A locally solvent-tethered polymer electrolyte for long-life lithium metal batteries.

Solid polymer electrolytes exhibit enhanced Li+ conductivity when plasticized with highly dielectric solvents such as N,N-dimethylformamide (DMF). However, the application of DMF-containing electrolytes in solid-state batteries is hindered by poor cycle life caused by continuous DMF degradation at the anode surface and the resulting unstable solid-electrolyte interphase. Here we report a composite polymer electrolyte with a rationally designed Hofmann-DMF coordination complex to address this issue. DMF is engineered on Hofmann frameworks as tethered ligands to construct a locally DMF-rich interface which promotes Li+ conduction through a ligand-assisted transport mechanism. A high ionic conductivity of 6.5 × 10-4 S cm-1 is achieved at room temperature. We demonstrate that the composite electrolyte effectively reduces the free shuttling and subsequent decomposition of DMF. The locally solvent-tethered electrolyte cycles stably for over 6000 h at 0.1 mA cm-2 in Li | |Li symmetric cell. When paired with sulfurized polyacrylonitrile cathodes, the full cell exhibits a prolonged cycle life of 1000 cycles at 1 C. This work will facilitate the development of practical polymer-based electrolytes with high ionic conductivity and long cycle life.

U-shaped convolutional transformer GAN with multi-resolution consistency loss for restoring brain functional time-series and dementia diagnosis.

Introduction: The blood oxygen level-dependent (BOLD) signal derived from functional neuroimaging is commonly used in brain network analysis and dementia diagnosis. Missing the BOLD signal may lead to bad performance and misinterpretation of findings when analyzing neurological disease. Few studies have focused on the restoration of brain functional time-series data. Methods: In this paper, a novel U-shaped convolutional transformer GAN (UCT-GAN) model is proposed to restore the missing brain functional time-series data. The proposed model leverages the power of generative adversarial networks (GANs) while incorporating a U-shaped architecture to effectively capture hierarchical features in the restoration process. Besides, the multi-level temporal-correlated attention and the convolutional sampling in the transformer-based generator are devised to capture the global and local temporal features for the missing time series and associate their long-range relationship with the other brain regions. Furthermore, by introducing multi-resolution consistency loss, the proposed model can promote the learning of diverse temporal patterns and maintain consistency across different temporal resolutions, thus effectively restoring complex brain functional dynamics. Results: We theoretically tested our model on the public Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, and our experiments demonstrate that the proposed model outperforms existing methods in terms of both quantitative metrics and qualitative assessments. The model's ability to preserve the underlying topological structure of the brain functional networks during restoration is a particularly notable achievement. Conclusion: Overall, the proposed model offers a promising solution for restoring brain functional time-series and contributes to the advancement of neuroscience research by providing enhanced tools for disease analysis and interpretation.

A Large-Scale Fabrication of Flexible, Ultrathin, and Robust Solid Electrolyte for Solid-State Lithium-Sulfur Batteries.

All-solid-state lithium metal batteries (ASSLMBs) are considered as the most promising candidates for the next-generation high-safety batteries. To achieve high energy density in ASSLMBs, it is essential that the solid-state electrolytes (SSEs) are lightweight, thin, and possess superior electrochemical stability. In this study, a feasible and scalable fabrication approach to construct 3D supporting skeleton using an electro-blown spinning technique is proposed. This skeleton not only enhances the mechanical strength but also hinders the migration of Li-salt anions, improving the lithium-ion transference number of the SSE. This provides a homogeneous distribution of Li-ion flux and local current density, promoting uniform Li deposition. As a result, based on the mechanically robust and thin SSEs, the Li symmetric cells show outstanding Li plating/stripping reversibility. Besides, a stable interface contact between SSE and Li anode has been established with the formation of an F-enriched solid electrolyte interface layer. The solid-state Li|sulfurized polyacrylonitrile (Li|SPAN) cell achieves a capacity retention ratio of 94.0% after 350 cycles at 0.5 C. Also, the high-voltage Li|LCO cell shows a capacity retention of 92.4% at 0.5 C after 500 cycles. This fabrication approach for SSEs is applicable for commercially large-scale production and application in high-energy-density and high-safety ASSLMBs.

Mechanisms of the Accelerated Li+ Conduction in MOF-Based Solid-State Polymer Electrolytes for All-Solid-State Lithium Metal Batteries.

