Micro Trojan horses: Engineering extracellular vesicles crossing biological barriers for drug delivery.

The biological barriers of the body, such as the blood-brain, placental, intestinal, skin, and air-blood, protect against invading viruses and bacteria while providing necessary physical support. However, these barriers also hinder the delivery of drugs to target tissues, reducing their therapeutic efficacy. Extracellular vesicles (EVs), nanostructures with a diameter ranging from 30 nm to 10 µm secreted by cells, offer a potential solution to this challenge. These natural vesicles can effectively pass through various biological barriers, facilitating intercellular communication. As a result, artificially engineered EVs that mimic or are superior to the natural ones have emerged as a promising drug delivery vehicle, capable of delivering drugs to almost any body part to treat various diseases. This review first provides an overview of the formation and cross-species uptake of natural EVs from different organisms, including animals, plants, and bacteria. Later, it explores the current clinical applications, perspectives, and challenges associated with using engineered EVs as a drug delivery platform. Finally, it aims to inspire further research to help bioengineered EVs effectively cross biological barriers to treat diseases.

Effect of biochar on the fate of antibiotic resistant genes and integrons in compost amended agricultural soil.

The persistence and transmission of emerging pollutants such as antibiotic resistance genes (ARGs) via mobile genetic elements (MGEs) have caused concern to scientific community. Composting practises are often adapted for the reduction of organic waste or to enhance fertility in agriculture soil but its continuous usage has posed a potential risk of increased abundance of ARGs in soil. Thus, the present study scrutinises the emerging risk of ARGs and MGEs in agriculture soil and its potential mitigation using biochar owing to its proven environmental sustainability and performance. After 30 days incubation, ARG distribution of SulI, SulII, dfrA1, dfrA12, tetA, flor, and ErmA was 50, 37.5, 37.5, 62.5, 42.11, 62.5, and 52.63% in control samples whereas it was 5, 15.78, 21.05, 15.79, 10.53, 21.05, and 31.58%, respectively, for biochar amended samples. Similarly, IntI1 and IntI2 in control and biochar amended samples were 18.75 and 6.25% and 10.53 and 5.26%, respectively. Principal component analysis (PCA) factor suggests that biochar amendment samples showed enhanced value for pH, organic matter, and organic carbon over control samples. Furthermore, Pearson's correlation analysis performed between detected ARGs and MGEs demonstrated the positive and significant correlation at p < 0.05 for both control and biochar amended samples.

Investigation of target genes and potential mechanisms related to compound Xiao-ai-fei honey ointment based on network pharmacology and bioinformatics analysis.

BACKGROUND: Compound Xiao-ai-fei honey ointment (CXHO) is an anticancer preparation with a long history in Uyghur folk medicine in China and has been used for the treatment of gastric cancer (GC) in Xinjiang, China. Nevertheless, the mechanism of its anticancer effect remains to be investigated. METHODS: Bioactive ingredients of CXHO were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database. Target genes of ingredients were acquired via the PubChem and Swiss target prediction database. Gene expression profiling of GC was obtained from GSE54129 in the GEO database and analyzed using the limma package in R. The hub genes associated with CXHO in GC were validated using the TIMER2.0 database, GEPIA2 database and Auto Dock tools. The effect of CXHO on migration of GC cells was detected by Transwell chamber assay and Wound healing assay. The effect of CXHO on expression levels of MMP2/MMP9 and NF-κb, PI3K/AKT signaling pathway was detected by Western blot assay. RESULTS: Forty-five bioactive ingredients and their 819 related genes were found. A total of 462 differentially expressed genes were identified between GC patients and healthy controls. Seventeen common target genes were identified as hub genes CXHO against GC. Among them, MMP2 and MMP9 were significantly associated with tumor immune infiltrates and had good binding affinity with effective ingredients. Moreover, we validated the mRNA and protein expression levels and prognostic value of MMP2 and MMP9 by different databases. In addition, Kyoto encyclopedia of genes and genomes and gene ontology analyses showed that the 17 common target genes were mainly involved in steroid hormone biosynthesis and cancer-related pathways. Experimental results showed that CXHO inhibited migration of GC cells and down regulated the expression levels of MMP2/MMP9, NF-κb. In addition, CXHO can inhibited PI3K/AKT signaling pathway. CONCLUSION: We identified and experimental validated 2 pivotal target genes of CXHO against GC and preliminarily analyzed the potential mechanisms by which CXHO inhibits the development of GC. All these findings support CXHO as a promising drug for the treatment of GC.

