The association of hearing loss with frailty among community-dwelling older adults: findings from the National Health and Aging Trends Study.

BACKGROUND: The identification of modifiable risk factors is crucial for the prevention and/or reversal of frailty, which is associated with significant morbidity and mortality. Hearing loss affects two-thirds of older adults in the United States (U.S.) and is associated with physical and cognitive decline which may increase frailty risk. We investigated the association of hearing loss and hearing aid use with frailty and pre-frailty in a nationally representative sample of older adults in the U.S. METHODS: Cross-sectional analysis of the National Health and Aging Trends Study (2021 round). The better-hearing ear pure-tone average (BPTA) at speech-frequencies (0.5-4 kHz) was modeled continuously (per 10 dB) and categorically (no ≤ 25 dB, mild 26-40 dB, moderate or greater > 40 dB hearing loss). Hearing aid use was self-reported. The physical frailty phenotype (frail, pre-frail, robust) was determined based on Fried criteria: unintentional weight loss, exhaustion, low physical activity, weakness, slow walking speed. We used multinomial multivariable regression adjusted for sociodemographic and health characteristics (odds ratios [95% Confidence Intervals]). RESULTS: Among 2,361 participants (mean age = 81 years, 56% female, 19% Black), 860 (36%) had mild and 864 (37%) had moderate or greater hearing loss. Worse hearing was associated with greater odds of being frail versus robust (OR = 1.20 [1.05-1.38] per 10 dB difference). Categorically, moderate or greater hearing loss was associated with greater odds of being frail (OR = 1.84 [1.01-3.08]) and pre-frail (OR = 1.46 [1.01-2.10]) versus robust. Among 1,724 participants with hearing loss, compared to hearing aid users (N = 522), nonusers had greater odds of being frail (OR = 2.54 [1.54-4.18]) and pre-frail (OR = 1.51 [1.05-2.17]) versus robust, and frail versus pre-frail (OR = 1.68 [1.04-2.72]). CONCLUSIONS: In a nationally representative sample of older adults in the U.S., using gold-standard hearing measures and a validated frailty phenotype, hearing loss and lack of hearing aid use was cross-sectionally associated with frailty and pre-frailty. Future longitudinal studies are needed to establish if hearing loss is a risk factor for frailty, which may have significant clinical importance.

Fast lightweight framework for time-of-flight super-resolution based on block compressed sensing.

Compressive time-of-flight (ToF) imaging for super-resolution (SR) has tremendous development potential owing to its cost-effectiveness and simplicity. However, existing compressive ToF methods are difficult to apply in practical situations because of their low efficiency and high data storage requirements. In this paper, we propose a fast and lightweight compressive ToF framework for SR. The block compressed sensing method, which shows distinct characteristics of high efficiency and low implementation cost, is introduced into the SR image acquisition and data transmission processes. Based on this framework, we establish a prototype system and verify it experimentally. Compared with existing compressive ToF systems, both the reconstruction time and data storage requirements are significantly decreased. We believe that this study provides a development direction for compressive ToF imaging and effective guidance for researchers realizing highly efficient and lightweight SR image reconstruction.

A systematic non-uniformity correction method for correlation-based ToF imaging.

Correlation-based time-of-flight (ToF) imaging enables a diverse range of applications for its high frame rate, high resolution and low cost. However, the non-uniformity of the sensor significantly affects the flat-field accuracy of the ToF imaging system. In this paper, we analyze the sources of the non-uniformity and propose a systematic non-uniformity correction (NUC) method. The method utilizes the amplitude image, which can directly reflect the non-uniformity characteristics of the ToF sensor, to conduct NUC. Based on the established NUC system, the effectiveness and feasibility of the proposed NUC method are verified. Compared with the traditional methods, the RMSE was significantly reduced, while the SNR and PSNR were effectively improved. We believe this study provides new insights into the understanding of noise in the correlation-based ToF imaging system, and also provides effective references for the NUC of the three-dimensional measuring instruments.