Solid polymer electrolytes (SPEs) for lithium metal batteries have garnered considerable interests owing to their low cost, flexibility, lightweight, and favorable interfacial compatibility with battery electrodes. Their soft mechanical nature compared to solid inorganic electrolytes give them a large advantage to be used in low pressure solid-state lithium metal batteries, which can avoid the cost and weight of the pressure cages. However, the application of SPEs is hindered by their relatively low ionic conductivity. In addressing this limitation, enormous efforts are devoted to the experimental investigation and theoretical calculations/simulation of new polymer classes. Recently, metal-organic frameworks (MOFs) have been shown to be effective in enhancing ion transport in SPEs. However, the mechanisms in enhancing Li+ conductivity have rarely been systematically and comprehensively analyzed. Therefore, this review provides an in-depth summary of the mechanisms of MOF-enhanced Li+ transport in MOF-based solid polymer electrolytes (MSPEs) in terms of polymer, MOF, MOF/polymer interface, and solid electrolyte interface aspects, respectively. Moreover, the understanding of Li+ conduction mechanisms through employing advanced characterization tools, theoretical calculations, and simulations are also reviewed in this review. Finally, the main challenges in developing MSPEs are deeply analyzed and the corresponding future research directions are also proposed.

Occlusal force orchestrates alveolar bone homeostasis via Piezo1 in female mice.

Healthy alveolar bone is the cornerstone of oral function and oral treatment. Alveolar bone is highly dynamic during the entire lifespan and is affected by both systemic and local factors. Importantly, alveolar bone is subjected to unique occlusal force in daily life, and mechanical force is a powerful trigger of bone remodeling, but the effect of occlusal force in maintaining alveolar bone mass remains ambiguous. In this study, the Piezo1 channel is identified as an occlusal force sensor. Activation of Piezo1 rescues alveolar bone loss caused by a loss of occlusal force. Moreover, we identify Piezo1 as the mediator of occlusal force in osteoblasts, maintaining alveolar bone homeostasis by directly promoting osteogenesis and by sequentially regulating catabolic metabolism through Fas ligand (FasL)-induced osteoclastic apoptosis. Interestingly, Piezo1 activation also exhibits remarkable efficacy in the treatment of alveolar bone osteoporosis caused by estrogen deficiency, which is highly prevalent among middle-aged and elderly women. Promisingly, Piezo1 may serve not only as a treatment target for occlusal force loss-induced alveolar bone loss but also as a potential target for metabolic bone loss, especially in older patients.

Daily occlusal force and estrogen synergistically maintain alveolar bone homeostasis. PIEZO1 in osteoblasts plays a critical role in sensing occlusal force and maintaining bone mass. PIEZO1 may promote osteoclastic apoptosis through osteoblast-secreted FasL through a PIEZO1-STAT3/ESR1-FasL pathway. Restoration of occlusal force with dental therapies as early as possible to prevent alveolar bone loss is the major priority in oral health care. PIEZO1 may serve as a potential target for bone metabolism disorders.

Repeated high­intensity focused ultrasound combined with iodine­125 seed interstitial brachytherapy offers improved quality of life and pain control for patients with advanced pancreatic cancer: A 52­patient retrospective study.

Patients diagnosed with pancreatic cancer who have 5-year survival rates of ~5% are typically in the advanced stage. Pancreatic cancer has become the third leading cause of cancer-related death in the United States and there is still a lack of effective treatments to improve patient survival rate. Hence, the purpose of the present retrospective study was to assess the potential clinical impact of repeated high-intensity focused ultrasound (HIFU) combined with iodine-125 (125I) interstitial brachytherapy for the treatment of patients with advanced pancreatic cancer who were ineligible for or declined surgery and chemotherapy. A total of 52 patients diagnosed with advanced pancreatic cancer were included in the study. At least one course of HIFU therapy combined with percutaneous ultrasound-guided 125I seed implantation was administered to each patient. The clinical assessment included an evaluation of Karnofsky Performance Scale (KPS) score at baseline, and at 1 and 2 months after combined therapy. Pain intensity was additionally evaluated with the numerical rating score (NRS). Overall survival (OS) times and survival rates at 3, 6, 9 and 12 months after combined treatment were evaluated. Adverse events commonly associated with HIFU and 125I seed implantation were recorded, and the severity of adverse events was graded according to the Common Terminology Criteria for Adverse Events, version 4. All 52 patients received successful repeated HIFU treatment combined with 125I seed implantation and were included in the analysis of efficacy and safety. The median OS time of patients was estimated to be 13.1 months (95% CI, 11.3-14.8). The survival rates at 3, 6, 9 and 12 months were 100.0, 86.5, 61.5 and 53.8%, respectively. The mean KPS score was 62.7±6.3 at baseline, 73.7±7.9 at 1 month and 68.8±6.5 at 2 months after combined treatment. KPS score increased significantly after combined therapy. The mean NRS score was 6.7±1.6 at baseline, and 4.7±1.7 and 5.4±1.5 at 1 and 2 months after combined treatment, respectively. The number of patients with severe pain and the NRS score were both significantly lower at 1 and 2 months after 125I seed implantation compared with those at baseline. No serious complications were detected during the follow-up period. In conclusion, the present study demonstrated the survival benefit and improvement in quality of life of patients with advanced pancreatic cancer receiving repeated HIFU treatment combined with 125I interstitial brachytherapy, which may provide new ideas and methods for the treatment of pancreatic cancer.

