Brown-top millet: an overview of breeding, genetic, and genomic resources development for crop improvement.

MAIN CONCLUSION: Brown-top millet is a lesser-known millet with a high grain nutrient value, early maturation, and drought tolerance that needs basic research to understand and conserve food security. Brown-top millet [Urochloa ramosa (L.)] is currently cultivated in some developing countries (especially in India) for food and fodder, although it is less known among the small millets. Like other millets, it contains macro- and micronutrients, vitamins, minerals, proteins, and fiber, all of which have rich health benefits. The nutritional importance and health benefits of brown-top millet are still unknown to many people due to a lack of awareness, wide cultivation, and research. Hence, this millet is currently overshadowed by other major cereals. This review article aims to present the nutritional, breeding, genetic, and genomic resources of brown-top millet to inform millet and other plant researchers. It is important to note that genetic and genomic resources have not yet been created for this millet. To date, there are no genomic and transcriptomic resources for brown-top millet to develop single nucleotide polymorphisms (SNP) and insertion/Deletions (InDels) for breeding studies. Furthermore, studies regarding nutritional significance and health benefits are required to investigate the exact nutritional contents and health benefits of the brown-top millet. The present review delves into the nutritional value and health advantages of brown-top millet, as supported by the available literature. The limitations of producing brown-top millet have been enumerated. We also cover the status of marker-assisted breeding and functional genomics research on closely related species. Lastly, we draw insights for further research such as developing omics resources and applying genome editing to study and improve brown-top millet. This review will help to start breeding and other molecular studies to increase the growth and development of this cereal.

DNA hypomethylation activates Cdk4/6 and Atr to induce DNA replication and cell cycle arrest to constrain liver outgrowth in zebrafish.

Coordinating epigenomic inheritance and cell cycle progression is essential for organogenesis. UHRF1 connects these functions during development by facilitating maintenance of DNA methylation and cell cycle progression. Here, we provide evidence resolving the paradoxical phenotype of uhrf1 mutant zebrafish embryos which have activation of pro-proliferative genes and increased number of hepatocytes in S-phase, but the liver fails to grow. We uncover decreased Cdkn2a/b and persistent Cdk4/6 activation as the mechanism driving uhrf1 mutant hepatocytes into S-phase. This induces replication stress, DNA damage and Atr activation. Palbociclib treatment of uhrf1 mutants prevented aberrant S-phase entry, reduced DNA damage, and rescued most cellular and developmental phenotypes, but it did not rescue DNA hypomethylation, transposon expression or the interferon response. Inhibiting Atr reduced DNA replication and increased liver size in uhrf1 mutants, suggesting that Atr activation leads to dormant origin firing and prevents hepatocyte proliferation. Cdkn2a/b was downregulated pro-proliferative genes were also induced in a Cdk4/6 dependent fashion in the liver of dnmt1 mutants, suggesting DNA hypomethylation as a mechanism of Cdk4/6 activation during development. This shows that the developmental defects caused by DNA hypomethylation are attributed to persistent Cdk4/6 activation, DNA replication stress, dormant origin firing and cell cycle inhibition.

Clinical standards for the management of adverse effects during treatment for TB.

BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.

The First Differentiated TB Care Model From India: Delays and Predictors of Losses in the Care Cascade.

To reduce TB deaths in resource-limited settings, a differentiated care strategy can be used to triage patients with high risk of severe illness (i.e., those with very severe undernutrition, respiratory insufficiency, or inability to stand without support) at diagnosis and refer them for comprehensive assessment and inpatient care. Globally, there are few examples of implementing this type of strategy in routine program settings. Beginning in April 2022, the Indian state of Tamil Nadu implemented a differentiated care strategy called Tamil Nadu-Kasanoi Erappila Thittam (TN-KET) for all adults aged 15 years and older with drug-susceptible TB notified by public facilities. Before evaluating the impact on TB deaths, we sought to understand the retention and delays in the care cascade as well as predictors of losses. During April-June 2022, 14,961 TB patients were notified and 11,599 (78%) were triaged. Of those triaged, 1,509 (13%) were at high risk of severe illness; of these, 1,128 (75%) were comprehensively assessed at a nodal inpatient care facility. Of 993 confirmed as severely ill, 909 (92%) were admitted, with 8% unfavorable admission outcomes (4% deaths). Median admission duration was 4 days. From diagnosis, the median delay in triaging and admission of severely ill patients was 1 day each. Likelihood of triaging decreased for people with extrapulmonary TB, those diagnosed in high-notification districts or teaching hospitals, and those transferred out of district. Predictors of not being comprehensively assessed included: aged 25-34 years, able to stand without support, and diagnosis at a primary or secondary-level facility. Inability to stand without support was a predictor of unfavorable admission outcomes. To conclude, the first quarter of implementation suggests that TN-KET was feasible to implement but could be improved by addressing predictors of losses in the care cascade and increasing admission duration.