Traumatic temporomandibular joint bony ankylosis in growing rats.

BACKGROUND: The pathogenesis of traumatic temporomandibular joint (TMJ) bony ankylosis remains unknown. This study aimed to explore the pathogenesis of traumatic TMJ bony ankylosis in a rat model. METHODS: Twenty-four 3-week-old male Sprague-Dawley rats were used in this study. Excision of the whole disc, the fibrocartilage damage of the condyle and glenoid fossa, and narrowed joint space were performed in the left TMJ of the operation group to induce TMJ bony ankylosis (experimental side). The right TMJ underwent a sham operation (sham side). The control group did not undergo any operations. At 1, 4, and 8 weeks postoperatively, rats of the operation group were sacrificed and TMJ complexes were evaluated by gross observation, Micro-CT, histological examinations, and immunofluorescence microscopy. Total RNA of TMJ complexes in the operation group were analyzed using RNA-seq. RESULTS: Gross observations revealed TMJ bony ankylosis on the experimental side. Micro-CT analysis demonstrated that compared to the sham side, the experimental side showed a larger volume of growth, and a considerable calcified bone callus formation in the narrowed joint space and on the rougher articular surfaces. Histological examinations indicated that endochondral ossification was observed on the experimental side, but not on the sham side. RNA-seq analysis and immunofluorescence revealed that Matrix metallopeptidase 13 (MMP13) and Runt-related transcription factor 2 (RUNX2) genes of endochondral ossification were significantly more downregulated on the experimental side than on the sham side. The primary pathways related to endochondral ossification were Parathyroid hormone synthesis, secretion and action, Relaxin signaling pathway, and IL-17 signaling pathway. CONCLUSIONS: The present study provided an innovative and reliable rat model of TMJ bony ankylosis by compound trauma and narrowed joint space. Furthermore, we demonstrated the downregulation of MMP13 and RUNX2 in the process of endochondral ossification in TMJ bony ankylosis.

Modeling and simulations of a three-dimensional ghost imaging method with differential correlation sampling.

The quality of depth maps acquired by a time-of-flight three-dimensional ghost imaging (3DGI) system is limited by dynamic ambient light and electrical noise. We developed a novel method that integrates the differential-correlation-sampling (DCS) method and a modulated continuous-wave laser source to realize the 3DGI and reduce the noise influence. The simulation results for the proposed method, DCS-3DGI, verify its feasibility. The analysis of mean-square-error, peak signal-to-noise ratio, structural similarity index measure, and edge preservation index demonstrates a superior anti-interference performance than conventional 3DGI methods.

TMT-labelled quantitative proteomic analysis to predict the target promoting human odontogenic inflammatory granulation tissue transform into reparative granulation tissue.

OBJECTIVES: Odontogenic inflammatory diseases are main causes for alveolar bone breakdown and teeth loss, leaving great difficulties in denture restoration. Local inflammatory granulation tissue (IGT) is considered as pathological tissue and required to be removed. However, there are many evidences supporting that under appropriate intervention, IGT in alveolar bone maybe transformed into reparative granulation tissue (RGT), followed by ossification. Therefore, this study aimed to discover a specific target to promote this transformation. MATERIALS AND METHODS: After drawing out histological differences between IGT and RGT with haematoxylin and eosin (H&E) and immunohistochemical (IHC) assay staining, TMT-labelled quantitative proteomic analysis was applied to identify potential targets. RESULTS: The most striking histological property of RGT was found to be ECM deposition, which significantly decreased inflammatory cells, prominently increased fibroblasts as well as triggered changes of vascular types. Combined with histological findings and proteomic analysis, five KEGG pathways were associated with ECM, inflammation and angiogenesis and 49 pathways involved in differentially expressed proteins. COL1A1 was not only the most up-regulated protein, but also one of main hubs in protein-protein interaction regulatory network. Specific protease cathepsin K (CTSK) was identified. Level of CTSK in RGT was down-regulated to 69.10-76.97% (p < .05), with significantly up-regulated COL1A1, COL1A2, FN1 and TGFB1 included in focal adhesion, PI3K-Akt signalling pathways and angiogenesis. CTSK involved in transformation from IGT to RGT. CONCLUSIONS: CTSK might be a target to regulate transformation from IGT to RGT in alveolar bone through ECM, stem cells and angiogenesis mechanisms. However, further research is also clearly required.