Structuring Cu Membrane Electrode for Maximizing Ethylene Yield from CO2 Electroreduction.

Electrocatalytic ethylene (C2H4) evolution from CO2 reduction is an intriguing route to mitigate both the energy and environmental crises; however, to acquire industrially relevant high productivity and selectivity at low energy cost remains to be challenging. Membrane assembly electrode has shown great prospect and tailoring its architecture for maximizing C2H4 yield at minimum voltage with long-term stability becomes critical. Here a freestanding Cu membrane cathode is designed and constructed by electrochemically depositing mesoporous Cu film on Cu foam to simultaneously manage CO2, electron, water, and product transport, which shows an extraordinary C2H4 Faradaic efficiency of 85.6% with a full cell power conversion efficiency of 33% at a current density of 368 mA cm-2, heading the techno-economic viability for electrocatalytic C2H4 production.

Subtractive transformation of cathode materials in spent Li-ion batteries to a low-cobalt 5 V-class cathode material.

Adding extra raw materials for direct recycling or upcycling is prospective for battery recycling, but overlooks subtracting specific components beforehand can facilitate the recycling to a self-sufficient mode of sustainable production. Here, a subtractive transformation strategy of degraded LiNi0.5Co0.2Mn0.3O2 and LiMn2O4 to a 5 V-class disordered spinel LiNi0.5Mn1.5O4-like cathode material is proposed. Equal amounts of Co and Ni from degraded materials are selectively extracted, and the remaining transition metals are directly converted into Ni0.4Co0.1Mn1.5(CO3)2 precursor for preparing cathode material with in-situ Co doping. The cathode material with improved conductivity and bond strength delivers high-rate (10 C and 20 C) and high-temperature (60 °C) cycling stability. This strategy with no extra precursor input can be generalized to practical degraded black mass and reduces the dependence of current cathode production on rare elements, showing the potential of upcycling from the spent to a next-generation 5 V-class cathode material for the sustainable Li-ion battery industry.

Adaptive metabolic response to short-term intensive fasting.

BACKGROUND & AIMS: Short-term intensive fasting (STIF), known as beego in Chinese phonetic articulation, has been practiced for more than two thousand years. However, the potential risk of STIF and the body's response to the risk have not been adequately evaluated. This study aims to address this issue, focusing on the STIF-triggered metabolic response of the liver and kidney. METHODS: The STIF procedure in the clinical trial includes a 7-day water-only intensive fasting phase and a 7-day gradual refeeding phase followed by a regular diet. The intensive fasting in humans was assisted with psychological induction. To gain insights not available in the clinical trial, we designed a STIF program for mice that resulted in similar phenotypes seen in humans. Plasma metabolic profiling and examination of gene expression as well as liver and kidney function were performed by omics, molecular, biochemical and flow cytometric analyses. A human cell line model was also used for mechanistic study. RESULTS: Clinically significant metabolites of fat and protein were found to accumulate during the fasting phase, but they were relieved after gradual refeeding. Metabolomics profiling revealed a universal pattern in the consumption of metabolic intermediates, in which pyruvate and succinate are the two key metabolites during STIF. In the STIF mouse model, the accumulation of metabolites was mostly counteracted by the upregulation of catabolic enzymes in the liver, which was validated in a human cell model. Kidney filtration function was partially affected by STIF but could be recovered by refeeding. STIF also reduced oxidative and inflammatory levels in the liver and kidney. Moreover, STIF improved lipid metabolism in mice with fatty liver without causing accumulation of metabolites after STIF. CONCLUSIONS: The accumulation of metabolites induced by STIF can be relieved by spontaneous upregulation of catabolic enzymes, suggesting an adaptive and protective metabolic response to STIF stress in the mammalian body.

