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Temporomandibular joint (TMJ) osteoarthritis causes fibrocartilage damage to the TMJ disc and mandibular condyle, resulting in local pain and functional impairment that further reduces patients’ quality of life. Tissue engineering offers a potential treatment for fibrocartilage regeneration of the TMJ disc and mandibular condyle. However, the heterogeneous structure of TMJ fibrocartilage tissue poses significant challenges for the fabrication of biomimetic scaffolds. Over the past two decades, some researchers have attempted to adopt three-dimensional (3D) printing techniques to fabricate biomimetic scaffolds for TMJ fibrocartilage regeneration, but publications on such attempts are limited and rarely report satisfactory results, indicating an urgent need for further development. This review outlines several popular 3D printing techniques and the significant elements of tissue-engineered scaffolds: seed cells, scaffold materials, and bioactive factors. Current research progress on 3D-printed scaffolds for fibrocartilage regeneration of the TMJ disc and mandibular condyle is reviewed. The current challenges in TMJ tissue engineering are mentioned along with some emerging tissue-engineering strategies, such as machine learning, stimuli-responsive delivery systems, and extracellular vesicles, which are considered as potential approaches to improve the performance of 3D-printed scaffolds for TMJ fibrocartilage regeneration. This review is expected to inspire the further development of 3D printing techniques for TMJ fibrocartilage regeneration.

An optical fiber humidity sensor with a microfiber knot resonator (MKR) nested U-shaped Mach-Zehnder (MZ) interferometer based on the Vernier effect is proposed. While the reference arm is protected by cured ultraviolet glue, the sensing arm is coated by agarose. The Vernier effect is realized by superimposing the comb-like transmission spectra of the MKR and MZ interfernce, which are designed to have slightly different free spectral ranges. Experimental results indicate that the proposed sensor can provide a maximum humidity sensitivity of 2.442 nm/%RH with a measurement range from 60% RH to 95% RH. The sensor temperature response, reversibility and repeatability are also investigated. The response time is found to be 102 ms for a change of 30% RH. This sensor not only retains key features and merits of the MKR, including low cost and small footprint, but also has a simpler preparation process compared with conventional sensors based on the Vernier effect.

Inflammatory osteolysis is usually linked to the activation of proinflammatory macrophage and the consequent excessive osteoclast formation. Emerging evidence indicates that agents or drugs targeting lipid metabolism in macrophages might be potential in the prevention and treatment of osteolysis. d -mannose, as a natural-existed metabolic regulator, exerts strong effects on attenuating osteopenia and inflammation. However, whether d -mannose is therapeutically effective on osteolysis and whether a metabolic mechanism counts for the effect remain to be addressed. Here, by using an in vivo lipopolysaccharide (LPS)-induced inflammatory osteolysis mouse model as well as an in vitro LPS-induced inflammatory macrophage culture system, we show that d -mannose attenuates inflammatory osteolysis and inhibits excessive osteoclastogenesis by reversing the LPS-induced activation of proinflammatory macrophage. Mechanically, d -mannose recovers LPS-suppressed Cpt1a transcription and promotes lipid metabolism of macrophage. Treatment with etomoxir, an inhibitor of CPT1A, abolishes the effects of d -mannose on LPS-treated macrophage in vitro and eliminates its protection against osteolysis in vivo. Collectively, our results imply that d -mannose attenuates LPS-induced osteolysis by manipulating CPT1A-mediated lipid metabolism in macrophages. Our results disclose the unrecognized utilization of d -mannose as an effective intervention against inflammatory osteolysis and provide evidence to manage inflammatory scenarios by therapeutically targeting lipid metabolism in macrophage.

The underlying mechanisms and treatment of painful temporomandibular disorders (TMDs) are important but understudied topics in craniofacial research. As a group of musculoskeletal diseases, the onset of painful TMD is proved to be a result of disturbance of multiple systems. Recently, emerging evidence has revealed the involvement of neuroimmune interactions in painful TMD. Inflammatory factors play an important role in peripheral sensitization of temporomandibular joint (TMJ), and neurogenic inflammation in turn enhances TMJs dysfunction in TMD. Furthermore, centralized neuroimmune communications contribute to neuron excitability amplification, leading to pain sensitization, and is also responsible for chronic TMD pain and other CNS symptoms. Therapeutics targeting neuroimmune interactions may shed light on new approaches for treating TMD. In this review, we will discuss the role of neuroimmune interactions in the onset of painful TMD from the peripheral and centralized perspectives, and how understanding this mechanism could provide new treatment options. Insights into the neuroimmune interactions within TMJs and painful TMD would broaden the knowledge of mechanisms and treatments of this multifactorial disease.