An Improved Calibration Method for Photonic Mixer Device Solid-State Array Lidars Based on Electrical Analog Delay.

As a typical application of indirect-time-of-flight (ToF) technology, photonic mixer device (PMD) solid-state array Lidar has gained rapid development in recent years. With the advantages of high resolution, frame rate and accuracy, the equipment is widely used in target recognition, simultaneous localization and mapping (SLAM), industrial inspection, etc. The PMD Lidar is vulnerable to several factors such as ambient light, temperature and the target feature. To eliminate the impact of such factors, a proper calibration is needed. However, the conventional calibration methods need to change several distances in large areas, which result in low efficiency and low accuracy. To address the problems, this paper presents an improved calibration method based on electrical analog delay. The method firstly eliminates the lens distortion using a self-adaptive interpolation algorithm, meanwhile it calibrates the grayscale image using an integral time simulating based method. Then, the grayscale image is used to estimate the parameters of ambient light compensation in depth calibration. Finally, by combining four types of compensation, the method effectively improves the performance of depth calibration. Through several experiments, the proposed method is more adaptive to multiscenes with targets of different reflectivities, which significantly improves the ranging accuracy and adaptability of PMD Lidar.

How Does the Remodeling Capacity of Children Affect the Morphologic Changes of Fractured Mandibular Condylar Processes After Conservative Treatment?

PURPOSE: Our aim was to explore how the remodeling capacity of children's mandibular condyles affected the morphologic changes of fractured condyles after conservative treatment. PATIENTS AND METHODS: A retrospective study was designed and performed in children and adult patients with mandibular condylar fractures. Computed tomographic imaging was reviewed for all patients to analyze the morphologic changes and risk factors for traumatic temporomandibular joint ankylosis. RESULTS: From 2012 to 2017, 81 patients younger than 18 years and 10 adult patients accepted treatment in our department. There were 23 young patients (aged <18 years) with 41 fractured condyles and 10 adults with 14 fractured condyles who were managed with conservative treatment, and the morphologic changes were analyzed with the aid of Mimics 19.0 software (Materialise, Leuven, Belgium). The fractured condyles with intracapsular fractures completed the remodeling progress within 3 to 4 months, and condyles with neck or base fractures took more than 6 months. In contrast, we found no remodeling in adults. Of the 81 young patients, 3 had temporomandibular joint ankylosis. Each case was analyzed regarding the risk factors, morphologic changes, and remodeling features. Finally, the common points of these cases were summarized. CONCLUSIONS: The shape of fractured condyles can be remodeled after conservative treatment in young patients instead of bony fusion between the fractured fragments compared with adult patients.

Experimental Investigation on the Detection of Multiple Surface Cracks Using Vibrothermography with a Low-Power Piezoceramic Actuator.

Vibrothermography often employs a high-power actuator to generate heat on a specimen to reveal damage, however, the high-power actuator brings inconvenience to the application and possibly introduces additional damage to the inspected objects. This study uses a low-power piezoceramic transducer as the actuator of vibrothermography and explores its ability to detect multiple surface cracks in a metal part. Experiments were conducted on a thin aluminum beam with three cracks in different orientations. Detailed analyses of both thermograms and temperature data are presented to validate the proposed vibrothermography method. To further investigate the performance of the proposed vibrothermography method, we experimentally studied the effects of several critical factors, including the amplitude of excitation signal, specimen constraints, relative position between the transducer and cracks (the transducer is mounted on the same or the opposite side with the cracks). The results demonstrate that all cracks can be detected conveniently and simultaneously by using the proposed low-power vibrothermography. We also found that the magnitude of excitation signal and the specimen constraints have a great influence on detection results. Combined with effective data processing methods, such as Fourier transformation employed in this study, the proposed method provides a promising potential to detect multiple cracks on a metal surface in a safe and effective manner.