Exploring the hub genes and mechanisms of Daphne altaica treating esophageal squamous cell carcinoma based on network pharmacology and bioinformatics analysis.

PURPOSE: Esophageal squamous cell carcinoma (ESCC), is a frequent digestive tract malignant carcinoma with a high fatality rate. Daphne altaica (D. altaica), a medicinal plant that is frequently employed in Kazakh traditional medicine, and which has traditionally been used to cure cancer and respiratory conditions, but research on the mechanism is lacking. Therefore, we examined and verified the hub genes and mechanism of D. altaica treating ESCC. METHODS: Active compounds and targets of D. altaica were screened by databases such as TCMSP, and ESCC targets were screened by databases such as GeneCards and constructed the compound-target network and PPI network. Meantime, data sets between tissues and adjacent non-cancerous tissues from GEO database (GSE100942, GPL570) were analyzed to obtain DEGs using the limma package in R. Hub genes were validated using data from the Kaplan-Meier plotter database, TIMER2.0 and GEPIA2 databases. Finally, AutoDock software was used to predict the binding sites through molecular docking. RESULTS: In total, 830 compound targets were obtained from TCMSP and other databases. In addition, 17,710 disease targets were acquired based on GeneCards and other databases. In addition, we constructed the compound-target network and PPI network. Then, 127 DEGs were observed (82 up-regulated and 45 down-regulated genes). Hub genes were screened including TOP2A, NUF2, CDKN2A, BCHE, and NEK2, and had been validated with the help of several publicly available databases. Finally, molecular docking results showed more stable binding between five hub genes and active compounds. CONCLUSIONS: In the present study, five hub genes were screened and validated, and potential mechanisms of action were predicted, which could provide a theoretical understanding of the treatment of ESCC with D. altaica.

Efficient mitigation of emerging antibiotics residues from water matrix: Integrated approaches and sustainable technologies.

The prevalence of antibiotic traces in the aquatic matrices is a concern due to the emanation of antibiotic resistance which requires a multifaceted approach. One of the potential sources is the wastewater treatment plants with a lack of advance infrastructure leading to the dissemination of contaminants. Continuous advancements in economic globalization have facilitated the application of several conventional, advanced, and hybrid techniques for the mitigation of rising antibiotic traces in the aquatic matrices that have been thoroughly scrutinized in the current paper. Although the implementation of existing mitigation techniques is associated with several limiting factors and barriers which require further research to enhance their removal efficiency. The review further summarizes the application of the microbial processes to combat antibiotic persistence in wastewater establishing a sustainable approach. However, hybrid technologies are considered as most efficient and environmental-benign due to their higher removal efficacy, energy-efficiency, and cost-effectiveness. A brief elucidation has been provided for the mechanism responsible for lowering antibiotic concentration in wastewater through biodegradation and biotransformation. Overall, the current review presents a comprehensive approach for antibiotic mitigation using existing methods however, policies and measures should be implemented for continuous monitoring and surveillance of antibiotic persistence in aquatic matrices to reduce their potential risk to humans and the environment.

Quince extract resists atherosclerosis in rats by down-regulating the EGFR/PI3K/Akt/GSK-3ß pathway.