Axially swept light sheet microscopy (ASLM) is an emerging technique that enables isotropic, subcellular resolution imaging with high optical sectioning capability over a large field-of-view (FOV). Due to its versatility across a broad range of immersion media, it has been utilized to image specimens that may range from live cells to intact chemically cleared organs. However, because of its design, the performance of ASLM-based microscopes is impeded by a low detection signal and the maximum achievable frame-rate for full FOV imaging. Here we present a new optical concept that pushes the limits of ASLM further by scanning two staggered light sheets and simultaneously synchronizing the rolling shutter of a scientific camera. For a particular peak-illumination-intensity, this idea can make ASLMs image twice as fast without compromising the detection signal. Alternately, for a particular frame rate our method doubles the detection signal without requiring to double the peak-illumination-power, thereby offering a gentler illumination scheme compared to tradition single-focus ASLM. We demonstrate the performance of our instrument by imaging fluorescent beads and a PEGASOS cleared-tissue mouse brain.

Periodontium possesses stem cell populations for its self-maintenance and regeneration, and has been proved to be an optimal stem cell source for tissue engineering. In vitro studies have shown that stem cells can be isolated from periodontal ligament, alveolar bone marrow and gingiva. In recent years, more studies have focused on identification of periodontal stem cells in vivo. Multiple genetic markers, including Gli1, Prx1, Axin2, αSMA, and LepR, were identified with the lineage tracing approaches. Characteristics, functions, and regulatory mechanisms of specific populations expressing one of these markers have been investigated. In vivo studies also revealed that periodontal stem cells can be regulafrted by different niche and mechanisms including intercellular interactions, ECM and multiple secreted factors. In this review, we summarized the current knowledge of in vitro characteristics and in vivo markers of periodontal stem cells, and discussed the specific regulating niche.

Monitoring the dynamic humidity requires sensors with fast response and anti-electromagnetic interference, especially for human respiration. Here, an ultrafast fiber-optic breath sensor based on the humidity-sensitive characteristics of gelatin film is proposed and experimentally demonstrated. The sensor consists of a microknot resonator superimposed on a Mach-Zehnder (MZ) interferometer produced by a tapered single-mode fiber, which has an ultrafast response (84 ms) and recovery time (29 ms) and a large dynamic transmission range. The humidity in dynamic ambient causes changes in the refractive index of gelatin coating, which could trigger spectral intensity transients that can be explicitly distinguished between the two states. The sensing principle is analyzed using the traditional transfer-matrix analysis method. The influence of coating thickness on the sensor's trigger threshold is further investigated. Experiments on monitoring breath patterns indicate that the proposed breath sensor has high repeatability, reliability, and validity, which enable many other potential applications such as food processing, health monitoring, and other biomedical applications.

Normal development of craniofacial sutures is crucial for cranial and facial growth in all three dimensions. These sutures provide a unique niche for suture stem cells (SuSCs), which are indispensable for homeostasis, damage repair, as well as stress balance. Expansion appliances are now routinely used to treat underdevelopment of the skull and maxilla, stimulating the craniofacial sutures through distraction osteogenesis. However, various treatment challenges exist due to a lack of full understanding of the mechanism through which mechanical forces stimulate suture and bone remodeling. To address this issue, we first identified crucial steps in the cycle of suture and bone remodeling based on the established standard suture expansion model. Observed spatiotemporal morphological changes revealed that the remodeling cycle is approximately 3 to 4 weeks, with collagen restoration proceeding more rapidly. Next, we traced the fate of the Gli1

