An insight to the recent advancements in detection of Mycobacterium tuberculosis using biosensors: A systematic review.

Since ancient times, Tuberculosis (TB) has been a severe invasive illness that has been prevalent for thousands of years and is also known as "consumption" or phthisis. TB is the most common chronic lung bacterial illness in the world, killing over 2 million people each year, caused by Mycobacterium tuberculosis (MTB). As per the reports of WHO, in spite of technology advancements, the average rate of decline in global TB infections from 2000-2018 was only 1.6% per year, and the worldwide reduction in TB deaths was only 11%. In addition, COVID-19 pandemic has reversed years of global progress in tackling TB with fewer diagnosed cases. The majority of undiagnosed patients of TB are found in low- and middle-income countries where the GeneXpert MTB/RIF assay and sputum smear microscopy have been approved by the WHO as reference procedures for quickly detecting TB. Biosensors, like other cutting-edge technologies, have piqued researchers' interest since they offer a quick and accurate way to identify MTB. Modern integrated technologies allow for the rapid, low-cost, and highly precise detection of analytes in extremely little amounts of sample by biosensors. Here in this review, we outlined the severity of tuberculosis (TB) and the most recent developments in the biosensors sector, as well as their various kinds and benefits for TB detection. The review also emphasizes how widespread TB is and how it needs accurate diagnosis and effective treatment.

Salinity alleviates arsenic stress-induced oxidative damage via antioxidative defense and metabolic adjustment in the root of the halophyte Salvadora persica.

MAIN CONCLUSION: Arsenic tolerance in the halophyte Salvadora persica is achieved by enhancing antioxidative defense and modulations of various groups of metabolites like amino acids, organic acids, sugars, sugar alcohols, and phytohormones. Salvadora persica is a facultative halophyte that thrives under high saline and arid regions of the world. In present study, we examine root metabolic responses of S. persica exposed to individual effects of high salinity (750 mM NaCl), arsenic (600 µM As), and combined treatment of salinity and arsenic (250 mM NaCl + 600 µM As) to decipher its As and salinity resistance mechanism. Our results demonstrated that NaCl supplementation reduced the levels of reactive oxygen species (ROS) under As stress. The increased activities of antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione reductase (GR) maintained appropriate levels of ROS [superoxide (O2•-) and hydrogen peroxide (H2O2)] under salinity and/or As stress. The metabolites like sugars, amino acids, polyphenols, and organic acids exhibited higher accumulations when salt was supplied with As. Furthermore, comparatively higher accumulations of glycine, glutamate, and cystine under combined stress of salt and As may indicate its role in glutathione and phytochelatins (PCs) synthesis in root. The levels of phytohormones such as salicylate, jasmonate, abscisic acid, and auxins were significantly increased under high As with and without salinity stress. The amino acid metabolism, glutathione metabolism, carbohydrate metabolism, tricarboxylic acid cycle (TCA cycle), phenylpropanoid biosynthesis, and phenylalanine metabolism are the most significantly altered metabolic pathways in response to NaCl and/or As stress. Our study decoded the important metabolites and metabolic pathways involved in As and/or salinity tolerance in root of the halophyte S. persica providing clues for development of salinity and As resistance crops.

An amide to thioamide substitution improves the permeability and bioavailability of macrocyclic peptides.

Solvent shielding of the amide hydrogen bond donor (NH groups) through chemical modification or conformational control has been successfully utilized to impart membrane permeability to macrocyclic peptides. We demonstrate that passive membrane permeability can also be conferred by masking the amide hydrogen bond acceptor (>C = O) through a thioamide substitution (>C = S). The membrane permeability is a consequence of the lower desolvation penalty of the macrocycle resulting from a concerted effect of conformational restriction, local desolvation of the thioamide bond, and solvent shielding of the amide NH groups. The enhanced permeability and metabolic stability on thioamidation improve the bioavailability of a macrocyclic peptide composed of hydrophobic amino acids when administered through the oral route in rats. Thioamidation of a bioactive macrocyclic peptide composed of polar amino acids results in analogs with longer duration of action in rats when delivered subcutaneously. These results highlight the potential of O to S substitution as a stable backbone modification in improving the pharmacological properties of peptide macrocycles.

Interplay between MYZUS PERSICAE-INDUCED LIPASE 1 and OPDA signaling in limiting green peach aphid infestation on Arabidopsis thaliana.

