Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection.

Neuroepithelial crosstalk is critical for gut physiology. However, the mechanisms by which sensory neurons communicate with epithelial cells to mediate gut barrier protection at homeostasis and during inflammation are not well understood. Here, we find that Nav1.8+CGRP+ nociceptor neurons are juxtaposed with and signal to intestinal goblet cells to drive mucus secretion and gut protection. Nociceptor ablation led to decreased mucus thickness and dysbiosis, while chemogenetic nociceptor activation or capsaicin treatment induced mucus growth. Mouse and human goblet cells expressed Ramp1, receptor for the neuropeptide CGRP. Nociceptors signal via the CGRP-Ramp1 pathway to induce rapid goblet cell emptying and mucus secretion. Notably, commensal microbes activated nociceptors to control homeostatic CGRP release. In the absence of nociceptors or epithelial Ramp1, mice showed increased epithelial stress and susceptibility to colitis. Conversely, CGRP administration protected nociceptor-ablated mice against colitis. Our findings demonstrate a neuron-goblet cell axis that orchestrates gut mucosal barrier protection.

Critical Role for the DNA Sensor AIM2 in Stem Cell Proliferation and Cancer.

Colorectal cancer is a leading cause of cancer-related deaths. Mutations in the innate immune sensor AIM2 are frequently identified in patients with colorectal cancer, but how AIM2 modulates colonic tumorigenesis is unknown. Here, we found that Aim2-deficient mice were hypersusceptible to colonic tumor development. Production of inflammasome-associated cytokines and other inflammatory mediators was largely intact in Aim2-deficient mice; however, intestinal stem cells were prone to uncontrolled proliferation. Aberrant Wnt signaling expanded a population of tumor-initiating stem cells in the absence of AIM2. Susceptibility of Aim2-deficient mice to colorectal tumorigenesis was enhanced by a dysbiotic gut microbiota, which was reduced by reciprocal exchange of gut microbiota with healthy wild-type mice. These findings uncover a synergy between a specific host genetic factor and gut microbiota in determining the susceptibility to colorectal cancer. Therapeutic modulation of AIM2 expression and microbiota has the potential to prevent colorectal cancer.

A deep catalogue of protein-coding variation in 983,578 individuals.

Rare coding variants that substantially affect function provide insights into the biology of a gene1-3. However, ascertaining the frequency of such variants requires large sample sizes4-8. Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The catalogue includes more than 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss of function (LOF), we identify 3,988 LOF-intolerant genes, including 86 that were previously assessed as tolerant and 1,153 that lack established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions that are depleted of missense variants despite being tolerant of pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this resource of coding variation from the RGC-ME dataset publicly accessible through a variant allele frequency browser.

Epithelial IFNγ signalling and compartmentalized antigen presentation orchestrate gut immunity.

All nucleated cells express major histocompatibility complex I and interferon-γ (IFNγ) receptor1, but an epithelial cell-specific function of IFNγ signalling or antigen presentation by means of major histocompatibility complex I has not been explored. We show here that on sensing IFNγ, colonic epithelial cells productively present pathogen and self-derived antigens to cognate intra-epithelial T cells, which are critically located at the epithelial barrier. Antigen presentation by the epithelial cells confers extracellular ATPase expression in cognate intra-epithelial T cells, which limits the accumulation of extracellular adenosine triphosphate and consequent activation of the NLRP3 inflammasome in tissue macrophages. By contrast, antigen presentation by the tissue macrophages alongside inflammasome-associated interleukin-1α and interleukin-1ß production promotes a pathogenic transformation of CD4+ T cells into granulocyte-macrophage colony-stimulating-factor (GM-CSF)-producing T cells in vivo, which promotes colitis and colorectal cancer. Taken together, our study unravels critical checkpoints requiring IFNγ sensing and antigen presentation by epithelial cells that control the development of pathogenic CD4+ T cell responses in vivo.

SYK-CARD9 Signaling Axis Promotes Gut Fungi-Mediated Inflammasome Activation to Restrict Colitis and Colon Cancer.

