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1.
Int J Biol Macromol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31730991

RESUMO

In order to develop the antioxidant and gas permeability packaging film, the effects of three plant extracts (pine nut shell, peanut shell and jujube leaf) on the physical, antioxidative and structural properties of chitosan based biodegradable films were studied. The results showed that three plant extracts improved the antioxidant capacity of films. The DPPH radical scavenging activity of chitosan-jujube leaf films increased by 3.8 times compared with the control films. The chitosan-pine nut shell films had the highest water vapor and oxygen permeability, while chitosan-peanut shell films showed greatest increase in CO2 permeability with a value of 1.71 × 104 cm3/(m2·24h) under standard test. In addition, three plant extracts reduced the homogeneity and caused porous structure of chitosan films. Chitosan-peanut shell films had the highest thermal stability compared with the control and other two films. X-ray diffraction and FTIR indicated three plant extracts changed the hydrogen bonding of film matrix and caused the changes of crystal and chemical structure. The study provided a reference for the preparation of polysaccharide-based active films with strong antioxidant and gas permeability.

2.
Anal Chem ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31743002

RESUMO

Activity-based chemical proteomics approaches used for identifying cellular targets of drugs are mainly dependent on the availability of probes derived from drugs. However, all chemical probes are structurally different from the drugs themselves and cannot fully mimic the real actions of drugs in cells. Here we present a concise and unbiased immunoaffinity-based strategy for identifying covalent drug targets in vivo. By using the specific antibody, we not only confirm the well-known ibrutinib-binding target BTK, but also identify some previously undescribed strongly binding proteins, such as CKAP4 in human cell lines and TAP1 in mouse organs. The observed target profiles between species may partially explain why certain drug candidates are very effective in mice but not in humans. This approach avoids the chemical modification of drugs, eliminates the nonspecific bindings of chemical probes, and allows to unbiasedly decode the underlying mechanisms of action of covalent drugs.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31780357

RESUMO

OBJECTIVE: To investigate the prevalence, risk factors, and clinical outcomes associated with early fluid overload (FO) in a special group of pediatric patients undergoing repair of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). DESIGN: It was a retrospective study performed with multiple variable regression analysis. SETTING: A single cardiac surgical institution. PARTICIPANTS: Eighty-eight patients younger than 18 years of age undergoing ALCAPA surgical repair with cardiopulmonary bypass were recruited at the authors' institution from June 2010 to September 2017. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: Of 88 pediatric patients with ALCAPA after surgical repair, 37.5% developed early FO, defined as fluid accumulation ≥5% within the period from surgery until midnight of postoperative day 1. Patients with early FO were younger, weighed less, and had worse preoperative cardiac dysfunction. With logistic regression analysis, being underweight was confirmed to be a risk factor for FO development (odds ratio, 8.66; 95% confidence interval, 2.83-26.52; p < 0.001). Early FO also predicted severe acute kidney injury, respiratory morbidity, and low cardiac output syndrome after reimplantation procedure. Patients with early FO also had significantly longer mechanical ventilation hours (p  <  0.001), intensive care unit length of stay (p = 0.003), and hospital length of stay (p = 0.009). CONCLUSION: Early FO ≥5% has been linked to adverse postoperative outcomes in pediatric patients undergoing repair for ALCAPA. The use of restrictive fluid management is crucial for patients who have lower weight and poor myocardial function before and after complex surgical procedures such as in ALCAPA settings.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31691016

RESUMO

PURPOSES: This study provides an approach to estimating tympanic membrane perforation-induced hearing loss (HL) using a human middle ear model. METHODS: Sixty-one cases of tympanic membrane perforation originating from fireworks were reported from the Ear-Nose-Throat Department. The otoscope, audiometry data and diagnosis records were organized, and gender, age, etiology, perforation size and diseased ear side were classified as independent variables. A multinomial regression model was used to analyze the potential effects of the variables on HL. Meanwhile, a human middle ear model was implemented to calculate the ensued HL resulting from different perforation areas and sites. In addition, linear regression models were used to establish functions between perforation size and HL. RESULTS: The audiometry data indicate that HL at high frequencies (f > 2 kHz) is much more profound than that at the speech frequency band (f < 1 kHz). Compared with mild HL (<15 dB), mediate HL (15-30 dB) was correlated with the perforation area (p < 0.05, 95% CI), while severe HL (>30 dB) was affected by both perforation size and age (p < 0.05, 95% CI). However, other factors, including gender and diseased ear side, do not show a statistically significant effect on HL. Furthermore, the Kruskal-Wallis test result reveals that HL at frequencies of 0.25 kHz ≤ f ≤ 8 kHz is strongly associated with the perforation size (p < 0.05, 95% CI). CONCLUSIONS: It is conclusive that HL is positively proportional to the perforation size. However, HL is not correlated with the perforation site for small perforation areas of < 10% (p > 0.05, 95% CI).

