Novel regulation pathway of eclosion hormones in Tribolium castaneum by distinct transcription factors through the initiation of 20-Hydroxyecdysone.

Eclosion hormone (EH) is not only a key trigger of insect ecdysis, but is also involved in the regulation of important physiological processes such as development, diapause, metamorphosis and reproduction. EH is an ideal target for RNAi treatment and prevention of the Tribolium castaneum. However, two EH genes in Tribolium castaneum demonstrate distinct replication and functional conversion relationships, and the mechanisms of transcriptional regulation of eclosion hormone remain largely unexplored and poorly understood. In this study, the activity of highly active promoter fragments and potential transcription factors of TcEH and TcEHL were identified using the Dual-Luciferase reporter system and TANSFAC. TcSlbo and TcCAD were revealed to be important transcription factors for TcEH and TcEHL, respectively. Knockdown of TcSlbo failed to slough off the old epidermis of Tribolium castaneum and prevented them from developing into adults. Furthermore, we demonstrated for the first time that 20-hydroxyecdysone (20E) affects the expression of TcEH and TcEHL by regulating the transcriptional activities of TcSlbo and TcCAD. This study provides new insights into the transcription regulation of TcEH and TcEHL, their roles in insect growth and development, and the involvement of 20E in eclosion regulation, offering potential molecular targets for future pest management strategies.

Is antenatal or early-life vitamin D associated with eczema or food allergy in childhood? A systematic review.

OBJECTIVE: To summarise the associations between antenatal or early-life blood vitamin D and the development of eczema/food allergy in childhood. DESIGN: A systematic review and meta-analyses were conducted to synthesize the published literature. Two reviewers independently performed the study selection and data extraction on Covidence. We assessed the risk of bias for observational studies by using the Newcastle-Ottawa Scale and the Cochrane Risk of Bias tool for clinical trials. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluations (GRADE). DATA SOURCES: We systematically searched PubMed and Embase from inception and April 2022. ELIGIBILITY CRITERIA: Human studies that investigated prospective associations between antenatal or early-life blood vitamin D levels, dietary intake or supplementation and childhood eczema/food allergy. RESULTS: Forty-three articles including six randomised controlled trials (RCTs) were included. Four RCTs of vitamin D supplementation during pregnancy showed no evidence of an effect on the incidence of eczema (pooled odds ratio [OR] = 0.85; 0.67-1.08, I2  = 6.7%, n = 2074). Three RCTs reported null associations between supplementation in pregnancy/infancy and food allergy. From six cohort studies, increasing cord blood vitamin D levels were associated with reduced prevalence of eczema at/close to age one (OR per 10 nmol/L increase = 0.89; 0.84-0.94, I2  = 0%, 2025 participants). We found no evidence of an association between maternal antenatal or infant vitamin D level or dietary intake and the development of food allergy or eczema in offspring. CONCLUSIONS: We found an association between higher vitamin D levels in cord blood and reduced risk of eczema in cohort studies. Further trials with maternal and infant supplementation are needed to confirm if vitamin D supplementation can effectively prevent eczema or food allergy in childhood. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, No. CRD42013005559.

Reply to Chan et al.

We agree that smoking might be a risk factor for the severity of COVID-19, but in our previous study, smoking was not so robust compared with our conclusion. Also, we strongly agreed that COVID-19 patients with diabetes or other chronic diseases might worsen the situation of the disease. But these factors were out of the scope of our study and we had published other research on this topic related to diabetes. Because of the limited sample size and original medical records, our study could not cover many factors. But we wish our study will be a useful and meaningful pilot study for future studies.

The clinical and bioinformatics analysis for the role of antihypertension drugs on mortality among patients with hypertension hospitalized with COVID-19.