Traditional two-dimensional histological sections and microcomputed tomography remain to be the major tools for studying craniofacial bones despite the complicated spatial organization of craniofacial organs. Recently, our laboratory developed the Poly(Ethylene Glycol) Associated Solvent System (PEGASOS) tissue clearing method, which can efficiently render hard tissues, including bones and teeth fully transparent without losing endogenous fluorescent signals. Complete tissue transparency enables us to acquire three-dimensional (3D) images of craniofacial bone vasculature, osteogenesis utilizing various labeling strategies, thus to investigate the spatial relationship among different tissues during postnatal craniofacial development. We found out that during the early stage of postnatal development, craniofacial osteogenesis occurs throughout the entire craniofacial bones, including the periosteum, dura, bone marrow, and suture. After 3–4 weeks, craniofacial osteogenesis is gradually restricted to the suture region and remaining bone marrow space. Similarly, craniofacial bone vasculature gradually restricts to the suture region. Osteogenesis is spatially associated with vasculature during the entire postnatal development. Importantly, we demonstrated that in adult calvarial bones, Gli1+ mesenchymal stem cells were also spatially associated with the vasculature. These findings indicate that craniofacial bones share similar osteogenesis mechanism as the long bone despite their distinct osteogenic mechanisms. In addition, the PEGASOS tissue clearing method-based 3D imaging technique is a useful new tool for craniofacial research.

Mechanical force–induced external root resorption is a major clinical side effect of orthodontic treatment. Recent work has revealed that M1 macrophages play a vital role in promoting orthodontic root resorption (ORR), but the mechanism of how mechanical force stimulation increases the M1/M2 macrophage ratio in periodontal tissue is poorly understood. In the current study, we showed that C-X-C motif chemokine 12 (CXCL12)+ periodontal ligament cells (PDLCs) and C-X-C chemokine receptor type 4 (CXCR4)+ monocytes in the periodontal ligament (PDL) were significantly increased after force application with ongoing root resorption, and these effects were partially rescued after force removal in mice. The expression of CXCL12 in PDLCs was increased by force stimulation in a time- and intensity-dependent manner in vitro. Blockage of the CXCL12/CXCR4 axis using CXCR4 antagonist AMD3100 was sufficient to alleviate ORR and reverse the force-enhanced M1/M2 macrophage ratio. Further mechanism exploration showed that Ly6Chi inflammatory monocytes homed in a CXCL12/CXCR4 axis-dependent manner. The number and proportion of CD11b+ Ly6Chi inflammatory monocytes in cervical lymph nodes were significantly increased by force loading, accompanied by decreased CD11b+ Ly6Chi monocytes in the blood. These changes were blunted by intraperitoneal injection of AMD3100. In addition, blockage of the CXCL12/CXCR4 axis effectively reversed M2 suppression and promoted M1 polarization. Collectively, results indicate that force-induced CXCL12/CXCR4 axis mediates ORR by increasing the M1/M2 ratio in periodontal tissues through attracting Ly6Chi inflammatory monocytes and modulating macrophage polarization. The results also imply that AMD3100 is potentially inhibitory to root resorption.

SummaryUnderstanding the connections and projections of neurons has been a fundamental issue for neuroscience. Although strategies have been developed to map the projection of individual axons within the mouse brain, high resolution mapping of individual peripheral nerve axons in peripheral organs or spinal cord has never been achieved. Here, we designed the Transparent Embedding Solvent System (TESOS) method and developed a technical pipeline for imaging, reconstructing and analyzing large samples containing various tissue types at sub-micron resolution. The mouse whole body was reconstructed at micron-scale resolution. We were able to image, reconstruct and analyze the complete axonal projection of individual sensory neurons within an intact mouse paw or spinal cord at sub-micron resolution. Furtherly, we imaged and reconstructed the entire projection course of individual sensory neurons from adult mouse digits to the spinal cord. The TESOS method provides an efficient tool for micron-scale connectome mapping of the peripheral nervous system.

Hydrogels consisting of a three-dimensional hydrophilic network of biocompatible polymers have been widely used in tissue engineering. Owing to their tunable mechanical properties, hydrogels have been applied in both hard and soft tissues. However, most hydrogels lack self-adhesive properties that enable integration with surrounding tissues, which may result in suture or low repair efficacy. Self-adhesive hydrogels (SAHs), an emerging class of hydrogels based on a combination of three-dimensional hydrophilic networks and self-adhesive properties, continue to garner increased attention in recent years. SAHs exhibit reliable and suitable adherence to tissues, and easily integrate into tissues to promote repair efficiency. SAHs are designed either by mimicking the adhesion mechanism of natural organisms, such as mussels and sandcastle worms, or by using supramolecular strategies. This review summarizes the design and processing strategies of SAHs, clarifies underlying adhesive mechanisms, and discusses their applications in tissue engineering, as well as future challenges.