Caregiving Time of Unpaid Family Caregivers Assisting Older Adults With Hearing Difficulty.

Objectives: We aimed to investigate the association of older adults' hearing difficulty status with caregiving time. Methods: We used data from two linked surveys of Medicare beneficiaries and family caregivers. Hearing difficulty was defined by hearing aid use and hearing capacity in functional settings. Weighted multivariable linear regression examined the association between hearing difficulty and caregiving time. Stratified analyses were conducted to investigate the moderation effects of caregiving networks and care recipient's dementia status. Results: Among 3003 caregivers, those who assisted older adults with hearing difficulty were observed to spend greater time providing care (ß = 1.18, 95% Confidence Interval [CI]: 1.04, 1.32). Stronger associations in magnitude were observed among caregivers without caregiving networks (ß = 1.35, 95% CI: 1.13, 1.56) and assisting older adults without dementia (ß = 1.22; 95% CI = 1.06, 1.37). Discussion: Hearing difficulty may contribute to greater caregiving time and remains a potential target for caregiver support programs.

Umbilical cord mesenchymal stem cell-derived apoptotic extracellular vesicles ameliorate cutaneous wound healing in type 2 diabetic mice via macrophage pyroptosis inhibition.

BACKGROUND: Delayed healing of diabetic cutaneous wounds is one of the most common complications of type 2 diabetes mellitus (T2DM), which can bring great distress to patients. In diabetic patients, macrophages accumulate around skin wounds and produce NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) inflammasomes, which in turn undergo pyroptosis and produce inflammatory factors such as interleukin-1ß that affect wound healing. Although our previous study revealed that apoptotic extracellular vesicles (ApoEVs) produced from mesenchymal stem cells (MSCs) improve cutaneous wound healing in normal C57BL/6 mice, whether ApoEVs can also improve diabetic wound healing remains unclear. METHODS: Umbilical cord mesenchymal stem cells (UCMSCs) were cultured in vitro and apoptosis was induced. ApoEVs were extracted and identified and used in a T2DM mouse cutaneous wound model to evaluate the efficacy. The inhibitory effect of ApoEVs on macrophage pyroptosis was verified in vivo and in vitro, and the level of oxidative stress in macrophages was assessed to explore the mechanism by which ApoEVs play a role. RESULTS: UCMSC-derived ApoEVs improved skin defect healing in T2DM mice. Moreover, UCMSC-derived ApoEVs inhibited macrophage pyroptosis in T2DM mice in vivo as well as in vitro under high-glucose culture conditions. In addition, we demonstrated that ApoEVs reduce oxidative stress levels, which is a possible mechanism by which they inhibit macrophage pyroptosis. CONCLUSIONS: Our study confirmed that local application of UCMSC-derived ApoEVs improved cutaneous wound healing in T2DM mice. ApoEVs, as products of MSC apoptosis, can inhibit macrophage pyroptosis and regulate the death process by decreasing the level of oxidative stress.

Suicide ideation and anhedonia among clinically stable adolescents with the recurrent depressive disorder during the COVID-19 pandemic: A network perspective.