Fungi represent a significant proportion of the gut microbiota. Aberrant immune responses to fungi are frequently observed in inflammatory bowel diseases (IBD) and colorectal cancer (CRC), and mutations in the fungal-sensing pathways are associated with the pathogenesis of IBD. Fungal recognition receptors trigger downstream signaling via the common adaptor protein CARD9 and the kinase SYK. Here we found that commensal gut fungi promoted inflammasome activation during AOM-DSS-induced colitis. Myeloid cell-specific deletion of Card9 or Syk reduced inflammasome activation and interleukin (IL)-18 maturation and increased susceptibility to colitis and CRC. IL-18 promoted epithelial barrier restitution and interferon-γ production by intestinal CD8+ T cells. Supplementation of IL-18 or transfer of wild-type myeloid cells reduced tumor burden in AOM-DSS-treated Card9-/- and Sykfl/flLysMCre/+ mice, whereas treatment with anti-fungal agents exacerbated colitis and CRC. CARD9 deletion changes the gut microbial landscape, suggesting that SYK-CARD9 signaling maintains a microbial ecology that promotes inflammasome activation and thereby restrains colitis and colon tumorigenesis.

Pan-ancestry exome-wide association analyses of COVID-19 outcomes in 586,157 individuals.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that can result in hospitalization or death. We used exome sequence data to investigate associations between rare genetic variants and seven COVID-19 outcomes in 586,157 individuals, including 20,952 with COVID-19. After accounting for multiple testing, we did not identify any clear associations with rare variants either exome wide or when specifically focusing on (1) 13 interferon pathway genes in which rare deleterious variants have been reported in individuals with severe COVID-19, (2) 281 genes located in susceptibility loci identified by the COVID-19 Host Genetics Initiative, or (3) 32 additional genes of immunologic relevance and/or therapeutic potential. Our analyses indicate there are no significant associations with rare protein-coding variants with detectable effect sizes at our current sample sizes. Analyses will be updated as additional data become available, and results are publicly available through the Regeneron Genetics Center COVID-19 Results Browser.

RNA editing sites and triplet usage in exomes of bat RNA virus genomes of the family Paramyxoviridae.

Bats contain a diverse spectrum of viral species in their bodies. The RNA virus family Paramyxoviridae tends to infect several vertebrate species, which are accountable for a variety of devastating infections in both humans and animals. Viruses of this kind include measles, mumps, and Hendra. Some synonymous codons are favoured over others in mRNAs during gene-to-protein synthesis process. Such phenomenon is termed as codon usage bias (CUB). Our research emphasized many aspects that shape the CUB of genes in the Paramyxoviridae family found in bats. Here, the nitrogenous base A occurred the most. AT was found to be abundant in the coding sequences of the Paramyxoviridae family. RSCU data revealed that A or T ending codons occurred more frequently than predicted. Furthermore, 3 overrepresented codons (CAT, AGA, and GCA) and 7 underrepresented codons (CCG, TCG, CGC, CGG, CGT, GCG and ACG) were detected in the viral genomes. Correspondence analysis, neutrality plot, and parity plots highlight the combined impact of mutational pressure and natural selection on CUB. The neutrality plot of GC12 against GC3 yielded a regression coefficient value of 0.366, indicating that natural selection had a significant (63.4%) impact. Moreover, RNA editing analysis was done, which revealed the highest frequency of C to T mutations. The results of our research revealed the pattern of codon usage and RNA editing sites in Paramyxoviridae genomes.

Metal-free oxidative coupling of aryl acetylene with elemental sulphur and amines: facile access to α-ketothioamides.

A simple and efficient oxidative coupling of aromatic alkynes with elemental sulphur and secondary amines has been reported. The iodine/DMSO system easily promoted the transformations, affording thioglyoxamides via C-S, C-O, and C-N bond formations. In this context, acetylenic C-H bond oxidation has occurred through iodination, leading to the desired products. Moreover, this metal-free, one-pot protocol is accomplished by using readily available starting materials, without external oxidants, and under aerobic conditions, providing a variety of α-ketothioamide compounds in moderate to good yields.

Design, development and bio-evaluation of a novel radio-ligand 99mTc-THQ-DTPA as a sigma 2 receptor specific breast tumor imaging agent.

