The current status of various preclinical therapeutic approaches for tendon repair.

Tendons are fibroblastic structures that link muscle and bone. There are two kinds of tendon injuries, including acute and chronic. Each form of injury or deterioration can result in significant pain and loss of tendon function. The recovery of tendon damage is a complex and time-consuming recovery process. Depending on the anatomical location of the tendon tissue, the clinical outcomes are not the same. The healing of the wound process is divided into three stages that overlap: inflammation, proliferation, and tissue remodeling. Furthermore, the curing tendon has a high re-tear rate. Faced with the challenges, tendon injury management is still a clinical issue that must be resolved as soon as possible. Several newer directions and breakthroughs in tendon recovery have emerged in recent years. This article describes tendon injury and summarizes recent advances in tendon recovery, along with stem cell therapy, gene therapy, Platelet-rich plasma remedy, growth factors, drug treatment, and tissue engineering. Despite the recent fast-growing research in tendon recovery treatment, still, none of them translated to the clinical setting. This review provides a detailed overview of tendon injuries and potential preclinical approaches for treating tendon injuries.

MLLT6/ATF2 axis restrains breast cancer progression by driving DDIT3/4 expression.

Epigenetic deregulation is strongly associated with tumour progression. The identification of natural tumour suppressors to overcome cancer metastasis is urgent for cancer therapy. We investigate whether myeloid/lymphoid or mixed-lineage leukaemia translocated (MLLT) family members contribute to breast cancer progression and found that high MLLT6 expression predicted a better prognosis and that gradually decreased MLLT6 expression was accompanied by breast cancer malignancy. MLLT6 was downregulated by hypoxia-induced enrichment of DNMT1 at the MLLT6 promoter. The results of in vitro functional experiments indicated that MLLT6 depletion promoted colony formation and cell migration, probably by hampering apoptosis. RNA profiling revealed that the apoptotic pathway was downregulated following stable knockdown of MLLT6. DNA damage-inducible transcript 3/4 (DDIT3/4) were among the top 10 downregulated genes and may have expression patterns similar to that of MLLT6. Restoring DDIT3/4 expression in cells with MLLT6 depletion blocked colony formation and cell migration and attenuated the successful colonization of breast cancer cells in vivo. We also determined that the transcription factor activating transcription factor 2 (ATF2) is a binding partner of MLLT6 and participates in the MLLT6/ATF2 axis, which was reinforced by inhibition of AKT signalling, in turn inducing DDIT3/4 expression by establishing an active chromatin structure at the DDIT3/4 gene promoters. Because MLLT6 promotes breast cancer cell apoptosis by inducing DDIT3/4 expression during metastasis, it could be a novel tumour suppressor. Implications: Control of MLLT6 expression via inhibition of PI3K/AKT kinase activity is a potential therapeutic approach for the management of metastatic breast cancer.

Biochar dose-dependent impacts on soil bacterial and fungal diversity across the globe.

Biochar, a widely used material for soil amendment, has been found to offer numerous advantages in improving soil properties and the habitats for soil microorganisms. However, there is still a lack of global perspectives on the influence of various levels of biochar addition on soil microbial diversity and primary components. Thus, in our study, we performed a global meta-analysis of studies to determine how different doses of biochar affect soil total carbon (C), nitrogen (N), pH, alpha- and beta-diversity, and the major phyla of both bacterial and fungal communities. Our results revealed that biochar significantly increased soil pH by 4 %, soil total C and N by 68 % and 22 %, respectively, in which the positive effects increased with biochar doses. Moreover, biochar promoted soil bacterial richness and evenness by 3-8 % at the biochar concentrations of 1-5 % (w/w), while dramatically shifting bacterial beta-diversity at the doses of >2 % (w/w). Specifically, biochar exhibited significantly positive effects on bacterial phyla of Acidobacteria, Bacteroidetes, Gemmatimonadetes, and Proteobacteria, especially Deltaproteobacteria and Gammaproteobacteria, by 4-10 % depending on the concentrations. On the contrary, the bacterial phylum of Verrucomicrobia and fungal phylum of Basidiomycota showed significant negative responses to biochar by -8 % and -24 %, respectively. Therefore, our meta-analysis provides theoretical support for the development of optimized agricultural management practices by emphasizing biochar application dosing.

Manganese Dioxide-Based Nanomaterials for Medical Applications.

