Search

Intestinal stem cell (ISC) differentiation is regulated precisely by a niche in the crypt, where lymphocytes may interact with stem and transient amplifying (TA) cells. However, whether and how lymphocyte–stem/TA cell contact affects ISC differentiation is largely unknown. Here, we uncover a novel role of T cell–stem/TA cell contact in ISC fate decisions. We show that intestinal lymphocyte depletion results in skewed ISC differentiation in mice, which can be rescued by T cell transfer. Mechanistically, integrin αEβ7 expressed on T cells binds to E-cadherin on ISCs and TA cells, triggering E-cadherin endocytosis and the consequent Wnt and Notch signaling alterations. Blocking αEβ7−E-cadherin adhesion suppresses Wnt signaling and promotes Notch signaling in ISCs and TA cells, leading to defective ISC differentiation. Thus, αEβ7(+) T cells regulate ISC differentiation at single-cell level through cell–cell contact-mediated αEβ7−E-cadherin adhesion signaling, highlighting a critical role of the T cell–stem/TA cell contact in maintaining intestinal homeostasis.

SUMMARYFasting is known to improve health, but the precisely beneficial effects of specific types of fasting and their underlying mechanisms are not fully understood. We herein report that in humans, occasional short-term intensive fasting (STIF), a traditional fasting format favored by Asians, promotes erythropoiesis and boosts the function of red blood cells (RBCs) in oxygen transportation, ATP generation, antioxidant capacity, and innate immune response. The rejuvenation of erythropoiesis is more pronounced in humans with low RBC counts. Using mouse models and a human erythroid progenitor cell model, we found that occasional STIF rejuvenates erythropoiesis by enhancing megakaryocyte-erythroid progenitor selfrenewal and erythroid-biased differentiation without compromising normal hematopoiesis. Molecularly, STIF relies on an autophagy-dependent but erythropoietin (EPO) upregulation-independent MS4A3-CDK2 module to augment the production of RBCs. Our findings thus suggest that STIF can occasionally be practiced as an efficient noninvasive intervention for better erythropoiesis, particularly for adults with low RBC counts.Graphical abstractIn briefXu et al showed that short-term intensive fasting (STIF), when occasionally practiced, boosts red blood cell function and promotes erythropoiesis by regulating MS4A3-CDK2 module to enhance megakaryocyte-erythroid progenitor selfrenewal and erythroid-biased differentiation.HighlightsOccasional STIF boosts the function of red blood cellsOccasional STIF promotes erythropoiesis, which is more significant in adults with low red blood cell countsOccasional STIF selectively enhances MEP selfrenewal and erythroid-biased differentiation via MS4A3-CDK2 moduleThe erythropoietic MS4A3-CDK2 response to STIF is autophagy-dependent but EPO upregulation-independent.

Photoalignment of liquid crystal polarization grating based on optical imprinting is a promising technique for polarization grating mass production. However, when the period of the optical imprinting grating is in the sub-micrometer level, the zero-order energy from the master grating will become high, and it will strongly affect the photoalignment quality. This paper proposes a double-twisted polarization grating structure to eliminate the zero-order disturbance of master grating and gives the design method. Based on the designed results, a master grating was prepared, and the optically imprinted photoalignment of polarization grating with a period of 0.5μm was fabricated. This method has the advantages of high efficiency and significantly greater environmental tolerance than the traditional polarization holographic photoalignment methods. It has the potential to be used for large-area polarization holographic gratings production.