--Eleven tips for operational researchers working with health programmes: our experience based on implementing differentiated tuberculosis care in south India.

Due to the workload and lack of a critical mass of trained operational researchers within their ranks, health systems and programmes may not be able to dedicate sufficient time to conducting operational research (OR). Hence, they may need the technical support of operational researchers from research/academic organisations. Additionally, there is a knowledge gap regarding implementing differentiated tuberculosis (TB) care in programme settings. In this 'how we did it' paper, we share our experience of implementing a differentiated TB care model along with an inbuilt OR component in Tamil Nadu, a southern state in India. This was a health system initiative through a collaboration of the State TB cell with the Indian Council of Medical Research institutes and the World Health Organisation country office in India. The learnings are in the form of eleven tips: four broad principles (OR on priority areas and make it a health system initiative, implement simple and holistic ideas, embed OR within routine programme settings, aim for long-term engagement), four related to strategic planning (big team of investigators, joint leadership, decentralised decision-making, working in advance) and three about implementation planning (conducting pilots, smart use of e-tools and operational research publications at frequent intervals). These may act as a guide for other Indian states, high TB burden countries that want to implement differentiated care, and for operational researchers in providing technical assistance for strengthening implementation and conducting OR in health systems and programmes (TB or other health programmes). Following these tips may increase the chances of i) an enriching engagement, ii) policy/practice change, and iii) sustainable implementation.

Clinical standards for the dosing and management of TB drugs.

BACKGROUND: Optimal drug dosing is important to ensure adequate response to treatment, prevent development of drug resistance and reduce drug toxicity. The aim of these clinical standards is to provide guidance on 'best practice´ for dosing and management of TB drugs.METHODS: A panel of 57 global experts in the fields of microbiology, pharmacology and TB care were identified; 51 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all participants.RESULTS: Six clinical standards were defined: Standard 1, defining the most appropriate initial dose for TB treatment; Standard 2, identifying patients who may be at risk of sub-optimal drug exposure; Standard 3, identifying patients at risk of developing drug-related toxicity and how best to manage this risk; Standard 4, identifying patients who can benefit from therapeutic drug monitoring (TDM); Standard 5, highlighting education and counselling that should be provided to people initiating TB treatment; and Standard 6, providing essential education for healthcare professionals. In addition, consensus research priorities were identified.CONCLUSION: This is the first consensus-based Clinical Standards for the dosing and management of TB drugs to guide clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment to improve patient care.

Effect of SARS-CoV-2 seropositivity on antigen - specific cytokine and chemokine responses in latent tuberculosis.