Bone stromal cells are critical for bone homeostasis and regeneration. Growing evidence suggests that non-stem bone niche cells support bone homeostasis and regeneration via paracrine mechanisms, which remain to be elucidated. Here, we show that physiologically quiescent SM22α-lineage stromal cells expand after bone injury to regulate diverse processes of intramembranous bone regeneration. The majority of SM22α-lineage cells neither act as stem cells in vivo nor show their expression patterns. Dysfunction of SM22α-lineage niche cells induced by loss of platelet-derived growth factor receptor β (PDGFRβ) impairs bone repair. We further show that PDGFRβ-triggered hydrogen sulfide (H

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a user-friendly system that can address diverse imaging applications with varied requirements in terms of resolution (mesoscopic to sub-micron), sample geometry (size, shape, and number), and compatibility with tissue-clearing protocols of different refractive indices. We present a hybrid system that combines a novel non-orthogonal dual-objective and conventional open-top light-sheet architecture for highly versatile multi-scale volumetric imaging. One sentence summary Glaser et al. describe a hybrid open-top light-sheet microscope to image cleared tissues at mesoscopic to sub-micron resolution and depths of up to 1 cm.

Objectives Chondrocyte ferroptosis contributes to osteoarthritis (OA) progression, and D‐mannose shows therapeutic value in many inflammatory conditions. Here, we investigated whether D‐mannose interferes in chondrocyte ferroptotic cell death during osteoarthritic cartilage degeneration. Materials and methods In vivo anterior cruciate ligament transection (ACLT)‐induced OA mouse model and an in vitro study of chondrocytes in an OA microenvironment induced by interleukin‐1β (IL‐1β) exposure were employed. Combined with Epas1 gene gain‐ and loss‐of‐function, histology, immunofluorescence, quantitative RT‐PCR, Western blot, cell viability and flow cytometry experiments were performed to evaluate the chondroprotective effects of D‐mannose in OA progression and the role of hypoxia‐inducible factor 2 alpha (HIF‐2 α) in D‐mannose‐induced ferroptosis resistance of chondrocytes. Results D‐mannose exerted a chondroprotective effect by attenuating the sensitivity of chondrocytes to ferroptosis and alleviated OA progression. HIF‐2α was identified as a central mediator in D‐mannose‐induced ferroptosis resistance of chondrocytes. Furthermore, overexpression of HIF‐2α in chondrocytes by Ad‐Epas1 intra‐articular injection abolished the chondroprotective effect of D‐mannose during OA progression and eliminated the role of D‐mannose as a ferroptosis suppressor. Conclusions D‐mannose alleviates osteoarthritis progression by suppressing HIF‐2α‐mediated chondrocyte sensitivity to ferroptosis, indicating D‐mannose to be a potential therapeutic strategy for ferroptosis‐related diseases., D‐Mannose effectively alleviates osteoarthritis progression by suppressing cartilage degeneration. D‐mannose protects osteoarthritic chondrocytes by attenuating sensitivity to ferroptosis. HIF‐2α is vital in potentiating the susceptibility of chondrocytes to ferroptosis. HIF‐2α is a central mediator in D‐mannose‐induced ferroptosis resistance.

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a flexible system that can address imaging applications with varied requirements in terms of resolution, sample size, tissue-clearing protocol, and transparent sample-holder material. Here, we present a 'hybrid' system that combines a unique non-orthogonal dual-objective and conventional (orthogonal) open-top light-sheet (OTLS) architecture for versatile multi-scale volumetric imaging. We demonstrate efficient screening and targeted sub-micrometer imaging of sparse axons within an intact, cleared mouse brain. The same system enables high-throughput automated imaging of multiple specimens, as spotlighted by a quantitative multi-scale analysis of brain metastases. Compared with existing academic and commercial light-sheet microscopy systems, our hybrid OTLS system provides a unique combination of versatility and performance necessary to satisfy the diverse requirements of a growing number of cleared-tissue imaging applications.

