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Abstract Rotator cuff tendinopathy is the most common tendinopathy type with the worst prognosis. Conventional treatments often elicit heterogeneous drug responses due to the diversity of tendinopathy. Hence, this study attempted a classification of 126 diseased tendons into three distinct subtypes with opposite pathogenic mechanisms based on transcriptomic and clinical features. The hypoxic atrophic subtype with white appearance (Hw) exhibits downregulated neovascularization pathways. The inflammatory proliferative subtype with white appearance (Iw) shows a moderate upregulation of inflammatory characteristics. The inflammatory proliferative subtype with red appearance (Ir) exhibits the highest levels of upregulated neovascularization and inflammatory pathways, along with severe joint dysfunction. We then established research models, including subtype-specific simulations in animal models and clinical data analysis. These revealed that glucocorticoid, a controversial commonly used drug, was only effective in treating the Ir subtype. Hence, the tendinopathy subtypes elucidated in this study have significant implications for developing precision treatment of tendinopathy.

Objective: To validated a classifier to distinguish the status of rotator cuff tear and predict post-operative re-tear by utilizing magnetic resonance imaging (MRI) markers. Methods: This retrospective study included patients with healthy rotator cuff and patients diagnosed as rotator cuff tear (RCT) by MRI. Radiomics features were identified from the pre-operative shoulder MRI and selected by using maximum relevance minimum redundancy (MRMR) methods. A radiomics model for diagnosis of RCT was constructed, based on the 3D volume of interest (VOI) of supraspinatus. Another model for the prediction of rotator re-tear after rotator cuff repair (Re-RCT) was constructed based on VOI of humerus, supraspinatus, infraspinatus and other clinical parameters. Results: The model for diagnosing the status of RCT produced an area under the receiver operating characteristic curve (AUC) of 0.989 in the training cohort and 0.979 for the validation cohort. The radiomics model for predicting Re-RCT produced an AUC of 0.923 ± 0.017 for the training dataset and 0.790 ± 0.082 for the validation dataset. The nomogram combining radiomics features and clinical factors yielded an AUC of 0.961 ± 0.020 for the training dataset and 0.808 ± 0.081 for the validation dataset, which displayed the best performance among all models. Conclusion: Radiomics models for the diagnosis of rotator cuff tear and prediction of post-operative Re-RCT yielded a decent prediction accuracy.

Abstract The knee joint has long been considered a closed system. The pathological effects of joint diseases on distant organs have not been investigated. Herein, our clinical data showed that post-traumatic joint damage, combined with joint bleeding (hemarthrosis), exhibits a worse liver function compared with healthy control. With mouse model, hemarthrosis induces both cartilage degeneration and remote liver damage. Next, we found that hemarthrosis induces the upregulation in ratio and differentiation towards Th17 cells of CD4+ T cells in peripheral blood and spleen. Deletion of CD4+ T cells reverses hemarthrosis-induced liver damage. Degeneration of cartilage matrix induced by hemarthrosis upregulates serological type II collagen (COL II), which activates CD4+ T cells. Systemic application of a COL II antibody blocks the activation. Furthermore, bulk RNAseq and single-cell qPCR analysis revealed that the cartilage Akt pathway is inhibited by blood treatment. Intra-articular application of Akt activator blocks the cartilage degeneration and thus protects against the liver impairment in mouse and pig models. Taken together, our study revealed a pathological joint–liver axis mediated by matrikine-activated CD4+ T cells, which refreshes the organ-crosstalk axis and provides a new treatment target for hemarthrosis-related disease. Intra-articular bleeding induces cartilage degradation through down-reulation of cartilage Akt pathway. During this process, the soluble COL II released from the damaged cartilage can activate peripheral CD4+ T cells, differention into Th17 cells and secretion of IL-17, which consequently induces liver impairment. Intra-articular application of sc79 (inhibitor of Akt pathway) can prevent the cartilage damage as well as its peripheral influences.