Over-expression of sigma-2 receptor in cancer cells provides an opportunity to develop molecular probes for diagnosis, even for non-receptor specific malignancies like triple negative breast cancers. In this work, a novel sigma-2 receptor ligand [THQ-DTPA] has been synthesized and characterized using 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (THQ) and diethylenetriaminepentaacetic acid (DTPA). The ligand is further chelated with 99mTc for application as metal based radiotracer [99mTc-THQ-DTPA]. Radiolabelling with 99mTc was achieved in an excellent yield of 98.0 ± 0.5% using stannous chloride as a reducing agent. The radioligand was found to be stable in human serum up-to 24 h, bio-compatible with less than 4% hemolysis, and exhibited high binding with sigma receptors isolated from rat liver membrane (Kd of 16.32 ± 4.93 nM and Bmax of 0.5232 ± 0.06 pmol/mg). Bio-distribution studies in triple-negative breast tumor bearing nude mice showed high tumor uptake after 30 min of injection with tumor/muscle (T/M) ratio of 3.58 ± 0.09. At 240 min, the T/M ratio (2.84 ± 0.20) decreased by 35% when administered in sigma blocked tumor bearing mice (1.81 ± 0.16) suggesting the selectivity of the ligand. Tumor imaging in gamma camera indicated a contrast of 3.56 at 30 min p.i. The above findings indicate that the ligand 99mTc-THQ-DTPA binds to sigma-2 receptors with high affinity and has potential for triple-negative breast tumor imaging.

Appraising LaQshya's potential in measuring quality of care for mothers and newborns: a comprehensive review of India's Labor Room Quality Improvement Initiative.

BACKGROUND: Poor intrapartum care in India contributes to high maternal and newborn mortality. India's Labor Room Quality Improvement Initiative (LaQshya) launched in 2017, aims to improve intrapartum care by minimizing complications, enforcing protocols, and promoting respectful maternity care (RMC). However, limited studies pose a challenge to fully examine its potential to assess quality of maternal and newborn care. This study aims to bridge this knowledge gap and reviews LaQshya's ability to assess maternal and newborn care quality. Findings will guide modifications for enhancing LaQshya's effectiveness. METHODS: We reviewed LaQshya's ability to assess the quality of care through a two-step approach: a comprehensive descriptive analysis using document reviews to highlight program attributes, enablers, and challenges affecting LaQshya's quality assessment capability, and a comparison of its measurement parameters with the 352 quality measures outlined in the WHO Standards for Maternal and Newborn Care. Comparing LaQshya with WHO standards offers insights into how its measurement criteria align with global standards for assessing maternity and newborn care quality. RESULTS: LaQshya utilizes several proven catalysts to enhance and measure quality- institutional structures, empirical measures, external validation, certification, and performance incentives for high-quality care. The program also embodies contemporary methods like quality circles, rapid improvement cycles, ongoing facility training, and plan-do-check, and act (PDCA) strategies for sustained quality enhancement. Key drivers of LaQshya's assessment are- leadership, staff mentoring, digital infrastructure and stakeholder engagement from certified facilities. However, governance issues, understaffing, unclear directives, competency gaps, staff reluctance towards new quality improvement approaches inhibit the program, and its capacity to enhance quality of care. LaQshya addresses 76% of WHO's 352 quality measures for maternal and newborn care but lacks comprehensive assessment of crucial elements: harmful labor practices, mistreatment of mothers or newborns, childbirth support, and effective clinical leadership and supervision. CONCLUSION: LaQshya is a powerful model for evaluating quality of care, surpassing other global assessment tools. To achieve its maximum potential, we suggest strengthening district governance structures and offering tailored training programs for RMC and other new quality processes. Furthermore, expanding its quality measurement metrics to effectively assess provider accountability, patient outcomes, rights, staff supervision, and health facility leadership will increase its ability to assess quality improvements.

HES1 is a novel downstream modifier of the SHH-GLI3 Axis in the development of preaxial polydactyly.

Sonic Hedgehog/GLI3 signaling is critical in regulating digit number, such that Gli3-deficiency results in polydactyly and Shh-deficiency leads to digit number reductions. SHH/GLI3 signaling regulates cell cycle factors controlling mesenchymal cell proliferation, while simultaneously regulating Grem1 to coordinate BMP-induced chondrogenesis. SHH/GLI3 signaling also coordinates the expression of additional genes, however their importance in digit formation remain unknown. Utilizing genetic and molecular approaches, we identified HES1 as a downstream modifier of the SHH/GLI signaling axis capable of inducing preaxial polydactyly (PPD), required for Gli3-deficient PPD, and capable of overcoming digit number constraints of Shh-deficiency. Our data indicate that HES1, a direct SHH/GLI signaling target, induces mesenchymal cell proliferation via suppression of Cdkn1b, while inhibiting chondrogenic genes and the anterior autopod boundary regulator, Pax9. These findings establish HES1 as a critical downstream effector of SHH/GLI3 signaling in the development of PPD.

GripAble: Interrater reliability and normative grip strength of UK population.