This work reports a microsphere laser at ∼2.0 μm in a Tm3+-doped ZrF4-BaF2-YF3-AlF3 (ZBYA) fluoride glass. The ZBYA glass microsphere was fabricated by reflowing the tip of a 1.0 mol% Tm3+-doped ZBYA glass fiber with a CO2 laser. By using a fiber taper for input and output coupling in the Tm3+-doped ZBYA microsphere, single and multi-mode laser outputs at around 2.0 μm were observed under 808 nm laser excitation. The radiation lifetime and emission cross-section of Tm3+ ions in ZBYA glass were calculated to be 6.42 ms and 5.86 × 10−21 cm2, respectively. Our results indicate that the Tm3+-doped ZBYA fluoride glass has potential applications for 2.0 μm lasers.

A periodic optical filter based on nested knots resonator structure is proposed. The structure consists of a knot resonator with a number of smaller coupled-knot-resonators nested in it, similarly to a dual-bus coupled ring resonator, where the end bus terminations are connected to form a Mach–Zehnder interferometer. The variation of periodical transmission output is shown to be mainly due to the change of field components that results in constructive or destructive interference between the nested multiple coupled-knots and the outer loop. The coupling matrix formalism is used to investigate the influence of the number of coupled-knots and their coupling coefficient on the transmission spectrum. The theoretical result shows that the temperature effect can be eliminated by immersing the resonator in ethanol solution. The output spectrum from a fabricated sample with high-Q is also presented. The device is capable of generating a periodical spectral filtering response and has potential applications as a filter or interleaver.

Aim To obtain the distribution of different maxilla-mandibular characteristics in Chinese skeletal class II mixed dentition patients and to compare the differences of cephalometric variables among different maxilla-mandibular types. Materials and methods A cross-sectional study was conducted among 310 skeletal class II patients in mixed dentition. The patients were divided into 6 groups according to SNA and SNB angle of the cephalogram. A total of 38 cephalometric measurements were measured on their cephalograms. Differences among groups were tested by one-way analysis of variance. Results There were 34 (10.97%) patients in group I, 10 (3.23%) in group II, 4(1.29%) in group III, 69 (22.26%) in group IV, 133 (42.90%) in group V, and 60 (19.35%) in group VI. In all, 14.19% of the patients exhibited maxillary protrusion (MxP), and 62.26% exhibited mandibular retrusion (MnR) with either normal or retruded maxilla. Groups II and III were excluded for statistical comparison due to a limited sample size. Statistical differences were found in 25 cephalometric measurements among the other 4 groups. Patients with MnR (groups V and VI) exhibited bigger sella angle, gonial angle, Frankfort mandibular plane angle, and smaller mandibular body length and ramus height than patients without MnR (p value Conclusion The most common etiology forming skeletal class II malocclusion in Chinese children was MnR, which was mainly caused by the small size and hyperdivergent growth direction of mandible. Clinical significance The study presents various cephalometric characteristics of Chinese skeletal class II malocclusions. The results indicated that for the early orthodontic treatment of Chinese class II children with mixed dentition, orthodontists might emphasize more importance to mandibular length augmentation and growth direction change in mandible.

Confronting the outbreak of COVID-19, this cross-sectional study was aimed to assess psychological status of temporomandibular disorders (TMD) patients, orthodontic patients and the general population in China during the pandemic. An online anonymous questionnaire was developed in Chinese, including the individual background information, the perception of the epidemic, and level of anxiety and depression through Kessler Psychological Distress Scale (K10). The respondents were divided into ORTHO group, TMD group and Control group. Descriptive analysis and multiple linear regression modelling were performed. In total, 1241 valid questionnaires were collected, covering 587 orthodontic patients and 220 TMD patients. It is shown that the overall mental health is not quite optimistic during the COVID-19 pandemic with the mean score of K10 being 18.65. TMD patients have higher level of anxiety and depression than orthodontic patients as well as the general population. Younger age, female gender, having close contact with individuals from Hubei province, higher self-rated infection possibility, concern about psychological barriers and distrust are negatively affecting patients' psychological status. Mental health care should be emphasized when hospitals and clinics reopen after the COVID-19 pandemic, especially to patients with these relevant characteristics.

