA binding with One Finger) genes. Their subcellular localization, phylogenetic relationship, conserved motifs identification, chromosomal allocation, expression patterns, and interaction networks were analyzed. The Dof (DNA binding with One Finger) family of transcription factors represents a particular class of plant-specific transcriptional regulators, contain a highly conserved region of 50-52 amino acids (Dof domain) and involved in various plant developmental processes and response to various environmental stresses. Few (Oryza sativa) OsDof genes have been demonstrated previously for their biological functions but there is no comprehensive study on most of the Dof genes of rice. In the current study, exhaustive searches of the rice genome revealed 30 different potential OsDof genes, and then their subcellular localization, phylogenetic relationship, conserved motifs identification, chromosomal allocation, expression patterns, and interaction networks were analyzed. Phylogenetic analysis of Dof proteins in rice showed that they are distributed in 4 groups. By genome-wide observation of gene expression profiles, we found that OsDof genes showed significant variances in expression levels in different tissues across multiple developmental stages. Protein-protein correlation network analysis, shows a statically significant overlap of some OsDofs, suggesting their similar functions and a high degree of co-expression. The Dof family transcription factors have been reported for their involvement in the regulation of various gene expression processes in rice but still, most of the Dof genes are not characterized for their specific physiological functions. This study revealed useful information and clues about predicting the potential roles of OsDofs in rice by combining their genome-wide characterization, expression profiling, protein-protein interactions, and for further studies to develop high-quality rice varieties.

A High-Performance Asymmetric Supercapacitor Based on Tungsten Oxide Nanoplates and Highly Reduced Graphene Oxide Electrodes.

Tungsten oxide/graphene hybrid materials are attractive semiconductors for energy-related applications. Herein, we report an asymmetric supercapacitor (ASC, HRG//m-WO3 ASC), fabricated from monoclinic tungsten oxide (m-WO3 ) nanoplates as a negative electrode and highly reduced graphene oxide (HRG) as a positive electrode material. The supercapacitor performance of the prepared electrodes was evaluated in an aqueous electrolyte (1 m H2 SO4 ) using three- and two-electrode systems. The HRG//m-WO3 ASC exhibits a maximum specific capacitance of 389 F g-1 at a current density of 0.5 A g-1 , with an associated high energy density of 93 Wh kg-1 at a power density of 500 W kg-1 in a wide 1.6 V operating potential window. In addition, the HRG//m-WO3 ASC displays long-term cycling stability, maintaining 92 % of the original specific capacitance after 5000 galvanostatic charge-discharge cycles. The m-WO3 nanoplates were prepared hydrothermally while HRG was synthesized by a modified Hummers method.

CRISPR-Cas technology based genome editing for modification of salinity stress tolerance responses in rice (Oryza sativa L.).

Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR associated protein (Cas) technology is an effective tool for site-specific genome editing, used to precisely induce mutagenesis in different plant species including rice. Salinity is one of the most stressful environmental constraints affecting agricultural productivity worldwide. As plant adaptation to salinity stress is under polygenic control therefore, 51 rice genes have been identified that play crucial role in response to salinity. This review offers an exclusive overview of genes identified in rice genome for salinity stress tolerance. This will provide an idea to produce rice varieties with enhanced salt tolerance using the potentially efficient CRISPR-Cas technology. Several undesirable off-target effects of CRISPR-Cas technology and their possible solutions have also been highlighted.

Hematite and Magnetite Nanostructures for Green and Sustainable Energy Harnessing and Environmental Pollution Control: A Review.

The optoelectrical and magnetic characteristics of naturally existing iron-based nanostructures, especially hematite and magnetite nanoparticles (H-NPs and M-NPs), gained significant research interest in various applications, recently. The main purpose of this Review is to provide an overview of the utilization of H-NPs and M-NPs in various environmental remediation. Iron-based NPs are extensively explored to generate green energy from environmental friendly processes such as water splitting and CO2 conversion to hydrogen and low molecular weight hydrocarbons, respectively. The latter part of the Review provided a critical overview to use H-NPs and M-NPs for the detection and decontamination of inorganic and organic contaminants to counter the environmental pollution and toxicity challenge, which could ensure environmental sustainability and hygiene. Some of the future perspectives are comprehensively presented in the final portion of the script, optimiztically, and it is supported by some relevant literature surveys to predict the possible routes of H-NPs and M-NPs modifications that could enable researchers to use these NPs in more advanced environmental applications. The literature collection and discussion on the critical assessment of reserving the environmental sustainability challenges provided in this Review will be useful not only for experienced researchers but also for novices in the field.