The immune system requires a high energy expenditure to resist pathogen invasion. Macrophages undergo metabolic reprogramming to meet these energy requirements and immunologic activity and polarize to M1-type macrophages. Understanding the metabolic pathway switching in large yellow croaker (Larimichthys crocea) macrophages in response to lipopolysaccharide (LPS) stimulation and whether this switching affects immunity is helpful in explaining the stronger immunity of hypoxia-tolerant L. crocea. In this study, transcript levels of glycolytic pathway genes (Glut1 and Pdk1), mRNA levels or enzyme activities of glycolytic enzymes [hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase A (LDHA)], aerobic respiratory enzymes [pyruvate dehydrogenase (PDH), isocitrate dehydrogenase (IDH), and succinate dehydrogenase (SDH)], metabolites [lactic acid (LA) and adenosine triphosphate (ATP)], levels of bactericidal products [reactive oxygen species (ROS) and nitric oxide (NO)], and transcripts and level changes of inflammatory factors [IL1β, TNFα, and interferon (IFN) γ] were detected in LPS-stimulated L. crocea head kidney macrophages. We showed that glycolysis was significantly induced, the tricarboxylic acid (TCA) cycle was inhibited, and metabolic reprogramming occurred, showing the Warburg effect when immune cells were activated. To determine the potential regulatory mechanism behind these changes, LcHIF-1α was detected and found to be significantly induced and transferred to the nucleus after LPS stimulation. LcHif-1α interference led to a significant reduction in glycolytic pathway gene transcript expression, enzyme activity, metabolites, bactericidal substances, and inflammatory factor levels; a significant increase in the aerobic respiration enzymes; and decreased migration, invasion, and phagocytosis. Further ultrastructural observation by electron microscopy showed that fewer microspheres contained phagocytes and that more cells were damaged after LcHif-1α interference. LcHif-1α overexpression L. crocea head kidney macrophages showed the opposite trend, and promoter activities of Ldha and Il1β were significantly enhanced after LcHif-1α overexpression in HEK293T cells. Our data showed that LcHIF-1α acted as a metabolic switch in L. crocea macrophages and was important in polarization. Hypoxia-tolerant L. crocea head kidney showed a stronger Warburg effect and inhibited the TCA cycle, higher metabolites, and bactericidal substance levels. These results collectively revealed that LcHif-1α may promote the functional activities of head kidney macrophages in protecting hypoxia-tolerant L. crocea from Aeromonas hydrophila infection.

Abstract Tendinopathy is a debilitating and crippling syndrome resulting from the degeneration of tendon tissue, leading to loss of mechanical properties and function, and eventual tendon rupture. Unfortunately, there is currently no treatment for tendinopathy that can prevent or delay its progression. Exosomes are small extracellular vesicles that transport bioactive substances produced by cells, such as proteins, lipids, mRNAs, non-coding RNAs, and DNA. They can generate by mesenchymal stem cells (MSCs) throughout the body and play a role in intercellular communication and regulation of homeostasis. Recent research suggests that MSCs-derived exosomes (MSCs-exos) may serve as useful therapeutic candidates for promoting tendon healing. This review focuses on the function and mechanisms of MSCs-exos in tendinopathy treatment and discusses their potential application for treating this condition.

Rotator cuff tendinopathy is a common musculoskeletal disorder that imposes significant health and economic burden. Stem cell therapy has brought hope for tendon healing in patients with final stage rotator cuff tendinopathy. Some clinical trials have confirmed the effectiveness of stem cell therapy for rotator cuff tendinopathy, but its application has not been promoted and approved. There are still many issues that should be solved prior to using stem cell therapy in clinical applications. The optimal source and dose of stem cells for rotator cuff tendinopathy should be determined. We also proposed novel prospective approaches that can overcome cell population heterogeneity and standardize patient types for stem cell applications. The translational potential of this article: This review explores the optimal sources of stem cells for rotator cuff tendinopathy and the principles for selecting stem cell dosages. Key strategies are provided for stem cell population standardization and recipient selection.

