Standardisation is the key to the sustained, rapid and healthy development of stem cell-based therapy.

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.

Strategies to improve the performance of polyetheretherketone (PEEK) as orthopedic implants: from surface modification to addition of bioactive materials.

Polyetheretherketone (PEEK), as a high-performance polymer, is widely used for bone defect repair due to its homogeneous modulus of elasticity of human bone, good biocompatibility, excellent chemical stability and projectability. However, the highly hydrophobic surface of PEEK is biologically inert, which makes it difficult for cells and proteins to attach, and is accompanied by the development of infections that ultimately lead to failure of PEEK implants. In order to further enhance the potential of PEEK as an orthopedic implant, researchers have explored modification methods such as surface modification by physical and chemical means and the addition of bioactive substances to PEEK-based materials to enhance the mechanical properties, osteogenic activity and antimicrobial properties of PEEK. However, these current modification methods still have obvious shortcomings in terms of cost, maneuverability, stability and cytotoxicity, which still need to be explored by researchers. This paper reviews some of the modification methods that have been used to improve the performance of PEEK over the last three years in anticipation of the need for researchers to design PEEK orthopedic implants that better meet clinical needs.

Leaf Senescence Database v5.0: A Comprehensive Repository for Facilitating Plant Senescence Research.

Through an extensive literature survey, we have upgraded the Leaf Senescence Database (LSD v5.0; https://ngdc.cncb.ac.cn/lsd/), a curated repository of comprehensive senescence-associated genes (SAGs) and their corresponding mutants. Since its inception in 2010, LSD undergoes frequent updates to encompass the latest advances in leaf senescence research and its current version comprises a high-quality collection of 31,740 SAGs and 1,209 mutants from 148 species, which were manually searched based on robust experimental evidence and further categorized according to their functions in leaf senescence. Furthermore, LSD was greatly enriched with comprehensive annotations for the SAGs through meticulous curation using both manual and computational methods. In addition, it was equipped with user-friendly web interfaces that facilitate text queries, BLAST searches, and convenient download of SAG sequences for localized analysis. Users can effortlessly navigate the database to access a plethora of information, including literature references, mutants, phenotypes, multi-omics data, miRNA interactions, homologs in other plants, and cross-links to various databases. Taken together, the upgraded version of LSD stands as the most comprehensive and informative plant senescence-related database to date, incorporating the largest collection of SAGs and thus bearing great utility for a wide range of studies related to plant senescence.

The application of impantable sensors in the musculoskeletal system: a review.

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.

Non-coding RNAs and leaf senescence: Small molecules with important roles.

Non-coding RNAs (ncRNAs) are a special class of functional RNA molecules that are not translated into proteins. ncRNAs have emerged as pivotal regulators of diverse developmental processes in plants. Recent investigations have revealed the association of ncRNAs with the regulation of leaf senescence, a complex and tightly regulated developmental process. However, a comprehensive review of the involvement of ncRNAs in the regulation of leaf senescence is still lacking. This manuscript aims to summarize the molecular mechanisms underlying ncRNAs-mediated leaf senescence and the potential applications of ncRNAs to manipulate the onset and progression of leaf senescence. Various classes of ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are discussed in terms of their regulatory mechanisms in leaf senescence. Furthermore, we explore the interactions between ncRNA and the key regulators of senescence, including transcription factors as well as core components in phytohormone signaling pathways. We also discuss the possible challenges and approaches related to ncRNA-mediated leaf senescence. This review contributes to a further understanding of the intricate regulatory network involving ncRNAs in leaf senescence.

Entecavir versus tenofovir for prevention of hepatitis B virus-associated hepatocellular carcinoma after curative resection: study protocol for a randomized, open-label trial.