Comorbidities such as hypertension could exacerbate symptoms of coronaviral disease 2019 (COVID)-19 infection. Patients with hypertension may receive both anti-COVID-19 and antihypertension therapies when infected with COVID-19. However, it is not clear how different classes of anti-hypertension drugs impact the outcome of COVID-19 treatment. Herein, we explore the association between the inpatient use of different classes of anti-hypertension drugs and mortality among patients with hypertension hospitalized with COVID-19. We totally collected data from 278 patients with hypertension diagnosed with COVID-19 admitted to hospitals in Wuhan from February 1 to April 1, 2020. A retrospective study was conducted and single-cell RNA-sequencing (RNA-Seq) analysis of treatment-related genes was performed. The results showed that Angiotensin II receptor blocker (ARB) and calcium channel blocker (CCB) drugs significantly increased the survival rate but the use of angiotensin-converting enzyme inhibitor/ß-block/diuretic drugs did not affect the mortality caused by COVID-19. Based on the analysis of four public data sets of single-cell RNA-Seq on COVID-19 patients, we concluded that JUN, LST1 genes may play a role in the effect of ARB on COVID-19-related mortality, whereas CALM1 gene may contribute to the effect of CCB on COVID-19-related mortality. Our results provide guidance on the selection of antihypertension drugs for hypertensive patients infected with COVID-19.

Monocular Perception of Equidistance: The Effects of Viewing Experience and Motion-generated Information.

SIGNIFICANCE: Using static depth information, normal observers monocularly perceived equidistance with high accuracy. With dynamic depth information and/or monocular viewing experience, they perceived with high precision. Therefore, monocular patients, who were adapted to monocular viewing, should be able to perceive equidistance and perform related tasks. PURPOSE: This study investigated whether normal observers could accurately and precisely perceive equidistance with one eye, in different viewing environments, with various optical information and monocular viewing experience. METHODS: Sixteen normally sighted observers monocularly perceived the distance (5 to 30 m) between a target and the self and replicated it either in some hallways that contained ample static monocular depth information but had a limited field of view or on a lawn that contained less depth information but had a large field of view. Participants remained stationary or walked 5 m before performing the task, as a manipulation of the availability of dynamic depth information. Eight observers wore eye patches for 3 hours before the experiment and gained monocular viewing experience, whereas the others did not. Both accuracy and precision were measured. RESULTS: As long as static monocular depth information was available, equidistance perception was effectively accurate, despite minute underestimation. Perception precision was improved by prior monocular walking and/or experience with monocularity. Accuracy and precision were not affected by the viewing environments. CONCLUSIONS: Using static and dynamic monocular depth information and/or with monocular experience, normal observers judged equidistance with reliable accuracy and precision. This implied that patients with monocular vision, who are better adapted than participants of this study, should also be able to perceive equidistance and perform distance-dependent tasks in natural viewing environments.

Chondrogenic potential of manganese-loaded composite scaffold combined with chondrocytes for articular cartilage defect.

Cartilage is an alymphatic, avascular and non-innervated tissue. Lack of potential regenerative capacity to reconstruct chondral defect has accelerated investigation and development of new strategy for cartilage repair. We prepared a manganese ion-incorporated natupolymer-based scaffold with chitosan-gelatin by freeze-drying procedure. The scaffold was characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, energy dispersive spectroscopy, compressive testing, and analysis of porosity and flexibility. Live/dead assay confirmed the good cytocompatibility of prepared scaffold on rat articular chondrocytes after 10 days and 4 weeks of culture. The manganese-loaded composite scaffold upregulated the expression of chondrogenic-related markers (Sox9, integrin, and Col II) in chondrocytes. Western blot analysis of proteins extracted from chondrocytes grown on scaffolds indicated the signaling pathways of p-Akt and p-ERK1/2 played a key role. Histological analysis following implantation of current composite scaffold loaded with chondrocytes into a rat articular cartilage defect model showed that the scaffolds promoted the formation of collagen II and cartilage repair. These findings suggested the potential of manganese-loaded scaffold to promote new cartilage formation and a promising strategy for articular cartilage engineering application.

Target-induced activation of polymerase activity for recycling signal amplification cascades for sensitive aptamer-based detection of biomarkers.

It is of great importance to develop biosensing methods for the sensitive and selective analysis of biomarkers at very low levels in biological samples. Using a new target-induced activation of the DNA polymerase activity for recycling amplification cascades, we describe an aptamer-based method for highly sensitive detection of platelet-derived growth factor BB (PDGF-BB) in human serums. The polymerase activity is initially inhibited by the binding of the polymerase to the enzyme aptamer sequence. PDGF-BB associates with and switches a PDGF-BB binding aptamer to trigger the release of an active polymerase, which further initiates the simultaneous recycling of the target PDGF-BB molecules and the enzyme aptamer sequence for the subsequent displacement of the fluorescently quenched probes to recover the fluorescence. Due to two recycling cascades, substantial fluorescence magnification is obtained for the highly sensitive detection of PDGF-BB with a low detection limit of 5.1 pM. Moreover, the potential applicability of this method for real samples was verified by determining PDGF-BB in diluted human serums, relying on the excellent specificity and selectivity of the aptamer. The demonstration of the PDGF-BB assay method here thus can be expanded for the construction of diverse sensing platforms for detecting different trace biomarkers with the integration of an elaborate design of the aptamer probes.

