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Intervertebral disc degeneration (IDD) due to multiple causes is one of the major causes of low back pain (LBP). A variety of traditional treatments and biologic therapies are currently used to delay or even reverse IDD; however, these treatments still have some limitations. Finding safer and more effective treatments is urgent for LBP patients. With increasing reports it has been found that the intervertebral disc (IVD) can convert pressure loads from the spine into electrical stimulation in a variety of ways, and that this electrical stimulation is of great importance in modulating cell behavior, the immune microenvironment and promoting tissue repair. However, when intervertebral disc degeneration occurs, the normal structures within the IVD are destroyed. This eventually leads to a weakening or loss of self-powered. Currently various piezoelectric materials with unique crystal structures can mimic the piezoelectric effect of normal tissues. Based on this, tissue-engineered scaffolds prepared using piezoelectric materials have been widely used for regenerative repair of various types of tissues, however, there are no reports of their use for the treatment of IDD. For this reason, we propose to utilize tissue-engineered scaffolds prepared from piezoelectric biomaterials with excellent biocompatibility and self-powered properties to be implanted into degenerated IVD to help restore cell type and number, restore extracellular matrix, and modulate immune responses. It provides a feasible and novel therapeutic approach for the clinical treatment of IDD.

Abstract Background Stem cell‐based therapy (SCT) is an important component of regenerative therapy that brings hope to many patients. After decades of development, SCT has made significant progress in the research of various diseases, and the market size has also expanded significantly. The transition of SCT from small‐scale, customized experiments to routine clinical practice requires the assistance of standards. Many countries and international organizations around the world have developed corresponding SCT standards, which have effectively promoted the further development of the SCT industry. Methods We conducted a comprehensive literature review to introduce the clinical application progress of SCT and focus on the development status of SCT standardization. Results We first briefly introduced the types and characteristics of stem cells, and summarized the current clinical application and market development of SCT. Subsequently, we focused on the development status of SCT‐related standards as of now from three levels: the International Organization for Standardization (ISO), important international organizations, and national organizations. Finally, we provided perspectives and conclusions on the significance and challenges of SCT standardization. Conclusions Standardization plays an important role in the sustained, rapid and healthy development of SCT.

Testicular germ cell tumors (TGCT) are the most common type of testicular cancer, comprising 90–95% of cases and representing the most prevalent solid malignancy in young adult men. Immune infiltrates play important regulatory roles in tumors, but their role in TGCT remains unclear. Molecular subtyping is a promising way to provide precisely personalized treatment and avoid unnecessary toxicities. This study investigated immune infiltrates, key biomarkers, and immune subtyping of TGCT. In GSE3218, 24 differentially expressed immune genes (immDEGs) were identified. A new risk signature consisting of six immDEGs was developed using these genes. Individuals in the high‐risk group had poor overall survival (OS; hazard ratio of 4.61 and P‐value

Background: Currently, metal implants are widely used in orthopedic surgeries, including fracture fixation, spinal fusion, joint replacement, and bone tumor defect repair. However, conventional implants are difficult to be customized according to the recipient's skeletal anatomy and defect characteristics, leading to difficulties in meeting the individual needs of patients. Additive manufacturing (AM) or three-dimensional (3D) printing technology, an advanced digital fabrication technique capable of producing components with complex and precise structures, offers opportunities for personalization. Methods: We systematically reviewed the literature on 3D printing orthopedic metal implants over the past 10 years. Relevant animal, cellular, and clinical studies were searched in PubMed and Web of Science. In this paper, we introduce the 3D printing method and the characteristics of biometals and summarize the properties of 3D printing metal implants and their clinical applications in orthopedic surgery. On this basis, we discuss potential possibilities for further generalization and improvement. Results: 3D printing technology has facilitated the use of metal implants in different orthopedic procedures. By combining medical images from techniques such as CT and MRI, 3D printing technology allows the precise fabrication of complex metal implants based on the anatomy of the injured tissue. Such patient-specific implants not only reduce excessive mechanical strength and eliminate stress-shielding effects, but also improve biocompatibility and functionality, increase cell and nutrient permeability, and promote angiogenesis and bone growth. In addition, 3D printing technology has the advantages of low cost, fast manufacturing cycles, and high reproducibility, which can shorten patients' surgery and hospitalization time. Many clinical trials have been conducted using customized implants. However, the use of modeling software, the operation of printing equipment, the high demand for metal implant materials, and the lack of guidance from relevant laws and regulations have limited its further application. Conclusions: There are advantages of 3D printing metal implants in orthopedic applications such as personalization, promotion of osseointegration, short production cycle, and high material utilization. With the continuous learning of modeling software by surgeons, the improvement of 3D printing technology, the development of metal materials that better meet clinical needs, and the improvement of laws and regulations, 3D printing metal implants can be applied to more orthopedic surgeries. The translational potential of this paper: Precision, intelligence, and personalization are the future direction of orthopedics. It is reasonable to believe that 3D printing technology will be more deeply integrated with artificial intelligence, 4D printing, and big data to play a greater role in orthopedic metal implants and eventually become an important part of the digital economy. We aim to summarize the latest developments in 3D printing metal implants for engineers and surgeons to design implants that more closely mimic the morphology and function of native bone.

As the population ages and the incidence of traumatic events rises, there is a growing trend toward the implantation of devices to replace damaged or degenerated tissues in the body. In orthopedic applications, some implants are equipped with sensors to measure internal data and monitor the status of the implant. In recent years, several multi-functional implants have been developed that the clinician can externally control using a smart device. Experts anticipate that these versatile implants could pave the way for the next-generation of technological advancements. This paper provides an introduction to implantable sensors and is structured into three parts. The first section categorizes existing implantable sensors based on their working principles and provides detailed illustrations with examples. The second section introduces the most common materials used in implantable sensors, divided into rigid and flexible materials according to their properties. The third section is the focal point of this article, with implantable orthopedic sensors being classified as joint, spine, or fracture, based on different practical scenarios. The aim of this review is to introduce various implantable orthopedic sensors, compare their different characteristics, and outline the future direction of their development and application.

AbstractBackground Spinal disorders affect millions of people worldwide, and can cause significant disability and pain. The paraspinal muscles, located on either side of the spinal column, play a crucial role in the movement, support, and stabilization of the spine. Many spinal disorders can affect paraspinal muscles, as evidenced by changes in their morphology, including hypertrophy, atrophy, and degeneration.Objectives The objectives of this review were to examine the current literature on the relationship between the paraspinal muscles and spinal disorders, summarize the methods used in previous studies, and identify areas for future research.Methods We reviewed studies on the morphological characteristics of the paravertebral muscle and discussed their relationship with spinal disorders, as well as the current limitations and future research directions.Results The paraspinal muscles play a critical role in spinal disorders and are important targets for the treatment and prevention of spinal disorders. Clinicians should consider the role of the paraspinal muscles in the development and progression of spinal disorders and incorporate assessments of the paraspinal muscle function in clinical practice.Conclusion The findings of this review highlight the need for further research to better understand the relationship between the paraspinal muscles and spinal disorders, and to develop effective interventions to improve spinal health and reduce the burden of spinal disorders.