Selective Synthesis of Monodisperse CoO Nanooctahedra as Catalysts for Electrochemical Water Oxidation.

Thermal decomposition is a promising route for the synthesis of metal oxide nanoparticles because size and morphology can be tuned by minute control of the reaction variables. We synthesized CoO nanooctahedra with diameters of ∼48 nm and a narrow size distribution. Full control over nanoparticle size and morphology could be obtained by controlling the reaction time, surfactant ratio, and reactant concentrations. We show that the particle size does not increase monotonically with time or surfactant concentration but passes through minima or maxima. We unravel the critical role of the surfactants in nucleation and growth and rationalize the observed experimental trends in accordance with simulation experiments. The as-synthesized CoO nanooctahedra exhibit superior electrocatalytic activity with long-term stability during oxygen evolution. The morphology of the CoO particles controls the electrocatalytic reaction through the distinct surface sites involved in the oxygen evolution reaction.

Vanillic Acid, a Bioactive Phenolic Compound, Counteracts LPS-Induced Neurotoxicity by Regulating c-Jun N-Terminal Kinase in Mouse Brain.

The receptor for advanced glycation end products (RAGE), a pattern recognition receptor signaling event, has been associated with several human illnesses, including neurodegenerative diseases, particularly in Alzheimer's disease (AD). Vanillic acid (V.A), a flavoring agent, is a benzoic acid derivative having a broad range of biological activities, including antioxidant, anti-inflammatory, and neuroprotective effects. However, the underlying molecular mechanisms of V.A in exerting neuroprotection are not well investigated. The present study aims to explore the neuroprotective effects of V.A against lipopolysaccharides (LPS)-induced neuroinflammation, amyloidogenesis, synaptic/memory dysfunction, and neurodegeneration in mice brain. Behavioral tests and biochemical and immunofluorescence assays were applied. Our results indicated increased expression of RAGE and its downstream phospho-c-Jun n-terminal kinase (p-JNK) in the LPS-alone treated group, which was significantly reduced in the V.A + LPS co-treated group. We also found that systemic administration of LPS-injection induced glial cells (microglia and astrocytes) activation and significantly increased expression level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-KB) and secretion of proinflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1 ß (IL1-ß), and cyclooxygenase (COX-2). However, V.A + LPS co-treatment significantly inhibited the LPS-induced activation of glial cells and neuroinflammatory mediators. Moreover, we also noted that V.A treatment significantly attenuated LPS-induced increases in the expression of AD markers, such as ß-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1) and amyloid-ß (Aß). Furthermore, V.A treatment significantly reversed LPS-induced synaptic loss via enhancing the expression level of pre- and post-synaptic markers (PSD-95 and SYP), and improved memory performance in LPS-alone treated group. Taken together; we suggest that neuroprotective effects of V.A against LPS-induced neurotoxicity might be via inhibition of LPS/RAGE mediated JNK signaling pathway; and encourage future studies that V.A would be a potential neuroprotective and neurotherapeutic candidate in various neurological disorders.

Metabolic Adaptation in Methicillin-Resistant Staphylococcus aureus Pneumonia.