Background: Tendinopathy is a common motor system disease that leads to pain and reduced function. Despite its prevalence, our mechanistic understanding is incomplete, leading to limited efficacy of treatment options. Animal models contribute significantly to our understanding of tendinopathy and some therapeutic options. However, the inadequacies of animal models are also evident, largely due to differences in anatomical structure and the complexity of human tendinopathy. Different animal models reproduce different aspects of human tendinopathy and are therefore suitable for different scenarios. This review aims to summarize the existing animal models of tendinopathy and to determine the situations in which each model is appropriate for use, including exploring disease mechanisms and evaluating therapeutic effects. Methods: We reviewed relevant literature in the PubMed database from January 2000 to December 2022 using the specific terms ((tendinopathy) OR (tendinitis)) AND (model) AND ((mice) OR (rat) OR (rabbit) OR (lapin) OR (dog) OR (canine) OR (sheep) OR (goat) OR (horse) OR (equine) OR (pig) OR (swine) OR (primate)). This review summarized different methods for establishing animal models of tendinopathy and classified them according to the pathogenesis they simulate. We then discussed the advantages and disadvantages of each model, and based on this, identified the situations in which each model was suitable for application. Results: For studies that aim to study the pathophysiology of tendinopathy, naturally occurring models, treadmill models, subacromial impingement models and metabolic models are ideal. They are closest to the natural process of tendinopathy in humans. For studies that aim to evaluate the efficacy of possible treatments, the selection should be made according to the pathogenesis simulated by the modeling method. Existing tendinopathy models can be classified into six types according to the pathogenesis they simulate: extracellular matrix synthesis-decomposition imbalance, inflammation, oxidative stress, metabolic disorder, traumatism and mechanical load. Conclusions: The critical factor affecting the translational value of research results is whether the selected model is matched with the research purpose. There is no single optimal model for inducing tendinopathy, and researchers must select the model that is most appropriate for the study they are conducting. The translational potential of this article: The critical factor affecting the translational value of research results is whether the animal model used is compatible with the research purpose. This paper provides a rationale and practical guide for the establishment and selection of animal models of tendinopathy, which is helpful to improve the clinical transformation ability of existing models and develop new models.

Abstract A novel geminivirus, soybean stay-green associated virus (SoSGV), was previously shown to cause soybean delayed senescence and is associated with the incidence of soybean stay-green syndrome. The modes of SoSGV transmission were not yet known. We captured insects belonging to 24 distinct species in a soybean field with the SoSGV outbreak and detected the presence of SoSGV only in leafhoppers and bean bugs (Riptortus pedestris). Caged feeding experiments using captured leafhoppers and bean bugs from soybean fields showed that leafhoppers, but not bean bugs, are vectors transmitting SoSGV. The common brown leafhopper (Orosius orientalis) is identified as the dominant leafhopper species and can establish colonies feeding on soybean plants in experimental conditions. An investigation of SoSGV defective DNA revealed that soybean genomic DNA fragments could be inserted into the SoSGV genome, while sequences from wild soybean, red bean, and cowpea were also identified. We further showed that the common brown leafhopper could transmit SoSGV to wild soybean and red bean plants, emphasizing a vector’s role of the leafhopper in the transmission of SoSGV in the field.

The optimization of the spatial structure of the city network is conducive to the scientific spatial distribution of industries and the promotion of coordinated regional development. This study selected the top 100 automobile enterprises in the Chinese stock market that belong to China’s pillar industry, a total of 1455 headquarters and branches, to establish an enterprise matrix. Based on the ownership linkage model, the evolution characteristics of city networks in China from 2000 to 2020 are revealed, and the influential factors of city networks are discussed using the negative binomial regression model. The findings are as follows: (1) there are significant differences in the status of automobile cities, forming a “pyramid network” hierarchy. (2) The agglomeration area of automobile cities has formed the development region of “4 + 4 + 1”. (3) The city network with hierarchical connections has formed a spatial structure of a “cross–cobweb” in the middle and “trapezoid–diamond” in the periphery. (4) Urban transportation conditions, the scientific research environment, the enterprise agglomeration economy, GDP per capita, and technological proximity positively impact the formation of a city network, but the total export–import volume has a negative impact. Overall, the government can use this study’s results to formulate policies for the automotive industry and urban development.

Abstract Soft and hard tissues possess distinct biological properties. Integrating the soft‐hard interface is difficult due to the inherent non‐osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c‐axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.

Here the authors investigate the role of the TET family of DNA demethylases in mammalian skeletal development. They find that loss of TETs leads to hypermethylation that results in decreased chromatin accessibility of RUNX2 target genes, repressing osteoblast differentiation and leading to skeletal defects in mouse such as short limbs.

