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Tissue engineering strategy that combine biomaterials with living cells has shown special advantages in tissue regeneration and promoted the development of regenerative medicine. In particular, the rising of 3D printing technology further enriched the structural design and composition of tissue engineering scaffolds, which also provided convenience for cell loading and cell delivery of living cells. In this review, two types of cell-delivery scaffolds for tissue regeneration, including 3D printed scaffolds with subsequent cell-seeding and 3D cells bioprinted scaffolds, are mainly reviewed. We devote a major part to present and discuss the recent advances of two 3D printed cell-delivery scaffolds in regeneration of various tissues, involving bone, cartilage, skin tissues etc. Although two types of 3D printed cell-delivery scaffolds have some shortcomings, they do have generally facilitated the exploration of tissue engineering scaffolds in multiple tissue regeneration. It is expected that 3D printed cell-delivery scaffolds will be further explored in function mechanism of seeding cells in vivo, precise mimicking of complex tissues and even organ reconstruction under the cooperation of multiple fields in future.

Cytoglobin is a highly conserved redox sensor heme protein with unknown physiological function. Unexpectedly, genetic deletion of zebrafish cytoglobin (cygb2) causes cardiac and gastro-intestinal tract laterality defects, modeling Kartagener’s syndrome, which in humans is associated with low airway epithelial nitric oxide (NO) production. Cygb2 co-localized with cilia and the NO synthase Nos2b in the Kupffer’s vesicle (KV) laterality organ and the structure and function of cilia were disrupted in cygb2 mutants, abolishing fluid flow within the KV. Abnormal ciliary function and organ laterality was phenocopied by depletion of nos2band gucy1a, the canonical NO receptor soluble guanylate cyclase (sGC) homolog in fish, and rescued by exposing cygb2 mutant embryos to an NO donor or an sGC stimulator and with over-expression of nos2b. Consistent with a conserved role in the modulation of ciliary function, cytoglobin knock out in the mouse also impaired airway epithelial ciliary structure and beat frequency. This is the first evidence that cytoglobin is essential for normal development stage-specific NO signaling, ciliogenesis and cilia motility, required for the establishment of left-right patterning.

Western blots are employed to detect and characterize amounts of proteins in biological samples. Quantifications are traditionally carried out through data normalization by housekeeping protein method. This approach does not account for variations not intrinsically dependent on the sample such as different experimental conditions and type of samples. Zebrafish researchers often face the challenge of comparing embryos at different developmental stages or from different strains. Housekeeping protein amount can change in these conditions therefore adding an unwanted quantification error. Here we describe the method to analyze mutant zebrafish embryos at different stages by western blot using the Stain-Free technology for normalization. We present Globin X quantification at 2 and 5 days postfertilization in wild type and in the bloodless Vlad Tepes (vlt) zebrafish mutant that lack red blood cells.

The construction of hierarchical porous structure in biomaterials is of great significance for improving nutrient transport and biological performance. However, it is still challenging to design porous bone substitutes with high strength and biological properties, which limits their clinical applications in load-bearing bone regeneration. Herein, based on hierarchical porous structure of renewable bamboo, the mineralized calcium phosphate/bamboo composite scaffolds with high strength and excellent transport performance are successfully prepared in combination of biotemplated approach and biomimetic mineralization. The mineralized biomaterials have simultaneously achieved high mechanical strength and low modulus, similar to those of cortical bone. Furthermore, the mineralized biomaterials exhibit good liquid transport capacity and can transport cells along anti-gravity direction. Based on density functional theory (DFT) calculations, the mineralized calcium phosphate reveals the optimal H

For the research of biomaterials in bone tissue engineering, it is still a challenge to fabricate bioceramics that overcome brittleness while maintaining the great biological performance. Here, inspired by the toughness of natural materials with hierarchical laminated structure, we presented a directional assembly-sintering approach to fabricate laminated MXene/calcium silicate-based (L-M/CS) bioceramics. Benefiting from the orderly laminated structure, the L-M/CS bioceramics exhibited significantly enhanced toughness (2.23 MPa·m1/2) and high flexural strength (145 MPa), which were close to the mechanical properties of cortical bone. Furthermore, the L-M/CS bioceramics possessed more suitable degradability than traditional CaSiO3 bioceramics due to the newly formed CaTiSiO5 after sintering. Moreover, the L-M/CS bioceramics showed good biocompatibility and could stimulate the expression of osteogenesis-related genes. The mechanism of promoting osteogenic differentiation had been shown to be related to the Wnt signaling pathway. This work not only fabricated calcium silicate-based bioceramics with excellent mechanical and biological properties for bone tissue engineering but also provided a strategy for the combination of bionics and bioceramics.