BACKGROUND: Hand grip strength is an established indicator of individual health status and is used as a biomarker for predicting mortality, disability, and disease risks. GripAble hand grip dynamometer offers a modernized approach to measuring grip strength with its digital and high-accuracy measurement system. PURPOSE: This study aimed to (1) assess the interrater reliability of maximum grip strength (MGS) measurement and (2) establish GripAble's own gender-, age group- and hand-stratified normative MGS reference values of the adult UK population. STUDY DESIGN: Cross-sectional study design. METHODS: Interrater reliability among three raters assessing 30 participants across diverse age groups was measured using the intraclass correlation. In the second study, 11 investigators gathered MGS data from 907 participants across diverse age groups and gender. The average, standard deviation, minimum, median, maximum, and percentiles of MGS were computed for each gender, age group, and hand (L/R). The relationship between MGS and age was examined using quantile regression analysis. Additionally, generalized linear model regression analysis was conducted to explore the influence of participants' demographics (gender, hand [L/R], hand length, hand circumference, age, weight, and height) on MGS. RESULTS: MGS measurements between raters showed excellent agreement (ICC(2,1) = 0.991, 95% confidence interval [0.98, 1.0]). The MGS and age relationship follows a curvilinear pattern, reaching a peak median MGS values of up to 20 kg between 30 and 49 years for females and up to 35 kg between 30 and 59 years for males. Subsequently, MGS declined as age advanced. Gender and hand (L/R) emerged as the primary factors influencing MGS, followed by hand length, hand circumference, age, weight, and height. CONCLUSIONS: The presented normative MGS reference values can be used for interpreting MGS measurements obtained from adults in the United Kingdom using GripAble. This study, along with previous studies on GripAble devices, confirms GripAble as a reliable and valid tool for measuring MGS.

Biphasic regulation of glutamine consumption by WNT during osteoblast differentiation.

Osteoblasts are the principal bone-forming cells. As such, osteoblasts have enhanced demand for amino acids to sustain high rates of matrix synthesis associated with bone formation. The precise systems utilized by osteoblasts to meet these synthetic demands are not well understood. WNT signaling is known to rapidly stimulate glutamine uptake during osteoblast differentiation. Using a cell biology approach, we identified two amino acid transporters, γ(+)-LAT1 and ASCT2 (encoded by Slc7a7 and Slc1a5, respectively), as the primary transporters of glutamine in response to WNT. ASCT2 mediates the majority of glutamine uptake, whereas γ(+)-LAT1 mediates the rapid increase in glutamine uptake in response to WNT. Mechanistically, WNT signals through the canonical ß-catenin (CTNNB1)-dependent pathway to rapidly induce Slc7a7 expression. Conversely, Slc1a5 expression is regulated by the transcription factor ATF4 downstream of the mTORC1 pathway. Targeting either Slc1a5 or Slc7a7 using shRNA reduced WNT-induced glutamine uptake and prevented osteoblast differentiation. Collectively, these data highlight the critical nature of glutamine transport for WNT-induced osteoblast differentiation.This article has an associated First Person interview with the joint first authors of the paper.

Synthetic Strategies of N-Heterocyclic Olefin (NHOs) and Their Recent Application of Organocatalytic Reactions and Beyond.

N-heterocyclic olefin (NHO) derivatives have an electron-rich as well as highly polarized carabon-carbon (C=C) double bond because of the electron-donating nature of nitrogen and sulphur atoms. While NHOs have been developing as novel organocatalysts and ligands for transition-metal complexes in various organic compound syntheses, different research groups are currently interested in preparing imidazole and triazolium-based chiral NHO catalysts. Some of them have been used for enantioselective organic transformations, but were still elusive. N-heterocyclic olefins, the alkylidene derivatives of N-heterocyclic carbenes (NHC), have shown promising results as effective promoters for numerous organic syntheses such as asymmetric catalysis, hydroborylation, hydrosilylation, reduction, CO2 sequestration, alkylation, cycloaddition, polymerization and the ring-opening reaction of aziridine and epoxides, esterification, C-F bond functionalization, amine coupling, trifluoromethyl thiolation, amination etc. NHOs catalysts with suitable structures can serve as a novel class of Lewis/Bronsted bases with strong basicity and high nucleophilicity properties.These facts strongly suggest their enormous chemical potential as sustainable catalysts for a wide variety of reactions in synthetic chemistry. The synthesis of NHOs and their properties are briefly reviewed in this article, along with a summary of the imidazole and triazole core of NHOs' most recent catalytic uses.