Summary: The global prevalence and burden of musculoskeletal (MSK) disorders are immense. Advancements in next-generation sequencing (NGS) have generated vast amounts of data, accelerating the research of pathological mechanisms and the development of therapeutic approaches for MSK disorders. However, scattered datasets across various repositories complicate uniform analysis and comparison. Here, we introduce MSdb, a database for visualization and integrated analysis of next-generation sequencing data from human musculoskeletal system, along with manually curated patient phenotype data. MSdb provides various types of analysis, including sample-level browsing of metadata information, gene/miRNA expression, and single-cell RNA-seq dataset. In addition, MSdb also allows integrated analysis for cross-samples and cross-omics analysis, including customized differentially expressed gene/microRNA analysis, microRNA-gene network, scRNA-seq cross-sample/disease integration, and gene regulatory network analysis. Overall, systematic categorizing, standardized processing, and freely accessible knowledge features MSdb a valuable resource for MSK research community.

Musculoskeletal diseases are the leading causes of chronic pain and physical disability, affecting millions of individuals worldwide. Over the past two decades, significant progress has been made in the field of bone and cartilage tissue engineering to combat the limitations of conventional treatments. Among various materials used in musculoskeletal tissue regeneration, silk biomaterials exhibit unique mechanical robustness, versatility, favorable biocompatibility, and tunable biodegradation rate. As silk is an easy-to-process biopolymer, silks have been reformed into various materials formats using advanced bio-fabrication technology for the design of cell niches. Silk proteins also offer active sites for chemical modifications to facilitate musculoskeletal system regeneration. With the emergence of genetic engineering techniques, silk proteins have been further optimized from the molecular level with other functional motifs to introduce new advantageous biological properties. In this review, we highlight the frontiers in engineering natural and recombinant silk biomaterials, as well as recent progress in the applications of these new silks in the field of bone and cartilage regeneration. The future potentials and challenges of silk biomaterials in musculoskeletal tissue engineering are also discussed. This review brings together perspectives from different fields and provides insight into improved musculoskeletal engineering.

Musculoskeletal disorders are common in clinical practice. Repairing critical-sized defects in musculoskeletal systems remains a challenge for researchers and surgeons, requiring the application of tissue engineering biomaterials. Successful application depends on the response of the host tissue to the biomaterial and specific healing process of each anatomical structure. The commonly-held view is that biomaterials should be biocompatible to minimize local host immune response. However, a growing number of studies have shown that active modulation of the immune cells, particularly macrophages, via biomaterials is an effective way to control immune response and promote tissue regeneration as well as biomaterial integration. Therefore, we critically review the role of macrophages in the repair of injured musculoskeletal system soft tissues, which have relatively poor regenerative capacities, as well as discuss further enhancement of target tissue regeneration via modulation of macrophage polarization by biomaterial-mediated immunomodulation (biomaterial properties and delivery systems). This active regulation approach rather than passive-evade strategy maximizes the potential of biomaterials to promote musculoskeletal system soft tissue regeneration and provides alternative therapeutic options for repairing critical-sized defects.

Tendon/ligament-to-bone healing poses a formidable clinical challenge due to the complex structure, composition, cell population and mechanics of the interface. With rapid advances in tissue engineering, a variety of strategies including advanced biomaterials, bioactive growth factors and multiple stem cell lineages have been developed to facilitate the healing of this tissue interface. Given the important role of structure-function relationship, the review begins with a brief description of enthesis structure and composition. Next, the biomimetic biomaterials including decellularized extracellular matrix scaffolds and synthetic-/natural-origin scaffolds are critically examined. Then, the key roles of the combination, concentration and location of various growth factors in biomimetic application are emphasized. After that, the various stem cell sources and culture systems are described. At last, we discuss unmet needs and existing challenges in the ideal strategies for tendon/ligament-to-bone regeneration and highlight emerging strategies in the field.