Surface electromyography (sEMG) has emerged as a valuable tool for assessing muscle activity in various clinical and research settings. This review focuses on the application of sEMG specifically in the context of paraspinal muscles. The paraspinal muscles play a critical role in providing stability and facilitating movement of the spine. Dysfunctions or alterations in paraspinal muscle activity can lead to various musculoskeletal disorders and spinal pathologies. Therefore, understanding and quantifying paraspinal muscle activity is crucial for accurate diagnosis, treatment planning, and monitoring therapeutic interventions. This review discusses the clinical applications of sEMG in paraspinal muscles, including the assessment of low back pain, spinal disorders, and rehabilitation interventions. It explores how sEMG can aid in diagnosing the potential causes of low back pain and monitoring the effectiveness of physical therapy, spinal manipulative therapy, and exercise protocols. It also discusses emerging technologies and advancements in sEMG techniques that aim to enhance the accuracy and reliability of paraspinal muscle assessment. In summary, the application of sEMG in paraspinal muscles provides valuable insights into muscle function, dysfunction, and therapeutic interventions. By examining the literature on sEMG in paraspinal muscles, this review offers a comprehensive understanding of the current state of research, identifies knowledge gaps, and suggests future directions for optimizing the use of sEMG in assessing paraspinal muscle activity.

Abstract Background Minimally invasive percutaneous transpedicular screw fixation (MIPTSF) is generally accepted as a minimally invasive treatment for thoracolumbar fracture. However, hidden blood loss (HBL) caused by this procedure is usually disregarded. This study aimed to investigate the amount of HBL and its influencing factors after MIPTSF in thoracolumbar fracture. Methods Between October 2017 and December 2020, a total of 146 patients (106 males and 40 females, age range 21–59 years) were retrospectively examined, and their clinical and radiological data were recorded and analyzed. The Pearson or Spearman correlation analysis was used to investigate an association between patient’s characteristics and HBL. Multivariate linear regression analysis was performed to elucidate the related clinical or radiological factors of HBL. Results A substantial amount of HBL (164.00 ± 112.02 ml, 40.65% of total blood loss (TBL)) occurred after transpedicular screw internal fixation. Multivariate linear regression analysis revealed that HBL was positively associated with TBL (p

Abstract Xenograft bone scaffolds have certain advantages such as mechanical strength, osteoinductive properties, sufficient source and safety. This study aimed to compare osteogenesis of the two main bovine bone xenografts namely true bone ceramics (TBC) and decalcified bone matrix (DBM), and TBC or DBM combined with bone morphogenetic protein (BMP)-2 (TBC&BMP-2 and DBM&BMP-2). The characteristics of TBC and DBM were investigated by observing the appearance and scanning electron microscopic images, examining mechanical strength, evaluating cytotoxicity and detecting BMP-2 release after being combined with BMP-2 in vitro. The femoral condyle defect and radial defect models were successively established to evaluate the performance of the proposed scaffolds in repairing cortical and cancellous bone defects. General observation, hematoxylin and eosin (HE) staining, mirco-CT scanning, calcein double labeling, X-ray film observation, three-point bending test in vivo were then performed. It indicated that the repair with xenograft bone scaffolds of 8 weeks were needed and the repair results were better than those of 4 weeks whatever the type of defects. To femoral condyle defect, TBC and TBC&BMP-2 were better than DBM and DBM&BMP-2, and TBC&BMP-2 was better than TBC alone; to radial defect, DBM and DBM&BMP-2 were better than TBC and TBC&BMP-2, and DBM&BMP-2 was better than DBM alone. This study has shown that TBC and DBM xenograft scaffolds can be more suitable for the repair of cancellous bone and cortical bone defects for 8 weeks in rats, respectively. We also have exhibited the use of BMP-2 in combination with DBM or TBC provides the possibility to treat bone defects more effectively. We thus believe that we probably need to select the more suitable scaffold according to bone defect types, and both TBC and DBM are promising xenograft materials for bone tissue engineering and regenerative medicine. Graphical abstract

Abstract Background Osteochondral lesions of the talus (OLTs) are a common orthopedic condition. The image presentation is very similar to that of ischemic necrosis of the talus complicated by a talar neck fracture, but the two are very different lesions. When abnormalities in bone density (or signal) of the talar body (apex of the fornix) with concomitant bone defects and cystic changes are found on X-ray, computed tomography (CT), or magnetic resonance imaging, it is important to accurately determine the nature of the lesion and make a correct diagnosis for the treatment and prognosis of the patient. The purpose of this study was to explore the imaging features of three-phase single-photon emission computed tomography (SPECT)/CT images of cystic lesions of the talus. Methods A total of 189 patients with chronic pain in the ankle joint suspected to be caused by cystic degeneration of the talus were enrolled. All patients underwent 99mTc-methyl diphosphonate (99mTc-MDP) three-phase SPECT/CT bone imaging and delayed scans in our hospital. The location, range of involvement, classification, CT value, and radioactivity uptake of the sclerotic areas of cystic lesions on the talus, and the continuity of the articular surface, were recorded. All recorded parameters were analyzed in comparison with pathological results. Results Eighty-three percent (157/189) of the talar cysts were located on the medial fornix, largely involving the anterior middle part (43.27%), with larger cysts involving the posterior part (9.6%). Sixty-three percent (119/189) of the patients had type I lesions and 37% (70/189) had type II lesions. The articular surface of the medial dome of the talus was intact in all patients, but the subchondral bony articular surface was rough in 88% (166/189) of patients. The coincidence rate for the location, type, and range of involvement of cystic lesions with the pathological results was 87.83% (166/189). The mean CT value of the cystic lesions was 45 ± 15 HU (30–60 HU). The percentages of pathological chondrogenesis in high CT value ≥ 50 HU (19/70) and low CT value

BackgroundIrreversible electroporation (IRE) is a novel local tumor ablation approach with the potential to stimulate an antitumor immune response. However, it is not effective in preventing distant metastasis in isolation. This study aimed to compare the potential of augmenting the antitumor immune response in patients with locally advanced pancreatic cancer (LAPC) who underwent IRE combined with chemotherapy and PD-1/PD-L1 blockade with those who underwent IRE combined with chemotherapy.MethodsA retrospective review was conducted on LAPC patients treated either with IRE in combination with chemotherapy and PD-1/PD-L1 blockade (group A) or with IRE with chemotherapy alone (group B) from July 2015 to June 2021. The primary outcomes were overall survival (OS) and progression-free survival (PFS), with immune responses and adverse events serving as secondary endpoints. Risk factors for OS and PFS were identified using univariate and multivariate analyses.ResultsA total of 103 patients were included in the final analysis, comprising 25 in group A and 78 in group B. The median duration of follow-up was 18.2 months (3.0–38.6 months). Group A patients demonstrated improved survival compared to group B (median OS: 23.6 vs. 19.4 months, p = 0.001; median PFS: 18.2 vs. 14.7 months, p = 0.022). The data suggest a robust immune response in group A, while adverse events related to the treatment were similar in both groups. The multivariate analysis identified the combination of IRE, chemotherapy, and PD-1/PD-L1 blockade as an independent prognostic factor for OS and PFS.ConclusionThe addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.