Introduction The ongoing coronavirus disease 2019 (COVID-19) outbreak impacts the mental health of patients, health workers and the public. The level of impact on the mental health of orthodontic patients in treatment is unknown. The objective of the study was to evaluate the mental health of orthodontic patients in China during the early stage of the pandemic. Methods An online questionnaire type of survey was conducted on a convenien ce sample of anonymous participants. The questionnaire, in Chinese (Mandarin), comprised 5 sections. Sections 1 to 3 included demographic, epidemical, and orthodontic status of the patients. Section 4 assessed the mental health related to orthodontics. Section 5 was the Kessler-10 mental distress scale. A total of 48 orthodontists were invited to distribute the questionnaires to their patients. Descriptive statistics, principle component analysis, k-means cluster analysis and bivariate logistics regression analysis were performed with statistical significance set at P, Highlights ● 38% of the patients had orthodontic-related mental distress during the pandemic. ● Orthodontic patients in the epicenter revealed higher odds of mental distress. ● Orthodontists contacting the patients personally might relieve their anxiety. ● Patients with invisible appliances felt less anxiety about the duration of treatment. ● The results could guide orthodontists from other countries with similar situations.

BACKGROUND: To detect parameters associated with the craniomaxillofacial system that could be altered during hyperdivergent skeletal class II malocclusion camouflage treatment for better profile improvement. METHODS: Forty-two subjects with hyperdivergent skeletal class II malocclusion who had finished their orthodontic treatments and achieved good soft tissue responses were included in this study. Cephalometric analyses of these patients were taken before (T1) and after (T2) treatment. Measurements were made at each treatment stage and analyzed within and between groups. RESULTS: No obvious decrease in the cant of occlusal plane (OP) (the line of point L1 and point L7) and mandibular plane (MP) was observed. However, an obvious decrease in the cant of the posterior occlusal plane (POP) and the angle of plane NA and plane NB (ANB) and a significant increase in the distance from the condylar center (Dc) to OP (DPO) were observed in the subjects (P

In this Letter, we report lasing at 2.3 µm in Tm

Light-sheet microscopy has emerged as the preferred means for high-throughput volumetric imaging of cleared tissues. However, there is a need for a user-friendly system that can address diverse imaging applications with varied requirements in terms of resolution (mesoscopic to sub-micron), sample geometry (size, shape, and number), and compatibility with tissue-clearing protocols of different refractive indices. We present a hybrid system that combines a novel non-orthogonal dual-objective and conventional open-top light-sheet architecture for highly versatile multi-scale volumetric imaging. One sentence summary Glaser et al. describe a hybrid open-top light-sheet microscope to image cleared tissues at mesoscopic to sub-micron resolution and depths of up to 1 cm.

Stromal cells in adult bone marrow that express leptin receptor (LEPR) are a critical source of growth factors, including stem cell factor (SCF), for the maintenance of haematopoietic stem cells and early restricted progenitors1–6. LEPR+ cells are heterogeneous, including skeletal stem cells and osteogenic and adipogenic progenitors7–12, although few markers have been available to distinguish these subsets or to compare their functions. Here we show that expression of an osteogenic growth factor, osteolectin13,14, distinguishes peri-arteriolar LEPR+ cells poised to undergo osteogenesis from peri-sinusoidal LEPR+ cells poised to undergo adipogenesis (but retaining osteogenic potential). Peri-arteriolar LEPR+osteolectin+ cells are rapidly dividing, short-lived osteogenic progenitors that increase in number after fracture and are depleted during ageing. Deletion of Scf from adult osteolectin+ cells did not affect the maintenance of haematopoietic stem cells or most restricted progenitors but depleted common lymphoid progenitors, impairing lymphopoiesis, bacterial clearance, and survival after acute bacterial infection. Peri-arteriolar osteolectin+ cell maintenance required mechanical stimulation. Voluntary running increased, whereas hindlimb unloading decreased, the frequencies of peri-arteriolar osteolectin+ cells and common lymphoid progenitors. Deletion of the mechanosensitive ion channel PIEZO1 from osteolectin+ cells depleted osteolectin+ cells and common lymphoid progenitors. These results show that a peri-arteriolar niche for osteogenesis and lymphopoiesis in bone marrow is maintained by mechanical stimulation and depleted during ageing. A peri-arteriolar niche in the bone marrow for osteogenesis and lymphopoiesis is maintained by mechanical stimulation and is depleted during ageing.