We identified the effective components and the underlying mechanisms of Quince (Cydonia oblonga Mill, COM) extract against atherosclerosis. The effective components of COM extract were identified with UHPLC-Q-TOF-MS/MS. Network pharmacology was performed. A rat model of atherosclerosis induced by high-fat emulsion combined with vitamin D3 was established. The anti-atherosclerosis effect of COM extract was evaluated from various aspects such as blood lipid regulation, anti-oxidative stress, anti-inflammatory response, and vascular protection function. We identified 14 serum components of COM extract using UHPLC-Q-TOF-MS/MS. Through prediction, 573 targets were obtained, among which 224 targets were atherosclerosis specific targets. The key targets included GSK3ß, ESR1, EGFR, and HSP90AA1. The key signaling pathway was PI3K-Akt signaling pathway. Pharmacodynamics analysis showed that COM extract reduced the levels of TC, TG, and LDL-C as well as ALT and AST, while increased the level of HDL-C. Mechanistically, COM extract significantly increased serum SOD and GSH-Px activities, but decreased MDA content in atherosclerosis rats, showing antioxidant effects. Meanwhile, COM extract significantly down-regulated the levels of pro-inflammatory factors IL-1ß, IL-6, TNF-α and CRP, but up-regulated anti-inflammatory factor IL-10. Additionally, COM extract increased the levels of NO, eNOS, and 6-keto-PGF1α; whereas, decreased the levels of ET-1 and TXB2. Furthermore, COM extract significantly inhibited the mRNA and protein levels of EGFR, p-PI3K, p-AKT, GSK-3ß, Bax, and Caspase-3 as well as the Bax/Bcl-2 ratio. Conclusively, COM extract exerts hypolipidemic, anti-oxidative, anti-inflammatory, anti-thrombotic and vascular endothelium protective effects on atherosclerosis rat model, which may be related to the inhibition of EGFR/PI3K/AKT/GSK-3ß signaling pathway.

Effect of Adjunctive Simvastatin on Depressive Symptoms Among Adults With Treatment-Resistant Depression: A Randomized Clinical Trial.

Importance: Immune-metabolic disturbances have been implicated in the pathophysiology of major depressive disorder and may be more prominent in individuals with treatment-resistant depression (TRD). Preliminary trials suggest that lipid-lowering agents, including statins, may be useful adjunctive treatments for major depressive disorder. However, no adequately powered clinical trials have assessed the antidepressant efficacy of these agents in TRD. Objective: To assess the efficacy and tolerability of adjunctive simvastatin compared with placebo for reduction of depressive symptoms in TRD. Design, Setting, and Participants: This 12-week, double-blind, placebo-controlled randomized clinical trial was conducted in 5 centers in Pakistan. The study involved adults (aged 18-75 years) with a Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) major depressive episode that had failed to respond to at least 2 adequate trials of antidepressants. Participants were enrolled between March 1, 2019, and February 28, 2021; statistical analysis was performed from February 1 to June 15, 2022, using mixed models. Intervention: Participants were randomized to receive standard care plus 20 mg/d of simvastatin or placebo. Main Outcomes and Measures: The primary outcome was the difference between the 2 groups in change in Montgomery-Åsberg Depression Rating Scale total scores at week 12. Secondary outcomes included changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, and the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. C-reactive protein and plasma lipids were measured at baseline and week 12. Results: A total of 150 participants were randomized to simvastatin (n = 77; median [IQR] age, 40 [30-45] years; 43 [56%] female) or placebo (n = 73; median [IQR] age, 35 [31-41] years; 40 [55%] female). A significant baseline to end point reduction in Montgomery-Åsberg Depression Rating Scale total score was observed in both groups and did not differ significantly between groups (estimated mean difference for simvastatin vs placebo, -0.61; 95% CI, -3.69 to 2.46; P = .70). Similarly, there were no significant group differences in any of the secondary outcomes or evidence for differences in adverse effects between groups. A planned secondary analysis indicated that changes in plasma C-reactive protein and lipids from baseline to end point did not mediate response to simvastatin. Conclusions and Relevance: In this randomized clinical trial, simvastatin provided no additional therapeutic benefit for depressive symptoms in TRD compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT03435744.

Potential health risk assessment, spatio-temporal hydrochemistry and groundwater quality of Yamuna river basin, Northern India.