Idiopathic pulmonary fibrosis (IPF) is a lethal, medically refractory syndrome characterized by intrapulmonary accumulations of extracellular matrix (ECM) proteins produced by fibroblasts. Activation, clonal expansion, and differentiation of lymphocytes are also frequently present in IPF. Activated T cells are known to exert several effects that promote ECM production, but opposing homeostatic actions, wherein T cells can inhibit fibrosis, are less well understood. We found that CD27, a TNF receptor ubiquitously expressed on naive T cells, is downregulated on CD4 T cells of patients with IPF and that CD70, the sole ligand for CD27, is present on human pulmonary fibroblasts. We hypothesized that cognate engagements between lymphocyte CD27 and fibroblast CD70 could have functional consequences. Accordingly, a series of subsequent studies were conducted to examine the possible role of CD27–CD70 interactions in the regulation of fibrogenesis. Using IB, flow cytometry, RT-PCR, and kinomic assays, we found that fibroblast CD70 expression was inversely correlated with cell density and upregulated by TGF-β1 (transforming growth factor-β1). CD70 agonists, including T-cell–derived soluble CD27, markedly diminished fibroblast collagen and fibronectin synthesis, and these effects were potent enough to also inhibit profibrotic actions of TGF-β1 on ECM production in vitro and in two distinct ex vivo human skin models. CD70 activation was mediated by AKT (protein kinase B) and complex interconnected signaling pathways, and it was abated by prior CD70 knockdown. These results show that the CD70–CD27 axis modulates T-cell–fibroblast interactions and may be an important regulator of fibrosis and wound healing. Fibroblast CD70 could also be a novel target for specific mechanistically based antifibrosis treatments.

Aims: Nitrite is reduced to nitric oxide (NO) under physiological and pathological hypoxic conditions to modulate angiogenesis and improve ischemia–reperfusion injury. Although adult mammals lack the ability to regenerate the heart after injury, this is preserved in neonates and efforts to reactivate this process are of great interest. Unlike mammals, the adult zebrafish maintain the innate ability to regenerate their hearts after injury, providing an important model to study cardiac regeneration. We thus explored the effects of physiological levels of nitrite on cardiac and fin regeneration and downstream cellular and molecular signaling pathways in response to amputation and cryoinjury. Results: Nitrite treatment of zebrafish after ventricular amputation or cryoinjury to the heart in hypoxic water (∼3 parts per million of oxygen) increases cardiomyocyte proliferation, improves angiogenesis, and enhances early recruitment of thrombocytes, macrophages, and neutrophils to the injury. When tested in a fin regeneration model, neutrophil recruitment to the injury site was found to be dependent on NO. Innovation: This is the first study to evaluate effects of physiological levels of nitrite on cardiac regeneration in response to cardiac injury, with the observation that nitrite in water accelerates zebrafish heart regeneration. Conclusion: Physiological and therapeutic levels of nitrite increase thrombocyte, neutrophil, and macrophage recruitment to the heart after amputation and cryoinjury in zebrafish, resulting in accelerated cardiomyocyte proliferation and angiogenesis. Translation of this finding to mammalian models of injury during early development may provide an opportunity to improve outcomes during intrauterine fetal or neonatal cardiac surgery.

Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors. The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response. Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease. We hypothesized anti-GRP78 autoreactivity might also be a risk factor for atherosclerosis in COPD patients. Carotid intima-medial thickness (cIMT) was measured in 144 current and former smokers by ultrasound. Concentrations of circulating IgG autoantibodies against full-length GRP78, determined by ELISA, were greater among subjects with abnormally increased cIMT (p < 0.01). Plasma levels of autoantibodies against a singular GRP78 peptide segment, amino acids 246–260 (anti-GRP78aa 246–260), were even more highly correlated with cIMT, especially among males with greater than or equal to moderate COPD (rs = 0.62, p = 0.001). Anti-GRP78aa 246–260 concentrations were independent of CRP, IL-6, and TNF-α levels. GRP78 autoantigen expression was upregulated among human aortic endothelial cells (HAECs) stressed by incubation with tunicamycin (an unfolded protein response inducer) or exposure to culture media flow disturbances. Autoantibodies against GRP78aa 246–260, isolated from patient plasma by immunoprecipitation, induced HAEC production of proatherosclerotic mediators, including IL-8. In conclusion, anti-GRP78 autoantibodies are highly associated with carotid atherosclerosis in COPD patients and exert atherogenic effects on HAECs. These data implicate Ag-specific autoimmunity in the pathogenesis of atherosclerosis among COPD patients and raise possibilities that directed autoantibody reduction might ameliorate vascular disease in this high-risk population.

The 3D printing technology with unique strategies for accurate fabrication of biomaterials in regenerative medicine has been widely applied in bone regeneration. However, the traditional 3D printing scaffolds are only stacked by solid struts without any hollow channel structures, which limits the new bone tissue formation. In this study, a special 3D scaffold with hollow channels and a micro-nano surface was prepared by a modified 3D printing strategy combined with the hydrothermal treatment approach. By regulating the reaction solution of hydrothermal treatment, the micro-nano structures formed on the surface of scaffolds can be successfully controlled. Moreover, the scaffolds have the ability to facilitate the attachment and proliferation of BMSCs after culturing for 1, 3, and 7 days in vitro. Interestingly, the in vivo results demonstrated that the hollow channels and the micro-nano surface present synergistic effects on bone regeneration. They both boost the new bone formation in femur defects in rabbits for 12 weeks after operation. The study demonstrates a 3D scaffold with special surface microstructures and hollow struts that can overcome the shortages of most traditional scaffolds and meanwhile improve the bioactivity of biomaterials for bone tissue engineering.

Developing multifunctional wound dressing with desired mechanical strength is of great significance for the treatment of different types of skin wounds. Inspired by the close relationship between strength and hierarchical structure of nacre, hierarchical and porous graphene oxide-chitosan-calcium silicate (GO-CTS-CS) film biomaterials are fabricated by a combination of vacuum filtration-assisted assembly and freeze-drying methods. The bioinspired hierarchical materials emulate an orderly porous lamellar micron-scale structure and the "brick-and-mortar"-layered nanostructure. The hierarchical microstructure endows the GO-CTS-CS biomaterials with good tensile strength, compatible breathability, and water absorption. Furthermore, the hierarchical GO-CTS-CS biomaterials exhibit ideal photothermal performance, leading to significant photothermal antibacterial and antitumor efficacy. Further, the hierarchical GO-CTS-CS biomaterials show stimulatory effect on in vivo chronic wound healing. Therefore, such a high performance and multifunctional biomaterial is believed to offer a promising alternative to traditional wound dressing in future. STATEMENT OF SIGNIFICANCE: Although it is an effective strategy to prepare high-performance materials by mimicking the hierarchical microstructure of nacre, the preparation of nacre-inspired materials in tissue engineering fields still needs to be investigated. In this work, we prepared a nacre-inspired multifunctional graphene oxide-chitosan-calcium silicate (GO-CTS-CS) biomaterial with a hierarchical microstructure. The hierarchical microstructure endows the biomaterials with desired properties of strength, breathability, and water absorption. Further, the hierarchical GO-CTS-CS biomaterial showed good photothermal antibacterial/antitumor and wound healing effects. This work may provide an approach to combine the preparation of multifunctional biomaterials with bioinspired engineering by constructing a hierarchical microstructure, indicating that the assembling hierarchical microstructure in biomaterials is of great importance for tissue engineering and regenerative medicine.