Methicillin-resistant Staphylococcus aureus (MRSA) is a versatile human pathogen that is associated with diverse types of infections ranging from benign colonization to sepsis. We postulated that MRSA must undergo specific genotypic and phenotypic changes to cause chronic pulmonary disease. We investigated how MRSA adapts to the human airway to establish chronic infection, as occurs during cystic fibrosis (CF). MRSA isolates from patients with CF that were collected over a 4-year period were analyzed by whole-genome sequencing, transcriptional analysis, and metabolic studies. Persistent MRSA infection was associated with staphylococcal metabolic adaptation, but not changes in immunogenicity. Adaptation was characterized by selective use of the tricarboxylic acid cycle cycle and generation of biofilm, a means of limiting oxidant stress. Increased transcription of specific metabolic genes was conserved in all host-adapted strains, most notably a 10,000-fold increase in fumC, which catalyzes the interconversion of fumarate and malate. Elevated fumarate levels promoted in vitro biofilm production in clinical isolates. Host-adapted strains preferred to assimilate glucose polymers and pyruvate, which can be metabolized to generate N-acetylglucosamine polymers that comprise biofilm. MRSA undergoes substantial metabolic adaptation to the human airway to cause chronic pulmonary infection, and selected metabolites may be useful therapeutically to inhibit infection.

Paracrine IL-2 Is Required for Optimal Type 2 Effector Cytokine Production.

IL-2 is a pleiotropic cytokine that promotes the differentiation of Th cell subsets, including Th1, Th2, and Th9 cells, but it impairs the development of Th17 and T follicular helper cells. Although IL-2 is produced by all polarized Th subsets to some level, how it impacts cytokine production when effector T cells are restimulated is unknown. We show in this article that Golgi transport inhibitors (GTIs) blocked IL-9 production. Mechanistically, GTIs blocked secretion of IL-2 that normally feeds back in a paracrine manner to promote STAT5 activation and IL-9 production. IL-2 feedback had no effect on Th1- or Th17-signature cytokine production, but it promoted Th2- and Th9-associated cytokine expression. These data suggest that the use of GTIs results in an underestimation of the presence of type 2 cytokine-secreting cells and highlight IL-2 as a critical component in optimal cytokine production by Th2 and Th9 cells in vitro and in vivo.

Antinociceptive, muscle relaxant and sedative activities of gold nanoparticles generated by methanolic extract of Euphorbia milii.

BACKGROUND: Nanotechnology has potential future for enhancing therapeutic efficacy and reducing the unwanted effects of herbal drugs. The biological research on Euphorbia species has been supported by the use of some plants in traditional medicines. Many species of Euphorbia have been reported as having strong sedative and analgesic effects. In the present research work gold nanoparticles of Euphorbia milii methanolic extract (Au-EM) were synthesized, characterized and tested for antinociceptive, muscle relaxant and sedative activities. METHODS: Au-EM was prepared by stirring 1 mM warm trihydrated tetrachloroaurate solution with E. milii methanolic extract without using any external reducing agents. The gold nanoparticles were characterized by UV-Visible spectroscopy, infrared spectrophotometery, atomic force microscopy and scanning electron microscopy while their stability was evaluated against varying pH and different volumes of sodium chloride (NaCl). The metal sensing capacity of Au-EM was tested towards cobalt, copper, lead, mercury and nickel. Au-EM was evaluated in BALB/c mice at a dose of 10 and 20 mg/kg for antinociceptive, muscle relaxant and sedative activities in comparison with the crude E. milii methanolic extract. RESULTS: Au-EM showed remarkable stability in different NaCl and pH solutions. Au-EM produced significant (P < 0.01) antinociceptive effect at doses of 10 and 20 mg/kg as compared to the crude E. milii methanolic extract. In the rotarod test, Au-EM showed significant muscle relaxant effect at 10 mg/kg (P < 0.05) and 20 mg/kg (P < 0.01) after 30, 60 and 90 min. In an open field test significant sedative effect (P < 0.05) of Au-EM was observed at 10 and 20 mg/kg. Moreover significant detection sensitivity was demonstrated towards all the tested heavy metals. CONCLUSIONS: These results concluded that the gold nanoparticles improved the potency of E. milii methanolic extract and exhibited significant analgesic, muscle relaxant and sedative properties. The significant metals sensing ability and enhanced stability in different NaCl and pH solutions may enable us to explore different formulations of E. milii gold nanoparticles for potentially effective and safe nano-herbal therapy.