Manganese dioxide (MnO2) nanomaterials can react with trace hydrogen peroxide (H2O2) to produce paramagnetic manganese (Mn2+) and oxygen (O2), which can be used for magnetic resonance imaging and alleviate the hypoxic environment of tumors, respectively. MnO2 nanomaterials also can oxidize glutathione (GSH) to produce oxidized glutathione (GSSG) to break the balance of intracellular redox reactions. As a consequence of the sensitivity of the tumor microenvironment to MnO2-based nanomaterials, these materials can be used as multifunctional diagnostic and therapeutic platforms for tumor imaging and treatment. Importantly, when MnO2 nanomaterials are implanted along with other therapeutics, synergetic tumor therapy can be achieved. In addition to tumor treatment, MnO2-based nanomaterials display promising prospects for tissue repair, organ protection, and the treatment of other diseases. Herein, we provide a thorough review of recent progress in the use of MnO2-based nanomaterials for biomedical applications, which may be helpful for the design and clinical translation of next-generation MnO2 nanomaterials.

Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis.

Preventing and treating avascular necrosis at the distal end of the flaps are critical to surgery success, but current treatments are not ideal. A recent study shows that apoptotic bodies (ABs) generated near the site of apoptosis can be taken up and promote cell proliferation. The study reveals that ABs derived from fibroblast-like cells in the subcutaneous connective tissue (FSCT cells) of skin flaps promoted ischaemic flap survival. It is also found that ABs inhibited cell death and oxidative stress and promoted M1-to-M2 polarization in macrophages. Transcriptome sequencing and protein level testing demonstrated that ABs promoted ischaemic flap survival in endothelial cells and macrophages by inhibiting ferroptosis via the KEAP1-Nrf2 axis. Furthermore, microRNA (miR) sequencing data and in vitro and in vivo experiments demonstrated that ABs inhibited KEAP1 by delivering miR-339-5p to exert therapeutic effects. In conclusion, FSCT cell-derived ABs inhibited ferroptosis, promoted the macrophage M1-to-M2 transition via the miR-339-5p/KEAP1/Nrf2 axis and promoted ischaemic flap survival. These results provide a potential therapeutic strategy to promote ischaemic flap survival by administering ABs.

Current developments and future perspectives of nanotechnology in orthopedic implants: an updated review.

Orthopedic implants are the most commonly used fracture fixation devices for facilitating the growth and development of incipient bone and treating bone diseases and defects. However, most orthopedic implants suffer from various drawbacks and complications, including bacterial adhesion, poor cell proliferation, and limited resistance to corrosion. One of the major drawbacks of currently available orthopedic implants is their inadequate osseointegration at the tissue-implant interface. This leads to loosening as a result of immunological rejection, wear debris formation, low mechanical fixation, and implant-related infections. Nanotechnology holds the promise to offer a wide range of innovative technologies for use in translational orthopedic research. Nanomaterials have great potential for use in orthopedic applications due to their exceptional tribological qualities, high resistance to wear and tear, ability to maintain drug release, capacity for osseointegration, and capability to regenerate tissue. Furthermore, nanostructured materials possess the ability to mimic the features and hierarchical structure of native bones. They facilitate cell proliferation, decrease the rate of infection, and prevent biofilm formation, among other diverse functions. The emergence of nanostructured polymers, metals, ceramics, and carbon materials has enabled novel approaches in orthopaedic research. This review provides a concise overview of nanotechnology-based biomaterials utilized in orthopedics, encompassing metallic and nonmetallic nanomaterials. A further overview is provided regarding the biomedical applications of nanotechnology-based biomaterials, including their application in orthopedics for drug delivery systems and bone tissue engineering to facilitate scaffold preparation, surface modification of implantable materials to improve their osteointegration properties, and treatment of musculoskeletal infections. Hence, this review article offers a contemporary overview of the current applications of nanotechnology in orthopedic implants and bone tissue engineering, as well as its prospective future applications.

Simulated in vitro infant digestion and lipidomic analysis to explore how the milk fat globule membrane modulates fat digestion.