SARS-CoV-2 and latent Mycobacterium tuberculosis infection are both highly co-prevalent in many parts of the globe. Whether exposure to SARS-CoV-2 influences the antigen specific immune responses in latent tuberculosis has not been investigated. We examined the baseline, mycobacterial antigen and mitogen induced cytokine and chemokine responses in latent tuberculosis (LTBI) individuals with or without SARS-CoV-2 seropositivity, LTBI negative individuals with SARS-CoV-2 seropositivity and healthy control (both LTBI and SARS-CoV-2 negative) individuals. Our results demonstrated that LTBI individuals with SARS-CoV-2 seropositivity (LTBI+/IgG +) were associated with increased levels of unstimulated and TB-antigen stimulated IFNγ, IL-2, TNFα, IL-17, IL-1ß, IL-6, IL-12, IL-4, CXCL1, CXCL9 and CXCL10 when compared to those without seropositivity (LTBI+/IgG-). In contrast, LTBI+/IgG+ individuals were associated with decreased levels of IL-5 and IL-10. No significant difference in the levels of cytokines/chemokines was observed upon mitogen stimulation between the groups. SARS-CoV-2 seropositivity was associated with enhanced unstimulated and TB-antigen stimulated but not mitogen stimulated production of cytokines and chemokines in LTBI+ compared to LTBI negative individuals. Finally, most of these significant differences were not observed when LTBI negative individuals with SARS-CoV-2 seropositivity and controls were examined. Our data clearly demonstrate that both baseline and TB - antigen induced cytokine responses are augmented in the presence of SARS-CoV-2 seropositivity, suggesting an augmenting effect of prior SARS-CoV-2 infection on the immune responses of LTBI individuals.

Nuclear Organization during Hepatogenesis in Zebrafish Requires Uhrf1.

Acquisition of cellular fate during development is initiated and maintained by well-coordinated patterns of gene expression that are dictated by the epigenetic landscape and genome organization in the nucleus. While the epigenetic marks that mediate developmental gene expression patterns during organogenesis have been well studied, less is known about how epigenetic marks influence nuclear organization during development. This study examines the relationship between nuclear structure, chromatin accessibility, DNA methylation, and gene expression during hepatic outgrowth in zebrafish larvae. We investigate the relationship between these features using mutants that lack DNA methylation. Hepatocyte nuclear morphology was established coincident with hepatocyte differentiation at 80 h post-fertilization (hpf), and nuclear shape and size continued to change until the conclusion of outgrowth and morphogenesis at 120 hpf. Integrating ATAC-Seq analysis with DNA methylation profiling of zebrafish livers at 120 hpf showed that closed and highly methylated chromatin occupies most transposable elements and that open chromatin correlated with gene expression. DNA hypomethylation, due to mutation of genes encoding ubiquitin-like, containing PHD and RING Finger Domains 1 (uhrf1) and DNA methyltransferase (dnmt1), did not block hepatocyte differentiation, but had dramatic effects on nuclear organization. Hepatocytes in uhrf1 mutants have large, deformed nuclei with multiple nucleoli, downregulation of nucleolar genes, and a complete lack of the nuclear lamina. Loss of lamin B2 staining was phenocopied by dnmt1 mutation. Together, these data show that hepatocyte nuclear morphogenesis coincides with organ morphogenesis and outgrowth, and that DNA methylation directs chromatin organization, and, in turn, hepatocyte nuclear shape and size during liver development.

uhrf1 and dnmt1 Loss Induces an Immune Response in Zebrafish Livers Due to Viral Mimicry by Transposable Elements.

Activation of transposable elements (TEs) can cause cellular damage. Cytoplasmic nucleic acid sensing pathways evolved to detect pathogens, but can also serve to cull cells with inappropriate TE activation as TEs can be viral mimetics. Epigenetic silencing of TEs is mediated in part by DNA methylation, but it is not clear if TE activation or the immune system contribute to the cellular damage caused by loss of DNA methylation. Here, we provide mechanistic insight into the observation of an activated interferon response in the liver of zebrafish larvae with deletion in critical components of the DNA methylation machinery, uhrf1 and dnmt1. We focus on dissecting the relationship between DNA methylation, TE activation and induction of an immune response through cytoplasmic DNA and double stranded RNA sensing pathways and identify tnfa as a mediator of cell death in the liver of these mutants. Integrated RNAseq and methylome analysis identified LTR transposons as the most upregulated in these mutants and also the most methylated in control larvae, indicating a direct role of DNA methylation in suppressing this TE subclass. RNAseq analysis from these same samples revealed expression signatures of a type-I interferon response and of tnfa activation, mimicking the pattern of gene expression in virally infected cells. CRISPR/Cas9 mediated depletion of the cellular antiviral sensors sting and mavs reduced expression of interferon response genes and tnfa depletion dramatically reduced cell death in uhrf1 mutant livers. This suggests that the antiviral response induced by DNA hypomethylation and TE activation in the liver is mediated by the signaling pathways activated by both cytoplasmic double stranded RNA and DNA and that tnfa mediates cell death as a potential mechanism to eliminate these damaged cells.