Multivalent butyrylcholinesterase inhibitor discovered by exploiting dynamic combinatorial chemistry.

In this study, we report the generation of a polymer-based dynamic combinatorial library (DCL) incorporating exchangeable side chains using acylhydrazone formation reaction. In combination with tetrameric butyrylcholinesterase (BChE), the most potent binding side chain was identified, and the information obtained was further used for the synthesis of a multivalent BChE inhibitor. In the in vitro biological evaluation, this multivalent inhibitor exhibited not only better inhibitory effect than the commercial reference but also high selectivity on BChE over acetylcholinesterase (AChE).

Prevalence of urolithiasis among the Uyghur children of China: a population-based cross-sectional study.

OBJECTIVES: To investigate the prevalence and associated factors of urolithiasis amongst Uyghur children. SUBJECTS AND METHODS: A cross-sectional survey was conducted of Uyghur children (aged ≤14 years) in the Kashgar Region of China, from July to December 2016. Children were selected by a two-stage random clustered sampling method, evaluated by urinary tract ultrasonography, low-dose computed tomography (CT) examination, blood and urine analysis, and a questionnaire. The prevalence by CT, the prevalence by self-report in the questionnaires, and the lifetime prevalence were evaluated. Binary logistic regression was used to estimate the associated factors. RESULTS: A total of 5605 children were selected and invited to participate in the study. In all, 4813 Uyghur children (2471 boys and 2342 girls), with an mean (SD; range) age of 75.79 (43.81; 2-177) months, were included in the final analysis, with a response rate of 85.9%. The prevalence of paediatric urolithiasis was 1.8% (95% confidence interval [CI] 1.5-2.2) by CT, 2.3% (95% CI 1.9-2.7) by self-report, and 3.6% (95% CI 3.0-4.1) for the overall life-time. The age-sex adjusted prevalence was 2.0% (95% CI 1.6-2.4) by CT. Binary logistic regression analysis showed that body mass index, urinary tract infection, a family history of urolithiasis, and excessive sweating could increase the risk of stone formation, whilst breast feeding and drinking water at midnight could decrease the risk. CONCLUSIONS: Urolithiasis is a major public health problem amongst Uyghur children, and strategies aimed at the prevention of urolithiasis are needed.

Spatiotemporal distribution of nitrogen and phosphorus in alpine lakes in the Sanjiangyuan Region of the Tibetan Plateau.

To provide a theoretical basis for alpine source lake protection, ten samples were taken from each lake annually from 2012 to 2015. Each year, the various species of nitrogen and phosphorus nutrients were measured. The average contents of nitrate nitrogen, ammonia nitrogen, nitrite nitrogen, total phosphorus, and total nitrogen in the four lakes are 0.195-0.0 mg/L, 0.038-0.143 mg/L, 0.004-0.168 mg/L, 0.006-0.740 mg/L, and 0.050-0.547 mg/L, respectively. The total phosphorus contents in Eling Lake, Longbao Lake and Sea Star were higher than Class I water quality standards, and the total nitrogen contents in Eling Lake, Sea Star and Zhaling Lake were higher than Class I water quality standards as well. The concentration contour maps of the nitrate nitrogen, ammonia nitrogen, nitrite nitrogen, total phosphorus and total nitrogen showed that the indicators of the four lakes in the east, the west, and the center of the lake did not have the same trend. From 2012 to 2015, each of the measured nutrients showed a rising trend year by year. The four lakes are polluted by both endogenous and exogenous pollution, and it is necessary to limit the exogenous pollution and protect the alpine lakes immediately.

Morphological and functional characterization of circulating hemocytes in Tribolium castaneum larvae.