The application of three-dimensional printing technology in the medical field has great potential for bone defect repair, especially personalized and biological repair. As a green manufacturing process that does not involve liquefication through heating, low-temperature deposition manufacturing (LDM) is a promising type of rapid prototyping manufacturing and has been widely used to fabricate scaffolds in bone tissue engineering. The scaffolds fabricated by LDM have a multi-scale controllable pore structure and interconnected micropores, which are beneficial for the repair of bone defects. At the same time, different types of cells or bioactive factor can be integrated into three-dimensional structural scaffolds through LDM. Herein, we introduced LDM technology and summarize its applications in bone tissue engineering. We divide the scaffolds into four categories according to the skeleton materials and discuss the performance and limitations of the scaffolds. The ideas presented in this review have prospects in the development and application of LDM scaffolds.

Intervertebral disc degeneration is thought to be a major contributor to low back pain, the etiology of which is complex and not yet fully understood. To compensate for the lack of drug and surgical treatment, mesenchymal stem cells have been proposed for regenerative treatment of intervertebral discs in recent years, and encouraging results have been achieved in related trials. Mesenchymal stem cells can be derived from different parts of the body, among which mesenchymal stem cells isolated from the fetal umbilical cord have excellent performance in terms of difficulty of acquisition, differentiation potential, immunogenicity and ethical risk. This makes it possible for umbilical cord derived mesenchymal stem cells to replace the most widely used bone marrow-derived and adipose tissue derived mesenchymal stem cells as the first choice for regenerating intervertebral discs. However, the survival of umbilical cord mesenchymal stem cells within the intervertebral disc is a major factor affecting their regenerative capacity. In recent years biomaterial scaffolds in tissue engineering have aided the survival of umbilical cord mesenchymal stem cells by mimicking the natural extracellular matrix. This seems to provide a new idea for the application of umbilical cord mesenchymal stem cells. This article reviews the structure of the intervertebral disc, disc degeneration, and the strengths and weaknesses of common treatment methods. We focus on the cell source, cell characteristics, mechanism of action and related experiments to summarize the umbilical cord mesenchymal stem cells and explore the feasibility of tissue engineering technology of umbilical cord mesenchymal stem cells. Hoping to provide new ideas for the treatment of disc degeneration.

BackgroundThe predominant and most prevalent form of metastatic bladder cancer (BCa) is lymphatic metastasis, which is associated with a highly dismal prognosis for patients. Aging-related genes (ARGs) are believed to contribute significantly to tumor development. However, the effect of ARGs on lymphatic metastasis of BCa is unclear. This research sought to establish a prognosis model based on ARGs associated with lymphatic metastasis in BCa.MethodsWe downloaded BCa data from the TCGA and GEO databases and ARGs from the Aging Atlas database. The least absolute shrinkage and selection operator (LASSO) approach was applied to obtain the characteristic ARGs of risk signature in the TCGA cohort. Verification was done using the GSE13507 dataset. The R package ‘ConsensusClusterPlus’ was employed to identify the molecular subtypes based on the characteristic ARGs. Protein-Protein interaction network, MCODE analysis, enrichment analysis (KEGG, GO, GSEA), and immune infiltration analysis were performed to investigate underlying mechanisms. EdU, migration and invasion assays, wound healing assays, immunofluorescence staining, and quantitative polymerase chain reaction were conducted to evaluate the impact of ELN on the proliferative, migratory, and invasive capacities of BCa cells.ResultsWe identified 20 differently expressed ARGs. A four ARGs risk signature (EFEMP1, UCHL1, TP63, ELN) was constructed in the TCGA cohort. The high-risk group (category) recorded a reduced overall survival (OS) rate relative to the low-risk category (hazard ratio, 2.15; P

In this study, a phosducin-like protein, PoPlp1, was identified and functionally studied in the cellulase-producing strain Penicillium oxalicum 114-2. PoPlp1 was proven to participate in several biological processes, including mycelium development, conidiation, and expression of cellulases and amylases. With deletion of Poplp1, morphology and development varied significantly in ΔPoplp1. Colony growth, glucose utilization, and the hydrolysis capability of starch and cellulose were limited, whereas conidiation was enhanced. Based on detection of the levels of expression of transcription factors involved in asexual development, we conjectured that PoPlp1 is involved in conidiation via the major factor BrlA. We explored the effect of PoPlp1 on cellulase and amylase expression and observed that cellulase and amylase activity and major gene transcription levels were all dramatically reduced in ΔPoplp1. Deletion of PoPlp1 caused a decrease in intracellular cAMP levels, and the cellulase gene expression level of ΔPoplp1 was restored to a certain extent through external addition of cAMP. These findings demonstrate that PoPlp1 may affect cellulase and amylase expression by regulating cAMP concentration. To comprehensively explore the mechanism of PoPlp1 in regulating multiple biological processes, we performed a comparative transcriptomic analysis between strains P. oxalicum 114-2 and ΔPoplp1. The major cellulase and amylase genes were all downregulated, congrent with the results of real-time quantitative polymerase chain reaction analysis. The genes involved in the G protein–cAMP signaling pathway, including several G-protein-coupled receptors, one regulator of G protein signaling, and two cAMP phosphodiesterases, were disrupted by deletion of PoPlp1. These results confirm the positive function of PoPlp1 in the G protein–cAMP signaling pathway. This functional analysis of PoPlp1 will be very beneficial for further study of the regulatory mechanisms of cellulase expression and other biological processes in P. oxalicum 114-2 via the G protein–cAMP signaling pathway.

Morchella esculenta is a precious edible and medicinal fungus rich in protein, polysaccharides, polyphenols, amino acids, triterpenes, and other active components. In this study, MS-1 was isolated from the fruiting body of M. esculenta. Through conducting single-factor experiments and the response surface analysis of the culture conditions, the optimal culture components of an M. esculenta fermentation broth for extracellular polysaccharide production were determined, namely, 3.7% glucose, 2% yeast extract, and 0.15% sodium chloride. The polysaccharides MSF and MSL were extracted from the fruiting body of M. esculenta and the fermentation broth, respectively, and analyzed with gel permeation chromatography (GPC), monosaccharide composition, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and in vivo and in vitro antioxidant and anti-inflammatory activity analyses. The research results show that the calculated MW of MSF is 2.34 × 105 Da, and the calculated MW of MSL is 1.40 × 105 Da. MSF is composed of three monosaccharides: D-galactose, D-glucose, and D-mannose (molar ratio of 4.34:90.22:5.45). MSL consists of five monosaccharides: D-arabinose, D-galactose, D-glucose, D-mannose, and glucuronic acid (molar ratio of 0.31:14.71:13.03:71.43:0.53). The in vitro antioxidant test results show that MSF and MSL both have significant antioxidant activities. Activity experiments on MSF and MSL in zebrafish showed that MSF and MSL have significant repair effects on the oxidative damage caused by metronidazole in zebrafish embryos, and there were significant changes in the transcriptional activity levels of the oxidative stress-related genes SOD, Keap1, and Nrf2. Therefore, the polysaccharides MSF and MSL from MS-1 can be used as important raw materials for functional foods and drugs.