In situ generation of copper(â ¡)/diethyldithiocarbamate complex through tannic acid/copper(â ¡) network coated hollow mesoporous silica for enhanced cancer chemodynamic therapy.

The Cu2+ complex formed by the coordination of disulfiram (DSF) metabolite diethyldithiocarbamate (DTC), Cu(DTC)2, can effectively inhibit tumor growth. However, insufficient Cu2+ levels in the tumor microenvironment can impact tumor-suppressive effects of DTC. In this study, we proposed a Cu2+ and DSF tumor microenvironment-targeted delivery system. This system utilizes hollow mesoporous silica (HMSN) as a carrier, after loading with DSF, encases it using a complex of tannic acid (TA) and Cu2+ on the outer layer. In the slightly acidic tumor microenvironment, TA/Cu undergoes hydrolysis, releasing Cu2+ and DSF, which further form Cu(DTC)2 to inhibit tumor growth. Additionally, Cu2+ can engage in a Fenton-like reaction with H2O2 in the tumor microenvironment to form OH, therefore, chemodynamic therapy (CDT) and Cu(DTC)2 are used in combination for tumor therapy. In vivo tumor treatment results demonstrated that AHD@TA/Cu could accumulate at the tumor site, achieving a tumor inhibition rate of up to 77.6 %. This study offers a novel approach, circumventing the use of traditional chemotherapy drugs, and provides valuable insights into the development of in situ tumor drug therapies.

Low Anterior Resection Syndrome in Total Mesorectal Excision: Risk Factors and Its Relationship with Quality of Life.

Background: Low anterior resection syndrome (LARS) is a bowel dysfunction following sphincter-sparing proctectomy. The occurrence of LARS may affect a patient's overall quality of life (QoL) after surgery. Current research was aimed to investigate related factors of LARS and major LARS in total mesorectal excision (TME) and its relationship with QoL. Methods: This study included patients who underwent TME at authors' institutes. LARS was evaluated with an LARS score. QoL was identified using the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, version 3.0. Appropriate statistical methods were used to ascertain risk factors for LARS and major LARS and to analyze the relationships between QoL and LARS. The primary objective was to identify related factors of LARS and major LARS. The secondary objective was to examine the relationships between QoL and LARS. Results: Multivariable analysis identified neoadjuvant chemoradiotherapy (odds ratio [OR] 4.923, 95% confidence interval [CI] 2.335-10.379, P < .001), local anal distance from the lower edge of the tumor (OR 6.199, 95% CI 2.701-14.266, P < .001), and anastomotic leakage (OR 5.624, 95% CI 1.463-21.614, P = .012) as independent predictors for development of LARS. Meanwhile, neoadjuvant chemoradiotherapy (OR 4.693, 95% CI 1.368-16.107, P = .014) and local anal distance from the lower edge of the tumor (OR 4.935, 95% CI 1.332-18.285, P = .017) were dramatically correlated with development of major LARS in a multivariable analysis. In the major LARS group, statistically significant differences (P < .05) were ascertained, include physical functioning, role functioning, emotional functioning, social functioning, and global health. In addition, pain and diarrhea were evidently higher. Conclusions: Neoadjuvant chemoradiotherapy, local anal distance from the lower edge of the tumor, and anastomotic leakage correlated strongly with development of LARS, and neoadjuvant chemoradiotherapy and local anal distance from the lower edge of the tumor correlated strongly with development of major LARS. Meanwhile, the QoL of patients with major LARS was lower than that of patients with no/minor LARS.

The role of surgical factors eliciting oculocardiac reflex of patients undergoing orbital tumor surgery: a retrospective study.