Groundwater which is an essential source of freshwater for various domestic, agricultural, industrial applications is facing a severe deterioration in quality due to demographic pressure and intense industrial activities. Present study appraises the influence of human induced activities on groundwater quality of Agra-Firozabad industrial belts of Western Uttar Pradesh, Yamuna basin, India. The maximum concentrations of metals and anions found during pre and post monsoon are as follows: Lead 0.302; 0.086, calcium 672; 1260, magnesium 215; 16.8, cadmium 0.0; 0.066, chromium 0.016; 0.005, manganese 0.340; 0.076, nickel 0.044; 0.028, sulfate 514; 286, nitrate 66.7; 3.56 and fluoride 1.17; 2.02 mg/L respectively. Based on results of Water Quality Index, groundwater samples were classified under 'Poor water' category in 34.2% and 52.63% during pre and post-monsoon period, respectively. Accordingly, higher concentrations of bicarbonate and sulfate might have attributed to excess hardness, instrumental in making it unsuitable for industrial usage. However, values of Percent Sodium, Sodium Adsorption Ratio, Magnesium Hazard and Permeability Index signified that groundwater from majority of locations was fit for agricultural use. Health risk assessment studies revealed that children consuming polluted water were affected more as compared to adults. Timely action and strict compliance of regulation is recommended towards groundwater management for defined usage to avert severe health effects and to meet sustainable development goals.

A lipoglycopeptide antibiotic for Gram-positive biofilm-related infections.

Drug-resistant Gram-positive bacterial infections are still a substantial burden on the public health system, with two bacteria (Staphylococcus aureus and Streptococcus pneumoniae) accounting for over 1.5 million drug-resistant infections in the United States alone in 2017. In 2019, 250,000 deaths were attributed to these pathogens globally. We have developed a preclinical glycopeptide antibiotic, MCC5145, that has excellent potency (MIC90 ≤ 0.06 µg/ml) against hundreds of isolates of methicillin-resistant S. aureus (MRSA) and other Gram-positive bacteria, with a greater than 1000-fold margin over mammalian cell cytotoxicity values. The antibiotic has therapeutic in vivo efficacy when dosed subcutaneously in multiple murine models of established bacterial infections, including thigh infection with MRSA and blood septicemia with S. pneumoniae, as well as when dosed orally in an antibiotic-induced Clostridioides difficile infection model. MCC5145 exhibited reduced nephrotoxicity at microbiologically active doses in mice compared to vancomycin. MCC5145 also showed improved activity against biofilms compared to vancomycin, both in vitro and in vivo, and a low propensity to select for drug resistance. Characterization of drug action using a transposon library bioinformatic platform showed a mechanistic distinction from other glycopeptide antibiotics.

Advances from conventional to real time detection of heavy metal(loid)s for water monitoring: An overview of biosensing applications.

The rapid growth of the industrial sector has expedited the accumulation of heavy metal(loid)s in the environment at hazardous levels. The elements such as arsenic, lead, mercury, cadmium and chromium are lethal in terms of toxicity with severe health impacts. With issues like water scarcity, limitations in wastewater treatment, and costs pertaining to detection in environmental matrices; their rapid and selective detection for reuse of effluents is of the utmost priority. Biosensors are the futuristic tool for the accurate qualitative and quantitative analysis of a specific analyte and integrate biotechnology, microelectronics and nanotechnology to fabricate a miniaturized device without compromising the sensitivity, specificity and accuracy. The characteristic features of supporting matrix largely affect the biosensing ability of the device and incorporation of highly sensitive and durable metal organic frameworks (MOFs) are reported to enhance the efficiency of advanced biosensors. Electrochemical biosensors are among the most widely developed biosensors for the detection of heavy metal(loids), while direct electron transfer approach from the recognition element to the electrode has been found to decrease the chances of interference. This review provides an insight into the recent progress in biosensor technologies for the detection of prevalent heavy metal(loid)s; using advanced support systems such as functional metal-based nanomaterials, carbon nanotubes, quantum dots, screen printed electrodes, glass beads etc. The review also delves critically in comparison of various techno-economic studies and the latest advances in biosensor technology.

Degradation of ß-lactam antibiotic ampicillin using sustainable microbial peroxide producing cell system.

The enormous use of synthetic antibiotic and personal care products has impacted the natural microbiome and ecosystem. Overtime, treatment technologies developed suffered due to incomplete removal hence, a pilot dual-chambered microbial peroxide-producing cell that degrades ampicillin catalyzed by homogenous Fenton-reaction was designed. The system reported maximum current at 16.714 ± 0.048 µAcm-2, power output of 1.956 ± 0.015 mW m-2; 88 ± 2.90 mM of H2O2 generation with Na2SO4 that degraded 95.9 ± 3.00 to 97.8 ± 3.20% of 10 mg L-1ampicillin within 72 hrs with electro-active Shewanella putrefaciens. An E. coli bioactivity assay with ampicillin exhibited no sensitivity zone due to the loss of activity. Analytical spectroscopic studies reveal ß-Lactam ring deformation; Liquid Chromatography-Mass Spectroscopy clearly shows the presence of degradation metabolites. A sustainable wastewater treatment with 72 ± 4.5% reduction in anodic chemical oxygen demand was achieved. Present results designate the technology, as promising for effective antibiotics removal for wastewater treatment concomitant with electricity generation.