5.
Eye (Lond) ; 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31649348

RESUMO

BACKGROUND: Ophthalmic emergencies comprise a significant portion of junior doctors' workload in accident and emergency (A&E). However, previous studies have demonstrated a lack of training and confidence in the management of such emergencies. This study assessed changes in basic ophthalmic training that A&E junior doctors received in dealing with eye emergencies, their perceived level of confidence and the availability of appropriate ophthalmic equipment in A&E over the last 15 years. METHODS: A prospective, national, combined online and telephone survey using a previously published questionnaire was performed. Foundation year two doctors (FY2s) from each A&E department in the UK listed on the official NHS directory were contacted for participation. RESULTS: Two hundred and ten A&E departments were contacted and 202 responded (response rate of 96.2%). There was no significant change in the number of A&E departments equipped with slit lamps (82.5% in 2003 vs 79.7% in 2018; p = 0.26). However, the prevalence of training in its use has decreased significantly (68.4% in 2003 vs 52% in 2018; p = 0.005). There was also a significant reduction in the prevalence of training in the management of eye emergencies (77.4% in 2003 vs 45.5% in 2018; p < 0.001) and the proportion of FY2s who felt confident in dealing with such cases (36.1% in 2003 vs 6% in 2018; p < 0.001). CONCLUSION: There is a concerning decline in basic ophthalmic training for A&E FY2s, reflected by the alarmingly low level of confidence in the management of eye emergencies. This highlights an urgent need to improve ophthalmic training for junior doctors in A&E.

6.
Life Sci ; 238: 116953, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31626793

RESUMO

AIMS: This study focused on investigating whether NS8593 reverses airway smooth muscle (ASM) contraction and the underlying mechanism. MAIN METHODS: ASM contraction in mouse tracheal rings and lung slices was measured. Currents mediated by voltage dependent Ca2+ channels (VDCCs) and ACH-activated channels were measured using the whole-cell patch-clamp technique in single tracheal smooth muscle cells (TSMCs). Intracellular Ca2+ level and cell length were measured using an LSM 700 laser confocal microscope and a Zen 2010 software. Mouse respiratory system resistance (Rrs) was assessed using a FlexiVent FX system. KEY FINDINGS: High K+ (80 mM K+) and ACH induced ASM contraction in mouse tracheal rings and lung slices, which was partially relaxed by nifedipine (blocker of L-type VDCCs, LVDCCs), YM-58483 (blocker of store-operated Ca2+ entry (SOCE), transient receptor potential C3 (TRPC3) and TRPC5 channels), respectively. However, the contraction was completely reversed by NS8593, whereas, slightly relaxed by formoterol. ACH activated inward currents, which displayed linear and reversed around 0 mV, indicating the currents were mediated by non-selective cation channels (NSCCs). Moreover, these currents were blocked by YM-58483. In addition, such currents were abolished by NS8593, implicating that NS8593 inhibits the same channels. Besides, NS8593 inhibited increases of intracellular Ca2+ and the associated cell shortening. Finally, NS8593 inhibited ACH-induced increases of mouse respirator system resistance (Rrs). SIGNIFICANCE: Our results indicate that NS8593 inhibits LVDCCs and NSCCs, resulting in decreases of intracellular Ca2+ and then leading to ASM relaxation. These data suggest that NS8593 might be a new bronchodilator.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31612576