Bioceramics are widely used in bone tissue repair and regeneration due to their desirable biocompatibility and bioactivity. However, the brittleness of bioceramics results in difficulty of surgical operation, which greatly limits their clinical applications. The spicules of the marine sponge Euplectella aspergillum (Ea) possess high flexibility and fracture toughness resulting from concentric layered silica glued by a thin organic layer. Inspired by the unique properties of sponge spicules, flexible bioceramic-based scaffolds with spicule-like concentric layered biomimetic microstructures were constructed by combining two-dimensional (2D) bioceramics and 3D printing. 2D bioceramics could be assembled and aligned by modulating the shear force field in the direct ink writing (DIW) of 3D printing. The prepared spicules-inspired flexible bioceramic-based (SFB) scaffolds differentiated themselves from traditional 3D-printed irregular particles-based bioceramic-based scaffolds as they could be adaptably compressed, cut, folded, rolled and twisted without the occurrence of fracture, significantly breaking through the bottleneck of inherent brittleness of traditional bioceramic scaffolds. In addition, SFB scaffolds showed significantly enhanced in vitro and in vivo bone-forming bioactivity as compared to conventional β-tricalcium phosphate (β-TCP) scaffolds, suggesting that SFB scaffolds combined both of excellent mechanical and bioactive characteristics, which is believed to greatly promote the bioceramic science and their clinical applications.

A role for hereditary influences in the susceptibility for chronic obstructive pulmonary disease (COPD) is widely recognized. Cytotoxic lymphocytes are implicated in COPD pathogenesis, and functions of these leukocytes are modulated by interactions between their killer-cell immunoglobulin-like receptors (KIR) and human leukocyte antigen (HLA)-Class I molecules on target cells. We hypothesized HLA-Class I and KIR inheritance affect risks for COPD. HLA-Class I alleles and KIR genotypes were defined by candidate gene analyses in multiple cohorts of COPD patients (total n=392) and control smokers with normal spirometry (total n=342). Compared to controls, COPD patients had over-representations of HLA-C*07 and activating KIR2DS1, with under-representations of HLA-C*12. Particular HLA-KIR permutations were synergistic; e.g. the presence of HLA-C*07 + KIR2DS1 + HLA-C12null vs. HLAC*07null + KIR2DS1null + HLA-C12 was associated with COPD, especially among HLA-C1 allotype homozygotes (OR=18.5, 95%CI=3.7-90.9, p

Background Cartilage endplate (CEP) degeneration plays a vital role in the pathological process of intervertebral disc degeneration. It has been previously reported that microRNAs may participate in the occurrence and development of intervertebral disc degeneration through regulating its target genes directly. The regulatory roles of miR-142-3p/HMGB1 in some orthopedic diseases have been determined successively, but there was no report about the degeneration of CEP. Therefore, we aimed to determine the regulation of miR-142-3p/HMGB1 or potential molecular mechanisms on proliferation, apoptosis, migration, and autophagy of CEP cells. Methods The target gene of miR-142-3p was determined by double luciferase assay. We selected ATDC5 cell lines. CCK-8 method was used to detect cell proliferation. Real-time fluorescence quantitative polymerase chain reaction was used to determine gene expression levels, and western blot analysis was used to determine protein expression levels. We chose flow cytometry to measure cell apoptosis and cell cycle. Results The result of luciferase detection showed that the target gene of miR-142-3p in CEP cells was HMGB1. Knockdown of the miR-142-3p inhibited the expression level of HMGB1, the proliferation and migration of CEP cells, but it promoted apoptosis of CEP cells. In addition, the detection results of the proteins related to apoptosis or autophagy showed that knockdown of miR-142-3p promoted apoptosis and autophagy. Conclusion The negative regulation of miR-142-3p/HMGB1 can affect the proliferation, apoptosis, migration, and autophagy of CEP cells. Our results provide a new idea for the targeted treatment of CEP degeneration by inhibiting the expression of HMGB1.

Additional file 1: Table S1. Sequences of miR-142-3p mimic, inhibitors and negative control. Table S2. Antibodies used in this study.