Signaling pathways play a crucial role in regulating cellulase production. The pathway mediated by signaling proteins plays a crucial role in understanding how cellulase expression is regulated. In this study, using affinity purification of ClrB, we have identified sixteen proteins that potentially interact with ClrB. One of the proteins, the catalytic subunit of cAMP-dependent protein kinase A (PoPKA-C), is an important component of the cAMP/PKA signaling pathway. Knocking out PoPKA-C resulted in significant decreases in the growth, glucose utilization, and cellulose hydrolysis ability of the mutant strain. Furthermore, the cellulase activity and gene transcription levels were significantly reduced in the ΔPoPKA-C mutant, while the expression activity of CreA, a transcriptional regulator of carbon metabolism repression, was notably increased. Additionally, deletion of PoPKA-C also led to earlier timing of conidia production. The expression levels of key transcription factor genes stuA and brlA, which are involved in the production of the conidia, showed significant enhancement in the ΔPoPKA-C mutant. These findings highlight the involvement of PoPKA-C in mycelial development, conidiation, and the regulation of cellulase expression. The functional analysis of PoPKA-C provides insights into the mechanism of the cAMP/PKA signaling pathway in cellulase expression in filamentous fungi and has significant implications for the development of high-yielding cellulase strains.

Background: With increasing requirements for medical effects, and huge differences among individuals, traditional surgical instruments are difficult to meet the patients' growing medical demands. 3D printing is increasingly mature, which connects to medical services critically as well. The patient specific surgical guide plate provides the condition for precision medicine in orthopaedics. Methods: In this paper, a systematic review of the orthopedic guide template is presented, where the history of 3D-printing-guided technology, the process of guides, and basic clinical applications of orthopedic guide templates are described. Finally, the limitations of the template and possible future directions are discussed. Results: The technology of 3D printing surgical templates is increasingly mature, standard, and intelligent. With the help of guide templates, the surgeon can easily determine the direction and depth of the screw path, and choose the angle and range of osteotomy, increasing the precision, safety, and reliability of the procedure in various types of surgeries. It simplifies the difficult surgical steps and accelerates the growth of young and mid-career physicians. But some problems such as cost, materials, and equipment limit its development. Conclusions: In different fields of orthopedics, the use of guide templates can significantly improve surgical accuracy, shorten the surgical time, and reduce intraoperative bleeding and radiation. With the development of 3D printing, the guide template will be standardized and simplified from design to production and use. 3D printing guides will be further sublimated in the application of orthopedics and better serve the patients. The translational potential of this paper: Precision, intelligence, and individuation are the future development direction of orthopedics. It is more and more popular as the price of printers falls and materials are developed. In addition, the technology of meta-universe, digital twin, and artificial intelligence have made revolutionary effects on template guides. We aim to summarize recent developments and applications of 3D printing guide templates for engineers and surgeons to develop more accurate and efficient templates.

Background: Periosteum plays a significant role in bone formation and regeneration by storing progenitor cells, and also acts as a source of local growth factors and a scaffold for recruiting cells and other growth factors. Recently, tissue-engineered periosteum has been studied extensively and shown to be important for osteogenesis and chondrogenesis. Using biomimetic methods for artificial periosteum synthesis, membranous tissues with similar function and structure to native periosteum are produced that significantly improve the efficacy of bone grafting and scaffold engineering, and can serve as direct replacements for native periosteum. Many problems involving bone defects can be solved by preparation of idealized periosteum from materials with different properties using various techniques. Methods: This review summarizes the significance of periosteum for osteogenesis and chondrogenesis from the aspects of periosteum tissue structure, osteogenesis performance, clinical application, and development of periosteum tissue engineering. The advantages and disadvantages of different tissue engineering methods are also summarized. Results: The fast-developing field of periosteum tissue engineering is aimed toward synthesis of bionic periosteum that can ensure or accelerate the repair of bone defects. Artificial periosteum materials can be similar to natural periosteum in both structure and function, and have good therapeutic potential. Induction of periosteum tissue regeneration and bone regeneration by biomimetic periosteum is the ideal process for bone repair. Conclusions: Periosteum is essential for bone formation and regeneration, and it is indispensable in bone repair. Achieving personalized structure and composition in the construction of tissue engineering periosteum is in accordance with the design concept of both universality and emphasis on individual differences and ensures the combination of commonness and individuality, which are expected to meet the clinical needs of bone repair more effectively. The translational potential of this article: To better understand the role of periosteum in bone repair, clarify the present research situation of periosteum and tissue engineering periosteum, and determine the development and optimization direction of tissue engineering periosteum in the future. It is hoped that periosteum tissue engineering will play a greater role in meeting the clinical needs of bone repair in the future, and makes it possible to achieve optimization of bone tissue therapy.

Abstract Intervertebral disc degeneration (IDD) is a common disease that increases with age, and its occurrence is stressful both psychologically and financially. Stem cell therapy for IDD is emerging. For this therapy, stem cells from different sources have been proven in vitro, in vivo, and in clinical trials to relieve pain and symptoms, reverse the degeneration cascade, delay the aging process, maintain the spine shape, and retain mechanical function. However, further research is needed to explain how stem cells play these roles and what effects they produce in IDD treatment. This review aims to summarize and objectively analyse the current evidence on stem cell therapy for IDD.

The presence of periosteum can greatly affect the repair of a bone fracture. An artificial periosteum imitates the biological function of natural periosteum, which is capable of protecting and maintaining bone tissue structure and promoting bone repair. In our artificial periosteum, biocompatible methacrylate gelatin was used to provide the mechanical support of the membrane, E7 peptide added bioactivity, and Wharton's jelly provided the biological activity support of the membrane, resulting in a hydrogel membrane (G-E-W) for the chemotactic recruitment of bone marrow mesenchymal stem cells (BMSCs) and promoting cell proliferation and osteogenic differentiation. In an in vitro experiment, the G-E-W membrane recruited BMSCs and promoted cell proliferation and osteogenic differentiation. After 4 weeks and 8 weeks of implantation in a rat skull defect, the group implanted with a G-E-W membrane was superior to the blank control group and single-component membrane group in both quantity and quality of new bone. The artificial G-E-W membrane recruits BMSC chemotaxis and promotes cell proliferation and osteogenic differentiation, thereby effectively improving the repair efficiency of fractures and bone defects.

BackgroundDepression is a highly prevalent mental disorder, and we found that patients with preoperative depression had worse postoperative improvement in lumbar fusion. Are mental factors related to the prognosis of laminoplasty?ObjectiveTo analyze the relationship between depression and clinical outcomes after laminoplasty for the treatment of multilevel CSM.MethodsIn this retrospective study, 115 patients with multilevel cervical spondylotic myelopathy (CSM), who underwent laminoplasty and were followed up for more than 1 year, were enrolled in this study from October 2018 to October 2021. Patients with the scores of 21-item Beck Depression Inventory (BDI) ≥ 15 or Hamilton Depression Scale-24 (HAMD-24) > 20 were included in the depression group. The clinical outcomes were evaluated by the changes and recovery rate (RR) of Japanese Orthopaedic Association Scores (JOA) and Neck Disability Index (NDI) respectively. Univariate and multiple linear regression analyses were performed to reveal the relationship between preoperative depressive states and clinical outcomes.ResultsFourteen patients were diagnosed with depression by BDI and twenty-nine by HAMD-24. Between the depression group and the non-depression group, the age, gender, smoking history, and duration of symptoms were statistically significant (P

As simulation is playing an increasingly important role in medicine, providing the individual patient with a customised diagnosis and treatment is envisaged as part of future precision medicine. Such customisation will become possible through the emergence of digital twin (DT) technology. The objective of this article is to review the progress of prominent research on DT technology in medicine and discuss the potential applications and future opportunities as well as several challenges remaining in digital healthcare. A review of the literature was conducted using PubMed, Web of Science, Google Scholar, Scopus and related bibliographic resources, in which the following terms and their derivatives were considered during the search: DT, medicine and digital health virtual healthcare. Finally, analyses of the literature yielded 465 pertinent articles, of which we selected 22 for detailed review. We summarised the application examples of DT in medicine and analysed the applications in many fields of medicine. It revealed encouraging results that DT is being increasing applied in medicine. Results from this literature review indicated that DT healthcare, as a key fusion approach of future medicine, will bring the advantages of precision diagnose and personalised treatment into reality.