UHPLC-Q-TOF-MS/MS and Network Pharmacology Analysis to Reveal Quality Markers of Xinjiang Cydonia oblonga Mill. for Antiatherosclerosis.

Cydonia oblonga Mill. (COM), mature fruit of genus Rosaceae, is consumed as a kind of traditional Chinese medicinal herb. Previous studies have shown that the components in COM extract have antioxidant, anti-inflammatory, blood pressure-lowering, blood lipid-lowering, antithrombotic, and other biological activities. However, the quality markers (Q-markers) of atherosclerosis (AS) have not been elucidated. The Q-marker is based on the five core principles of traceability, transferability, specificity, measurability, validity, and prescription dispensing. In this study, the quality markers of quince were investigated by applying the ultraperformance liquid chromatography-time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) method and network pharmacology method to highlight the three core elements which are, respectively, traceability transmission, measurability, and validity. At the first step, 72 components were identified by applying the ultraperformance liquid chromatography-time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) method. In the next step, 46 candidate components of COM anti-AS were obtained by network pharmacology, and then, 27 active components were filtered with the molecular docking assay. Finally, the 27 active components were intersected with 10 active components obtained by mass transfer and traceable quality markers. Four anti-AS Q-markers of COM were identified, including caffeic acid, chlorogenic acid, ellagic acid, and vanillic acid, which provided a reference for the quality control of quince. The methods and strategies can also be applied to other traditional Chinese medicines and their compound preparations, providing new ideas on the quantitative evaluation and identification of quality markers.

Sustainable biochar: A facile strategy for soil and environmental restoration, energy generation, mitigation of global climate change and circular bioeconomy.

The increasing agro-demands with the burgeoning population lead to the accumulation of lignocellulosic residues. The practice of burning agri-residues has consequences viz. Release of soot and smoke, nutrient depletion, loss of soil microbial diversity, air pollution and hazardous effects on human health. The utilization of agricultural waste as biomass to synthesize biochar and biofuels, is the pertinent approach for attaining sustainable development goals. Biochar contributes in the improvement of soil properties, carbon sequestration, reducing greenhouse gases (GHG) emission, removal of organic and heavy metal pollutants, production of biofuels, synthesis of useful chemicals and building cementitious materials. The biochar characteristics including surface area, porosity and functional groups vary with the type of biomass consumed in pyrolysis and the control of parameters during the process. The major adsorption mechanisms of biochar involve physical-adsorption, ion-exchange interactions, electrostatic attraction, surface complexation and precipitation. The recent trend of engineered biochar can enhance its surface properties, pH buffering capacity and presence of desired functional groups. This review focuses on the contribution of biochar in attaining sustainable development goals. Hence, it provides a thorough understanding of biochar's importance in enhancing soil productivity, bioremediation of environmental pollutants, carbon negative concretes, mitigation of climate change and generation of bioenergy that amplifies circular bioeconomy, and concomitantly facilitates the fulfilment of the United Nation Sustainable Development Goals. The application of biochar as seen is primarily targeting four important SDGs including clean water and sanitation (SGD6), affordable and clean energy (SDG7), responsible consumption and production (SDG12) and climate action (SDG13).

Analysis of the active components and mechanism of Shufeng Jiedu capsule against COVID-19 based on network pharmacology and molecular docking.