Lifan Zhu,1,2,* Yanjun Yang,1,* Zhanjun Yan,1,* Jincai Zeng,1 Fengbiao Weng,1 Yuhui Shi,1 Pengcheng Shen,1 Ling Liu,2 Huilin Yang2 1Department of Orthopedics, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, 215200, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huilin Yang, Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, People’s Republic of China, Email suzhouspine@163.com Lifan Zhu, Department of Orthopedics, Suzhou Ninth Hospital affiliated to Soochow University, Suzhou, 215200, People’s Republic of China, Email zhulifan201608@163.comIntroduction: Intervertebral disc (IVD) degeneration (IDD) is one of the most widespread musculoskeletal diseases worldwide and remains an intractable clinical challenge. Currently, regenerative strategies based on biomaterials and biological factors to facilitate IVD repair have been widely explored. However, the harsh microenvironment, such as increased ROS and acidity, of the degenerative region impedes the efficiency of IVD repair. Here, an intelligent biodegradable nanoplatform using hollow manganese dioxide (H-MnO2) was developed to modulate the degenerative microenvironment and release transforming growth factor beta-3 (TGF-β 3), which may achieve good long-term therapeutic effects on needle puncture-induced IDD.Methods: Surface morphology and elemental analysis of the MnO2 nanoparticles (NPs) were performed by transmission electron microscopy and an energy-dispersive X-ray spectroscopy detector system, respectively. The biological effects of MnO2 loaded with TGF-β 3 (TGF-β 3/MnO2) on nucleus pulposus cells (NPCs) were assessed via cytoskeleton staining, EdU staining, qPCR and immunofluorescence. The efficacy of TGF-β 3/MnO2 on needle puncture-induced IDD was further examined using MRI and histopathological and immunohistochemical staining.Results: The MnO2 NPs had a spherical morphology and hollow structure that dissociated in the setting of a low pH and H2O2 to release loaded TGF-β 3 molecules. In the oxidative stress environment, TGF-β 3/MnO2 was superior to TGF-β 3 and MnO2 NPs in the suppression of H2O2-induced matrix degradation, ROS, and apoptosis in NPCs. When injected into the IVDs of a rat IDD model, TGF-β 3/MnO2 was able to prevent the degeneration and promote self-regeneration.Conclusion: Use of an MnO2 nanoplatform for biological factors release to regulate the IDD microenvironment and promote endogenous repair may be an effective approach for treating IDD.Graphical Abstract: Keywords: intervertebral disc degeneration, hollow manganese dioxide, transforming growth factor beta-3, oxidative stress, endogenous repair

Geometric optical waveguide display can significantly miniaturize the augmented reality eyeglasses, but suffers from the ghost image. In this paper, a method using surface micro-reflector array is proposed, which can dramatically suppress the ghost image. The transmission and expansion of the light bearing image are completed by using planar waveguide and micro-reflector array embedded in the surface layer of waveguide. The image quality is improved by using the dual channel to eliminate ghost image. The imaging process of optical system is modeled and simulated. The surface micro-reflector array waveguide element of 3 mm thickness is prepared for verification. The whole optical system has the advantages of simple structure, easy preparation and high structural strength. The display field of view is shown to be 25° × 25°, and the size of the full field of view area is 15 mm with even light distribution. What's more, the uniformity of imaging intensity is better than 20%, and the image is clear without ghost image, which can effectively realize the fusion of the virtual image and the real environment. Thus, the efficiency of augmented reality is greatly improved, and the danger of human eye safety is effectively avoided.

Tumor metastasis is the leading cause of cancer-associated mortality. Unfortunately, the underlying mechanism of metastasis is poorly understood. Expression of legumain (LGMN), an endo-lysosomal cysteine protease, positively correlates with breast cancer metastatic progression and poor prognosis. Here, we report that LGMN is secreted in the zymogen form by motile breast cancer cells. Through binding to cell surface integrin αvβ3 via an RGD motif, the autocrine pro-LGMN activates FAK-Src-RhoA signaling in cancer cells and promotes cancer cell migration and invasion independent of LGMN protease activity. Either silencing LGMN expression or mutationally abolishing pro-LGMN‒αvβ3 interaction significantly inhibits cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Finally, we developed a monoclonal antibody against LGMN RGD motif, which blocks pro-LGMN‒αvβ3 binding, and effectively suppresses cancer cell migration and invasion in vitro and breast cancer metastasis in vivo. Thus, disruption of pro-LGMN‒integrin αvβ3 interaction may be a potentially promising strategy for treating breast cancer metastasis.

A 27-year-old man presented with intermittent right knee pain for 1 year with no previous trauma. Physical examination revealed only tenderness over the patella. Typical fluid–fluid levels were visible on magnetic resonance imaging (MRI), which highly suggested aneurysmal bone cyst (ABC) of the patella. After removal of a large window of thin cortical bone, curettage and bone grafting followed by cerclage wiring was performed. Histology confirmed the initial diagnosis of primary ABC of the patella. At the final follow-up visit at 71 months after surgery, the patient had normal joint activity with no pain or evidence of recurrence. Previous publications indicated patellectomy in the initial series, but curettage and bone grafting have more recently provided excellent results and good graft incorporation in most cases, even for aggressive lesions. In our patient, thorough curettage and bone grafting through a wide cortical window followed by cerclage wiring fixation and figure-eight sutures was a successful treatment option for primary ABC of the patella without articular disruption.