PURPOSE: Orbital tumors are an interdisciplinary disease, and surgery is one of the main treatment methods. The oculocardiac reflex (OCR) is a condition of surgery for orbital tumors. The aim of this study was to investigate whether there is an association between many surgical factors and the incidence of OCR in orbital tumor surgery. METHODS: Comparisons were made between patients with and without OCR using the Mann-Whitney test, Fisher's exact test, and Chi-square test. When comparing multiple groups (groups > 2), to explain which two groups had differences, post hoc testing was used for analysis, and the differences between groups were judged according to the adjusted standardized residuals. RESULTS: The results showed that the incidence of intraoperative OCR was different based on the different exposed operative field locations (p = 0.021). The OCR incidence in those with lesions involving the orbital apex and lesions adhering to extraocular muscles was higher than that of others (p < 0.001 and p = 0.003). In addition, multivariate logistic regression analysis revealed that orbital apex involvement and extraocular muscle adhesion were highly associated with a higher incidence of OCR (p < 0.001 and p = 0.013), while the operative field located in the lateral-superior orbit was highly associated with a lower incidence of OCR (p = 0.029). CONCLUSION: In orbital tumor surgery under general anesthesia, lesions involving the orbital apex and lesion adhesion to the extraocular muscles were independent risk factors for OCR, and an operative field located in the lateral-superior orbit was a protective factor for OCR.

Band Structure Engineering and Orbital Orientation Control Constructing Dual Active Sites for Efficient Sulfur Redox Reaction.

The kinetics difference among multistep electrochemical processes leads to the accumulation of soluble polysulfides and thus shuttle effect in lithium-sulfur (Li-S) batteries. While the interaction between catalysts and representative species has been reported, the root of the kinetics difference, interaction change among redox reactions, remains unclear, which significantly impedes the catalysts design for Li-S batteries. Here, this work deciphers the interaction change among electrocatalytic sulfur reactions, using tungsten disulfide (WS2 ) a model system to demonstrate the efficiency of modifying electrocatalytic selectivity via dual-coordination design. Band structure engineering and orbital orientation control are combined to guide the design of WS2 with boron dopants and sulfur vacancies (B-WS2- x ), accurately modulating interaction with lithium and sulfur sites in polysulfide species for relatively higher interaction with short-chain polysulfides. The modified interaction trend is experimentally confirmed by distinguishing the kinetics of each electrochemical reaction step, indicating the effectiveness of the designed strategy. An Ah-level pouch cell with B-WS2- x delivers a gravimetric energy density of up to 417.6 Wh kg-1 with a low electrolyte/sulfur ratio of 3.6 µL mg-1 and negative/positive ratio of 1.2. This work presents a dual-coordination strategy for advancing evolutionarily catalytic activity, offering a rational strategy to develop effective catalysts for practical Li-S batteries.

Early-Responsive Immunoregulation Therapy Improved Microenvironment for Bone Regeneration Via Engineered Extracellular Vesicles.

Overactivated inflammatory reactions hinder the bone regeneration process. Timely transformation of microenvironment from pro-inflammatory to anti-inflammatory after acute immune response is favorable for osteogenesis. Macrophages play an important role in the immune response to inflammation. Therefore, this study adopts TIM3 high expression extracellular vesicles (EVs) with immunosuppressive function to reshape the early immune microenvironment of bone injury, mainly by targeting macrophages. These EVs can be phagocytosed by macrophages, thereby increasing the infiltration of TIM3-positive macrophages (TIM3+ macrophages) and M2 subtypes. The TIM3+ macrophage group has some characteristics of M2 macrophages and secretes cytokines, such as IL-10 and TGF-ß1 to regulate inflammation. TIM3, which is highly expressed in the engineered EVs, mediates the release of anti-inflammatory cytokines by inhibiting the p38/MAPK pathway and promotes osseointegration by activating the Bmp2 promoter to enhance macrophage BMP2 secretion. After evenly loading the engineered EVs into the hydrogel, the continuous and slow release of EVsTIM3OE recruits more anti-inflammatory macrophages during the early stages of bone defect repair, regulating the immune microenvironment and eliminating the adverse effects of excessive inflammation. In summary, this study provides a new strategy for the treatment of refractory wounds through early inflammation control.

Using machine learning to identify patients at high risk of developing low bone density or osteoporosis after gastrectomy: a 10-year multicenter retrospective analysis.