We hypothesized that the addition of milk fat globule membranes (MFGMs) to infant formula would improve its lipolysis, making it more similar to human milk (HM) and superior to commercial infant formula (CIF) in fat digestion. Therefore, we prepared two model infant formulas (MIFs) by adding MFGMs to dairy ingredients in different ways and compared their fat digestion behavior with those of HM and CIF. MFGMs were added alone (MIF1) and with other milk-based materials (MIF2) before homogenization. The addition of MFGMs reduced the flocculation of lipids and proteins in the gastric phase and promoted lipolysis in the intestine phase. The amount of free fatty acids released followed the order of HM > MIF1 > CIF ≥ MIF2. After digestion, the number of different glyceride species between each sample and HM reached 64 (MIF1), 73 (MIF2), 67 (CIF1), and 72 (CIF2). In conclusion, the fat digestion of MIF1 had the highest similarity with HM.

Assessment of the methodological, recommendation and reporting quality of global guidelines for neck pain and synthesis of evidence and recommendations: a systematic review protocol.

INTRODUCTION: Neck pain is a global health problem that can cause severe disability and a huge medical burden. Clinical practice guideline (CPG) is an important basis for clinical diagnosis and treatment. A high-quality CPG plays a significant role in clinical practice. However, the quality of the CPGs for neck pain lacks comprehensive assessment. This protocol aims to evaluate the methodological, recommendation, reporting quality of global CPGs for neck pain and identify key recommendations and gaps that limit evidence-based practice. METHOD: CPGs from January 2013 to November 2023 will be identified through a systematic search on 13 scientific databases (PubMed, Cochrane Library, Embase, etc) and 7 online guideline repositories. Six reviewers will independently evaluate the quality of CPGs for neck pain by using the Appraisal of Guidelines for Research and Evaluation, the Appraisal of Guidelines Research and Evaluation-Recommendations Excellence and the Reporting Items for Practice Guidelines in Healthcare tools. Intraclass correlation coefficient will be used to test the consistency of the assessment. We will identify the distribution of evidence and recommendations in each evidence-based CPGs for neck pain and regrade the level of evidence and strength of recommendations by adopting the commonly used Grading of Recommendations, Assessment, Development and Evaluations system. The key recommendations based on high-quality evidence will be summarised. In addition, we will categorise CPGs by different characteristics and conduct a subgroup analysis of the results of assessment. ETHICS AND DISSEMINATION: No subjects will be involved in this systematic review, so there is no need for ethical approval. The finding of this review will be summarised as a paper for publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023417717.

GeSe ovonic threshold switch: the impact of functional layer thickness and device size.

Three-dimensional phase change memory (3D PCM), possessing fast-speed, high-density and nonvolatility, has been successfully commercialized as storage class memory. A complete PCM device is composed of a memory cell and an associated ovonic threshold switch (OTS) device, which effectively resolves the leakage current issue in the crossbar array. The OTS materials are chalcogenide glasses consisting of chalcogens such as Te, Se and S as central elements, represented by GeTe6, GeSe and GeS. Among them, GeSe-based OTS materials are widely utilized in commercial 3D PCM, their scalability, however, has not been thoroughly investigated. Here, we explore the miniaturization of GeSe OTS selector, including functional layer thickness scalability and device size scalability. The threshold switching voltage of the GeSe OTS device almost lineally decreases with the thinning of the thickness, whereas it hardly changes with the device size. This indicates that the threshold switching behavior is triggered by the electric field, and the threshold switching field of the GeSe OTS selector is approximately 105 V/µm, regardless of the change in film thickness or device size. Systematically analyzing the threshold switching field of Ge-S and Ge-Te OTSs, we find that the threshold switching field of the OTS device is larger than 75 V/µm, significantly higher than PCM devices (8.1-56 V/µm), such as traditional Ge2Sb2Te5, Ag-In-Sb-Te, etc. Moreover, the required electric field is highly correlated with the optical bandgap. Our findings not only serve to optimize GeSe-based OTS device, but also may pave the approach for exploring OTS materials in chalcogenide alloys.

Effects of reverse osmosis membrane replacement of pure water system on clinical chemistry and immunoassay in clinical laboratory.