Background β7 integrins are responsible for the efficient recruitment of lymphocytes from the blood and their retention in gut-associated lymphoid tissues. Integrin α4β7 binds MAdCAM-1, mediating rolling adhesion of lymphocytes on blood vessel walls when inactive and firm adhesion when activated, thereby controlling two critical steps of lymphocyte homing to the gut. By contrast, integrin αEβ7 mediates the adhesion of lymphocytes to gut epithelial cells by interacting with E-cadherin. Integrin β7 blocking antibodies have shown efficacy in clinical management of inflammatory bowel disease (IBD); however, fully blocking β7 function leads to the depletion of colonic regulatory T (Treg) cells and exacerbates dextran sulfate sodium (DSS)-induced colitis by evoking aberrant innate immunity, implying its potential adverse effect for IBD management. Thus, a better therapeutic strategy targeting integrin β7 is required to avoid this adverse effect. Results Herein, we inhibited integrin α4β7 activation in vivo by creating mice that carry in their integrin β7 gene a mutation (F185A) which from structural studies is known to lock α4β7 in its resting state. Lymphocytes from β7-F185A knock-in (KI) mice expressed α4β7 integrins that could not be activated by chemokines and showed significantly impaired homing to the gut. The β7-F185A mutation did not inhibit αEβ7 activation, but led to the depletion of αEβ7+ lymphocytes in the spleen and a significantly reduced population of αEβ7+ lymphocytes in the gut of KI mice. β7-F185A KI mice were resistant to T cell transfer-induced chronic colitis, but did not show an increased susceptibility to DSS-induced innate colitis, the adverse effect of fully blocking β7 function. Conclusions Our findings demonstrate that specific inhibition of integrin α4β7 activation is a potentially better strategy than fully blocking α4β7 function for IBD treatment.

Laser scanning head-up display has the characteristics of small size, high contrast, and no background halo. However, the power of direct modulation laser diode and the driving current of laser driver chip with high frequency about 100 MHz are limited, and the high brightness advantage of laser scanning display is still difficult to play, which also hinders the application and development of this technology. In this paper, a simple and effective light module is designed by using the shaping and coupling technology of multi laser diodes array. Two driving chips and six laser diodes are introduced, which is optimized the layout of laser diodes according to the characteristics of fast and slow axis. Finally, a single beam is projected to the mirror of MOEMS for laser scanning display by optical coupling fiber. The multi laser diodes array significantly reduces the laser coherence and suppresses the laser projection speckle effect. The experimental results show that the light module achieves more than 300 mW laser output power, promotes the brightness of the display, and is conducive to expanding the application of laser scanning display technology in the fields of projection, avionics and vehicle head-up display.

HUD can significantly improve driving experience and driving safety. At present, the field of view of vehicle head up display is generally small, and the information of display screen is limited. This paper presents the design of a larger field of view vehicle head up display optical system. Through the method of curve imaging surface, the display field of view is improved under the condition of keeping the system concise. At the same time, the imaging surface is projected by laser scanning display technology. The design principle is introduced and the simulation analysis of optical system is carried out. The results show that the horizontal display field of view of the system is about 15°, the pitch display field of view is about 8°, and there is no display distortion. The system can provide more display information without disturbing the driver's line of sight, and enhance the driving safety of high-speed driving.