MYZUS PERSICAE-INDUCED LIPASE1 (MPL1) encodes a lipase in Arabidopsis thaliana that is required for limiting infestation by the green peach aphid (GPA; Myzus persicae), an important phloem sap-consuming insect pest. Previously, we demonstrated that MPL1 expression was up-regulated in response to GPA infestation, and GPA fecundity was higher on the mpl1 mutant, compared with the wild-type (WT), and lower on 35S:MPL1 plants that constitutively expressed MPL1 from the 35S promoter. Here, we show that the MPL1 promoter is active in the phloem and expression of the MPL1 coding sequence from the phloem-specific SUC2 promoter in mpl1 is sufficient to restore resistance to GPA. The GPA infestation-associated up-regulation of MPL1 requires CYCLOPHILIN 20-3 (CYP20-3), which encodes a 12-oxo-phytodienoic acid (OPDA)-binding protein that is involved in OPDA signaling, and is required for limiting GPA infestation. OPDA promotes MPL1 expression to limit GPA fecundity, a process that requires CYP20-3 function. These results along with our observation that constitutive expression of MPL1 from the 35S promoter restores resistance to GPA in the cyp20-3 mutant, and MPL1 acts in a feedback loop to limit OPDA levels in GPA-infested plants, suggest that an interplay between MPL1, OPDA, and CYP20-3 contributes to resistance to GPA.

Reduced Graphene Oxide-Polydopamine-Gold Nanoparticles: A Ternary Nanocomposite-Based Electrochemical Genosensor for Rapid and Early Mycobacterium tuberculosis Detection.

Tuberculosis (TB) has been a devastating human illness for thousands of years. According to the WHO, around 10.4 million new cases of tuberculosis are identified every year, with 1.8 million deaths. To reduce these statistics and the mortality rate, an early and accurate TB diagnosis is essential. This study offers a highly sensitive and selective electrochemical biosensor for Mycobacterium tuberculosis (MTB) detection based on a ternary nanocomposite of reduced graphene oxide, polydopamine, and gold nanoparticles (rGO-PDA-AuNP). Avidin-biotin coupling was used to bind the MTB probe DNA onto the rGO-PDA-AuNP modified glassy carbon electrode (ssDNA/avidin/rGO-PDA-AuNP). UV-Visible, Raman, XRD, and TEM were used to evaluate the structural and morphological characteristics of rGO-PDA-AuNP. Furthermore, DNA immobilization is validated using FESEM and FT-IR techniques. The modified electrodes were electrochemically analyzed using cyclic voltammetry (CV) and linear sweep voltammetry (LSV), and the results indicate that the produced electrode can detect target DNA up to 0.1 × 10-7 mM with 2.12 × 10-3 mA µM-1 sensitivity and a response time of 5 s. The constructed genosensor displayed high sensitivity and stability, and it also provides a unique strategy for diagnosing MTB at an early stage. Furthermore, our rGO-PDA-AuNP/GCE-based electrochemical platform has broad potential for creating biosensor systems for detecting various infectious pathogens and therapeutically significant biomarkers.

Bio-inspired polynorepinephrine based nanocoatings for reduced graphene oxide/gold nanoparticles composite for high-performance biosensing of Mycobacterium tuberculosis.

Polydopamine (PDA) has established itself as a promising grafting and coating material, particularly for functional group-deprived electrochemically active nanomaterials such as graphene, MXene, CNT, metal nanoparticles, and so on, and has proven its extensive applicability in the design and development of electrochemical biosensor devices. However, polynorepinephrine (PNE), a sister compound of PDA, having additional -OH groups and greater coating uniformity and biocompatibility, has never been studied in the field of biosensors. Herein, we investigated PNE as a coating material for reduced graphene oxide (RGO) and gold nanoparticles (Au) in order to build an electrochemical genosensor for Mycobacterium tuberculosis (MTB) detection. Biotin-Avidin chemistry was used to covalently immobilize probe DNA (ssDNA) specific to MTB to the nanocomposite surface on glassy carbon electrode (GCE) in order to construct biosensing electrodes. The formation of RGO/PNE and RGO/PNE/Au nanocomposite as well as the immobilization of ssDNA onto the bioelectrodes are both corroborated by UV-Visible, Raman, and XRD studies with FE-SEM and HR-TEM analysis. The electrochemical studies performed using cyclic voltammetry (CV) and linear sweep voltammetry (LSV) showed the significant enhancement in charge transfer kinetics of RGO/PNE/GCE and RGO/PNE/Au/GCE electrode compared to GO/GCE electrode. The biosensing investigations performed using ssDNA/avidin/RGO/PNE/Au/GCE bioelectrode showed high sensitivity (2.3 × 10-3 mA µM-1), low detection limit (0.1 × 10-7 µM), broad detection range (0.1 × 10-2 to 0.1 × 10-7 µM) with good selectivity and low response time (5 s) of the developed sensor. In comparison to the analogous RGO/PDA/Au material system, RGO/PNE/Au demonstrated increased enzyme loading, improved electrochemical responsiveness, and superior biosensing performance.