Background Intervertebral disk degeneration (IDD) is a degenerative disease characterized by cytoplasm loss and extracellular matrix degradation. Numerous evidence reported that miRNAs participated in IDD development. Nevertheless, the function of miR-142-3p in IDD development remains unknown. This study mainly explored the potential role and function of miR-142-3p in IDD development. Methods One percent fetal bovine serum was used to induce the degeneration of ATDC5 cells, and miR-142-3p level was examined by qRT-PCR. Then, miR-142-3p mimic/inhibitor and its corresponding negative control were transfected into ATDC5 normal and degenerative cells. Viability, migration, invasion, apoptosis, cycle, Bax, Bcl-2, P62, and Beclin1 expression levels were assessed using CCK8, wound healing assay, annexin V-FITC/PI staining, western blot, and qRT-PCR, respectively. Results The results revealed that the expression levels of MMP13, ADAMTS5, MMP3, and Col-X were increased as well as the expression levels of SOX-9 and Col-II were reduced in ATDC5 degenerative cells, indicating the degeneration model was constructed. We observed that miR-142-3p was decreased in ATDC5 degenerative cells and its suppression could promote ATDC5 cell degeneration. However, miR-142-3p overexpression could reverse the cell viability inhibition, as well as apoptosis and autophagy enhancement in ATDC5 degenerative cells. Conclusions Our results proved that miR-142-3p may play an important role in disk degeneration. Further animal study is needed to illustrate the role of the miR-142-3p in IDD development.

The improved three ratio method is a general algorithm for condition evaluation of oil immersed transformer. It has high accuracy in pre-test and laboratory analysis. However, the accuracy of DGA online monitoring data is not high, resulting in the decline of the positive judgment rate of transformer condition evaluation using the improved three ratio method, which is difficult to support the development requirements of transformer intelligence. To solve this problem, a DGA state evaluation method based on Naive Bayesian algorithm is proposed. The algorithm first performs preprocessing such as median filtering on the DGA online monitoring data to remove invalid data, then uses a triple composed of three conditional attributes to describe the characteristics of the DGA data, and finally calculates the a priori probability of training samples and the a posteriori probability of test samples by naive Bayesian algorithm for state evaluation. The verification of the algorithm on the measured data set shows that the accuracy of the algorithm is better than the improved three ratio method, and the algorithm is feasible and effective

Bioceramics have been developed from bioinert to bioactive or biodegradable materials in the past few decades. However, at present, traditional bioceramics are still mainly used in bone tissue regeneration and dental restoration. In this work, a new generation of "black bioceramics," extending the applications from tissue regeneration to disease therapy, is presented. Black bioceramics, through magnesium thermal reduction of traditional white ceramics, including silicate-based (e.g., CaSiO3 , MgSiO3 ) and phosphate-based (e.g., Ca3 (PO4 )2 , Ca5 (PO4 )3 (OH)), are successfully synthesized. Due to the presence of oxygen vacancies and structural defects, the black bioceramics possess photothermal functionality while maintaining their initial high bioactivity and regenerative capacity. These black bioceramics show excellent photothermal antitumor effects for both skin and bone tumors. At the same time, they have significantly improved bioactivity for skin/bone tissue repair in vitro and in vivo. These fascinating properties award the black bioceramics with profound applications in both tumor therapy and tissue regeneration, which should greatly promote the scientific relevance and clinical application of bioceramics, representing a promising new direction of cell-instructive biomaterials.

Hydroxyapatite (HA) is the main inorganic component of human bone. Inspired by nacre and cortical bone, hydroxyapatite-based coil scaffolds were successfully prepared. The scaffolds presented "brick and mortar" multi-layered structure of nacre and multi-layered concentric circular structure of cortical bone. Because of bioactive components and hierarchical structure, the scaffolds possessed good compressive strength (≈95 MPa), flexural strength (≈161 MPa) and toughness (≈1.1 MJ/m3). In addition, they showed improved angiogenesis and osteogenesis in rat and rabbit critical sized bone defect models. By mimicking co-biological systems, this work provided a feasible strategy to optimize the properties of traditional tissue engineering biological materials for vascularized bone regeneration.