We demonstrate a novel, to the best of our knowledge, refractive index (RI) sensor based on the Vernier effect in dual-microfiber coupler (MFC) structures. The sensor sensitivity was studied both theoretically and experimentally. The numerical results show that by tracing the wavelength shifts of the envelope formed by the Vernier effect, the sensitivity can be improved by several times compared to that obtained for normal coupler-based sensors. In this Letter, two MFCs with a width and free spectral range (FSR) of ∼ 3.5 µ m and 6 nm, respectively, were fabricated. Based on the sensitivity of 5820 nm/RIU for a single coupler, we experimentally achieved an ultra-high sensitivity of 126,540 nm/RIU using dual MFCs by the Vernier effect in the RI range of 1.3350 to 1.3455, which shows good agreement with numerical simulations. The proposed all-fiber RI sensor has the advantages of high sensitivity and low cost and can find applications in chemical and biological detection as well as electronic/magnetic field measurement.

Tissue clearing technique enables visualization of opaque organs and tissues in 3-dimensions (3-D) by turning tissue transparent. Current tissue clearing methods are restricted by limited types of tissues that can be cleared with each individual protocol, which inevitably led to the presence of blind-spots within whole body or body parts imaging. Hard tissues including bones and teeth are still the most difficult organs to be cleared. In addition, loss of endogenous fluorescence remains a major concern for solvent-based clearing methods. Here, we developed a polyethylene glycol (PEG)-associated solvent system (PEGASOS), which rendered nearly all types of tissues transparent and preserved endogenous fluorescence. Bones and teeth could be turned nearly invisible after clearing. The PEGASOS method turned the whole adult mouse body transparent and we were able to image an adult mouse head composed of bones, teeth, brain, muscles, and other tissues with no blind areas. Hard tissue transparency enabled us to reconstruct intact mandible, teeth, femur, or knee joint in 3-D. In addition, we managed to image intact mouse brain at sub-cellular resolution and to trace individual neurons and axons over a long distance. We also visualized dorsal root ganglions directly through vertebrae. Finally, we revealed the distribution pattern of neural network in 3-D within the marrow space of long bone. These results suggest that the PEGASOS method is a useful tool for general biomedical research.

Tissue clearing technique enables visualization of opaque organs and tissues in 3-dimensions (3-D) by turning tissue transparent. Current tissue clearing methods are restricted by limited types of tissues that can be cleared with each individual protocol, which inevitably led to the presence of blind-spots within whole body or body parts imaging. Hard tissues including bones and teeth are still the most difficult organs to be cleared. In addition, loss of endogenous fluorescence remains a major concern for solvent-based clearing methods. Here, we developed a polyethylene glycol (PEG)-associated solvent system (PEGASOS), which rendered nearly all types of tissues transparent and preserved endogenous fluorescence. Bones and teeth could be turned nearly invisible after clearing. The PEGASOS method turned the whole adult mouse body transparent and we were able to image an adult mouse head composed of bones, teeth, brain, muscles, and other tissues with no blind areas. Hard tissue transparency enabled us to reconstruct intact mandible, teeth, femur, or knee joint in 3-D. In addition, we managed to image intact mouse brain at sub-cellular resolution and to trace individual neurons and axons over a long distance. We also visualized dorsal root ganglions directly through vertebrae. Finally, we revealed the distribution pattern of neural network in 3-D within the marrow space of long bone. These results suggest that the PEGASOS method is a useful tool for general biomedical research.

We present cleared-tissue axially swept light-sheet microscopy (ctASLM), which enables isotropic, subcellular resolution imaging with high optical sectioning capability and a large field of view over a broad range of immersion media. ctASLM can image live, expanded, and both aqueous and non-aqueous chemically cleared tissue preparations. Depending on the optical configuration, ctASLM provides up to 260 nm of axial resolution, a three to tenfold improvement over confocal and other reported cleared-tissue light-sheet microscopes. We imaged millimeter-scale cleared tissues with subcellular three-dimensional resolution, which enabled automated detection of multicellular tissue architectures, individual cells, synaptic spines and rare cell–cell interactions. Cleared-tissue axially swept light-sheet microscopy (ctASLM) enables high-speed, refraction index-independent imaging of live, cleared and expanded samples with isotropic, submicron resolution.