Copper iodide nanoparticles (CuI NPs): an efficient catalyst for the synthesis of alkynyl esters.

An environmentally benign protocol for the synthesis of alkynyl esters, by the cross-coupling of diazoacetate with various substituted alkynes under neat reaction conditions, has been described. Copper iodide nanoparticles (CuI NPs) were found to promote the Sonogashira-type coupling to afford the corresponding alkynyl esters in good yields. The CuI nanoparticles were characterized by PXRD, FESEM, EDAX, and Raman techniques. The developed methodology has several advantages such as a broad substrate scope, less reaction time, atom economy, avoidance of an additive/base/solvent, and enhanced values of green chemistry. The catalyst was recycled up to threefold without the loss of its catalytic activity.

Ternary nanocomposite-based smart sensor: Reduced graphene oxide/polydopamine/alanine nanocomposite for simultaneous electrochemical detection of Cd2+, Pb2+, Fe2+, and Cu2+ ions.

Heavy metal ion (HMI) sensors are the most sought commercial devices for environmental monitoring and food analysis research due to serious health concerns associated with HMI overdosage. Herein, we developed an effective electrochemical sensor for simultaneous detection of four HMI (Cd2+, Pb2+, Fe2+, and Cu2+) using a ternary nanocomposite of reduced graphene oxide functionalized with polydopamine and alanine (ALA/pDA/rGO). Comprehensive spectroscopic and microscopic characterizations were performed to ensure the formation of the ternary nanocomposite. The developed nanocomposite on glassy carbon electrode (GCE) yields >2-fold higher current than GO/GCE electrode with excellent electrochemical stability and charge transfer rate. Using DPV, various chemical and electrochemical parameters, such as supporting electrolyte, buffer pH, metal deposition time, and potential, were optimized to achieve highly sensitive detection of targeted HMI. For Cd2+, Pb2+, Fe2+, and Cu2+ sensing devised sensor exhibited detection limits of 1.46, 2.86, 50.23, and 17.95 ppb and sensitivity of 0.0929, 0.0744, 0.0051, and 0.0394 µA/ppb, respectively, with <6% interference. The sensor worked similarly well for real water samples with HMI. This study demonstrates a novel strategy for concurrently detecting and quantifying multiple HMI in water and soil using a smart ternary nanocomposite-based electrochemical sensor, which can also detect HMI in food samples.

Regulation of chromium translocation to shoot and physiological, metabolomic, and ionomic adjustments confer chromium stress tolerance in the halophyte Suaeda maritima.

Chromium (Cr) is a highly toxic element adversely affecting the environment, cultivable lands, and human populations. The present study investigated the effects of Cr (VI) (100-400 µM) on plant morphology and growth, photosynthetic pigments, organic osmolytes, ionomics, and metabolomic dynamics of the halophyte Suaeda maritima to decipher the Cr tolerance mechanisms. Cr exposure reduced the growth and biomass in S. maritima. The photosynthetic pigments content significantly declined at higher Cr concentrations (400 µM). However, at lower Cr concentrations (100-300 µM), the photosynthetic pigments remained unaffected or increased. The results suggest that a high concentration of Cr exposure might have adverse effects on PS II in S. maritima. The enhanced uptake of Na+ in S. maritima imposed to Cr stress indicates that Na+ might have a pivotal role in osmotic adjustment, thereby maintaining water status under Cr stress. The proline content was significantly upregulated in Cr-treated plants suggesting its role in maintaining osmotic balance and scavenging ROS. The metabolomic analysis of control and 400 µM Cr treated plants led to the identification of 62 metabolites. The fold chain analysis indicated the upregulation of several metabolites, including phytohormones (SA and GA3), polyphenols (cinnamic acid, sinapic acid, coumaric acid, vanillic acid, and syringic acid), and amino acids (alanine, leucine, proline, methionine, and cysteine) under Cr stress. The upregulation of these metabolites suggests the enhanced metal chelation and sequestration in vacuoles, reducing oxidative stress by scavenging ROS and promoting photosynthesis by maintaining the chloroplast membrane structure and photosynthetic pigments. Furthermore, in S. maritima, Cr tolerance index (Ti) was more than 60% in all the treatments, and Cr bio-concentration factor (BCF) and translocation factor (Tf) values were all greater than 1.0, which clearly indicates the Cr-hyperaccumulator characteristics of this halophyte.