INTRODUCTION: Osteoporosis that emerges subsequent to gastrectomy poses a significant threat to the long-term health of patients. The primary objective of this investigation was to formulate a machine learning algorithm capable of identifying substantial preoperative, intraoperative, and postoperative risk factors. This algorithm, in turn, would enable the anticipation of osteoporosis occurrence after gastrectomy. METHODS: This research encompassed a cohort of 1125 patients diagnosed with gastric cancer, including 108 individuals with low bone density or osteoporosis. A total of 40 distinct variables were collected, comprising patient demographics, pertinent medical history, medication records, preoperative examination attributes, surgical procedure specifics, and intraoperative details. Four distinct machine learning algorithms-extreme gradient boosting (XGBoost), random forest (RF), support vector machine (SVM), and k-nearest neighbor algorithm (KNN)-were employed to establish the predictive model. Evaluation of the models involved receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Shapley additive explanation (SHAP) was employed for visualization and analysis. RESULTS: Among the four prediction models employed, the XGBoost algorithm demonstrated exceptional performance. The ROC analysis yielded excellent predictive accuracy, showcasing area under the curve (AUC) values of 0.957 and 0.896 for training and validation sets, respectively. The calibration curve further confirmed the robust predictive capacity of the XGBoost model. The DCA demonstrated a notably higher benefit rate for patients undergoing intervention based on the XGBoost model. Moreover, the AUC value of 0.73 for the external validation set indicated favorable extrapolation of the XGBoost prediction model. SHAP analysis outcomes unveiled numerous high-risk factors for osteoporosis development after gastrectomy, including a history of chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), hypoproteinemia, postoperative neutrophil-to-lymphocyte ratio (NLR) exceeding 3, steroid usage history, advanced age, and absence of calcitonin use. CONCLUSION: The osteoporosis prediction model derived through the XGBoost machine learning algorithm in this study displays remarkable predictive precision and carries significant clinical applicability.

Epirubicin and gait apraxia: a real-world data analysis of the FDA Adverse Event Reporting System database.

Introduction: Epirubicin is widely used in many malignancies with good efficacy and tolerability. However, investigations about adverse events (AEs) using real-world information are still insufficient. Methods: We extracted Epirubicin-related reports submitted between the first quarter of 2014 and first quarter of 2023 from FAERS database. Four algorithms were utilized to evaluate whether there was a significant correlation between Epirubicin and AEs. Results: After de-duplicating, a total of 3919 cases were extracted. Among the 3919 cases, we identified 1472 AEs, 253 of which were found to be adverse drug reactions (ADRs) associated with Epirubicin. We analysed the occurrence of Epirubicin-induced ADRs and found several unexpected significant ADRs, such as hepatic artery stenosis, hepatic artery occlusion, intestinal atresia and so on. Interestingly, we found gait apraxia, a neurological condition, was also significantly associated with Epirubicin. To our knowledge, there haven't studies that have reported an association between gait disorders and the usage of epirubicin. Discussion: Our study identified new unexpected significant ADRs related to Epirubicin, providing new perspectives to the clinical use of Epirubicin.

The odontoblastic differentiation of dental mesenchymal stem cells: molecular regulation mechanism and related genetic syndromes.

Dental mesenchymal stem cells (DMSCs) are multipotent progenitor cells that can differentiate into multiple lineages including odontoblasts, osteoblasts, chondrocytes, neural cells, myocytes, cardiomyocytes, adipocytes, endothelial cells, melanocytes, and hepatocytes. Odontoblastic differentiation of DMSCs is pivotal in dentinogenesis, a delicate and dynamic process regulated at the molecular level by signaling pathways, transcription factors, and posttranscriptional and epigenetic regulation. Mutations or dysregulation of related genes may contribute to genetic diseases with dentin defects caused by impaired odontoblastic differentiation, including tricho-dento-osseous (TDO) syndrome, X-linked hypophosphatemic rickets (XLH), Raine syndrome (RS), hypophosphatasia (HPP), Schimke immuno-osseous dysplasia (SIOD), and Elsahy-Waters syndrome (EWS). Herein, recent progress in the molecular regulation of the odontoblastic differentiation of DMSCs is summarized. In addition, genetic syndromes associated with disorders of odontoblastic differentiation of DMSCs are discussed. An improved understanding of the molecular regulation and related genetic syndromes may help clinicians better understand the etiology and pathogenesis of dentin lesions in systematic diseases and identify novel treatment targets.

Using Inducible Osteoblastic Lineage-Specific Stat3 Knockout Mice to Study Alveolar Bone Remodeling During Orthodontic Tooth Movement.