RESUMO

We report a novel modulation strategy by introducing transition metals into NiS2 nanosheets (NSs) to flexibly optimize the electronic configurations and atomic arrangement. The Co-NiS2 NSs exhibit excellent hydrogen evolution reaction (HER) performance with an overpotential of 80 mV at j=10 mA cm-2 and long-term stability of 90 h in alkaline media. The turnover frequencies (TOFs) of 0.55 and 4.1 s-1 at an overpotential of 100 and 200 mV also confirm their remarkable performance. DFT calculations reveal that the surface dopants abnormally sensitize surface Ni-3d bands in the long-range order towards higher electron-transfer activity, acting as the electron-depletion center. Meanwhile, the high lying surface S-sites possess substantially high selectivity for splitting the adsorbing H2 O that guarantee the high HER performance within alkaline conditions. This work opens opportunities for enhancing water splitting by atomic-arrangement-assisted electronic modulation via a facile doping strategy.

8.
J Neuroophthalmol ; 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31609840

RESUMO

BACKGROUND: To assess the utility of enhanced depth imaging optical coherence tomography (EDI-OCT), compared with other conventional imaging modalities, for detecting and characterizing optic nerve head drusen (ONHD) in children. METHODS: We report a retrospective cross-sectional case series of consecutive pediatric patients (age ≤16 years) with ONHD confirmed using B-scan ultrasonography. All eyes were evaluated using spectral-domain OCT of the optic nerve head in conventional (non-EDI) and EDI modes, fundus autofluorescence (FAF), and standard automated perimetry. Detection rates and the capacity to characterize ONHD were compared between EDI-OCT, non-EDI-OCT, and FAF. RESULTS: Twenty-eight eyes of 15 patients (mean age 11 years; 60% female) were identified with definite ONHD that were confirmed by B-scan ultrasound. Among the technologies, EDI-OCT, non-EDI-OCT, FAF, and automated perimetry had findings consistent with ONHD in 24, 21, 18, and 4 eyes, respectively. EDI-OCT had a significantly better detection capability (86% of eyes) compared with FAF (P = 0.04) but not with non-EDI-OCT (P = 0.15). Similar to results previously reported in adult patients, EDI-OCT detected ONHD at different levels of depth; most were located anterior to the lamina cribrosa. ONHD detected by EDI-OCT appeared as hypo-reflective ovoid regions bordered by hyper-reflective material or as isolated hyper-reflective bands without a hypo-reflective core. The mean greatest diameter of ONHD seen on EDI-OCT was 449.7 (SD ±114.1) µm. CONCLUSIONS: EDI-OCT detects ONHD in most eyes identified as having drusen on B-scan ultrasonography. This technique has the potential to be an effective alternative first-line diagnostic and monitoring tool for ONHD, particularly for detecting buried drusen in children.

10.
Nucleic Acid Ther ; 29(6): 359-366, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31513457

RESUMO

Amyloid-ß (Aß) plaque deposits in the brain are considered to be one of the main pathological markers of Alzheimer's disease (AD). The sequential proteolytic cleavage of amyloid precursor protein (APP) by the aspartyl proteases ß-site APP-cleaving enzyme 1 (BACE1) and γ-secretase produces Aß. Therefore, BACE1 inhibition is a very attractive target for the treatment of AD. Our previous work identified a DNA aptamer named A1 that can bind to BACE1 with high affinity and specificity and exhibits a distinct inhibitory effect on BACE1 activity in an AD cell model. The purpose of this research was to test the effect of aptamer A1 in Tg6799 mice. Four-month-old Tg6799 mice were randomly divided into two groups and treated with aptamer A1 and ineffective aptamer A1scr, respectively, by intracerebroventricular injection. Subsequent behavioral experiments showed that treatment with the aptamer A1 improved the cognitive abilities of the AD mice. Western blot indicated that BACE1 and soluble amyloid precursor protein ß (sAPPß) expression significantly decreased in the A1-treated mice. Moreover, aptamer A1 reduced the content of Aß42 and the number and density of senile plaques in AD mice. Therefore, our results indicate that aptamer A1 is a novel specific and potent BACE1 inhibitor and is a promising potential target for the treatment of AD.