In the freezing waters of the Southern Ocean, Antarctic teleost fish, the Notothenioidei, have developed unique adaptations to cope with cold, including, at the extreme, the loss of hemoglobin in icefish. As a consequence, icefish are thought to be the most vulnerable of the Antarctic fish species to ongoing ocean warming. Some icefish also fail to express myoglobin but all appear to retain neuroglobin, cytoglobin-1, cytoglobin-2, and globin-X. Despite the lack of the inducible heat shock response, Antarctic notothenioid fish are endowed with physiological plasticity to partially compensate for environmental changes, as shown by numerous physiological and genomic/transcriptomic studies over the last decade. However, the regulatory mechanisms that determine temperature/oxygen-induced changes in gene expression remain largely unexplored in these species. Proteins such as globins are susceptible to environmental changes in oxygen levels and temperature, thus playing important roles in mediating Antarctic fish adaptations. In this study, we sequenced the full-length transcripts of myoglobin, neuroglobin, cytoglobin-1, cytoglobin-2, and globin-X from the Antarctic red-blooded notothenioid Trematomus bernacchii and the white-blooded icefish Chionodraco hamatus and evaluated transcripts levels after exposure to high temperature and low oxygen levels. Basal levels of globins are similar in the two species and both stressors affect the expression of Antarctic fish globins in brain, retina and gills. Temperature up-regulates globin expression more effectively in white-blooded than in red-blooded fish while hypoxia strongly up-regulates globins in red-blooded fish, particularly in the gills. These results suggest globins function as regulators of temperature and hypoxia tolerance. This study provides the first insights into globin transcriptional changes in Antarctic fish.

The creation of a bone substitute with both excellent mechanical strength and bioactivity is still a challenge in bone tissue engineering biomaterials. To this end, inspired by the microstructure of nacre, multilayered graphene oxide/chitosan/calcium silicate (GO/CTS/CS) biomaterials were successfully prepared via a bottom-up assembly approach. The GO/CTS/CS biomaterials emulated the “brick and mortar” layered microstructure via chemical assembly and the multilayered helical cylinder macrostructure. In addition, benefiting from the interface interactions in the layered microstructure as well as the multilayered helical cylinder macrostructure, the GO/CTS/CS biomaterials possessed high flexural strength (137.2 MPa), compressive strength (80.2 MPa), toughness (1.46 MJ/m3), and specific strength (124.7 MPa Mg–1 m–3), which are close to those of cortical bone. Furthermore, because of the bioactive chemical components of GO and CS, the multilayered GO/CTS/CS biomaterials significantly improved osteogenesis and...

Transition-metal dichalcogenides (TMDs) have emerged in recent years as a special group of two-dimensional materials and have attracted tremendous attention. Among these TMD materials, molybdenum disulfide (MoS2) has shown promising applications in electronics, photonics, energy, and electrochemistry. In particular, the defects in MoS2 play an essential role in altering the electronic, magnetic, optical, and catalytic properties of MoS2, presenting a useful way to engineer the performance of MoS2. The mechanisms by which lattice defects affect the MoS2 properties are unsettled. In this work, we reveal systematically how lattice defects and substrate interface affect MoS2 electronic structure. We fabricated single-layer MoS2 by chemical vapor deposition and then transferred onto Au, single-layer graphene, hexagonal boron nitride, and CeO2 as substrates and created defects in MoS2 by ion irradiation. We assessed how these defects and substrates affect the electronic structure of MoS2 by performing X-ray pho...

It is a great challenge to endow the bioceramics with the bone-matched mechanical performances. Here, capturing inspiration from well ordered-microstructures in the high-performance natural composites, we propose a universal biomineralization-assembly-sintering approach for the fabrication of well ordered-microstructure meta-hydroxyapatite. Owing to the well ordered-microstructure and a new metal ions-related interface toughening mechanism, this well ordered-microstructure hydroxyapatite exhibits remarkable mechanical performances, which are far beyond those of existing hydroxyapatite-based bioceramic and totally matched with the human cortical bone. Furthermore, the ordered microstructure plays a significant role in modulating the cell fates and finally stimulating bone defects regeneration in vivo. This work not only provides a strategy for the fabrication of well ordered-microstructure bioceramic but also broadens the horizons for the interface toughening mechanism of composites and microstructure design of biomaterials for bone regeneration.