COVID-19 in Patients with Myasthenia Gravis: Mechanisms of Respiratory Failure.

This report describes a patient with thymomatous myasthenia gravis (MG) with aplastic anemia in pharmacological remission and COVID-19 who developed respiratory failure in the course of the disease and reviews the published literature on this topic. Analysis of the clinical characteristics of the eight patients with MG including our patient suggests two possible mechanisms for respiratory failure: myasthenic crisis (MC) or pulmonary complications of COVID-19. Patients with MC were young women in high-grade MGFA Class whereas patients with respiratory failure due to pulmonary complications of COVID-19 were elderly men in pharmacological remission or MGFA Class I. These observations suggest that COVID-19, like other infections, may precipitate MC in patients with severe grade MG before COVID-19. The only differentiating feature between the two types of failure was severity myasthenic weakness. This clinical distinction has management implications. These observations need to be validated in a larger sample.

Fabrication of chlorambucil loaded graphene- oxide nanocarrier and its application for improved antitumor activity.

The present study aims at designing a biodegradable and biocompatible nanocarrier using gelatin and reduced graphene oxide nanosheets functionalized with folic acid, for release of chlorambucil drug in controlled manner and achieving high loading efficiency. From scanning electron microscopic studies small pore like structure with rough and thick morphology on the plane of graphene oxide is clearly visible indicating high loading of drug. Further, Drug loading and encapsulation efficiency, in vitro release studies of the drug from the nanocarrier at different concentrations of reduced graphene oxide, different pH were studied. The mean particle size, entrapment efficiency (%) of optimized folic acid functionalized gelatin-graphene oxide formulation was observed to be 300 nm and 56% respectively. From the release studies it is clear that, after 24 h the release rate of the drug was found to be higher at acidic conditions compared to neutral conditions. It was found that 62.1% and 82% of the total bound drug was released from the nanocarrier at pH 5.4 and pH 1.2 respectively. Besides, under neutral conditions (pH 7.4), 43.7% of the total bound drug was released from the nanocarrier in the first 24 h. The % cell viability of free drug, drug loaded nanocomposites against human cervical adenocarcinoma cell line was found to be 11.7% and 28% respectively at the dose of 500 µg mL-1 after 24 h. IC50 values also manifest the significantly lower cytotoxicity of drug loaded nanocarrier (IC50 = 125.9 µg/mL) as compared to free-drug (IC50 = 86 µg/mL). For FAGGO, CLB and CLB-FAGGO the values of mean ± std. deviation were found to be 71.80 ± 6.66; 48.71 ± 23.15; 55.48 ± 19.65 respectively. The unique properties exhibited by biodegradable polymer like gelatin and carbon based materials such as graphene offers an excellent applications in biomedical field.

Development of rGO encapsulated polymeric beads as drug delivery system for improved loading and controlled release of doxycycline drug.

Objective: The aim of this study was to design a biodegradable core-shell structure where in reduced graphene-oxide (rGO) and doxycycline (DXC) drug comprise the core while polymer such as chitosan (CS) and alginate (ALG) acts as shell for attaining high loading efficiency and sustained release of drug.Significance: Cytotoxic drug used in conventional chemotherapeutic methods usually suffer from poor site selectivity and this has been resolved by using targeted delivery of anticancer drug with controlled drug release property.Methods: The structural and morphological properties of as synthesized drug delivery carrier were characterized by a range of techniques. Drug encapsulation efficiency and the studies on, in vitro release of the drug from these nanocarriers at different concentrations of rGO were carried out.Results: Across all batches of rGO-polymeric beads, the highest loading capacity of 85% was noted for rGO of wt 5 mg/ml. Further, for the formulations of only rGO, highest LE of 90% was noticed in 1 h and 100% loading was noticed in 3 h. The interaction of DXC and its release from the nanocarriers were controlled by the pH changes. At pH 1.2 for rGO-polymeric beads + DXC, the DXC release was reached 27.4% after 2 h; and at pH 5.4, the same beads liberated 57% of the drug after 4 h; and at pH 7.4 after 8 h, 90% of DXC was released into the medium.Conclusions: rGO-polymeric beads supported long-lasting and continuous DXC release which is slower at acidic pH (endosomal pH) than at physiological.