Introduction Discogenic low back pain (DLBP) is a common disease, and its occurrence is closely related to intervertebral disc (IVD) degeneration. At present, none of the traditional treatment methods can repair the degenerated IVD. The emergence of stem cell therapy makes it possible to repair and regenerate IVD tissue, among which adipose derived mesenchymal stem cells (ADMSCs) transplantation therapy has become a hot spot of current research. Therefore, this trial aimed to investigate the safety and efficacy of using autologous cultured ADMSCs combined with hyaluronic acid (HA) hydrogel in the treatment of DLBP.Methods and analysis This study is a randomised, dose-escalation, placebo-controlled, double-blind, single-centre, phase II clinical trial to evaluate the efficacy and safety of autologous cultured ADMSCs combined with HA hydrogel in the treatment of patients with DLBP. The 100 eligible patients will be randomly divided into three experimental groups with different doses and one placebo control group in a ratio of 1:1:1:1. All patients will undergo liposuction to obtain ADMSCs, followed by autologous cultured ADMSC mixtures or placebo transplantation after 3 weeks. The patients will be followed up to 24 months after the transplant. The primary end point of this trial is the Visual Analogue Scale. Secondary end points include the Oswestry Disability Index, Japanese Orthopaedic Association Scores, the Mos 36-item short form, the Modic classification, Pfirrmann grade, height and segment range of motion of the IVD, vital signs (temperature, pulse, respiration, blood pressure), blood routine, liver and kidney function, immunological examination, urinalysis and treatment emergent adverse events.Ethics and dissemination The study protocol has been approved by the Ethics Committee of the First Affiliated Hospital of Dalian Medical University and registered in the Chinese Clinical Trial Registry. Dissemination of the results will be presented at a conference and in peer-reviewed publications.Trial registration number ChiCTR2200058291.

Leaf senescence is a natural phenomenon that occurs during the aging process of plants and is influenced by various internal and external factors. These factors encompass plant hormones, as well as environmental pressures such as inadequate nutrients, drought, darkness, high salinity, and extreme temperatures. Abiotic stresses accelerate leaf senescence, resulting in reduced photosynthetic efficiency, yield, and quality. Gaining a comprehensive understanding of the molecular mechanisms underlying leaf senescence in response to abiotic stresses is imperative to enhance the resilience and productivity of crops in unfavorable environments. In recent years, substantial advancements have been made in the study of leaf senescence, particularly regarding the identification of pivotal genes and transcription factors involved in this process. Nevertheless, challenges remain, including the necessity for further exploration of the intricate regulatory network governing leaf senescence and the development of effective strategies for manipulating genes in crops. This manuscript provides an overview of the molecular mechanisms that trigger leaf senescence under abiotic stresses, along with strategies to enhance stress tolerance and improve crop yield and quality by delaying leaf senescence. Furthermore, this review also highlighted the challenges associated with leaf senescence research and proposes potential solutions.

Abstract Objective: To study the bone induction and defect repair of true bone ceramics (TBC) combined with rhBMP-2 and Sr. Methods: MC3T3-E1 cells were used to evaluate the bioactivity of the composite. Cell proliferation activity was detected by CCK-8, ALP activity was detected by p-nitrophenyl phosphate (PNPP), and the differences of material surface topography were observed by scanning electron microscopy (SEM). Bone induction was verified by the implantation in nude mice. The rabbit femoral condyle defect model was achieved to verify the bone defect repair ability of the material. Results: SEM results showed nearly the same surface morphology and cell proliferation quantified by CCK-8 showed that compared with TBC, both TBC&Sr and TBC&BMP-2&Sr had a significant promoting effect (P

Abstract At present, the pedicle screw is the most commonly used internal fixation device. However, there are many kinds of common posterior pedicle screw insertion techniques performed to reconstruct the lumbar stability. Therefore, spinal surgeons often face a difficult choice. The stress distribution of internal fixation system is an important index for evaluating safety. Unfortunately, little had been known about the difference of stress distribution of screw-rod systems that established by Roy-Camille, Magerl and Krag insertion techniques. Here, combination of finite element analysis and model measurement research was adopted to evaluate the difference of stress. Following different pedicle screw insertion techniques, three lumbar posterior surgery models were established after modeling and validation of the L1–S1 vertebrae finite element model. By analyzing the data, we found that stress concentration phenomenon was in all the postoperative models. Roy-Camille and Magerl insertion techniques led to the great stress on screw-rod systems. Then, fresh frozen calf spines were selected as a model for subsequent measurements. Fitted with a specially designed test pedicle screw, L5–L6 vertebrae were selected to repeat and verify the results of the finite element analysis. With the aid of universal testing machine and digital torque wrench, models simulated flexion, extension, lateral bending and rotation. Finally, the strain value was captured by the strain gauge and was then calculated as the stress value. Krag and Magerl were found to be the safer choice for pedicle screw insertion. Overall, our combination method obtained the reliable result that Krag insertion technique was the safer approach for pedicle screw implantation due to its relatively dispersive stress. Therefore, without the consideration of screw size, pedicle fill, bone density, and bone structures, we recommend the Krag insertion technique as the first choice to reconstruction of lumbar stability. Additionally, the combination method of finite element analysis and strain gauge measurement can provide a feasible way to study the stress distribution of spinal internal fixation.

There is a growing need for precise diagnosis and personalized treatment of disease in recent years. Providing treatment tailored to each patient and maximizing efficacy and efficiency are broad goals of the healthcare system. As an engineering concept that connects the physical entity and digital space, the digital twin (DT) entered our lives at the beginning of Industry 4.0. It is evaluated as a revolution in many industrial fields and has shown the potential to be widely used in the field of medicine. This technology can offer innovative solutions for precise diagnosis and personalized treatment processes. Although there are difficulties in data collection, data fusion, and accurate simulation at this stage, we speculated that the DT may have an increasing use in the future and will become a new platform for personal health management and healthcare services. We introduced the DT technology and discussed the advantages and limitations of its applications in the medical field. This article aims to provide a perspective that combining Big Data, the Internet of Things (IoT), and artificial intelligence (AI) technology; the DT will help establish high-resolution models of patients to achieve precise diagnosis and personalized treatment.

Leaf senescence is the last stage of leaf development, manifested by leaf yellowing due to the loss of chlorophyll, along with the degradation of macromolecules and facilitates nutrient translocation from the sink to the source tissues, which is essential for the plants' fitness. Leaf senescence is controlled by a sophisticated genetic network that has been revealed through the study of the molecular mechanisms of hundreds of senescence-associated genes (SAGs), which are involved in multiple layers of regulation. Leaf senescence is primarily regulated by plant age, but also influenced by a variety of factors, including phytohormones and environmental stimuli. Phytohormones, as important signaling molecules in plant, contribute to the onset and progression of leaf senescence. Recently, peptide hormones have been reported to be involved in the regulation of leaf senescence, enriching the significance of signaling molecules in controlling leaf senescence. This review summarizes recent advances in the regulation of leaf senescence by classical and peptide hormones, aiming to better understand the coordinated network of different pathways during leaf senescence.