Biochar is useful for soil organic carbon (SOC) sequestration. However, the effects of biochar aging and addition rates on SOC stabilization are unclear. A field experiment with four biochar application rates (0% (control), 1% (LB), 2% (MB), and 4% (HB) of dry fluvo-aquic soil) was conducted. Soil samples were sampled after 8, 12, and 24 months of its application to clarify the question. In general, SOC gradually increased with the biochar application rate. SOC with HB was higher than that in other treatments, while the ratio of microbial biomass carbon (MBC)/SOC and readily oxidizable carbon (ROC)/SOC with HB was lower than that in other treatments (p < 0.05), indicating a positive effect of HB for C stabilization over time. The effects of biochar on the soil carbon pool management index (CPMI) changed from negative to positive after 8 and 24 months of biochar application. The activities of β-D-glucosidase (βG), cellobiohydrolase (CBH), and β-N-acetylglucosaminidase (NAG) under HB were higher than with other treatments after 12 and 24 months of biochar application (p < 0.05) and negatively correlated with the ratio of MBC/SOC and ROC/SOC over time. The CPMI was positively related with βG and CBH activities after 8 and 24 months of biochar application, respectively (p < 0.05). HB increased the relative abundance of oligotrophs, including Acidobacteria, Actinobacteria, and Chloroflexi, but decreased the relative abundance of copiotrophs, including γ-Proteobacteria and Bacteroidetes over time (p < 0.05). The ratio of dissolved organic carbon (DOC)/SOC was positively correlated with the bacterial oligotroph/copiotroph ratio and significantly affected the oligotrophic and copiotrophic bacterial communities, especially after 8 and 12 months of biochar application (p < 0.05). These findings reinforce that increasing the biochar application rate and time enhances SOC stabilization by decreasing the proportions of labile organic carbon and making oligotrophic/copiotrophic communities and enzyme activities more conducive to C sequestration.

H3K4me3 is an important histone modification that could influence DNA replication and RNA translation in response to abiotic stress. Here, RNA-seq analyses were conducted in gill tissues of large yellow croaker to identify the function of H3K4me3 under low salinity stress. Additionally, CUT&Tag analyses were performed to identify the genome-wide dynamic changes in H3K4me3 and explore the mechanisms by which H3K4me3 regulates gene expression. A total of 201 differentially expressed genes (DEGs) were identified between the 5‰ low salinity group (S-group) and 25‰ normal salinity group (C-group), among which 23 DEGs (11 up-regulated H3K4me3 targets and 12 down-regulated targets) were directly regulated by H3K4me3. Our findings thus describe the epigenetic regulatory landscape of H3K4me3 in gill of large yellow croaker during low salinity stress, and provide novel insights into the regulation mechanisms of H3K4me3 mediating the responses of aquatic animals to abiotic stress.

Tendon is a vital connective tissue in human skeletal muscle system, and tendon injury is very common and intractable in clinic. Tendon development and repair are two closely related but still not fully understood processes. Tendon development involves multiple germ layer, as well as the regulation of diversity transcription factors (Scx et al.), proteins (Tnmd et al.) and signaling pathways (TGFβ et al.). The nature process of tendon repair is roughly divided in three stages, which are dominated by various cells and cell factors. This review will describe the whole process of tendon development and compare it with the process of tendon repair, focusing on the understanding and recent advances in the regulation of tendon development and repair. The study and comparison of tendon development and repair process can thus provide references and guidelines for treatment of tendon injuries.

The bloody clam Tegillarca granosa, is a commercial benthic bivalve in China that can selectively accumulate cadmium (Cd) among the metals in the marine environment, leading to high Cd accumulation. To explore the molecular mechanism of selective Cd enrichment in T. granosa, transcriptomic analyses of gills under heavy metal stress were performed. In this study, a copper (Cu)-exposed group was used as the positive control, a natural seawater group was used as the negative control, and the experimental groups were exposed to Cd or Cd & Cu. Twelve gill transcriptome libraries of T. granosa under heavy metals stress were constructed and comparatively analyzed. A total of 704,103,872 clean reads were obtained, 68.01% of which were successfully mapped to the reference genome of T. granosa. Additionally, 1045, 1201 and 931 differentially expressed genes (DEGs) were detected in the Cd vs. C, Cd & Cu vs. C and Cu vs. C comparisons, respectively. KEGG enrichment analysis showed that the “endocytosis”, “olfactory conduction” and “osteoclast differentiation” pathways were significantly enriched. Furthermore, seven genes involved in the cell entry, transportation, storage, and detoxification of heavy metals were screened and selected to validate the transcriptome data by qRT-PCR. Four selective Cd enrichment-related functional genes, CNGA3, NCXs (NCX1 and NCX2) and PIP5K, were screened; the processes of Cd cell entry, intracellular transport and storage were described, and hypotheses about these processes were put forth. In conclusion, the effective selective enrichment and regulatory network of Cd in T. granosa were revealed, providing a new theoretical basis for cultivating new varieties with low Cd accumulation in T. granosa.