BACKGROUND: Entecavir and tenofovir disoproxil fumarate (TDF) are standard first-line treatments to prevent viral reactivation and hepatocellular carcinoma (HCC) in individuals chronically infected with the hepatitis B virus (HBV), but the long-term efficacy of the two drugs remains controversial. Also unclear is whether the drugs are effective at preventing viral reactivation or HCC recurrence after hepatectomy to treat HBV-associated HCC. This trial will compare recurrence-free survival, overall survival, viral indicators and adverse events in the long term between patients with HBV-associated HCC who receive entecavir or TDF after curative resection. METHODS: This study is a randomized, open-label trial. A total of 240 participants will be randomized 1:1 into groups receiving TDF or entecavir monotherapy. The two groups will be compared in terms of recurrence-free and overall survival at 1, 3, and 5 years after surgery; adverse events; virological response; rate of alanine transaminase normalization; and seroreactivity at 24 and 48 weeks after surgery. DISCUSSION: This study will compare long-term survival between patients with HBV-associated HCC who receive TDF or entecavir monotherapy. Numerous outcomes related to prognosis will be analyzed and compared in this study. TRIAL REGISTRATION: ClinicalTrials.gov NCT02650271. Registered on January 7, 2016.

Hot versus cold subduction initiation.

Initiation of a new subduction zone could act in two different ways, forming either a hot or cold incipient subduction channel with contrasting geological records.

Percutaneous radiofrequency ablation and endoscopic neurotomy for lumbar facet joint syndrome: are they good enough?

OBJECTIVE: Lumbar facet joint (LFJ) syndrome is one of the common causes of low back pain (LBP). There are different views on percutaneous and endoscopic radiofrequency. The purpose of this systematic review and meta-analysis is to explore the therapeutic effect of radiofrequency ablation on LBP originating from LFJ and compare the therapeutic effect of percutaneous radiofrequency ablation and endoscopic neurotomy. METHODS: We included randomized controlled trials which compared the efficiency of percutaneous radiofrequency ablation and conservative treatment (sham procedures, facet joint injection, physiotherapy, exercise, or oral medication) or compared the efficiency of percutaneous radiofrequency ablation and endoscopic neurotomy for LFJ syndrome. We searched in PubMed and Web of Science from inception to March 27, 2023. Meta-analysis was performed using RevMan 5.4 software. RESULTS: A total of 11 randomized controlled trials were included. Among them, nine studies were used for evaluating efficiency of percutaneous radiofrequency ablation, and two studies were used for evaluating efficiency of endoscopic neurotomy. Pooled data from two studies reporting outcomes at 1 year did not show a benefit from facet joint denervation by comparing the percutaneous radiofrequency ablation and conservative treatment (standardized mean difference (SMD) = -0.87, 95% confidence interval (CI) [-2.10, 0.37], P = 0.17). There was no significant difference between percutaneous radiofrequency ablation and endoscopic neurotomy at 1-month follow-up (mean difference (MD) = -0.13, 95%CI [-0.18, -0.44], P = 0.41). At 12-month follow-up the pain relief in the endoscopic neurotomy was significantly better than that in the percutaneous radiofrequency ablation group (MD = 1.98, 95%CI [1.60, 2.36], P < 0 .0001). CONCLUSION: The LBP was significantly relieved shortly after percutaneous radiofrequency ablation. Compared with percutaneous radiofrequency ablation, endoscopic neurotomy seems to have a longer effect. A longer follow-up period is needed to confirm its effectiveness.

Functional Study of cAMP-Dependent Protein Kinase A in Penicillium oxalicum.

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.

Incidence and risk factors of surgical site infection following cervical laminoplasty: A retrospective clinical study.

There are many debates regarding the risk factors of surgical site infection (SSI) following posterior cervical surgery in previous studies. And, till now there is no such a study to examine cervical laminoplasty surgery. From January 2011 through October 2021, a total of 405 patients who were treated with unilateral open-door laminoplasty surgeries were enrolled in this study. We divided the patients into the SSI group and the non-SSI group and compared their patient-specific and procedure-specific factors. Univariate and multiple logistic regression analysis were performed to determine the risk factors. Of the 405 patients, 20 patients had SSI. The rate of SSI found to be 4.93%. There were significant differences between groups in the thicker subcutaneous fat thickness (FT) (p < 0.001), the higher ratio of subcutaneous FT to muscle thickness (MT) (p < 0.001), the higher preoperative Japanese Orthopaedic Association (JOA) Scores (p < 0.003), the decreased preoperative serum albumin (p < 0.001), the more postoperative drainage (p < 0.05) and the longer time of draining (p < 0.001). Logistic regression analysis of these differences showed that the higher ratio of subcutaneous FT/MT, the higher preoperative JOA scores, the decreased preoperative serum albumin and the longer time of draining were significantly related to SSI (p < 0.05). The higher ratio of subcutaneous FT/MT, the higher preoperative JOA scores, the decreased preoperative serum albumin and the longer time of draining are identified as the independent risk factors of SSI in cervical laminoplasty. Identification of these risk factors could be useful in reducing the SSI incidence and patients counselling.