Effectiveness of isoniazid preventive therapy on incidence of tuberculosis among HIV-infected adults in programme setting.

BACKGROUND & OBJECTIVES: As India and other developing countries are scaling up isoniazid preventive therapy (IPT) for people living with HIV (PLHIV) in their national programmes, we studied the feasibility and performance of IPT in terms of treatment adherence, outcome and post-treatment effect when given under programmatic settings. METHODS: A multicentre, prospective pilot study was initiated among adults living with HIV on isoniazid 300 mg with pyridoxine 50 mg after ruling out active tuberculosis (TB). Symptom review and counselling were done monthly during IPT and for six-month post-IPT. The TB incidence rate was calculated and risk factors were identified. RESULTS: Among 4528 adults living with HIV who initiated IPT, 4015 (89%) successfully completed IPT. IPT was terminated in 121 adults (3%) due to grade 2 or above adverse events. Twenty five PLHIVs developed TB while on IPT. The incidence of TB while on IPT was 1.17/100 person-years (p-y) [95% confidence interval (CI) 0.8-1.73] as compared to TB incidence of 2.42/100 p-y (95% CI 1.90-3.10) during the pre-IPT period at these centres (P=0.017). The incidence of TB post-IPT was 0.64/100 p-y (95% CI 0.04-1.12). No single factor was significantly associated with the development of TB. INTERPRETATION & CONCLUSIONS: Under programmatic settings, completion of IPT treatment was high, adverse events minimal with good post-treatment protection. After ruling out TB, IPT should be offered to all PLHIVs, irrespective of their antiretroviral therapy (ART) status. Scaling-up of IPT services including active case finding, periodic counselling on adherence and re-training of ART staff should be prioritized to reduce the TB burden in this community.

Tendon Stem/Progenitor Cells and Their Interactions with Extracellular Matrix and Mechanical Loading.

Tendons are unique connective tissues in the sense that their biological properties are largely determined by their tendon-specific stem cells, extracellular matrix (ECM) surrounding the stem cells, mechanical loading conditions placed on the tendon, and the complex interactions among them. This review is aimed at providing an overview of recent advances in the identification and characterization of tendon stem/progenitor cells (TSPCs) and their interactions with ECM and mechanical loading. In addition, the effects of such interactions on the maintenance of tendon homeostasis and the initiation of tendon pathological conditions are discussed. Moreover, the challenges in further investigations of TSPC mechanobiology in vitro and in vivo are outlined. Finally, future research efforts are suggested, which include using specific gene knockout models and single-cell transcription profiling to enable a broad and deep understanding of the physiology and pathophysiology of tendons.

Tuning Band Alignments and Charge-Transport Properties through MoSe2 Bridging between MoS2 and Cadmium Sulfide for Enhanced Hydrogen Production.

Transition-metal dichalcogenide materials play a major role in the state-of-the-art innovations for energy conversion because of potential applications resulting from their unique properties. These materials additionally show inordinate potential toward the progress of hygienic power sources to deal with increasing environmental disputes at the time of skyrocketing energy demands. Herein, we report earth-abundant, few-layered, MoSe2-bridged MoS2/cadmium sulfide (CdS) nanocomposites, which reduce photogenerated electron and hole recombination by effectively separating charge carriers to achieve a high photocatalytic efficiency. Accordingly, the MoSe2-bridged MoS2/CdS system produced effective hydrogen (193 µmol·h-1) as that of water using lactic acid as a hole scavenger with the irradiation of solar light. The presence of few-layered MoSe2 bridges in MoS2/CdS successfully separates photogenerated charge carriers, thereby enhancing the shuttling of electrons on the surface to active edge sites. To the best of our knowledge, this few-layered MoSe2-bridged MoS2/CdS system exhibits the most effective concert among altogether-reported MoS2-based CdS composites. Notably, these findings with ample prospective for the development of enormously real photocatalytic systems are due to their economically viable and extraordinary efficiency.