Background Ankylosing spondylitis (AS) is the second most common cause of inflammatory arthritis worldwide affecting the axial skeleton. Single nucleotide polymorphisms (SNPs) of matrix metalloproteinase‐3 (MMP3) in the development of AS has few been investigated in Chinese population. Methods A total of 362 patients with AS and 362 healthy controls were enrolled in the study. Five SNPs in MMP3 genotypes were identified by Agena MassARRAY. Chi‐squared tests and genetic model were used to evaluate associations. Results rs522616 had a significant risk of AS development compared to those with the TT genotype (p = 0.008). By multiple logistic regression models analysis, in codominant model, rs522616 CT genotypes also had a 1.44‐fold risk (95% CI = 1.06–1.96, p = 0.008) for AS development compared to those with TT genotypes. In recessive model, the CC genotypes was a significantly reduced AS risk for individuals with TT/CT genotype (OR = 0.64; 95% CI = 0.41–0.99, p = 0.040). Conclusion The present study suggests that MMP3 rs522616 polymorphism is associated with AS susceptibility and MMP3 might be a potential diagnostic biomarker for AS. Further independent studies with larger cohorts are warranted to validate our findings in different populations.

Current challenges in cutaneous tumor therapy are healing the skin wounds resulting from surgical resection and eliminating possible residual tumor cells to prevent recurrence. To address this issue, bifunctional biomaterials equipped with effective tumor therapeutic capacity for skin cancers and simultaneous tissue regenerative ability for wound closure are highly recommended. Herein, we report an injectable thermosensitive hydrogel (named BT-CTS thermogel) with the integration of nanosized black titania (B-TiO2–x, ∼50 nm) nanoparticles into a chitosan (CTS) matrix. The B-TiO2–x nanocrystal exhibits a crystalline/amorphous core–shell structure with abundant oxygen vacancies, which endows the BT-CTS thermogels with simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) effects under single-wavelength near-infrared laser irradiation, leading to an excellent therapeutic effect on skin tumors in vitro and in vivo. Moreover, the BT-CTS thermogel not only supports the adhesion, proliferation, a...

Background Lumbar disc herniation (LDH) is a common musculoskeletal disorder affliction and associated with several genes polymorphism. Storkhead box 1 (STOX1) gene is a transcriptional factor related with several signaling pathways including inflammatory pathway. However, little is known about single‐nucleotide polymorphisms (SNPs) of STOX1 associated with LDH risk. Methods We conducted a case–control study among 508 LDH cases and well‐matched 508 controls, and six candidate SNPs in STOX1 were genotyped by Agena MassARRAY. Chi‐squared test, genetic model, and haploview analysis were used to evaluate associations. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression. Results In the allelic model analysis, we found the minor allele “T” of rs7903209 and “A” of rs4472827 were associated with an increased risk of LDH (p = .029, p = .016). Furthermore, in the genotype model analysis, rs7903209 polymorphism was associated with the increased susceptibility of LDH based on dominant (p = .033) and additive model (p = .024); and rs4472827 variant was found to play a harmful role in the LDH risk based on genotype (p = .014), dominant (p = .012), and additive model (p = .015). In the haplotype analysis, the haplotype “GT” in block (rs10998461 and rs10998468) decreased LDH risk (OR = 0.7, 95% CI = 0.52–0.93, p = .016). Functional assessment indicated that rs7903209 and rs4472827 polymorphisms may influence the expression of STOX1. Conclusion Our results provide evidence for polymorphisms of rs7903209 and rs4472827 in STOX1 associated with LDH risk in Chinese Han population., We aimed to explore the association between STOX1 polymorphisms and LDH risk, and we found that STOX1 might be a functional factor for the occurrence and development of LDH.