The alveolar bone, with a high turnover rate, is the most actively-remodeling bone in the body. Orthodontic tooth movement (OTM) is a common artificial process of alveolar bone remodeling in response to mechanical force, but the underlying mechanism remains elusive. Previous studies have been unable to reveal the precise mechanism of bone remodeling in any time and space due to animal model-related restrictions. The signal transducer and activator of transcription 3 (STAT3) is important in bone metabolism, but its role in osteoblasts during OTM is unclear. To provide in vivo evidence that STAT3 participates in OTM at specific time points and in particular cells during OTM, we generated a tamoxifen-inducible osteoblast lineage-specific Stat3 knockout mouse model, applied orthodontic force, and analyzed the alveolar bone phenotype. Micro-computed tomography (Micro-CT) and stereo microscopy were used to access OTM distance. Histological analysis selected the area located within three roots of the first molar (M1) in the cross-section of the maxillary bone as the region of interest (ROI) to evaluate the metabolic activity of osteoblasts and osteoclasts, indicating the effect of orthodontic force on alveolar bone. In short, we provide a protocol for using inducible osteoblast lineage-specific Stat3 knockout mice to study bone remodeling under orthodontic force and describe methods for analyzing alveolar bone remodeling during OTM, thus shedding new light on skeletal mechanical biology.

The role of corneal biomechanics in visual field progression of primary open-angle glaucoma with ocular normotension or hypertension: a prospective longitude study.

Introduction: To analyze effects of dynamic corneal response parameters (DCRs) on visual field (VF) progression in normal-tension glaucoma (NTG) and hypertension glaucoma (HTG). Methods: This was a prospective cohort study. This study included 57 subjects with NTG and 54 with HTG, followed up for 4 years. The subjects were divided into progressive and nonprogressive groups according to VF progression. DCRs were evaluated by corneal visualization Scheimpflug technology. General linear models (GLMs) were used to compare DCRs between two groups, adjusting for age, axial length (AL), mean deviation (MD), etc. VF progression risk factors were evaluated by logistic regression and receiver operating characteristic (ROC) curves. Results: For NTG, first applanation deflection area (A1Area) was increased in progressive group and constituted an independent risk factor for VF progression. ROC curve of A1Area combined with other relevant factors (age, AL, MD, etc.) for NTG progression had an area under curve (AUC) of 0.813, similar to the ROC curve with A1area alone (AUC = 0.751, p = 0.232). ROC curve with MD had an AUC of 0.638, lower than A1Area-combined ROC curve (p = 0.036). There was no significant difference in DCRs between the two groups in HTG. Conclusion: Corneas in progressive NTG group were more deformable than nonprogressive group. A1Area may be an independent risk factor for NTG progression. It suggested that the eyes with more deformable corneas may also be less tolerant to pressure and accelerate VF progression. VF progression in HTG group was not related to DCRs. Its specific mechanism needs further studies.

Exercise maintains bone homeostasis by promoting osteogenesis through STAT3.

Bone exhibits changes in density, strength, and microarchitecture in relation to mechanical loading mediated by exercise. Appropriate exercise maintains bone homeostasis, while the absence of exercise leads to disuse bone loss. However, the acting mechanism of mechanotransduction in bone remains unclear. We performed the running-wheel exercise and tail suspension model to study the effects of exercise on bone metabolism, and found that osteoblastic Signal transducer and activator of transcription 3 (STAT3) activity was closely related to exercise-induced bone mass and metabolism changes. With the Flexcell tension-loading system in vitro, mechanical force promoted STAT3 activity, which was accompanied by increased osteoblastic differentiation of the bone marrow mesenchymal stem cells (BMSCs). In contrast, the inhibition of STAT3 phosphorylation blocked force-induced osteoblastic differentiation. Furthermore, pharmacological inactivation of STAT3 impaired the increase in exercise-induced bone mass and osteogenesis. With an inducible conditional deletion mouse model, we found that the osteoblast lineage-specific Stat3 deletion could also block force-induced osteoblastic differentiation in vitro and impair exercise-promoted bone mass and osteogenesis in vivo. This confirmed the crucial role of osteoblastic STAT3 in exercise-mediated bone metabolism. Finally, colivelin, a STAT3 agonist, promoted osteoblastic differentiation in vitro and partly rescued exercise loss-induced disuse bone loss by improving osteogenesis in the tail suspension model. Taken together, our study revealed the essential role of STAT3 in maintaining exercise-mediated bone homeostasis. In addition, STAT3 might act as a potential target for osteoporosis caused by exercise loss.