BACKGROUND: Anhedonia is a suicide risk factor among adolescent patients with recurrent depressive disorder (depression hereafter). This study examined associations between suicidal ideation (SI) and residual depressive symptoms (RSD), including anhedonia, among clinically stable adolescents with depression. METHOD: A network analysis was performed to examine the association between RDS and SI among adolescents with depression. Node-specific predictive betweenness was computed to examine short paths between anhedonia and SI. Additionally, a Network Comparison Test (NCT) was conducted to examine gender differences in derived network model characteristics. RESULTS: The network analysis identified close associations of PHQ9 ("Suicide ideation") with PHQ1 ("Anhedonia") as well as some other RDS including PHQ6 ("Guilt"), PHQ2 ("Sad mood") and PHQ8 ("Motor disturbances"). Additionally, PHQ2 ("Sad mood") and PHQ4 ("Fatigue") were the main bridge nodes linking anhedonia and SI. Comparisons of network models did not find significant differences in network global strength or edge weights. LIMITATION: Causal relations between anhedonia and SI could not be determined due to the cross-sectional study design. CONCLUSIONS: SI was directly related to Anhedonia in addition to Guilt, Sad mood and Motor disturbances. Sad mood and Fatigue were the main bridge nodes linking Anhedonia and SI. To reduce the risk of SI among clinically stable adolescents with depression during the COVID-19 pandemic, specific RDS including Anhedonia, Guilt, Sad mood, Motor disturbances and Fatigue should be targeted in interventions.

Internet addiction and residual depressive symptoms among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic: a network analysis perspective.

To assess the inter-relationships between residual depressive symptoms (RDS) and Internet addiction (IA) using network analysis among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic. RDS and IA were assessed using the Patient Health Questionnaire-9 (PHQ-9) and the Internet Addiction Test (IAT), respectively. Central symptoms and bridge symptoms in the network model were examined. A total of 1,454 adolescents met the study criteria and were included in the analyses. The prevalence of IA was 31.2% (95% CI: 28.8%-33.6%). In the network analysis, the nodes IAT15 ("Preoccupation with the Internet"), PHQ2 ("Sad mood"), and PHQ1 ("Anhedonia") were the most central symptoms in the IA-RDS network model. Bridge symptoms included IAT10 ("Sooth disturbing about your Internet use"), PHQ9 ("Suicide ideation"), and IAT3 ("Prefer the excitement online to the time with others"). Additionally, PHQ2 ("Sad mood") was the main node linking "Anhedonia" to other IA clusters. Internet addiction was common among clinically stable adolescents with major psychiatric disorders during the COVID-19 pandemic. Core and bridge symptoms identified in this study could be prioritized as targets for the prevention and treatment of IA in this population.

Onsager model for the structure of rigid rods confined on a spherical surface.

Recent studies have suggested that a monolayer of self-avoiding hard rods confined on a spherical surface may display a distribution texture corresponding to splay, tennis-ball, rectangle, or cut-and-rotate splay symmetries. We investigate the system on the basis of a generalized Onsager model which includes both excluded-volume and entropic effects. The numerical solution indicates that the splay state, where on average rods line up in parallel to the longitudinal lines on the spherical surface, is the only stable state.

Recent advances in systemic therapy for hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common and lethal malignant tumors in the world. Therapeutic options for advanced HCC are limited. Systemic treatment, especially with conventional cytotoxic drugs, is usually ineffective. For more than a decade, sorafenib has been the only systemic drug that has been proven to be clinically effective for treating advanced HCC. However, over the past three years, the rapid progress of molecular targeted therapies has dramatically changed the treatment landscape for advanced HCC. Immune checkpoint therapies are now being incorporated into HCC therapies, and their combination with molecular targeted therapy is emerging as a tool to enhance the immune response. In this review, we summarize the development and progress of molecular targeted agents and immunotherapies in HCC.

Structure of Hypomanic Symptoms in Adolescents With Bipolar Disorders: A Network Approach.