Background: Xenograft bone scaffolds have advantages such as mechanical strength, sufficient source and safety. Combined with siRNA properly targeting CKIP-1, a negative regulator of osteogenesis, may contribute to the repair result of calcine bone alone. Methods: Herein, we constructed a novel xenograft bovine bone scaffold namely (DSS)6-liposome/CKIP-1 siRNA/calcine bone, the characteristics of which were investigated by confirming the effect of (DSS)6-liposome, observing the appearance and testing mechanical strength of calcine bone, and observing the combined result of CKIP-1 siRNA by FAM immunofluorescence. In addition, cytotoxicity by CCK-8 and LDH activity of L929 ​cells and MC3T3-E1 osteoblasts cultured with the scaffold were tested in vitro, primary osteoblasts proliferation, the mRNA expressions of CKIP-1, ALP, COL1-α and OCN, the protein expressions of CKIP-1, BMP-2, COL-1 and Runx2 and calcium nodules were also determined by CCK-8, RT-qPCR, western-blot and Alizarin Red staining in vitro. Then, we successively established the skull defect model for evaluating the repair result of the novel scaffold by HE staining of 2, 4, 8 and 12 weeks, immumohistochemical stainings of 2, 4, 8 and 12 weeks such as ALP, COL-1α and OCN, Mirco-CT scanning of 4 and 12 weeks and the relative parameters and so on in vivo. Results: It indicated that (DSS)6-liposome/CKIP-1 siRNA/calcine bone could successfully knock down the CKIP-1 mRNA and protein expressions, promote osteoblasts proliferation with the little cytotoxicity in vitro, increase the protein expressions of BMP-2, COL-1 and Runx2 in vitro, increase mRNA expressions of ALP, COL-1α and OCN in vitro and in vivo, and have a better bone defect repair effect with few side effects in rats after 12 weeks. Conclusion: Our research indicates (DSS)6-liposome/CKIP-1 siRNA/calcine bone could repair skull defects well in rats, and it may lay the foundation of applicating the novel xenograft bone scaffold in the clinical. The Translational potential of this article: These findings provide evidence that (DSS)6- liposome/CKIP-1 siRNA/calcine bone could be used as a novel xenograft bone scaffold for osteogenesis with the good safety.

Abstract Background The decision to treat multilevel cervical spondylotic myelopathy (MCSM) remains controversial. The purpose of this study is to compare the biomechanical characteristics of the intervertebral discs at the adjacent segments and internal fixation, and to provide scientific experimental evidence for surgical treatment of MCSM. Methods An intact C2-C7 cervical spine model was developed and validated. Four additional models were developed from the fusion model, including multilevel anterior cervical discectomy and fusion (mACDF), anterior cervical corpectomy and fusion (ACCF), hybrid decompression and fusion (HDF), and mACDF with cage alone (mACDF-CA). Biomechanical characteristics on the plate and the disc of adjacent levels (C2/3, C6/7) were comparatively analyzed. Results Of the four models, stress on the upper (C2/3) adjacent intervertebral disc was the lowest in the mACDF-CA group and highest in the ACCF group. Stress on the intervertebral discs at adjacent segments was higher for the upper C2/3 than the lower C6/7 intervertebral disc. In all models, the mACDF-CA group had the lowest stress on the intervertebral disc, while the ACCF group had the highest stress. In the three surgical models with titanium plate fixation (mACDF, ACCF, and HDF), the ACCF group had the highest stress at the titanium plate-screw interface, while the mACDF group had the lowest stress. Conclusion Among the four anterior cervical reconstructive techniques for MCSM, mACDF-CA makes little effect on the adjacent disc stress, which might reduce the incidence of adjacent segment degeneration (ASD) after fusion. However, the accompanying risk of the increased incidence of cage subsidence should never be neglected.

Due to the high prevalence and rates of disability associated with musculoskeletal system diseases, more thorough research into diagnosis, pathogenesis, and treatments is required. One of the key contributors to the emergence of diseases of the musculoskeletal system is thought to be changes in the biomechanics of the human musculoskeletal system. However, there are some defects concerning personal analysis or dynamic responses in current biomechanical research methodologies. Digital twin (DT) was initially an engineering concept that reflected the mirror image of a physical entity. With the application of medical image analysis and artificial intelligence (AI), it entered our lives and showed its potential to be further applied in the medical field. Consequently, we believe that DT can take a step towards personalized healthcare by guiding the design of industrial personalized healthcare systems. In this perspective article, we discuss the limitations of traditional biomechanical methods and the initial exploration of DT in musculoskeletal system diseases. We provide a new opinion that DT could be an effective solution for musculoskeletal system diseases in the future, which will help us analyze the real-time biomechanical properties of the musculoskeletal system and achieve personalized medicine.

Leaf senescence is a complex biological process regulated at multiple levels, including chromatin remodeling, transcription, post-transcription, translation, and post-translational modifications. Transcription factors (TFs) are crucial regulators of leaf senescence, with NAC and WRKY families being the most studied. This review summarizes the progress made in understanding the regulatory roles of these families in leaf senescence in Arabidopsis and various crops such as wheat, maize, sorghum, and rice. Additionally, we review the regulatory functions of other families, such as ERF, bHLH, bZIP, and MYB. Unraveling the mechanisms of leaf senescence regulated by TFs has the potential to improve crop yield and quality through molecular breeding. While significant progress has been made in leaf senescence research in recent years, our understanding of the molecular regulatory mechanisms underlying this process is still incomplete. This review also discusses the challenges and opportunities in leaf senescence research, with suggestions for possible strategies to address them.

Bone defect disease causes damage to people’s lives and property, and how to effectively promote bone regeneration is still a big clinical challenge. Most of the current repair methods focus on filling the defects, which has a poor effect on bone regeneration. Therefore, how to effectively promote bone regeneration while repairing the defects at the same time has become a challenge for clinicians and researchers. Strontium (Sr) is a trace element required by the human body, which mainly exists in human bones. Due to its unique dual properties of promoting the proliferation and differentiation of osteoblasts and inhibiting osteoclast activity, it has attracted extensive research on bone defect repair in recent years. With the deep development of research, the mechanisms of Sr in the process of bone regeneration in the human body have been clarified, and the effects of Sr on osteoblasts, osteoclasts, mesenchymal stem cells (MSCs), and the inflammatory microenvironment in the process of bone regeneration have been widely recognized. Based on the development of technology such as bioengineering, it is possible that Sr can be better loaded onto biomaterials. Even though the clinical application of Sr is currently limited and relevant clinical research still needs to be developed, Sr-composited bone tissue engineering biomaterials have achieved satisfactory results in vitro and in vivo studies. The Sr compound together with biomaterials to promote bone regeneration will be a development direction in the future. This review will present a brief overview of the relevant mechanisms of Sr in the process of bone regeneration and the related latest studies of Sr combined with biomaterials. The aim of this paper is to highlight the potential prospects of Sr functionalized in biomaterials.