Converging Pathways: Exploring the Interplay of Malnutrition, Sarcopenia, and Frailty in Nursing Home Residents: A Cross-sectional Study.

Background: Within the context of nursing home care, malnutrition, sarcopenia, and frailty stand as notable conditions, each exerting distinct yet interconnected impacts on residents' well-being. The objective of this cross-sectional study is to elucidate the intricate interplay among malnutrition, sarcopenia, and frailty among nursing home residents. Methodology: It is a community-based, cross-sectional, descriptive study among nursing home residents of Vatsalyadham Vrudhsharam, which is an institution for aged old-age people in Jamnagar from April 2023 to July 2023. The estimated minimum sample size was 345. A self-structured questionnaire was used to collect the data containing sociodemographic characteristics, anthropometric assessment, and bio-impedance indices. The handgrip was measured by a hand dynamometer. Assessment of the risk of malnutrition was performed using the Mini Nutritional Assessment-Short Form questionnaire and was confirmed by the Global Leadership Initiative for Malnutrition (GLIM) criteria. Sarcopenia was assessed by a bio-impedance analyzer using the Asian Working Group of Sarcopenia 2019. Frailty was assessed using the fatigue, resistance, ambulation, illness, and loss (FRAIL) screener. Descriptive statistics were used for the representation of percentages and frequencies. Both Chi-square and logistic regression analyses were used for the association. P < 0.05 was considered statistically significant, respectively. Results: About 345 participants were included, and mean age of the participants was 85 ± 5.6 years, about 159 (49%) participants belonged to the age group of more than 80 years, 220 (63.7%) were males, then malnutrition was diagnosed by GLIM criteria, about 154 (44.6%) were found to have malnutrition. Sarcopenia was found in 184 (53%) participants. The FRAIL screening was used to identify frailty, according to that prefrail was around 170 (49%) and frail was about 122 (35%), respectively. Age, gender, and history of falls were associated with frailty and sarcopenia (P < 0.001). Only, age and gender were associated with malnutrition but not a history of falls. Conclusion: The findings of this study suggest that frailty, sarcopenia, and malnutrition are prevalent among nursing home residents. Health-care providers should identify and manage these conditions in older adults to improve their quality of life.

Assessment of Knowledge, Attitudes, and Practices Regarding Menstrual Hygiene Management Among Adolescent Schoolgirls (10-19 Years) in the Saurashtra Region, Gujarat.

Background Menstrual health management proves pivotal for the adoption of hygienic practices and the embracement of womanhood from the onset of menarche. Menstrual hygiene is pivotal yet under-addressed among adolescent girls in India. This study aimed to assess the knowledge, attitudes, and practices regarding menstrual hygiene and influencing factors. Methodology A cross-sectional study was conducted among 361 adolescent schoolgirls aged 10-19 years in the Saurashtra region of Gujarat using a pretested questionnaire. Multistage sampling was used. In the first stage, six schools (three rural and three urban) were selected through random sampling. In the second stage, all adolescent girls aged 10-19 years in the selected schools who had attained menarche were invited to participate. Those who provided written assent were included in the study. The data were analyzed with descriptive statistics and logistic regression. A p-value <0.05 was considered significant. Results Knowledge about menstruation was evenly distributed as good (47.65%) and poor (52.35%). Most relied on mothers for information and considered menstruation a normal phenomenon. Attitudes reflected complex cultural perceptions. The use of sanitary pads was high (96.12%), although 39.89% used reused absorbents. Multivariate analysis revealed age 16-19 years (adjusted odds ratio (AOR) = 2.08, 95% confidence interval (CI) = 1.14-3.81), higher parental education, pit latrine usage (AOR = 6.7, 95% CI = 2.97-15.15), and knowledge about menstruation (AOR = 8.21, 95% CI = 4.56-14.78) as positive predictors of good menstrual practices. Conclusions Despite the widespread use of sanitary pads, the persisting knowledge gap and sociocultural influences lead to unhygienic practices. Improving awareness and attitudes through educational interventions among adolescent girls and mothers, in particular, addressing cultural taboos through the engagement of all stakeholders, and improving sanitation infrastructure in schools are imperative.