Background: Bipolar disorders (BD) are severe mental illnesses that are often misdiagnosed or under-diagnosed. The self-report 33-item Hypomania Checklist (HCL-33) and the 33-item Hypomania Checklist - external assessment (HCL-33-EA) are well-validated scales for BD symptom detection. This study compared the network structure, central symptoms, and network stability of hypomanic symptoms measured by the HCL-33 vs. the HCL-33-EA. Methods: This cross-sectional study was conducted from January to December 2019. Adolescents (aged between 12 and 18 years) with BD were recruited from the outpatient department of Child Psychiatry, First Affiliated Hospital of Zhengzhou University. All participants were asked to complete the HCL-33, and their caregivers completed the HCL-33-EA. Network analyses were conducted. Results: A total of 215 adolescents with BD and their family caregivers were recruited. Node HCL17 ("talk more," node strength = 4.044) was the most central symptom in the HCL-33 network, followed by node HCL2 ("more energetic," node strength = 3.822), and HCL18 ("think faster," node strength = 3.801). For the HCL-33-EA network model, node HCL27 ("more optimistic," node strength = 3.867) was the most central node, followed by node HCL18 ("think faster," node strength = 3.077), and HCL17 ("talk more," node strength = 2.998). In the network comparison test, there was no significant difference at the levels of network structure (M = 0.946, P = 0.931), global strength (S: 5.174, P = 0.274), or each specific edge (all P's > 0.05 after Holm-Bonferroni corrections) between HCL-33 and HCL-33-EA items. Network stabilities for both models were acceptable. Conclusion: The nodes "talk more" and "think faster" acted as central symptoms in BD symptom network models based on the HCL-33 and HCL-33-EA. Although the most prominent central symptom differed between the two models ("talk more" in HCL-33 vs. "more optimistic" in HCL-33-EA model), networks based on each measure were highly similar and underscored similarities in BD symptom relations perceived by adolescents and their caregivers. This research provides foundations for future studies with larger sample sizes toward improving the accuracy and robustness of observed network structures.

Cyberbully victimization and its association with residual depressive symptoms among clinically stable adolescents with psychiatric disorders during the COVID-19 pandemic: A perspective from network analysis.

Objective: This study examined the prevalence of cyberbullying and its relationship with residual depressive symptoms in this patient population during the COVID-19 outbreak using network analysis. Methods: This was a multicenter, cross-sectional study. Adolescent patients attending maintenance treatment at outpatient departments of three major psychiatric hospitals were included. Experience of cyberbullying was measured with a standard question, while the severity of Internet addiction and depressive symptoms were measured using the Internet Addiction Test and the Patient Health Questionnaire-9, respectively. The network structure of depression and cyberbully were characterized and indices of "Expected Influence" was used to identify symptoms central to the network. To identify particular symptoms that were directly associated with cyberbully, the flow function was used. Results: Altogether 1,265 patients completed the assessments. The overall prevalence of cyberbullying was 92.3% (95% confidence interval (CI): 90.8-93.7%). Multiple logistic regression analysis revealed that male gender (p = 0.04, OR = 1.72, 95%CI: 1.04-2.85) was significantly associated with higher risk of cyberbullying, while a relapse of illness during the COVID-19 pandemic was significantly associated with a lower risk of cyberbullying (p = 0.03, OR = 0.50, 95%CI: 0.27-0.93). In the network of depression and cyberbully, "Sad mood," "Anhedonia" and "Energy" were the most central (influential) symptoms. Furthermore, "Suicidal ideation" had the strongest negative association with cyberbully followed by "Guilt". Conclusion: During the COVID-19 pandemic, the experience of cyberbullying was highly prevalent among clinically stable adolescent psychiatric patients, particularly male patients. This finding should raise awareness of this issue emphasizing the need for regular screening and interventions for adolescent patients. Central symptoms (e.g., "Sad mood," "Anhedonia" and "Energy") identified in this study should be targeted in interventions and preventive measures.

A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy.