Fundamentals of utilizing microbes in advanced cancer therapeutics: current understanding and potential applications.

One of the biggest health related issues in the twenty-first century is cancer. The current therapeutic platforms have not advanced enough to keep up with the number of rising cases. The traditional therapeutic approaches frequently fail to produce the desired outcomes. Therefore, developing new and more potent remedies is crucial. Recently, investigating microorganisms as potential anti-cancer treatments have garnered a lot of attention. Tumor-targeting microorganisms are more versatile at inhibiting cancer than the majority of standard therapies. Bacteria preferentially gather and thrive inside tumors, where they can trigger anti-cancer immune responses. They can be further trained to generate and distribute anticancer drugs based on clinical requirements using straightforward genetic engineering approaches. To improve clinical outcomes, therapeutic strategies utilizing live tumor-targeting bacteria can be used either alone or in combination with existing anticancer treatments. On the other hand, oncolytic viruses that target cancer cells, gene therapy via viral vectors, and viral immunotherapy are other popular areas of biotechnological investigation. Therefore, viruses serve as a unique candidate for anti-tumor therapy. This chapter describes the role of microbes, primarily bacteria and viruses in anti-cancer therapeutics. The various approaches to utilizing microbes in cancer therapy are discussed and examples of microorganisms that are now in use or that are undergoing experimental research are briefly discussed. We further point out the hurdles and the prospects of microbes-based remedies for cancer treatment.

Modulation of the chain-breaking antioxidant activity of phenolic organochalcogens with various co-antioxidants at various pH values.

Phenolic organochalcogen chain-breaking antioxidants, i.e. 6-bromo-8 (hexadecyltellanyl)-3,3-dimethyl-1,5-dihydro-[1,3]dioxepino[5,6-c]pyridin-9-ol and 2-methyl-2,3-dihydrobenzo[b]selenophene-5-ol, have been investigated in a two-phase (chlorobenzene/water) lipid peroxidation model system as potent inhibitors of lipid peroxyl radicals with various co-antioxidants at various pH values. The pH has a significant effect on the chain-breaking antioxidant activities of phenolic organochalcogens. The key chain-breaking mechanism profile was attributed to the first oxygen atom transfer from the lipid peroxyl radicals to the Se/Te atom, followed by hydrogen atom transfer in a solvent cage from the nearby phenolic group to the resulting alkoxyl radical. Finally, regeneration of organochalcogen antioxidants could take place in the presence of aqueous-soluble co-antioxidants. Also, in the presence of aqueous soluble N-acetylcysteine at pH 1-7, both antioxidants behaved as very good inhibitors of lipid peroxyl radicals. The role of aqueous soluble mild co-antioxidants in the regeneration studies of organochalcogen antioxidants has been investigated in a two-phase lipid peroxidation model system. The importance of the phase transfer catalyst has been explored in the inhibition studies of selenium containing antioxidants using an Fe(II) source. The overall pH-dependent antioxidant activities of organochalcogens depend on their hydrogen atom transfer ability, relative stability, and distribution in the aqueous/lipid phase.

Brevicillin, a novel lanthipeptide from the genus Brevibacillus with antimicrobial, antifungal, and antiviral activity.

AIM: This study was aimed to determine antimicrobial and antiviral activity of a novel lanthipeptide from a Brevibacillus sp. for disinfectant application. METHODS AND RESULTS: The antimicrobial peptide (AMP) was produced by a bacterial strain AF8 identified as a member of the genus Brevibacillus representing a novel species. Whole genome sequence analysis using BAGEL identified a putative complete biosynthetic gene cluster involved in lanthipeptide synthesis. The deduced amino acid sequence of lanthipeptide named as brevicillin, showed >30% similarity with epidermin. Mass determined by MALDI-MS and Q-TOF suggested posttranslational modifications like dehydration of all Ser and Thr amino acids to yield Dha and Dhb, respectively. Amino acid composition determined upon acid hydrolysis is in agreement with core peptide sequence deduced from the putative biosynthetic gene bvrAF8. Biochemical evidence along with stability features ascertained posttranslational modifications during formation of the core peptide. The peptide showed strong activity with 99% killing of pathogens at 12 µg ml-1 within 1 minute. Interestingly, it also showed potent anti-SARS-CoV-2 activity by inhibiting ∼99% virus growth at 10 µg ml-1 in cell culture-based assay. Brevicillin did not show dermal allergic reactions in BALB/c mice. CONCLUSION: This study provides detailed description of a novel lanthipeptide and demonstrates its effective antibacterial, antifungal and anti-SARS-CoV-2 activity.