Characterizing OPRM1 DNA methylation in prescription opioid users with chronic musculoskeletal pain.

Introduction: Many patients with chronic pain use prescription opioids. Epigenetic modification of the µ-opioid receptor 1 (OPRM1) gene, which codes for the target protein of opioids, may influence vulnerability to opioid abuse and response to opioid pharmacotherapy, potentially affecting pain outcomes. Objective: Our objective was to investigate associations of clinical and sociodemographic factors with OPRM1 DNA methylation in patients with chronic musculoskeletal pain on long-term prescription opioids. Methods: Sociodemographic variables, survey data (Rapid Estimate of Adult Health Literacy in Medicine-Short Form, Functional Comorbidity Index [FCI], PROMIS 43v2.1 Profile, Opioid Risk Tool, and PROMIS Prescription Pain Medication Misuse), and saliva samples were collected. The genomic DNA extracted from saliva samples were bisulfite converted, amplified by polymerase chain reaction, and processed for OPRM1-targeted DNA methylation analysis on a Pyrosequencing instrument (Qiagen Inc, Valencia, CA). General linear models were used to examine the relationships between the predictors and OPRM1 DNA methylation. Results: Data from 112 patients were analyzed. The best-fitted multivariable model indicated, compared with their counterparts, patients with > eighth grade reading level, degenerative disk disease, substance abuse comorbidity, and opioid use < 1 year (compared with >5 years), had average methylation levels that were 7.7% (95% confidence interval [CI] 0.95%, 14.4%), 11.7% (95% CI 2.7%, 21.1%), 21.7% (95% CI 10.7%, 32.5%), and 16.1% (95% CI 3.3%, 28.8%) higher than the reference groups, respectively. Methylation levels were 2.2% (95% CI 0.64%, 3.7%) lower for every 1 unit increase in FCI and greater by 0.45% (95% CI 0.08%, 0.82%) for every fatigue T score unit increase. Conclusions: OPRM1 methylation levels varied by several patient factors. Further studies are warranted to replicate these findings and determine potential clinical utility.

Targeting G protein coupled receptors for alleviating neuropathic pain.

Pain sensation is a normal physiological response to alert and prevent further tissue damage. It involves the perception of external stimuli by somatosensory neurons, then transmission of the message to various other types of neurons present in the spinal cord and brain to generate an appropriate response. Currently available analgesics exhibit very modest efficacy, and that too in only a subset of patients with chronic pain conditions, particularly neuropathic pain. The G protein-coupled receptors (GPCRs) are expressed on presynaptic, postsynaptic terminals, and soma of somatosensory neurons, which binds to various types of ligands to modulate neuronal activity and thus pain sensation in both directions. Fundamentally, neuropathic pain arises due to aberrant neuronal plasticity, which includes the sensitization of peripheral primary afferents (dorsal root ganglia and trigeminal ganglia) and the sensitization of central nociceptive neurons in the spinal cord or trigeminal nucleus or brain stem and cortex. Owing to the expression profiles of GPCRs in somatosensory neurons and other neuroanatomical regions involved in pain processing and transmission, this article shall focus only on four families of GPCRs: 1- Opioid receptors, 2-Cannabinoid receptors, 3-Adenosine receptors, and 4-Chemokine receptors.

Development of copper impregnated bio-inspired hydrophobic antibacterial nanocoatings for textiles.