Abstract Meniscus‐derived stem cells (MeSCs) are a potential cell source for meniscus tissue engineering. The stark morphological and structural changes of meniscus tissue during development indicate the complexity of MeSCs at different tissue regions and stages of development. In this study, we characterized and compared postnatal rat meniscus tissue and MeSCs at different tissue regions and stages of development. We observed that the rat meniscus tissue exhibited marked changes in tissue morphology during development, with day 7 being the most representative time point of different developmental stages. All rat MeSCs displayed typical stem cell characteristics. Rat MeSCs derived from day 7 inner meniscus tissue exhibited the highest self‐renewal capacity, cell proliferation, differentiation potential toward various mesenchymal lineage and the highest expression levels of chondrogenic genes and proteins. Transplantation of rat MeSCs derived from day 7 inner meniscus tissue promoted neo‐tissue formation and effectively protected joint surface cartilage in vivo. Our results demonstrated for the first time that rat MeSCs are not necessarily better at earlier developmental stages, and that rat MeSCs derived from day 7 inner meniscus tissue may be a superior cell source for effective meniscus regeneration and articular cartilage protection. This information could make a significant contribution to human meniscus tissue engineering in the future. Stem Cells Translational Medicine 2019;8:1318&1329

Tendon harbors a cell population that possesses stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity, commonly referred to as tendon stem/progenitor cells (TSPCs). Various techniques have been employed to study how TSPCs are implicated in tendon development, homeostasis and healing. Recent advances in single-cell analysis have enabled much progress in identifying and characterizing distinct subpopulations of TSPCs, which provides a more comprehensive view of TSPCs function in tendon biology. Understanding the mechanisms of physiological and pathological processes regulated by TSPCs, especially a particular subpopulation, would greatly benefit treatment of diseased tendons. Here, we summarize the current scientific literature on the various subpopulations of TSPCs, and discuss how TSPCs can contribute to tissue homeostasis and pathogenesis, as well as examine the key modulatory signaling pathways that determine stem/progenitor cell state. A better understanding of the roles that TSPCs play in tendon biology may facilitate the development of novel treatment strategies for tendon diseases.

Graft regeneration after anterior cruciate ligament (ACL) reconstruction surgery is a complex three-stage process, which usually takes a long duration and often results in fibrous scar tissue formation that exerts a detrimental impact on the patients’ prognosis. Hence, as a regeneration technique, stem cell transplantation has attracted increasing attention. Several different stem cell types have been utilized in animal experiments, and almost all of these have shown good capacity in improving tendon-bone regeneration. Various differentiation inducers have been widely applied together with stem cells to enhance specific lineage differentiation, such as recombinant gene transfection, growth factors, and biomaterials. Among the various different types of stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) have been investigated the most, while ligament stem progenitor cells (LDSCs) have demonstrated the best potential in generating tendon/ligament lineage cells. In the clinic, 4 relevant completed trials have been reported, but only one trial with BMSCs showed improved outcomes, while 5 relevant trials are still in progress. This review describes the process of ACL graft regeneration after implantation and summarizes the current application of stem cells from bench to bedside, as well as discusses future perspectives in this field.

Tendinopathy is a common disease of the musculoskeletal system, particularly in athletes and sports amateurs. In this review, we will present evidence for the critical role of inflammatory mediators and immunocytes in the pathogenesis of tendinopathy and the efficacy of current antiinflammatory therapy and regenerative medicine in the clinic. We hereby propose a hypothesis that in addition to pulling force there may be compressive forces being exerted on the tendon during physical activities, which may initiate the onset of tendinopathy.We performed literature searches on MEDLINE from the inception of this review to February 2018. No language restrictions were imposed. The search terms were as follows: (''Tendinopathy''[Mesh] OR ''Tendon Injuries''[Mesh] OR ''Tendinitis''[Mesh] OR ''Tendon''[Mesh]) AND (Inflammation OR ''Inflammatory mediator*'' OR Immunocyte*) OR (''anti inflammatory*'' OR ''regenerative medicine''). Inclusion criteria included articles that were original and reliable, with the main contents being highly relevant to our review. Exclusion criteria included articles that were not available online or have not been published. We scanned the abstract of these articles first. This was then followed by a careful screening of the articles which might be suitable for our review. Finally, 84 articles were selected as references. This review article is written in the narrative form.The translational potential of this article: Understanding the mechanisms of inflammation and existing antiinflammatory and regenerative therapies is key to the development of therapeutic strategies in tendinopathy. Keywords: Compression, Inflammatory mediators, Immunocytes, Pulling force, Tendinopathy