ABSTRACT: This study investigates the active components and mechanism of Shufeng Jiedu Capsules (SFJDC) against novel coronavirus through network pharmacology and molecular docking.The TCMSP, TCMID, and BATMAN-TCM databases were used to retrieve the components of SFJDC. The active components were screened by ADME (absorption, distribution, metabolism, and excretion) parameters, and identified by Pubchem, Chemical Book, and ChemDraw softwares. The molecular docking ligands were constructed. SARS Coronavirus-2 Major Protease (SARS-CoV-2-Mpro) and angiotension converting enzyme 2 (ACE2) were used as molecular docking receptors. AutoDock software was used for molecular docking. Cytoscape 3.7.1 software was used to generate an herbs-active components-targets network. Gene Ontology gene function and Kyoto Encyclopedia of Genes and Genomes signal pathway analysis were performed by DAVID data.A total of 1244 components were identified from SFJDC, and 210 active components were obtained. Among them, 97 active components were used as docking ligands to dock with SARS-CoV-2-Mpro and ACE2. There were 48 components with good binding activity to SARS-CoV-2-Mpro. Ten active components (including 7-Acetoxy-2-methylisoflavone, Kaempferol, Quercetin, Baicalein, Glabrene, Glucobrassicin, Isoglycyrol, Wogonin, Petunidin, and Luteolin) combined with SARS-CoV-2-Mpro and ACE2 simultaneously. Among them, Kaempferol, Wogonin, and Baicalein showed higher binding activity. The herbs-active components-targets network contained 7 herbs, 10 active components, and 225 targets. The 225 target targets were involved in 653 biological processes of Gene Ontology analysis and 130 signal pathways (false discovery rate ≤ 0.01) of Kyoto Encyclopedia of Genes and Genomes analysis.The active components of SFJDC (such as Kaempferol, Wogonin, and Baicalein) may combine with ACE2 and act on multiple signaling pathways and targets to exert therapeutic effect on novel coronavirus.

Effect of sewage sludge biochar on the soil nutrient, microbial abundance, and plant biomass: A sustainable approach towards mitigation of solid waste.

Soils functions, fertility, and microbial abundance may alter in various ways by the biochar amendments to the soil. This study revealed the way of pyrolysis temperature influences the biochar quality and its addition for improving soil properties. The SS biochar was synthesized via pyrolysis and characterized by SEM and FTIR for studying surface images and chemical functional groups. The biochar upon addition with soil was studied for physiological parameters of plants like seed germination index, root length, shoot length, biomass, metal (loid) analysis of soil, SS and SS biochar, total organic content, C: N ratio, NPK values, etc. Besides, combinations of biochar: soil {1:3 (25% + 75%), 1:1 (50% + 50%), and 3:1 (75% + 25%)} ratios were used for studying the effect of biochar on soil microbial community. The 16S rRNA metagenomic analysis revealed the dominance of phyla: Proteobacteria, Actinobacteria, and Acidobacteria that influence the soil nutrient cycle when applied at ratio 1:3. This study highlights the valorization of SS into biochar and studied the effect of biochar augmentation with soil; its impact on soil nutrients, microbial abundance, and plant biomass enhancement. The greener approach also mitigates and helps in the sustainable management of solid wastes, thus reducing GHGs emissions and improves nutrient cycling.

Targeted microbiome-sparing antibiotics.

A factor in our inability to meet the challenge of clinical antibiotic resistance has been the low productivity of research and development (R&D) efforts, with only incremental improvements on existing broad-spectrum classes coming into clinical use recently. The disappointing returns from this approach have focussed attention on narrower-spectrum antibiotics; such new agents are directed against the pathogen of relevance with the additional benefit of preserving the human microbiome(s). Our knowledge of the gut microbiome and its contribution to health homeostasis increases yearly and suggests that broad-spectrum treatments incur health costs beyond the initial infection. Improved diagnostics, antibiotic stewardship, and the crucial role of the gut microbiome in health indicate targeted agents as a more viable approach for future antibiotic R&D.

Biochar and environmental sustainability: Emerging trends and techno-economic perspectives.

Environmental pollutants including emerging contaminants are a growing concern worldwide. Organic wastes, such as food waste, compost, animal manure, crop residues, and sludge are generally used as feedstock. The conventional treatment methodologies (primary and secondary treatment process) do not mitigate or remove pollutants effectively. Hence, an effective, low-cost, and environmentally friendly tertiary treatment process is an urgent need. Biochar finds interesting applications in environmental processes like pollutant remediation, greenhouse gas mitigation, and wastewater treatment. Studies have shown that different types of adsorbents (biochars) like, native and engineered biochar are being used in the removal or mitigation of heavy metals, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls, pesticides, disinfectants, polychlorinated dibenzofurans, and dibenzo-p-dioxins from contaminated sites for environmental management. The review discusses ample studieswhich can offer solutions for environmental sustenance and managementand the emerging trends and techno-economic prospectives of biochar for sustainable environmental management.