Introduction: Reverse osmosis (RO) membrane, key component of water-purifying equipment, is often stored in protection fluid containing substances such as glycerol, which may contaminate the water at replacement. This study aims to explore the effects of RO membrane replacement on clinical chemistry and immunoassay, particularly triglyceride (TG), providing reference for managing test interference caused by RO membrane replacement. Materials and methods: The RO membrane of water-purifying equipment A, which provided water to C16000 biochemistry analyzer (Abbott Laboratories, Abbott Park, USA) and E801 electrochemiluminescence analyzer (Roche, Basel, Switzerland), was replaced. Water resistivity was recorded, and quality control (QC) tests were performed on C16000 and E801. Moreover, TG was measured in 29 of selected serum samples on C16000 at 0.5h and 10.5h after RO membrane replacement and on reference biochemistry analyzer BS2000M (Mindray Biomedical Electronics Co., Shenzhen, China), which was connected to water-purifying equipment B without RO membrane replacement. Finally, blank, calibrator 1 and calibrator 2 of TG reagent were measured on C16000 before and at 0.5h, 2.5h and 10.5h after RO membrane replacement. All statistical analyses of data were done using GraphPad Prism (GraphPad Software Inc., San Diego, USA), and a value of P < 0.05 was considered statistically significant. Results: After RO membrane replacement, all QC results of clinical chemistry and immune tests passed except TG that showed positive bias of 536% and 371% at two levels, respectively. Moreover, TG results of the same serum samples were significantly higher at 0.5h than 10.5h after RO membrane replacement. Meanwhile, there was worse agreement and correlation of TG results between C16000 and BS2000M at 0.5h than 10.5h after replacement. Furthermore, the absorbance of TG blank, calibrator 1 and calibrator 2 was significantly higher at 0.5h and 2.5h after replacement than before replacement, and the absorbance gradually returned to normal value at 10.5h after replacement. Conclusions: Replacement of RO membrane could cause significant interference to TG test while have no effects on other laboratory tests performed in the study, which may be due to glycerol contamination. Our data provides important reference for management of test interference caused by RO membrane replacement. Clinical laboratory should observe the effects of RO membrane replacement on laboratory tests through both water quality monitoring and QC detection.

Current advancements in therapeutic approaches in orthopedic surgery: a review of recent trends.

Recent advancements in orthopedic surgery have greatly improved the management of musculoskeletal disorders and injuries. This review discusses the latest therapeutic approaches that have emerged in orthopedics. We examine the use of regenerative medicine, including stem cell therapy and platelet-rich plasma (PRP) injections, to accelerate healing and promote tissue regeneration. Additionally, we explore the application of robotic-assisted surgery, which provides greater precision and accuracy during surgical procedures. We also delve into the emergence of personalized medicine, which tailors treatments to individual patients based on their unique genetic and environmental factors. Furthermore, we discuss telemedicine and remote patient monitoring as methods for improving patient outcomes and reducing healthcare costs. Finally, we examine the growing interest in using artificial intelligence and machine learning in orthopedics, particularly in diagnosis and treatment planning. Overall, these advancements in therapeutic approaches have significantly improved patient outcomes, reduced recovery times, and enhanced the overall quality of care in orthopedic surgery.

Comamonas endophytica sp. nov., a novel indole acetic acid producing endophyte isolated from bamboo in China.

Two novel indole acetic acid-producing strains, 5MLIRT and D4N7, were isolated from Indosasa shibataeoides in Yongzhou, Hunan province, and Phyllostachys edulis in Hangzhou, Zhejiang province, respectively. Based on their 16S rRNA sequences, strains 5MLIRT and D4N7 were closely related to Comamonas antarcticus 16-35-5T (98.4 % sequence similarity), and the results of 92-core gene phylogenetic trees showed that strains 5MLIRT and D4N7 formed a phylogenetic lineage within the clade comprising Comamonas species. The complete genome size of strain 5MLIRT was 4.49 Mb including two plasmids, and the DNA G+C content was 66.5 mol%. The draft genome of strain D4N7 was 4.26 Mb with 66.7 mol% G+C content. The average nucleotide identity and digital DNA-DNA hybridization values among strain 5MLIRT and species in the genus Comamonas were all below the species delineation threshold. The colonies of strain 5MLIRT and D4N7 were circular with regular margins, convex, pale yellow and 1.0-2.0 mm in diameter when incubated at 30 °C for 3 days. Strains 5MLIRT and D4N7 grew optimally at 30 °C, pH 7.0 and 1.0 % NaCl. The respiratory isoprenoid quinone was ubiquinone-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Polyphasic analyses indicated that strains 5MLIRT and D4N7 could be distinguished from related validly named Comamonas species and represent a novel species of the genus Comamonas, for which the name Comamonas endophytica sp. nov. is proposed. The type strain is 5MLIRT (=ACCC 62069T=GDMCC 1.2958T=JCM 35331T).