The large yellow croaker (Larimichthys crocea) is an important marine economic fish in China; however, its intolerance to hypoxia causes widespread mortality. To understand the molecular mechanisms underlying hypoxia tolerance in L. crocea, the transcriptome gene expression profiling of three different tissues (blood, gills, and liver) of L. crocea exposed to hypoxia and reoxygenation stress were performed. In parallel, the gene relationships were investigated based on weighted gene co-expression network analysis (WGCNA). Accordingly, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that several pathways (e.g., energy metabolism, signal transduction, oxygen transport, and osmotic regulation) may be involved in the response of L. crocea to hypoxia and reoxygenation stress. In addition, also, four key modules (darkorange, magenta, saddlebrown, and darkolivegreen) that were highly relevant to the samples were identified by WGCNA. Furthermore, some hub genes within the association module, including RPS16, EDRF1, KCNK5, SNAT2, PFKL, GSK-3β, and PIK3CD, were found. This is the first study to report the co-expression patterns of a gene network after hypoxia stress in marine fish. The results provide new clues for further research on the molecular mechanisms underlying hypoxia tolerance in L. crocea.

Multiple cropping systems boost grain yields and have an immense potential to increase land productivity. In such cropping systems in China, soybean is directly seeded after the wheat harvest in early June. After the wheat harvest, the farmland has low amounts of soil moisture and contains large amounts of wheat straw, which negatively affect soybean growth and yields. To address these challenges, an integrated management practice (IMP) than can achieve precise direct seeding and straw mulching return, was developed. In this study, differences in the soil temperature and moisture, seedling quality, dry matter accumulation, soybean yield, and greenhouse gas emissions were investigated between IMP and the farmers’ practices (FP). Compared with the FP treatment, IMP significantly increased the soil moisture and decreased the soil temperature in the topsoil layer. In addition, under the IMP treatment, the rate of emergence and developmental uniformity of soybean plants significantly increased by 21.7% and 99.5%, respectively, thus increasing the leaf area index by 30.0% and dry matter accumulation by 12.0% and, in turn, increasing soybean yields by 24.7%. A principal component analysis showed that the dry matter weight, relative water content, leaf area index, and developmental uniformity were strong sensitivity indices for the IMP treatment. In addition, the intensity of emission of N2O and greenhouse gases under IMP both decreased significantly by 25.1% and 28.9% compared with the FP, respectively. Thus, it was concluded that IMP is a suitable farming practice for sustainable agricultural production, and it has broad prospects for application in wheat–soybean double cropping systems in China and other similar areas globally.

Tendon stem/progenitor cells (TSPCs) were recently identified within tendon tissues. The aim of this study was to investigate TSPC-seeded knitted silk—collagen sponge scaffold for functional shoulder repair. The multidifferentiation potential, proliferation, and immune properties of TSPCs were investigated in vitro, while the efficacy of TSPC-seeded knitted silk—collagen sponge scaffolds in promoting rotator cuff regeneration was evaluated in vivo within a rabbit model. TSPCs, which exhibited universal stem cell characteristics (i.e., clonogenicity, high proliferative capacity, and multidifferentiation potential), nonimmunogenicity, and immunosuppression, proliferated well on our scaffold in vitro. Implantation of allogenous TSPC-seeded scaffolds within a rabbit rotator cuff injury model did not elicit an immunological reaction, but instead increased fibroblastic cell ingrowth and reduced infiltration of lymphocytes within the implantation sites at 4 and 8 weeks postsurgery. After 12 weeks, the allogenous TSPC-treated group exhibited increased collagen deposition and had better structural and biomechanical properties compared to the control group. This study thus demonstrated that the allogenous TSPC-seeded knitted silk—collagen sponge scaffold enhanced the efficacy of rotator cuff tendon regeneration by differentiating into tenocytes, and by secreting anti-inflammatory cytokines that prevent immunological rejection. Hence, allogenous TSPC-seeded knitted silk—collagen sponge scaffolds can be a clinically useful application for tendon tissue engineering.