The fabrication of bone regeneration biomaterials, which simultaneously possess superior mechanical performances and excellent bioactivity, remains challenging because these properties are usually mutually exclusive. Herein, inspired by the brick-and-mortar architecture of nacre, lamellar silicate-based bioceramic composites are successfully prepared by constructing orderly layered bioceramics infiltrated with a biomedical resin interlayer via the bidirectional freezing technique. The lamellar composites possess high strength and proper Young's moduli, which match with human cortical bone. Furthermore, the lamellar composites can release bioactive ions with a controlled profile, which significantly enhance the cell proliferation of both rabbit bone mesenchymal stem cells and periodontal ligament cells in vitro. Moreover, with the degradation of silicate bioceramics in vivo, newly formed bone tissue can grow into the materials to present the bioceramic/new bone/resin sandwich-like lamellar microstructure. The silicate-based bioceramic composites with brick-and-mortar architecture represent an excellent biomaterial in combination of superior mechanical performances matching that of human cortical bone, and excellent bioactivity for potential load-bearing bone regeneration.

Transition-metal dichalcogenides (TMDs) have emerged in recent years as a special group of two-dimensional materials and have attracted tremendous attention. Among these TMD materials, molybdenum disulfide (MoS

We hypothesized B cells are involved in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a progressive, restrictive lung disease that is refractory to glucocorticoids and other nonspecific therapies, and almost invariably lethal. Accordingly, we sought to identify clinically associated B cell–related abnormalities in these patients. Phenotypes of circulating B cells were characterized by flow cytometry. Intrapulmonary processes were evaluated by immunohistochemistry. Plasma B lymphocyte stimulating factor (BLyS) was assayed by ELISA. Circulating B cells of IPF subjects were more Ag differentiated, with greater plasmablast proportions (3.1 ± 0.8%) than in normal controls (1.3 ± 0.3%) (p < 0.03), and the extent of this differentiation correlated with IPF patient lung volumes (r = 0.44, p < 0.03). CD20+ B cell aggregates, diffuse parenchymal and perivascular immune complexes, and complement depositions were all prevalent in IPF lungs, but much less prominent or absent in normal lungs. Plasma concentrations of BLyS, an obligate factor for B cell survival and differentiation, were significantly greater (p < 0.0001) in 110 IPF (2.05 ± 0.05 ng/ml) than among 53 normal (1.40 ± 0.04 ng/ml) and 90 chronic obstructive pulmonary disease subjects (1.59 ± 0.05 ng/ml). BLyS levels were uniquely correlated among IPF patients with pulmonary artery pressures (r = 0.58, p < 0.0001). The 25% of IPF subjects with the greatest BLyS values also had diminished 1-y survival (46 ± 11%), compared with those with lesser BLyS concentrations (81 ± 5%) (hazard ratio = 4.0, 95% confidence interval = 1.8–8.7, p = 0.0002). Abnormalities of B cells and BLyS are common in IPF patients, and highly associated with disease manifestations and patient outcomes. These findings have implications regarding IPF pathogenesis and illuminate the potential for novel treatment regimens that specifically target B cells in patients with this lung disease.

The discovery of novel globins in diverse organisms has stimulated intense interest in their evolved function, beyond oxygen binding. Globin X (GbX) is a protein found in fish, amphibians, and reptiles that diverged from a common ancestor of mammalian hemoglobins and myoglobins. Like mammalian neuroglobin, GbX was first designated as a neuronal globin in fish and exhibits six-coordinate heme geometry, suggesting a role in intracellular electron transfer reactions rather than oxygen binding. Here, we report that GbX to our knowledge is the first six-coordinate globin and the first globin protein apart from hemoglobin, found in vertebrate RBCs. GbX is present in fish erythrocytes and exhibits a nitrite reduction rate up to 200-fold faster than human hemoglobin and up to 50-fold higher than neuroglobin or cytoglobin. Deoxygenated GbX reduces nitrite to form nitric oxide (NO) and potently inhibits platelet activation in vitro, to a greater extent than hemoglobin. Fish RBCs also reduce nitrite to NO and inhibit platelet activation to a greater extent than human RBCs, whereas GbX knockdown inhibits this nitrite-dependent NO signaling. The description of a novel, six-coordinate globin in RBCs with dominant electron transfer and nitrite reduction functionality provides new insights into the evolved signaling properties of ancestral heme-globins.