Can extracellular vesicles be considered as a potential frontier in the treatment of intervertebral disc disease?

As a global public health problem, low back pain (LBP) caused by intervertebral disc degeneration (IDD) seriously affects patients' quality of life. In addition, the prevalence of IDD tends to be younger, which brings a huge burden to individuals and society economically. Current treatments do not delay or reverse the progression of IDD. The emergence of biologic therapies has brought new hope for the treatment of IDD. Among them, extracellular vesicles (EVs), as nanoscale bioactive substances that mediate cellular communication, have now produced many surprising results in the research of the treatment of IDD. This article reviews the mechanisms and roles of EVs in delaying IDD and describes the prospects and challenges of EVs.

3D printing metal implants in orthopedic surgery: Methods, applications and future prospects.

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.

The association between morphological characteristics of paraspinal muscle and spinal disorders.

BACKGROUND: 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.

Irreversible electroporation combined with chemotherapy and PD-1/PD-L1 blockade enhanced antitumor immunity for locally advanced pancreatic cancer.

Background: Irreversible 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. Methods: A 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. Results: A 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. Conclusion: The addition of PD-1/PD-L1 blockade to the regimen of IRE combined with chemotherapy enhanced antitumor immunity and extended survival in LAPC patients.

Low-temperature deposition manufacturing technology: a novel 3D printing method for bone scaffolds.

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.

Spliceosomal protein U2B″ delays leaf senescence by enhancing splicing variant JAZ9ß expression to attenuate jasmonate signaling in Arabidopsis.

The regulatory framework of leaf senescence is gradually becoming clearer; however, the fine regulation of this process remains largely unknown. Here, genetic analysis revealed that U2 small nuclear ribonucleoprotein B (U2B″), a component of the spliceosome, is a negative regulator of leaf senescence. Mutation of U2B″ led to precocious leaf senescence, whereas overexpression of U2B″ extended leaf longevity. Transcriptome analysis revealed that the jasmonic acid (JA) signaling pathway was activated in the u2b″ mutant. U2B″ enhances the generation of splicing variant JASMONATE ZIM-DOMAIN 9ß (JAZ9ß) with an intron retention in the Jas motif, which compromises its interaction with CORONATINE INSENSITIVE1 and thus enhances the stability of JAZ9ß protein. Moreover, JAZ9ß could interact with MYC2 and obstruct its activity, thereby attenuating JA signaling. Correspondingly, overexpression of JAZ9ß rescued the early senescence phenotype of the u2b″ mutant. Furthermore, JA treatment promoted expression of U2B″ that was found to be a direct target of MYC2. Overexpression of MYC2 in the u2b″ mutant resulted in a more pronounced premature senescence than that in wild-type plants. Collectively, our findings reveal that the spliceosomal protein U2B″ fine-tunes leaf senescence by enhancing the expression of JAZ9ß and thereby attenuating JA signaling.

Identification of testicular cancer immune infiltrates and novel immune cell subtypes.

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 < 0.001). We validated the six-immDEGs risk signature in pure seminoma and mixed TGCT types. Two distinct immune patterns (Cluster 1 and Cluster 2) were identified using the consensusclusterplus, and Cluster 1 possessed an unfavorable OS compared with Cluster 2 (hazard ratio, 2.56; P < 0.001). Cluster 1 patients had significantly lower naive B cells, memory B cells, plasma cells, naive CD4 T cells, gamma delta T cells, and activated dendritic cells than Cluster 2 patients. Genes relating to the WNT signaling pathway, TGF-ß signaling pathway, antigen processing and presentation, and NK cell-mediated cytotoxicity were associated with TGCT. STC1 was elevated in TGCT tissues, and its high expression showed advanced clinicopathological characteristics and poor prognosis of TGCT. Our findings may contribute to an increased understanding of the onset and progression of TGCT.

Umbilical cord mesenchymal stem cells for regenerative treatment of intervertebral disc degeneration.

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.

Abiotic Stress-Induced Leaf Senescence: Regulatory Mechanisms and Application.

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.