A high-sensitivity ethanol gas sensor based on two microfiber couplers and the Vernier effect is examined in this Letter using the unique variation rate conversion point characteristics. The output spectrum of the two couplers connected in parallel are superimposed to form a symmetrical envelope curve, showing high responsivity to variations in the external environment. Ethanol sensitivity was achieved by coating the waist region of the coupler with a mixture of Nile red and polymethyl methacrylate. When the concentration of ethanol gas changes, the envelope spectrum shifts. Experimental results show that a high responsivity of 160 pm/ppm can be obtained by tracing the reference peaks in the envelope curve and that the response and recovery times are on the order of seconds.

In this paper, by using the bifurcation method of dynamical systems, we derive the traveling wave solutions of the nonlinear equation UUτyy − UyUτy + U2Uτ + 3Uy = 0. Based on the relationship of the solutions between the Novikov equation and the nonlinear equation, we present the parametric representations of the smooth and nonsmooth soliton solutions for the Novikov equation with cubic nonlinearity. These solutions contain peaked soliton, smooth soliton, W-shaped soliton and periodic solutions. Our work extends some previous results.

Objective Orthodontic treatment induces dental tissue remodeling; however, dental pulp stem cell (DPSC)-mediated pulp micro-environmental alteration is still largely uncharacterized. In the present study, we identified elevated interleukin-17A (IL17A) in the dental pulp, which induced the osteogenesis of DPSCs after orthodontic force loading. Design Tooth movement animal models were established in Sprague-Dawley rats, and samples were harvested at 1, 4, 7, 14, and 21 days after orthodontic treatment loading. DPSC self-renewal and differentiation at different time points were examined, as well as the alteration of the microenvironment of dental pulp tissue by histological analysis and the systemic serum IL17A expression level by an ELISA assay. In vitro recombinant IL17A treatment was used to confirm the effect of IL17A on the enhancement of DPSC self-renewal and differentiation. Results Orthodontic treatment altered the dental pulp microenvironment by activation of the pro-inflammatory cytokine IL17A in vivo . Orthodontic loading significantly promoted the self-renewal and differentiation of DPSCs. Inflammation and elevated IL17A secretion occurred in the dental pulp during orthodontic tooth movement. Moreover, in vitro recombinant IL17A treatment mimicked the enhancement of the self-renewal and differentiation of DPSCs. Conclusions Orthodontic treatment enhanced the differentiation and self-renewal of DPSCs, mediated by orthodontic-induced inflammation and subsequent elevation of IL17A level in the dental pulp microenvironment.

Summary Teeth are attached to alveolar bone by the periodontal ligament (PDL), which contains stem cells supporting tissue turnover. Here, we identified Gli1+ cells in adult mouse molar PDL as multi-potential stem cells (PDLSCs) giving rise to PDL, alveolar bone, and cementum. They support periodontium tissue turnover and injury repair. Gli1+ PDLSCs are surrounding the neurovascular bundle and more enriched in the apical region. Canonical Wnt signaling is essential for their activation. Alveolar bone osteocytes negatively regulate Gli1+ PDLSCs activity through sclerostin, a Wnt inhibitor. Blockage of sclerostin accelerates the PDLSCs lineage contribution rate in vivo. Sclerostin expression is modulated by physiological occlusal force. Removal of occlusal force upregulates sclerostin and inhibits PDLSCs activation. In summary, Gli1+ cells are the multipotential PDLSCs in vivo. Osteocytes provide negative feedback to PDLSCs and inhibit their activities through sclerostin. Physiological occlusal force indirectly regulates PDLSCs activities by fine-tuning this feedback loop.

In this Letter, we report lasing at 2.3 µm in Tm 3 + -single-doped and Tm 3 + / Ho 3 + -codoped fluorotellurite glass microsphere resonators. By employing a 793 nm diode laser as a pump and exploiting whispering gallery mode microresonators (WGMRs), dual-wavelength lasing at 1.9 and 2.3 µm and triple-wavelength lasing at 1.9, 2.07, and 2.3 µm are achieved in Tm 3 + -doped and Tm 3 + / Ho 3 + -codoped microspheres, respectively. The introduction of Ho 3 + ions significantly reduces the lasing threshold of Tm 3 + at 2.3 µm because of energy transfer.