Hemocytes are pivotal in the immune response of insects against invasive pathogens. However, our knowledge of hemocyte types and their specific function in Tribolium castaneum, an increasingly important Coleoptera model insect in various research fields, remains limited. Presently, a combination of morphological criteria and dye-staining properties were used to characterize hemocyte types from T. castaneum larvae, and 4 distinct types were identified: granulocytes, oenocytoids, plasmatocytes and prohemocytes. Following different immune challenges, the total hemocyte counts declined rapidly in the initial phase (at 2 h), then increased over time (at 4 and 6 h) and eventually returned to the naive state by 24 h post-injection. Notably, the morphology of granulocytes underwent dramatic changes, characterized by an expansion of the surface area and an increased production of pseudopods, and with the number of granulocytes rising significantly through mitotic division. Granulocytes and plasmatocytes, the main hemocyte types in T. castaneum larvae, can phagocytose bacteria or latex beads injected into the larval hemolymph in vivo. Furthermore, these hemocytes participate in the encapsulation and melanization processes in vitro, forming capsules to encapsulate and melanize nickel-nitrilotriacetic acid (Ni-NTA) beads. This study provides the first comprehensive characterization of circulating hemocytes in T. castaneum larvae, offering valuable insights into cell-mediated immunity in response to bacterial infection and the injection of latex beads. These results deepen our understanding of the cellular response mechanisms in T. castaneum larvae and lay a solid foundation for subsequent investigations of the involvement of T. castaneum hemocytes in combating pathogens.

Evaluation of transmission-blocking potential of PvPSOP25 using transgenic murine malaria parasite and clinical isolates.

BACKGROUND: Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The putative-secreted ookinete protein 25 (PSOP25), highly conserved in Plasmodium spp., is a promising TBV target. Here, we investigated PvPSOP25 from P. vivax as a TBV candidate using transgenic murine parasite P. berghei and clinical P. vivax isolates. METHODS AND FINDINGS: A transgenic P. berghei line expressing PvPSOP25 (TrPvPSOP25Pb) was generated. Full-length PvPSOP25 was expressed in the yeast Pichia pastoris and used to immunize mice to obtain anti-rPvPSOP25 sera. The transmission-blocking activity of the anti-rPvPSOP25 sera was evaluated through in vitro assays and mosquito-feeding experiments. The antisera generated by immunization with rPvPSOP25 specifically recognized the native PvPSOP25 antigen expressed in TrPvPSOP25Pb ookinetes. In vitro assays showed that the immune sera significantly inhibited exflagellation and ookinete formation of the TrPvPSOP25Pb parasite. Mosquitoes feeding on mice infected with the transgenic parasite and passively transferred with the anti-rPvPSOP25 sera showed a 70.7% reduction in oocyst density compared to the control group. In a direct membrane feeding assay conducted with five clinical P. vivax isolates, the mouse anti-rPvPSOP25 antibodies significantly reduced the oocyst density while showing a negligible influence on mosquito infection prevalence. CONCLUSIONS: This study supported the feasibility of transgenic murine malaria parasites expressing P. vivax antigens as a useful tool for evaluating P. vivax TBV candidates. Meanwhile, the moderate transmission-reducing activity of the generated anti-rPvPSOP25 sera necessitates further research to optimize its efficacy.

Bone regeneration with hydroxyapatite particles loaded in photo-cross-linkable hydrogel: An experimental study.

This study explores the use of in situ cross-linked hyaluronic acid methacryloyl (HAMA) and hydroxyapatite particles (HAP) for bone defect repair. Human periodontal ligament stem cells (PDLSCs) were isolated and co-cultured with the HAMA-HAP composite. Osteogenic differentiation was evaluated using Alizarin Red staining, alkaline phosphatase activity quantification, and polymerase chain reaction (PCR). A cranial defect was induced in Sprague-Dawley rats. This defect was then filled with the HAMA-HAP composite and cross-linked using UV light exposure. Bone formation was assessed through radiographic and histological analyses. The HAMA-HAP composite was found to promote cell viability similarly to pure HAP. It also enhanced gene expression of ALP, OPN, and Runx2, and increased ALP activity and mineralized nodule formation in vitro. Micro-CT scans showed defect restoration in the HAMA-HAP and HAP groups compared to the control group. The HAMA-HAP group exhibited higher Tb.N, Tb.Sp, Tb.Th, and BV/TV. Masson staining showed the HAMA-HAP composite restored the defect site, with new bone formation thicker than in the HAP group. The HAMA-HAP composite showed excellent biocompatibility and promoted osteogenic differentiation of PDLSCs. It effectively repaired cranial defects, indicating its potential for clinical use in bone defect repair.