Additional file 1: Figure S1. The secondary lymphoid tissues other than GALT appear normal in β7-F185A KI and β7-KO mice. Representative histological sections of the peripheral lymph node (PLN), mesenteric lymph node (MLN) and spleen (SP) of WT, β7-F185A KI (KI) and β7-KO (KO) mice were analyzed by hematoxylin and eosin staining. Scale bars, 500μm. Figure S2. Expression of integrins β7 in splenic lymphocytes of WT and β7-F185A mice. (A) Quantitative PCR analysis of integrin β7 expression in splenic lymphocytes from WT and KI mice. Results are normalized to GAPDH. (B) Total (cell surface plus intracellular) protein expression of integrin β7 in splenic lymphocytes was determined by flow cytometry using permeabilized cells. Data are mean ± s.d. of at least 3 independent experiments (A-B). Figure S3. Impaired adhesion and transmigration of Jurkat T-β7 F185A cells. (A) Expession of β7 and CCR9 in Jurkat T-β7 WT and Jurkat T-β7 F185A cell lines were determined by flow cytometry. (B) Adhesion of Jurkat T-β7 WT, Jurkat T-β7 F185A and Jurkat T cells to MAdCAM-1 substrates at 1 dyn/cm2 or 2 dyn/cm2 before and after chemokine stimulation. (C) Transmigration of Jurkat T-β7 WT, Jurkat T-F185A and Jurkat T cells through MAdCAM-1-coated insert. Data are mean ± s.d. of at least 3 independent experiments (B C). *** P < 0.001; ns, not significant (Student’s t-test). Asterisk in B indicates the changes of total adherent cells. Figure S4. β7-F185A mutation does not affect αEβ7-mediated cell adhesion to E-cadherin substrates. (A) Expession of β7 and αE in Jurkat T-αEβ7 WT and Jurkat T-αEβ7 F185A cell lines were determined by flow cytometry. The numbers within the panels show the specific mean fluorescence intensities of FIB504 (anti-β7) and M290 (anti-αE) mAbs. (B) Adhesion of Jurkat T-αEβ7 WT, Jurkat T-αEβ7 F185A and Jurkat T cells to the immobilized E-cadherin substrates (40 μg/ml) at 1dyn/cm2 before and after chemokine stimulation. αEβ7-E-cadherin binding was inhibited by pre-treatment of cells with 10 μg/ml αE blocking antibody M290. Data are mean ± s.d. of at least 3 independent experiments (A-B).*** P < 0.001; ns, not significant (Student’s t-test). Figure S5. Integrin αE+ lymphocytes in spleen, SI and colon. (A) Expression of αE in WT, +/-, KI and KO splenic lymphocytes was determined by flow cytometry. (B-C) Expression of αE in intestinal IEL and LPL was detected by flow cytometry. The numbers within the panels (A-B) show the percentage of αE+ lymphocytes. The numbers within the table (C) show the specific mean fluorescence intensities of M290 (anti-αE) mAb in αE+ lymphocytes. Data are mean ± s.d. of at least 3 independent experiments (A-C). AAP < 0.05; AAAP < 0.001 (Student's t-test in C). SP, spleen; SI, small intestine; IEL, intraepithelial lymphocyte; LPL, lamina propria lymphocyte.

Additional file 2: Table S1. The analysis of integrin β7-high splenic lymphocytes subsets in WT mice. Table S2. The list of primers used for genotyping. Table S3. The list of primers used for real-time quantitative PCR analyses

Light guided head-up display is an advanced display technology that realizes miniaturization and lightweight. It is very suitable for the increasingly stringent requirements of assembly space for HUD equipment in avionics and vehicle cockpits. This paper describes the basic principle of avionics light guided head-up display technology its technological advancement and feasibility, proposes a new type of light guided head-up display system, and analyzes the essential elements of light guided display technology in engineering application of head-up display for the first time. In this study, a polarization splitter array was embedded in the planar waveguide combiner to improve the transmittance of exterior light and the efficiency of light bearing virtual image and suppress the " window-blinds effect" of light guided head-up display. Experiments show that the transmittance rate of Combiner is over 80%, the imaging efficiency is better than 10%, and the virtual image is clear, uniform and continuous. This study is helpful to promote the application of the light guided display technology in head-up display system. The light guided display technology is expected to be developed in the field of avionics and vehicle fields.

Fever is an evolutionarily conserved response that confers survival benefits during infection. However, the underlying mechanism remains obscure. Here, we report that fever promoted T lymphocyte trafficking through heat shock protein 90 (Hsp90)-induced α4 integrin activation and signaling in T cells. By inducing selective binding of Hsp90 to α4 integrins, but not β2 integrins, fever increased α4-integrin-mediated T cell adhesion and transmigration. Mechanistically, Hsp90 bound to the α4 tail and activated α4 integrins via inside-out signaling. Moreover, the N and C termini of one Hsp90 molecule simultaneously bound to two α4 tails, leading to dimerization and clustering of α4 integrins on the cell membrane and subsequent activation of the FAK-RhoA pathway. Abolishment of Hsp90-α4 interaction inhibited fever-induced T cell trafficking to draining lymph nodes and impaired the clearance of bacterial infection. Our findings identify the Hsp90-α4-integrin axis as a thermal sensory pathway that promotes T lymphocyte trafficking and enhances immune surveillance during infection.