Nutritional status of school-age children and adolescents in low- and middle-income countries across seven global regions: a synthesis of scoping reviews.

OBJECTIVE: To summarise available evidence on the nutritional status of school-age children and adolescents (5-19 years) from seven global regions and on interventions implemented to improve malnutrition in this population. SETTING: Global. DESIGN: Findings were compiled from seven scoping literature reviews, including data from low- and middle-income countries within the following UNICEF-defined global regions: East Asia and Pacific; Europe and Central Asia; South Asia; West and Central Africa; Eastern and Southern Africa; Middle East and North Africa and Latin America and the Caribbean. RESULTS: A double burden of malnutrition was evident across the world regions reviewed: stunting, thinness, anaemia and other micronutrient deficiencies persisted, alongside rising overweight and obesity prevalence. Transitions towards diets increasingly high in energy-dense, processed and micronutrient-poor foods were observed. Evidence from intervention studies was limited, but suggested that providing multiple micronutrient-fortified foods or beverages at school may effectively target micronutrient deficiencies and facilitate weight gain in undernourished populations. Interventions to prevent or manage overweight and obesity were even more limited. There was minimal evidence of using novel technological approaches to engage school-age children and adolescents, or of involving them in designing interventions. CONCLUSION: The limited data available on nutrition of school-age children and adolescents are neither standardised nor comparable. Consensus on methods for assessing nutritional status and its determinants for this age group is urgently needed to set targets and monitor progress. Additionally, strategies are required to ensure that nutritious, safe and sustainable diets are available, affordable and appealing.

Fix my food: An urgent call to action from adolescents on how they experience and want to see change in their food systems.

BACKGROUND: Global food systems are failing adolescents. Poor diet quality driving malnutrition among adolescents around the world and the quality of foods eaten by adolescents not only determines their health and development, but also is the foundation of thriving communities. The present study aimed to engage adolescents across low-income, middle-income and high-income countries to determine their lived experience of food, food systems and the challenges they face within their food systems. METHODS: The study used the Distributed Data Generation method pioneered by the Young and Resilient Research Centre, at Western Sydney University, to conduct workshops with adolescents aged 10-19 years across the globe in collaboration with UNICEF. Participatory workshops were designed to capture qualitative data on adolescents lived experiences and perspectives of their food systems, food sustainability and food security, and how improvements can be made. Thematic analysis was undertaken to analyse qualitative data. Descriptive statistics were generated for demographic data captured. RESULTS: Six hundred and forty adolescents across 18 countries participated. Three key themes emerged, which included experiences of food, challenges to food systems and strengthening food systems. Adolescents saw potential in empowering communities to create change and contribute to food system transformation. Adolescents called for inclusion in decision-making from local food practice to large global policy development. CONCLUSIONS: The study results demonstrated how adolescents experience their food systems and want to see sustainable change, although they also want to be a part of the change. Adolescents described that there needs to be an active choice to work with them, listen to their lived experience and across all levels of society strengthen food systems. To achieve this, adolescents need to be involved in decision-making around their food systems for a sustainable future.

Nano vs Resistant Tuberculosis: Taking the Lung Route.

Tuberculosis (TB) is among the top 10 infectious diseases worldwide. It is categorized among the leading killer diseases that are the reason for the death of millions of people globally. Although a standardized treatment regimen is available, non-adherence to treatment has increased multi-drug resistance (MDR) and extensive drug-resistant (XDR) TB development. Another challenge is targeting the death of TB reservoirs in the alveoli via conventional treatment. TB Drug resistance may emerge as a futuristic restraint of TB with the scarcity of effective Anti-tubercular drugs. The paradigm change towards nano-targeted drug delivery systems is mostly due to the absence of effective therapy and increased TB infection recurrent episodes with MDR. The emerging field of nanotechnology gave an admirable opportunity to combat MDR and XDR via accurate diagnosis with effective treatment. The new strategies targeting the lung via the pulmonary route may overcome the new incidence of MDR and enhance patient compliance. Therefore, this review highlights the importance and recent research on pulmonary drug delivery with nanotechnology along with prevalence, the need for the development of nanotechnology, beneficial aspects of nanomedicine, safety concerns of nanocarriers, and clinical studies.