11.
Chem Commun (Camb) ; 55(80): 12080-12083, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31538178

RESUMO

From difunctionalization of a single alkene to radical-dual-difunctionalization of two different alkenes! Abundant aliphatic aldehydes were readily decarbonylated into alkyl radicals for the cascade construction of C(sp3)-C(sp3), C(sp3)-C(sp3) and C(sp3)-O bonds via double radical addition and radical-radical coupling, following the intrinsic nucleophilic/electrophilic reactivity of both the radicals and alkenes.

12.
Mol Cancer ; 18(1): 134, 2019 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-31484581

RESUMO

Emerging evidences demonstrate that circular RNAs (circRNAs) are abnormally expressed in tumors and could serve as prognostic markers for cancers. However, the expression patterns and clinical implications of circRNAs in non-small cell lung cancer (NSCLC) remain obscure. In this study, we profiled circRNA expressions in 10 pairs of lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) after ribosomal RNA-depletion and RNase R digestion to enrich circRNAs. Combining five circRNA computational programs, we found that LUAD and LUSC not only share common expression patterns, but also exhibit distinct circRNA expression signatures. Moreover, the Receiver Operating Characteristic (ROC) curve analysis indicated that hsa_circ_0077837 and hsa_circ_0001821 could serve as potential biomarkers for both LUAD and LUSC, while hsa_circ_0001073 and hsa_circ_0001495 could be diagnostic/subtyping marker for LUAD and LUSC, respectively. Therefore, our findings highlight the important diagnostic potential of circRNAs in NSCLC.

13.
Hepatology ; 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31509262

RESUMO

Tumor metastasis is a major factor of high recurrence and mortality in hepatocellular carcinoma (HCC), but its underlying mechanism remains elusive. Here we report that PDZ and LIM domain protein 1 (PDLIM1) is significantly downregulated in metastatic human HCC tissues, which predicts unfavorable prognosis, suggesting that PDLIM1 may play an important inhibitory role during HCC metastasis. Functional studies indicate that PDLIM1 knockdown induces epithelial-to-mesenchymal transition (EMT) of HCC cells, elevates their invasive capacity and promotes metastasis in vitro and in vivo, whereas overexpression of PDLIM1 exhibits opposite phenotypes. Mechanistically, PDLIM1 competitively binds to the cytoskeleton cross-linking protein ACTN4, leading to the disassociation of ACTN4 from F-actin, thus preventing F-actin overgrowth. In contrast, loss of PDLIM1 induces excessive F-actin formation, resulting in dephosphorylation of LATS1 and activation of YAP, thereby promoting HCC metastasis. Moreover, Asn145 (N145) of PDLIM1 is critical for its interaction with ACTN4, and N145A mutation abolishes its regulatory function in Hippo signaling and HCC metastasis. CONCLUSION: Our findings indicate that PDLIM1 suppresses HCC metastasis via modulating Hippo signaling, suggesting that PDLIM1 may be a potential prognostic marker for metastatic HCC.

14.
J Cell Mol Med ; 23(11): 7673-7684, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31468674

RESUMO

Stromal cell-derived factor-1 (SDF-1) is a well-characterized cytokine that protects heart from ischaemic injury. However, the beneficial effects of native SDF-1, in terms of promoting myocardial repair, are limited by its low concentration in the ischaemic myocardium. Annexin V (AnxA5) can precisely detect dead cells in vivo. As massive cardiomyocytes die after MI, we hypothesize that AnxA5 can be used as an anchor to carry SDF-1 to the ischaemic myocardium. In this study, we constructed a fusion protein consisting of SDF-1 and AnxA5 domains. The receptor competition assay revealed that SDF-1-AnxA5 had high binding affinity to SDF-1 receptor CXCR4. The treatment of SDF-1-AnxA5 could significantly promote phosphorylation of AKT and ERK and induce chemotactic response, angiogenesis and cell survival in vitro. The binding membrane assay and immunofluorescence revealed that AnxA5 domain had the ability to specifically recognize and bind to cells injured by hypoxia. Furthermore, SDF-1-AnxA5 administered via peripheral vein could accumulate at the infarcted myocardium in vivo. The treatment with SDF-1-AnxA5 attenuated cell apoptosis, enhanced angiogenesis, reduced infarcted size and improved cardiac function after mouse myocardial infarction. Our results suggest that the bifunctional SDF-1-AnxA5 can specifically bind to dead cells. The systemic administration of bifunctional SDF-1-AnxA5 effectively provides cardioprotection after myocardial infarction.