STUDY DESIGN A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD. OBJECTIVE The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD. SUMMARY OF BACKGROUND DATA Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive. METHODS Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarov-type apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8-9 was analyzed. RESULTS In three-level IVDD model, significant degeneration of the Co8-9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading altered the expression of integrin α2β1 (upregulated) and α10β1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin α1, α2, α11, and β1 were upregulated, whereas α10 was downregulated. Similar activation of integrin signaling was observed. CONCLUSION Static compression altered collagen and MMP expression, and promoted β1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force. LEVEL OF EVIDENCE N/A.

Integrin-mediated rolling and firm cell adhesion are two critical steps in leukocyte trafficking. Integrin α4β1 mediates a mixture of rolling and firm cell adhesion on vascular cell adhesion molecule-1 (VCAM-1) when in its resting state but only supports firm cell adhesion upon activation. The transition from rolling to firm cell adhesion is controlled by integrin activation. Kindlin-3 has been shown to bind to integrin β tails and trigger integrin activation via inside-out signaling. However, the role of kindlin-3 in regulating resting α4β1-mediated cell adhesion is not well characterized. Herein we demonstrate that kindlin-3 was required for the resting α4β1-mediated firm cell adhesion but not rolling adhesion. Knockdown of kindlin-3 significantly decreased the binding of kindlin-3 to β1 and down-regulated the binding affinity of the resting α4β1 to soluble VCAM-1. Notably, it converted the resting α4β1-mediated firm cell adhesion to rolling adhesion on VCAM-1 substrates, increased cell rolling velocity, and impaired the stability of cell adhesion. By contrast, firm cell adhesion mediated by Mn(2+)-activated α4β1 was barely affected by knockdown of kindlin-3. Structurally, lack of kindlin-3 led to a more bent conformation of the resting α4β1. Thus, kindlin-3 plays an important role in maintaining a proper conformation of the resting α4β1 to mediate both rolling and firm cell adhesion. Defective kindlin-3 binding to the resting α4β1 leads to a transition from firm to rolling cell adhesion on VCAM-1, implying its potential role in regulating the transition between integrin-mediated rolling and firm cell adhesion.

The planar wave-guided volume hologram (PWGVH) is recorded and reconstructed using light waves guided through optical substrates. In this paper, the variation of the diffracted light wave's central wavelength and wavelength range versus the angular deviation relative to the angle under Bragg condition was analyzed through numerical simulation. The study shows acceptable angular range with the high diffraction efficiency and color uniformity of unitary hologram is much less than the angular width. Multilayer volume holograms are designed to expand the acceptable angular range. The numerical simulation indicates that better color uniformity and wider acceptable angular range can be obtained.

Holograms recorded in dichromated gelatin (DCG) are usually sealed with a glass plate cemented with an epoxy glue to protect the holograms from moisture in the environment. An investigation of the wavelength properties of sealed DCG holograms had been carried out paying attention to holograms which were exposed to different temperature and humidity environment in this work. The investigation had revealed that (a) exposing the sealed DCG holograms to high relative humidity (RH=98%) environment or immersing them in room-temperature water for 20 hours can not affect the holograms; (b) the sealed DCG holograms can be used at temperature below 50°C without showing undue detrimental effects regarding their optical properties; (c) the peak wavelength of sealed DCG holograms can cause blue shift of several nanometers at 70°C~85°C and the velocity of blue shift is proportional to the environmental temperature; (d) the holograms can be destroyed at 100° or above. The experimental results above will be analyzed and discussed in this paper. A method to improve the stability of sealed DCG holograms is proposed: baking the sealed DCG holograms at proper temperature (e.g., 85°C in this study).

An improved virtual display is proposed by using a waveguide holographic configuration with two total internal reflection holographic gratings in conical mounting and two volume hologram in classical mounting recorded on a single transparent planar waveguide. Using this compact configuration, efficiency can be dramatically improved and assembly is easy to be realized. The main principle and the method of intensity uniformity control are present in the paper. The analysis and simulation results are also explained. The virtual display system design shows good optical performance with 25 deg. field of view, a large pupil about 43 mm, little distortion less than 1%, and low aberration. The configuration can be used to a portable or wearable display.