Investigation of zeolite H-ß effect on pyrolysis of polystyrene by multiple kinetic analysis methods.

For studying the effects of H-ß zeolite on the pyrolysis of polystyrene (PS), non-isothermal thermogravimetric measurements were conducted in N2 under 5, 10, 15, and 20 K/min. The results show that the addition of 10 ~ 30 wt.% H-ß zeolite can significantly decrease the initial pyrolysis temperature of PS, indicative of the catalytic effect of zeolite used. Through kinetic analysis of the pyrolysis of PS blends, the isoconversional activation energies are calculated to be 121.8 ~ 191.9, 92.1 ~ 173.8, and 116.7 ~ 192.4 kJ/mol for the PS blends with zeolite loading of 10, 20, and 30 wt.%, respectively. Meanwhile, the pyrolysis degradation functions are determined through the Master-plots method integrated with a recently developed compensation-effect method to follow chemical reaction mechanism with the reaction order of 0.9, 1.0, and 0.6 for PS/zeolite blends of 10, 20, and 30 wt.% loading, and their pre-exponential factors are respectively calculated to be 6.18 × 108 ~ 5.71 × 1011, 2.36 × 106 ~ 9.23 × 1011, and 8.38 × 107 ~ 1.11 × 1012 min-1. Our work may provide some insights for how to better describe experimental results with theoretical predications and necessary information for performing any potential pyrolysis designs.

Oxidative stress: The nexus of obesity and cognitive dysfunction in diabetes.

Obesity has been associated with oxidative stress. Obese patients are at increased risk for diabetic cognitive dysfunction, indicating a pathological link between obesity, oxidative stress, and diabetic cognitive dysfunction. Obesity can induce the biological process of oxidative stress by disrupting the adipose microenvironment (adipocytes, macrophages), mediating low-grade chronic inflammation, and mitochondrial dysfunction (mitochondrial division, fusion). Furthermore, oxidative stress can be implicated in insulin resistance, inflammation in neural tissues, and lipid metabolism disorders, affecting cognitive dysfunction in diabetics.

Flattening the Curve after the Initial Outbreak of Coronavirus Disease 2019: A Data-Driven Modeling Analysis for the Omicron Pandemic in China.

China is relaxing COVID-19 measures from the "dynamic zero tolerance" (DZT) level. The "flatten-the-curve" (FTC) strategy, which decreases and maintains the low rate of infection to avoid overwhelming the healthcare system by adopting relaxed nonpharmaceutical interventions (NPIs) after the outbreak, has been perceived as the most appropriate and effective method in preventing the spread of the Omicron variant. Hence, we established an improved data-driven model of Omicron transmission based on the age-structured stochastic compartmental susceptible-latent-infectious-removed-susceptible model constructed by Cai to deduce the overall prevention effect throughout China. At the current level of immunity without the application of any NPIs, more than 1.27 billion (including asymptomatic individuals) were infected within 90 days. Moreover, the Omicron outbreak would result in 1.49 million deaths within 180 days. The application of FTC could decrease the number of deaths by 36.91% within 360 days. The strict implementation of FTC policy combined with completed vaccination and drug use, which only resulted in 0.19 million deaths in an age-stratified model, will help end the pandemic within about 240 days. The pandemic would be successfully controlled within a shorter period of time without a high fatality rate; therefore, the FTC policy could be strictly implemented through enhancement of immunity and drug use.

Alterations in histology of the aging salivary gland and correlation with the glandular inflammatory microenvironment.

Aging-related salivary dysfunction typically causes reduced saliva volumes, which leads to debilitating consequences, even affecting patient quality of life. Understanding the respective clinicopathological characteristics and molecular mechanisms underlying salivary gland functioning during aging is vital for therapeutic purposes. Here, we provide a detailed atlas of the salivary gland microenvironment during aging, and we identified several phenotypes characteristic of aging salivary glands, including acini atrophy, increased inflammatory cells, altered immune responses, and accumulation of lysosomes and autophagosomes in aging cells, which may reflect progressive degeneration of salivary gland function. Furthermore, our analyses suggested significant enrichment of metabolic pathways in aging glands. Our results revealed complex cellular cross-talk among aging acinar cells, inflammatory factors, and immune responses. A natural aging animal model was established to verify these findings. This study provides mechanistic insights into age-related clinicopathogenesis, important implications for early diagnosis, and identification of new targets for improving salivary gland dysfunction.