15.
Theranostics ; 9(16): 4704-4716, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367251

RESUMO

Hepatocellular carcinoma (HCC) is in an urgent need of new, effective therapies to reduce morbidity and mortality. We have previously demonstrated that peptidyl-prolyl cis/trans isomerase Pin1 is a potential target for HCC therapy, due to its pivotal role in HCC development through regulating miRNA biogenesis, and discovered the small molecule API-1 as a novel and specific Pin1 inhibitor. Despite its significant anti-HCC activity, the low water solubility and in vivo bioavailability of API-1 limit its clinical application. To address these issues, we herein developed a liposomal formulation of API-1 to improve API-1 delivery and enhance its anti-HCC efficacy. Methods: We designed and developed a nanoscale liposomal formulation of API-1, named as API-LP. Subsequently, the mean diameter, polydispersity, zeta potential, encapsulation efficiency and thermal properties of the optimization API-LP were characterized. The enhanced anti-HCC activity and the molecular mechanism of API-LP were investigated both in vitro and in vivo. Finally, the safety and pharmacokinetic property of API-LP were evaluated systematically. Results: API-LP had good formulation characteristics and exhibited an enhanced in vitro activity of suppressing proliferation and migration of HCC cells when compared with free API-1. The mechanism study showed that API-LP upregulated miRNA biogenesis via inhibiting Pin1 activity followed by restoring the nucleus-to-cytoplasm export of XPO5. Because of the increased delivery efficiency, API-LP displayed a stronger ability to promote miRNA biogenesis than free API-1. Importantly, API-LP displayed higher systemic exposure than free API-1 in mice without apparent toxicity, resulting in an enhanced tumor inhibition in xenograft mice. Conclusion: The development and assessment of API-LP provide an attractive and safe anti-HCC agent, highlighting the miRNA-based treatment for human cancers.

16.
Zhen Ci Yan Jiu ; 44(7): 538-42, 2019 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-31368288

RESUMO

At present, intestinal flora has attracted more and more attention from scholars in China and foreign countries, and its association with ischemic stroke (IS) has gradually become a new research hotspot in the field of stroke. Studies also showed that intestinal flora may be a risk factor which directly or indirectly affects the occurrence and development of IS through bacterial metabolites and immune activities. In the present paper, we review the positive effect of acupuncture and moxibustion in alleviating the symptoms of limb locomotor, speech, swallowing dysfunction, cognition, etc. to improve the IS patients' daily life ability and in strengthening the cellular immune function of the body. In addition, acupuncture and moxibustion have a positive effect in regulating intestinal flora and immune inflammation. Hence, in the present paper, we discuss their relationship and the possibility of application of acupuncture and moxibustion therapies to the treatment of IS according to the theory of "intestinal flora-immune response". It is thus reasonable to speculate that acupuncture and moxibustion can be used to promote the recovery of brain tissue injury and neurological function after stroke via correcting intestinal flora disturbance and reducing immune inflammatory response. In-depth exploration of the role of "intestinal flora-immune response" in the treatment of IS and the specific regulatory function of acupuncture and moxibustion will provide new ideas and research approaches to reveal their mechanisms in the treatment of stroke from a new perspective.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , Microbioma Gastrointestinal , Moxibustão , Acidente Vascular Cerebral , China , Humanos , Acidente Vascular Cerebral/terapia
17.
Semin Cardiothorac Vasc Anesth ; : 1089253219867695, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31390944

RESUMO

The clinical, educational, and research facets of lung transplantation have advanced significantly since the first lung transplant in 1963. The formation of the International Society for Heart and Lung Transplantation (ISHLT) and subsequent Registry has forged a precedent of collaborative teamwork that has significantly affected current lung transplantation outcomes. The Society for the Advancement of Anesthesia (SATA) is dedicated to developing educational platforms for all facets of transplant anesthesia. Additionally, we believe that the anesthetic training for lung transplantation has not kept pace with other advances in the field. As such, SATA presents for consideration these educational milestones and competencies for anesthetic fellowship training in the field of lung transplantation. The proposed milestones were designed on the framework of 6 core competencies created by the Accreditation Council on Graduate Medical Education. The milestones were identified by combining the expert opinion of our Thoracic Transplant Committee, our experience as educators, and literature review. We offer this White Paper to the anesthesiology and transplant communities as a starting point for the discussion and evolution of perioperative anesthetic care in the field of lung transplantation.