High-density transposon libraries utilising outward-oriented promoters identify mechanisms of action and resistance to antimicrobials.

The use of bacterial transposon mutant libraries in phenotypic screens is a well-established technique for determining which genes are essential or advantageous for growth in conditions of interest. Standard, inactivating, transposon libraries cannot give direct information about genes whose over-expression gives a selective advantage. We report the development of a system wherein outward-oriented promoters are included in mini-transposons, generation of transposon mutant libraries in Escherichia coli and Pseudomonas aeruginosa and their use to probe genes important for growth under selection with the antimicrobial fosfomycin, and a recently-developed leucyl-tRNA synthase inhibitor. In addition to the identification of known mechanisms of action and resistance, we identify the carbon-phosphorous lyase complex as a potential resistance liability for fosfomycin in E. coli and P. aeruginosa. The use of this technology can facilitate the development of novel mechanism-of-action antimicrobials that are urgently required to combat the increasing threat worldwide from antimicrobial-resistant pathogenic bacteria.

ADAPT: Approach to Develop context-Aware solutions for Personalised asthma managemenT.

People with asthma have heterogeneous triggers and symptoms, which they need to be aware of in order to implement the strategies to manage their condition. Context-aware reasoning has the potential to provide the personalisation that is required to address the heterogeneity of asthma by helping people to define the information that is relevant considering the characteristics of their condition and delivering services based on this information. This research work proposes the Approach to Develop context-Aware solutions for Personalised asthma managemenT (ADAPT), whose aim is to facilitate the creation of solutions allowing the required customisation to address the heterogeneity of asthma. ADAPT is the result of the constant interaction with people affected by asthma throughout the research project, which was possible to achieve thanks to the collaboration formed with the Centre for Applied Research of Asthma UK. ADAPT context dimensions facilitate the development of preventive and reactive features that can be configured depending on the characteristics of the person with asthma. The approach also provides support to people not knowing their triggers through case-based reasoning and includes virtual assistant as a complementing technology supporting asthma management. ADAPT is validated by people with asthma, carers and experts in respiratory conditions, who evaluated a mobile application that was built based on the approach.

Using Thypro 39 Scale For Predicting The Quality Of Life In Hypothyroid Patients At Lady Reading Hospital.

BACKGROUND: Thyroid disorders are the second most common of the endocrine diseases. With regards to Hypothyroidism, it has a slow indolent course over the years, before its diagnosis. Most of the patient, on adequate treatment with biochemical euthyroid status, have generalised symptoms that affect their quality of life. Several tools to assess quality of life in thyroid disorders have been validated and recommended for use for those patients in clinical follow ups. ThyPRO 39 is one of a recently developed thyroid-specific quality of life (QoL) questionnaires applicable to patients with benign thyroid disorders (BTD). The purpose of this study was to predict the thyroid-related quality of life (QoL) instrument ThyPRO 39 in patients with Hypothyroidism, who were rendered euthyroid with thyroid replacement therapy prior to the administration of study tool and to assess the internal reliability of this scale in our population. METHODS: A sample of 52 patients undergoing maintenance treatment for Hypothyroidism who visited the outpatient Endocrinology clinics at Lady Reading Hospital was studied. They were interviewed for their baseline demographic details and details on ThyPRO 39 questionnaire were recorded after a written informed consent. The data was entered and analysed using SPSS 25. The Internal reliability of the ThyPRO 39 scale was assessed for multi-item scales using Cronbach's alpha coefficient. RESULTS: The ThyPRO 39 scale demonstrated good response across the whole range of QoL aspects in patients with hypothyroidism. Internal reliability for ThyPRO 39 scale was satisfactory. Cronbach's Alpha in our study was 0.928, which was comparable to the results of other studies. CONCLUSIONS: We suggest implementing this measurement tool as a patient-reported outcome in clinical studies in our indigenous population and further more to utilise it as a screening tool for QoL in clinical management of Hypothyroidism in our routine medical consultations.