Zwitterionic Copolymers for Anti-Scaling Applications in Simulated Spaceflight Wastewater Scenarios.

Water reclamation in spaceflight applications, such as those encountered on the International Space Station (ISS), requires complex engineering solutions to ensure maximum water recovery. Current vapor compression distillation (VCD) technologies are effective but produce highly concentrated brines and often cause scaling within a separation system. This work evaluates initial steps toward integrating pervaporation, a membrane separation process, as a brine management strategy for ISS wastewaters. Pervaporation performs separations driven by a chemical potential difference across the membrane created by either a sweep gas or a vacuum pull. Pervaporation membranes, as with most membrane processes, can be subject to scaling. Therefore, this work studies the anti-scaling properties of zwitterions (polymeric molecules with covalently tethered positive and negative ions) coated onto sulfonated pentablock terpolymer block polymer (Nexar) pervaporation membrane surfaces. We report a method for applying zwitterions to the surface of pervaporation membranes and the effect on performance parameters such as flux and scaling resistance. Membranes with zwitterions had up to 53% reduction in permeance but reduced scaling. The highest amount of scaling occurred in the samples exposed to calcium chloride, and uncoated membranes had weight percent increases as high as 1617 ± 241%, whereas zwitterion-coated membranes experienced only about 317 ± 87% weight increase in the presence of the same scalant.

Pollen allergens sensitization characteristics and risk factors among allergy rhinitis of children in mainland China: A multicenter study.

Background: No comprehensive multicenter study of sensitization patterns among patients with allergic rhinitis (AR) to various common pollen allergens was available nationwide, and risks factors of pollen-induced allergic rhinitis (PiAR) in mainland China was unclear. This study aimed to fill this gap. Methods: A multicenter study was performed on 736 AR patients aged below 18 from four regions of mainland China. Patients completed a standardized questionnaire asking for the environmental risk factors and AR severity, and undertook skin prick tests (SPT) with 14 common pollen allergens. Findings: Among the 736 patients, 341 patients (46.33%) suffered at least one positive pollen allergen sensitization. The positive rate of pollen allergens was significantly higher in the high-age group (Damato et al., 2007; Wang et al., 2018; Luo et al., 2016; Demoly et al., 2011; Sampson and Albergo, 1984; Li et al., 2009; Luo et al., 2021; Ziska and Beggs, 2011; Melén et al., 2020; Jensen-Jarolim, 2017; Rönmark et al., 2017; Ge et al., 2017) [6-17] than the low-age group ( ≤ 5), while no significant difference was found between the sexes. The sensitizations to pollen allergens varied widely among four geographical areas. The positive rate was higher in north China and west China than in east China, and south China had the lowest positive rate. The region of residence, ages, ethnic minorities, history of pollen exposure, the material of living room floor and material of pillow were statistically significant risks of PiAR. Interpretation: This study provides new insights into the pollen allergens sensitization characteristics in AR and the factors affecting PiAR in mainland China.

Nicotinamide Mononucleotide Alleviates Osteoblast Senescence Induction and Promotes Bone Healing in Osteoporotic Mice.

Combating the accumulated senescent cells and the healing of osteoporotic bone fractures in the older remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD+, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing. Here we show that NMN treatment partially reverses the effects of tumor necrosis factor-alpha (TNF-α) on human primary osteoblasts (HOBs): senescent cell induction, diminished osteogenic differentiation ability, and intracellular NAD+ and NADH levels. Mechanistically, NMN restores the mitochondrial dysfunction in HOBs induced by TNF-α evidenced by increased mitochondrial membrane potential and reduced reactive oxidative species and mitochondrial mass. NMN also increases mitophagy activity by down-regulating P62 expression and up-regulating light chain 3B-II protein expression. In addition, the cell senescence protective effects of NMN on HOBs are mitigated by a mitophagy inhibitor (Bafilomycin A1). In vivo, NMN supplementation attenuates senescent cell induction in growth plates, partially prevents osteoporosis in an ovariectomized mouse model, and accelerates bone healing in osteoporotic mice. We conclude that NMN can be a novel and promising therapeutic candidate to enhance bone fracture healing capacity in the older.