The treatment of periodontitis can be very challenging due to its complex etiologies. A new pharmacologic strategy entitled "host-modulation therapy," has been introduced to improve periodontal treatment outcomes. Supposedly, a multifunctional drug with the potential for bacterial infection prevention, host-response modulation and bone healing promotion would be a promising option for periodontitis therapy, but related studies remain substantially lacking. In this study, we successfully conjugated tetracycline with odanacatib (a selective inhibitor of cathepsin K) to construct a multifunctional drug (TC-ODN). We discovered that TC-ODN could promote macrophages polarizing toward anti-inflammatory phenotype and promote osteogenesis of PDLSCs under inflammatory microenvironment. In vivo, TC-ODN could be absorbed and distributed specifically to the bone after systemic administration, and accumulation of TC-ODN increased bone mineral density in ovariectomized rats. Importantly, periodontal administration of TC-ODN could successfully promote bone healing in periodontitis rats with alveolar bone loss. The findings in our study uncovered the excellent biocompatibility and multifunction of TC-ODN, including bone-targeted accumulation, immunoregulation, anti-inflammatory activity and promotion of bone healing, which might contribute to the clinical treatment of periodontitis.

Factors and potential treatments of cough after pulmonary resection: A systematic review.

Cough is a common complication following pulmonary resection. Persistent and severe cough after pulmonary resection can cause significant impairments in quality of life among postoperative patients. Complications of cough can be life-threatening. To improve patients' probability and quality of life, factors that induce cough after pulmonary resection (CAP) and potential treatments should be explored and summarized. Previous studies have identified various factors related to CAP. However, those factors have not been categorized and analyzed in a sensible manner. Here, we summarized the different factors and classified them into four groups. Potential therapies might be developed to selectively target different factors that affect CAP. However, the exact mechanism underlying CAP remains unknown, making it difficult to treat and manage CAP. In this review, we summarized the latest studies in our understanding of the factors related to CAP and potential treatments targeting those factors. This review can help understand the mechanism of CAP and develop efficient therapies and management.

Cathepsin K deficiency promotes alveolar bone regeneration by promoting jaw bone marrow mesenchymal stem cells proliferation and differentiation via glycolysis pathway.

OBJECTIVES: To clarify the possible role and mechanism of Cathepsin K (CTSK) in alveolar bone regeneration mediated by jaw bone marrow mesenchymal stem cells (JBMMSC). MATERIALS AND METHODS: Tooth extraction models of Ctsk knockout mice (Ctsk-/- ) and their wildtype (WT) littermates were used to investigate the effect of CTSK on alveolar bone regeneration. The influences of deletion or inhibition of CTSK by odanacatib (ODN) on proliferation and osteogenic differentiation of JBMMSC were assessed by CCK-8, Western blot and alizarin red staining. To explore the differently expressed genes, RNA from WT and Ctsk-/- JBMMSC was sent to RNA-seq. ECAR, glucose consumption and lactate production were measured to identify the effect of Ctsk deficiency or inhibition on glycolysis. At last, we explored whether Ctsk deficiency or inhibition promoted JBMMSC proliferation and osteogenic differentiation through glycolysis. RESULTS: We found out that Ctsk knockout could promote alveolar bone regeneration in vivo. In vitro, we confirmed that both Ctsk knockout and inhibition by ODN could promote proliferation of JBMMSC, up-regulate expression of Runx2 and ALP, and enhance matrix mineralization. RNA-seq results showed that coding genes of key enzymes in glycolysis were significantly up-regulated in Ctsk-/- JBMMSC, and Ctsk deficiency or inhibition could promote glycolysis in JBMMSC. After blocking glycolysis by 3PO, the effect of Ctsk deficiency or inhibition on JBMMSC's regeneration was blocked subsequently. CONCLUSIONS: Our findings revealed that Ctsk knockout or inhibition could promote alveolar bone regeneration by enhancing JBMMSC regeneration via glycolysis. These results shed new lights on the regulatory mechanism of CTSK on bone regeneration.