Okra (Abelmoschus esculentus) Plant Extract-Assisted Combustion Synthesis and Characterization Studies of Spinel ZnAl2O4 Nano-Catalysts.

Spinel ZnAl2O4 nano-catalysts were synthesized by a simple, economical and eco-friendly microwave irradiation (MIM) and conventional heating methods (CHM), using metal nitrates and Okra (Abelmoschus esculentus) plant extract, which play a dual role of both oxidizing and reducing nature. Powder X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy, energy dispersive X-ray (EDX) and selected area electron diffraction (SAED) pattern results were confirmed that the samples have a single-phase cubic spinel structure with high crystalline nature of ZnAl2O4. Surface morphology of the samples was revealed by high resolution scanning electron microscopy (HR-SEM) and high resolution transmission electron microscopy (HR-TEM) techniques and they are confirmed particle-like structure with grain size below 50 nm. The optical band gap (Eg) was measured using Kubelka-Munk model by UV-Vis diffuse reflectance spectroscopy (DRS) and photoluminescence (PL) and the Eg value is higher for MIM product than CHM, due to the smaller particle size of ZnAl2O4-MIM. The magnetic property of the samples was determined by vibrating sample magnetometer (VSM) and showed a superparamagnetic behavior. Spinel ZnAl2O4 nano-catalysts are magnetically recyclable and could be reused with no significant loss in catalytic activity. Both the samples were successfully tested as catalysts for the conversion of alcohols into respective carbonyl compounds using H2O2 (as oxidant) and acetonitrile (as a solvent) system. It was found that the ZnAl2O4-MIM nanocatalysts show best performance of conversion of alcohols into a carbonyl compounds than that of ZnAl2O4-CHM, due to the smaller particle size and higher surface area of ZnAl2O4-MIM samples.

Enhanced Catalytic Activity, Facile Synthesis and Characterization Studies of Spinel Mn-Co Aluminate Nano-Catalysts.

Undoped and Mn2+ doped CoAl2O4 (MnxCo1-xAl2O4; x = 0.0 to 1.0) spinel nanoparticles were successfully synthesized by a microwave heating method using glycine as the fuel. X-ray powder diffraction (XRD) was confirmed the cubic spinel structure. The average crystallite size of the samples was found to be in the range of 16.46 nm to 20.25 nm calculated by Scherrer's formula. The nano-sized particle-like morphology of the samples was confirmed by high resolution scanning electron microscopy (HR-SEM) and transmission electron microscopy (HR-TEM) analysis. Energy dispersive X-ray (EDX) results showed the pure form of spinel aluminate structure. The band gap energy (Eg) of pure CoAl2O4 was estimated to be 3.68 eV from UV-Visible diffuse reflectance spectroscopy (DRS), and the Eg values increased with increase of Mn2+ ions, due to the smaller grain size. The magnetic hysteresis (M-H) loop showed the superparamagnetic nature, and the magnetization and coercivity values increased with increasing Mn2+ ions, which was confirmed by vibrating sample magnetometer (VSM). All compositions of the nano-catalysts were tested as catalyst successfully for the conversion of benzyl alcohol into benzaldehyde and observed good catalytic activity.

Mechanobiology of young and aging tendons: In vivo studies with treadmill running.

Tendons are unique in the sense that they are constantly subjected to large mechanical loads and that they contain tendon-specific cells, including tenocytes and tendon stem/progenitor cells. The responses of these cells to mechanical loads can be anabolic or catabolic and as a result, change the biological properties of the tendon itself that may be beneficial or detrimental. On the other hand, aging also induces aberrant changes in cellular expression of various genes and production of various types of matrix proteins in the tendon, and consequently lead to tendon degeneration and impaired healing in aging tendons; both could be improved by moderate physiological mechanical loading such as treadmill running. This article gives an overview on the mechanobiology research of young and aging animal tendons using treadmill running model. The challenges in such treadmill running studies are also discussed. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:557-565, 2018.