Introduction Unresectable hilar cholangiocarcinoma (UHC) is a malignant tumor and has a poor prognosis. IRE is a novel non-thermal ablative therapy that causes cellular apoptosis via electrical impulses. To compare the curative effect for UHC, chemotherapy plus concurrent IRE and chemotherapy alone were set up. Materials and methods From July 2015 to May 2019, 47 patients with UHC were analyzed to chemotherapy + IRE group (n = 23) or chemotherapy alone group (n = 24) in this study. Treatment response was assessed with computed tomography (CT) or magnetic resonance imaging (MRI) 1 month after treatment and every 3 months thereafter. Local tumor progression (LTP), time to LTP, overall survival (OS) and procedure-related complications were compared between the two groups. Results Chemotherapy plus concurrent IRE group showed a tendency toward a decreased rate of LTP (16.7% vs. 39.5%; p = 0.039) and an increased complete response rate (52.2% vs. 12.5%; p = 0.011) compared with chemotherapy alone group. Time to LTP was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (11.2 months vs. 4.2 months; p = 0.001). Median OS was significantly longer in the chemotherapy plus concurrent IRE group compared to chemotherapy alone group (19.6 months vs. 10.2 months; p = 0.001). Conclusions Chemotherapy plus concurrent IRE improved local control and prolonged time to LTP and OS in patients with UHC.

Degenerative disc disease (DDD) is a pathological condition associated with intervertebral discs (IVDs) that causes chronic back pain. IVD degeneration has become a significant issue in contemporary society. To date, numerous biological therapies have been applied to alleviate the progression of DDD, among which therapeutic protein injection is the most direct and convenient. However, there are some limitations to applying direct protein injection therapy, the most significant being that the efficacy of this method has a short duration, which is a major factor in its effectiveness and the resulting patient satisfaction. How do we solve this problem? Or how can the effectiveness of the treatment be enhanced? It has been proved that manganese dioxide (MnO2) microspheres, widely used in environmental science, not only regulate the expression of cell genes and cytokines in the microenvironment, but also have the ability to release drugs slowly. We propose that direct injection of protein encapsulated in hollow MnO2 (h-MnO2) microspheres could solve the problem of rapid drug release. In addition, the use of a MnO2 and protein injection in the treatment of DDD may have a synergistic effect, which would be highly significant for the degradation of pro-inflammatory factors in the DDD microenvironment. Therefore, the combination of MnO2 and protein may provide a new therapeutic approach to alleviate the progression of DDD.

Abstract Background With respect to spinal surgeries, elucidating absolute and relative amount of hidden blood loss (HBL) is of great importance in order to avoid aforementioned potential complications. To evaluate HBL and its possible risk factors among patients undergoing minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) for lumbar degenerative diseases. Methods Between June 2018 and March 2019, 137 consecutive patients with lumbar degenerative disease, who underwent operation with MIS-TLIF technique, were enrolled in this study. The patient’s demographic characteristics and blood loss-related parameters were collected, respectively. The Pearson or Spearman correlation analysis was used to investigate an association between patient’s characteristics and HBL. Multivariate linear regression analysis was used to confirm independent risk factors of HBL. Results A total of 137 patients (86 males and 51 females, age range 19–78 years) were reviewed in our hospital. A substantial amount of HBL (488.4 ± 294.0 ml, 52.5% of TBL) occurred after MIS-TLIF. Multivariate linear regression showed that the age, muscle thickness, the Patients’ Society of Anesthesiologists (ASA) classification, patient’s blood volume (PBV), total blood loss (TBL), postoperative (i.e., day 2 or 3) hematocrit (Hct), Hct loss, and fibrinogen level were independent risk factors for HBL (P1 = 0.000, P2 = 0.002, P3 = 0.006, P4 = 0.002, P5 = 0.003, P6 = 0.048, P7 = 0.004, P8 = 0.000). Conclusion A large amount of HBL was incurred in patients undergoing MIS-TLIF. More importantly, the age, muscle thickness, ASA classification, PBV, TBL, postoperative Hct, Hct loss, and fibrinogen level were independent risk factors for HBL in MIS-TLIF. HBL and its risk factors should be paid more attention to during the perioperative period.

Abstract Background Accumulating evidence has proved the significant influence of long non-coding RNAs (lncRNAs) in cancer formation and development, including PCa. Methods The role of LINC00689 in PCa was confirmed by RT-qPCR, MTT, colony formation, flow cytometry, western blot and transwell assays. Besides, the binding ability between LINC00689 and miR-496 was validated by using luciferase reporter assay. Then RT-qPCR, RIP and luciferase reporter and western blot assays were employed to verify the interactions among LINC00689, miR-496 and CTNNB1. Furthermore, the rescuing role of CTNNB1 in Wnt pathway was proved by RT-qPCR, TOP/FOP Flash and western blot assays. Results LINC00689 was upregulated in PCa tissues and cells as well as at the terminal stage. Further, knock down of LINC00689 repressed PCa cell proliferation, migration and invasion, and initiated PCa cell apoptosis. Additionally, miR-496 inhibitor and pcDNA3.1/CTNNB1 could neutralize the prohibitive effects of LINC00689 silencing on cell proliferation, migration and invasion, meanwhile, could offset the encouraging role of knocking down LINC00689 in cell apoptosis. Moreover, CTNNB1 upregulation exerted redemptive function in Wnt pathway inhibited by LINC00689 depletion. Conclusions To sum up, LINC00689 promotes PCa progression via regulating miR-496/CTNNB1 to activate Wnt pathway, which may contribute to research about new targets for PCa treatment.

Abstract Background Facet orientation (FO) and facet tropism (FT) are two important structural parameters of lumbar facet joint. The purpose of this study was to evaluate the association between facet joint parameters and chronic low back pain (LBP). Methods From June 2017 to January 2019, a total of 542 cases were enrolled in this study. There were 237 males and 305 females with a mean age of 35.8 years (range 18~59 years). All the cases were divided into a LBP group (LBP group) and a non-LBP group (N-LBP group) in this study. We compared their clinical parameters and facet joint parameters between two groups. Results The LBP group was composed of 190 male and 252 female, whose ages ranged from 17 to 59 years (35.6 ±7.9 y). The N- LBP group was composed of 47 male and 53 female, whose ages ranged from 18 to 59 years (35.9 ± 7.5 y). Of these parameters, BMI (P = 0.008) and FT (P = 0.003) at all three levels were found to be significantly associated with incidence of chronic LBP (P < 0.05), but FO were only found to be significant at L3-L4 level and L5-S1 level (P < 0.05). Logistic regression analysis showed that high BMI and large FT were significant risk factors for chronic LBP (P < 0.05), and FT were found to might be independent risk factors for chronic LBP. Conclusion FT may play a more important role in the pathogenesis of chronic LBP.

Intervertebral disc degeneration is the main cause of low back pain. Traditional treatment methods cannot repair degenerated intervertebral disc tissue. The emergence of stem cell therapy makes it possible to regenerate and repair degenerated intervertebral disc tissue. At present, mesenchymal stem cells are the most studied, and different types of mesenchymal stem cells have their own characteristics. However, due to the harsh and complex internal microenvironment of the intervertebral disc, it will affect the biological behaviors of the implanted mesenchymal stem cells, such as viability, proliferation, migration, and chondrogenic differentiation, thereby affecting the therapeutic effect. This review is aimed at summarizing the influence of each intervertebral disc microenvironmental factor on the biological behavior of mesenchymal stem cells, so as to provide new ideas for using tissue engineering technology to assist stem cells to overcome the influence of the microenvironment in the future.