Due to their bactericidal and fluid repellent capabilities, antimicrobial textiles with hydrophobic properties have aroused a lot of interest in healthcare, hygiene, air purifiers, water purification systems, food packaging, and other domains. Silver and silver-derived compounds have long been employed in antimicrobial coatings; nevertheless, they are costly, limiting their widespread use. In this work, we combined mussel-inspired polydopamine (pDA) coating chemistry with graphene oxide (GO) and antimicrobial copper compounds (Cu(NO3)2, CuCl2, Cu nanoparticles (CuNPs), and Cu-Carbon nanofibers (Cu-CNF)) to create hydrophobic antimicrobial nanocoatings on cotton fabric. The structural, morphological, wettability, and antibacterial characteristics of the produced coatings were evaluated. The fabric coated with Cu(NO3)2 and CuNPs had good hydrophobicity, which was stabilized for 30 min following GO integration. The coated fabric with GO and CuNPs showed 100% bacterial inhibition for S. aureus and a 99.995% reduction for P. aeruginosa bacteria. Overall, this bioinspired approach to developing antimicrobial coatings on fabric utilizing Cu(NO3)2 and CuNPs with GO shows a lot of promise in preventing the transmission of bacterial and viral infections through contaminated garments and has potential in designing clothing for healthcare settings such as PPEs, gowns, aprons, face mask filters, curtains, and so on.

Recent applications of nanoparticles in organic transformations.

A variation in the size of metal nanoparticles leads to a difference in their properties. As the size of metal nanoparticles decreases, the surface area increases which leads to an increase in the reactivity of metal nanoparticles. Metals like Au, Ag, Pd, and Pt have interesting properties when used in nanometric dimensions. They function efficiently in significant industrial processes as electrocatalysts and photocatalysts in various organic reactions. Recently, the green biosynthesis of nanoparticles has attracted the attention of researchers. With environmental pollution rising over the past few decades, metal nanoparticle catalysts could be the key to subdue the toxic effects. Being versatile, they can be used to degrade pollutants, develop solar cells, convert toxic nitroaromatic compounds, significantly reduce CO2 emissions per unit of energy, and many more. Owing to their unique properties, nanoparticles have wide applications in biomedicine, for example, gold cages are promising agents for cancer diagnosis and therapy. Transition metal-oxide nanoparticles have been considered one of the best supercapacitor electrodes with high electrochemical performance. In this review, we have summarised fundamental concepts of metal nanoparticles over the last decade's main emphasis from 2010 to 2021. It focuses on the exceptional use of these nanocatalysts in various organic reactions. Additionally, we have also discussed the utility of these reactions and their crucial role in solving the problems of today. Through this article, we hope to provide the necessary framework needed to further advance the applications of metal nanoparticles as catalysts.

Transition-metal-free regioselective hydroamination of styrenes with amino-heteroarenes.

The base-mediated anti-Markovnikov hydroamination of functionally varied styrenes with amino-substituted pyridine, quinoline, pyrimidine, pyrazine, and phenanthridine with excellent regioselectivity has been described. Double hydroamination was observed chemoselectively on the secondary amine, leaving the primary amine intact. Experimental evidence suggests that the proposed reaction involves the nucleophilic addition of the aminopyridyl radical onto vinyl arenes via a single electron transfer.

Successful treatment of acute worsening complex regional pain syndrome in affected dominant right-hand from secondary pathology of new onset third and fourth digit trigger finger.

65 year old male with preexisting Complex Regional Pain Syndrome (CRPS) in right dominant hand with sudden onset of right third and fourth digit trigger finger successfully treated with flexor tendon sheath corticosteroid and lidocaine injection resulting in long-term resolution of symptoms without causing widely believed aggravation of CRPS.

Frataxin deficiency lowers lean mass and triggers the integrated stress response in skeletal muscle.

Friedreich's ataxia (FRDA) is an inherited disorder caused by reduced levels of frataxin (FXN), which is required for iron-sulfur cluster biogenesis. Neurological and cardiac comorbidities are prominent and have been a major focus of study. Skeletal muscle has received less attention despite indications that FXN loss affects it. Here, we show that lean mass is lower, whereas body mass index is unaltered, in separate cohorts of adults and children with FRDA. In adults, lower lean mass correlated with disease severity. To further investigate FXN loss in skeletal muscle, we used a transgenic mouse model of whole-body inducible and progressive FXN depletion. There was little impact of FXN loss when FXN was approximately 20% of control levels. When residual FXN was approximately 5% of control levels, muscle mass was lower along with absolute grip strength. When we examined mechanisms that can affect muscle mass, only global protein translation was lower, accompanied by integrated stress response (ISR) activation. Also in mice, aerobic exercise training, initiated prior to the muscle mass difference, improved running capacity, yet, muscle mass and the ISR remained as in untrained mice. Thus, FXN loss can lead to lower lean mass, with ISR activation, both of which are insensitive to exercise training.