18.
Sci Adv ; 5(8): eaaw8904, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31467976

RESUMO

The recent discovery of ferromagnetism in two-dimensional (2D) van der Waals (vdW) materials holds promises for spintronic devices with exceptional properties. However, to use 2D vdW magnets for building spintronic nanodevices such as magnetic memories, key challenges remain in terms of effectively switching the magnetization from one state to the other electrically. Here, we devise a bilayer structure of Fe3GeTe2/Pt, in which the magnetization of few-layered Fe3GeTe2 can be effectively switched by the spin-orbit torques (SOTs) originated from the current flowing in the Pt layer. The effective magnetic fields corresponding to the SOTs are further quantitatively characterized using harmonic measurements. Our demonstration of the SOT-driven magnetization switching in a 2D vdW magnet could pave the way for implementing low-dimensional materials in the next-generation spintronic applications.

19.
Mikrochim Acta ; 186(8): 494, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31267250

RESUMO

This study describes a universal fluorometric method for sensitive detection of analytes by using aptamers. It is based on the use of graphene oxide (GO) and cryonase-assisted signal amplification. GO is a strong quencher of FAM-labeled nucleic acid probes, while cryonase digests all types of nucleic acid probes. This makes the platform widely applicable to analytes for which the corresponding aptamers are available. Theophylline and ATP were chosen as model analytes. In the absence of targets, dye-labeled aptamers are in a flexible single strand state and adsorb on the GO. As a result, the probes are non-fluorescent due to the efficient quenching of dyes by GO. Upon the addition of a specific target, the aptamer/target complex desorbed from the GO surface and the probe becomes fluorescent. The released complex will immediately become a substrate for cryonase digestion and subsequently releasing the target to bind to another aptamer to initiate the next round of cleavage. This cyclic reaction will repeat again and again until all the related-probes are consumed and all fluorophores light up, resulting in significant fluorescent signal amplification. The detection limits are 47 nM for theophylline and 22.5 nM for ATP. This is much better than that of known methods. The assay requires only mix-and-measure steps that can be accomplished rapidly. In our perception, the detection scheme holds great promise for the design enzyme-aided amplification mechanisms for use in bioanalytical methods. Graphical abstract A cryonase-assisted signal amplification (CASA) method has been developed by using graphene oxide (GO) conjugated with a fluorophore-labeled aptamer for fluorescence signal generation. It has a large scope because it may be applied to numerous analytes.

20.
Bone ; 127: 324-333, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31260814

RESUMO

Mineralization of bone is a dynamic process, involving a complex interplay between cells, secreted macromolecules, signaling pathways, and enzymatic reactions; the dysregulation of bone mineralization may lead to serious skeletal disorders, including hypophosphatemic rickets, osteoporosis, and rheumatoid arthritis. Very few studies have reported the role of osteocytes - the most abundant bone cells in the skeletal system and the major orchestrators of bone remodeling in bone mineralization, which is owed to their nature of being deeply embedded in the mineralized bone matrix. The Wnt/ß-catenin signaling pathway is actively involved in various life processes including osteogenesis; however, the role of Wnt/ß-catenin signaling in the terminal mineralization of bone, especially in the regulation of osteocytes, is largely unknown. This research demonstrates that during the terminal mineralization process, the Wnt/ß-catenin pathway is downregulated, and when Wnt/ß-catenin signaling is activated in osteocytes, dendrite development is suppressed and the expression of dentin matrix protein 1 (DMP1) is inhibited. Aberrant activation of Wnt/ß-catenin signaling in osteocytes leads to the spontaneous deposition of extra-large mineralized nodules on the surface of collagen fibrils. The altered mineral crystal structure and decreased bonding force between minerals and the organic matrix indicate the inferior integration of minerals and collagen. In conclusion, Wnt/ß-catenin signaling plays a critical role in the terminal differentiation of osteocytes and as such, targeting Wnt/ß-catenin signaling in osteocytes may serve as a potential therapeutic approach for the management of bone-related diseases.

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