As eukaryotes, plants and animals have many commonalities on the genetic level, although they differ greatly in appearance and physiological habits. The primary goal of current plant research is to improve the crop yield and quality. However, plant research has a wider aim, exploiting the evolutionary conservatism similarities between plants and animals, and applying discoveries in the field of botany to promote zoological research that will ultimately serve human health, although very few studies have addressed this aspect. Here, we analyzed 35 human-disease-related gene orthologs in plants and characterized the genes in depth. Thirty-four homologous genes were found to be present in the herbaceous annual plant Arabidopsis thaliana and the woody perennial plant Populus trichocarpa, with most of the genes having more than two exons, including the ATM gene with 78 exons. More surprisingly, 27 (79.4%) of the 34 homologous genes in Arabidopsis were found to be senescence-associated genes (SAGs), further suggesting a close relationship between human diseases and cellular senescence. Protein–protein interaction network analysis revealed that the 34 genes formed two main subnetworks, and genes in the first subnetwork interacted with 15 SAGs. In conclusion, our results show that most of the 34 homologs of human-disease-associated genes in plants are involved in the leaf senescence process, suggesting that leaf senescence may offer a means to study the pathogenesis of human diseases and to screen drugs for the treat of diseases.

Leaf senescence is the last stage of leaf development and is an orderly biological process accompanied by degradation of macromolecules and nutrient recycling, which contributes to plant fitness. Forward genetic mutant screening and reverse genetic studies of senescence-associated genes (SAGs) have revealed that leaf senescence is a genetically regulated process, and the initiation and progression of leaf senescence are influenced by an array of internal and external factors. Recently, multi-omics techniques have revealed that leaf senescence is subjected to multiple layers of regulation, including chromatin, transcriptional and post-transcriptional, as well as translational and post-translational levels. Although impressive progress has been made in plant senescence research, especially the identification and functional analysis of a large number of SAGs in crop plants, we still have not unraveled the mystery of plant senescence, and there are some urgent scientific questions in this field, such as when plant senescence is initiated and how senescence signals are transmitted. This paper reviews recent advances in the multiple layers of regulation on leaf senescence, especially in post-transcriptional regulation such as alternative splicing.

Mesophyll protoplasts freshly isolated from leaves are a useful research system in plants. However, cell walls in woody plants contain more pectin, making mesophyll protoplasts isolation difficult in Populus. This has limited their application in biochemical, molecular, cellular, genetic, genomic, transcriptomic, and proteomic assays. In this protocol, a simple and efficient method to prepare and transfect mesophyll protoplasts of Populus tomentosa is presented in detail. Leaves of P. tomentosa plants grown in tissue culture media were pre-treated in D-mannitol solution and then digested with an enzyme solution. After washing with W5 and MMg buffers, the protoplasts were incubated in PEG/Ca2+ solution with plasmid for transfection. The mesophyll protoplasts isolated were used to express the histone variant H2B fused with green fluorescent protein (GFP) for confocal microscopy imaging. This “P. tomentosa mesophyll protoplasts preparation and transfection” system provides a useful tool for studying woody plants using a variety of applications, including gene expression, subcellular localization, protein-protein interaction, chromatin immunoprecipitation, western blot, single-cell sequencing, and genome editing.

Homeodomain-containing transcription factors (Htfs) play important roles in animals, fungi, and plants during some developmental processes. Here, a homeodomain-containing transcription factor PoHtf1 was functionally characterized in the cellulase-producing fungi Penicillium oxalicum 114-2. PoHtf1 was shown to participate in colony growth and conidiation through regulating the expression of its downstream transcription factor BrlA, the key regulator of conidiation in P. oxalicum 114-2. Additionally, PoHtf1 inhibited the expression of the major cellulase genes by coordinated regulation of cellulolytic regulators CreA, AmyR, ClrB, and XlnR. Furthermore, transcriptome analysis showed that PoHtf1 participated in the secondary metabolism including the pathway synthesizing conidial yellow pigment. These data show that PoHtf1 mediates the complex transcriptional-regulatory network cascade between developmental processes and cellulolytic gene expression in P. oxalicum 114-2. Our results should assist the development of strategies for the metabolic engineering of mutants for applications in the enzymatic hydrolysis for biochemical production.

Aging, resulting from degenerative changes in cell metabolism, affects fecundity and longevity. To increase lifespan in animals or plants, manipulation in gene modification or pharmacology intervention has been proved to be as feasible approaches. NAD+, spermidine, and rapamycin, as well as genetic editing, bring to light at the tunnel end for the longevity in animals. In plants, the existing evidence suggests that they may share common aging signaling pathway with animals. However, as sessile organisms, plants got to cope with complex environmental changes and evolved specific signaling pathways. Here, we reviewed the latest research advances in plant aging to make a gene network analysis of senescence-associated genes in annual plant and perform a comparative assessment of aging in perennials as well as animals. Keywords: Aging, Leaf senescence, Perennials, Gene network

Leaf senescence is a highly complex genetic process that is finely tuned by multiple layers of regulation. Among them, transcriptional regulation plays a critical role in controlling the initiation and progression of leaf senescence. Here, we found that the NAC transcription factor NAC075 functions as a novel negative regulator of leaf senescence. Loss of function of NAC075 promotes leaf senescence in an age-dependent manner, whereas constitutive overexpression of NAC075 delays senescence in Arabidopsis. Transcriptome analysis revealed that transcript levels of antioxidant enzymes such as catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD) are significantly suppressed in nac075 mutants compared with wild-type plants. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) analyses revealed that NAC075 directly binds the promoter of catalase 2 (CAT2). Moreover, genetic analysis showed that overexpression of CAT2 suppresses the overproduction of reactive oxygen species (ROS) and the early senescence phenotypes of nac075 mutants, suggesting that CAT2 acts downstream of NAC075 to delay leaf senescence by repressing ROS accumulation. Collectively, our findings provide a new regulatory module involving NAC075-CAT2-ROS in controlling leaf senescence in Arabidopsis.

Priming is an adaptive strategy that improves plant defenses against biotic and abiotic stresses. Stimuli from chemicals, abiotic cues, and pathogens can trigger the establishment of priming state. Priming with 5-aminolevulinic acid (ALA), a potential plant growth regulator, can enhance plant tolerance to the subsequent abiotic stresses, including salinity, drought, heat, cold, and UV-B. However, the molecular mechanisms underlying the remarkable effects of ALA priming on plant physiology remain to be elucidated. Here, we summarize recent progress made in the stress tolerance conferred by ALA priming in plants and provide the underlying molecular and physiology mechanisms of this phenomenon. Priming with ALA results in changes at the physiological, transcriptional, metabolic, and epigenetic levels, and enhances photosynthesis and antioxidant capacity, as well as nitrogen assimilation, which in turn increases the resistance of abiotic stresses. However, the signaling pathway of ALA, including receptors as well as key components, is currently unknown, which hinders the deeper understanding of the defense priming caused by ALA. In the future, there is an urgent need to reveal the molecular mechanisms by which ALA regulates plant development and enhances plant defense with the help of forward genetics, multi-omics technologies, as well as genome editing technology.