Oxygen generating biomaterials at the forefront of regenerative medicine: advances in bone regeneration.

Globally, an annual count of more than two million bone transplants is conducted, with conventional treatments, including metallic implants and bone grafts, exhibiting certain limitations. In recent years, there have been significant advancements in the field of bone regeneration. Oxygen tension regulates cellular behavior, which in turn affects tissue regeneration through metabolic programming. Biomaterials with oxygen release capabilities enhance therapeutic effectiveness and reduce tissue damage from hypoxia. However, precise control over oxygen release is a significant technical challenge, despite its potential to support cellular viability and differentiation. The matrices often used to repair large-size bone defects do not supply enough oxygen to the stem cells being used in the regeneration process. Hypoxia-induced necrosis primarily occurs in the central regions of large matrices due to inadequate provision of oxygen and nutrients by the surrounding vasculature of the host tissues. Oxygen generating biomaterials (OGBs) are becoming increasingly significant in enhancing our capacity to facilitate the bone regeneration, thereby addressing the challenges posed by hypoxia or inadequate vascularization. Herein, we discussed the key role of oxygen in bone regeneration, various oxygen source materials and their mechanism of oxygen release, the fabrication techniques employed for oxygen-releasing matrices, and novel emerging approaches for oxygen delivery that hold promise for their potential application in the field of bone regeneration.

Nanotechnology-based bone regeneration in orthopedics: a review of recent trends.

Nanotechnology has revolutionized the field of bone regeneration, offering innovative solutions to address the challenges associated with conventional therapies. This comprehensive review explores the diverse landscape of nanomaterials - including nanoparticles, nanocomposites and nanofibers - tailored for bone tissue engineering. We delve into the intricate design principles, structural mimicry of native bone and the crucial role of biomaterial selection, encompassing bioceramics, polymers, metals and their hybrids. Furthermore, we analyze the interface between cells and nanostructured materials and their pivotal role in engineering and regenerating bone tissue. In the concluding outlook, we highlight emerging frontiers and potential research directions in harnessing nanomaterials for bone regeneration.

Depth- and curvature-based quantitative susceptibility mapping analyses of cortical iron in Alzheimer's disease.

In addition to amyloid beta plaques and neurofibrillary tangles, Alzheimer's disease (AD) has been associated with elevated iron in deep gray matter nuclei using quantitative susceptibility mapping (QSM). However, only a few studies have examined cortical iron, using more macroscopic approaches that cannot assess layer-specific differences. Here, we conducted column-based QSM analyses to assess whether AD-related increases in cortical iron vary in relation to layer-specific differences in the type and density of neurons. We obtained global and regional measures of positive (iron) and negative (myelin, protein aggregation) susceptibility from 22 adults with AD and 22 demographically matched healthy controls. Depth-wise analyses indicated that global susceptibility increased from the pial surface to the gray/white matter boundary, with a larger slope for positive susceptibility in the left hemisphere for adults with AD than controls. Curvature-based analyses indicated larger global susceptibility for adults with AD versus controls; the right hemisphere versus left; and gyri versus sulci. Region-of-interest analyses identified similar depth- and curvature-specific group differences, especially for temporo-parietal regions. Finding that iron accumulates in a topographically heterogenous manner across the cortical mantle may help explain the profound cognitive deterioration that differentiates AD from the slowing of general motor processes in healthy aging.

A snake cathelicidin enhances transcription factor EB-mediated autophagy and alleviates ROS-induced pyroptosis after ischaemia-reperfusion injury of island skin flaps.

BACKGROUND AND PURPOSE: Ischaemia-reperfusion (I/R) injury is a major contributor to skin flap necrosis, which presents a challenge in achieving satisfactory therapeutic outcomes. Previous studies showed that cathelicidin-BF (BF-30) protects tissues from I/R injury. In this investigation, BF-30 was synthesized and its role and mechanism in promoting survival of I/R-injured skin flaps explored. EXPERIMENTAL APPROACH: Survival rate analysis and laser Doppler blood flow analysis were used to evaluate I/R-injured flap viability. Western blotting, immunofluorescence, TdT-mediated dUTP nick end labelling (TUNEL) and dihydroethidium were utilized to examine the levels of apoptosis, pyroptosis, oxidative stress, transcription factor EB (TFEB)-mediated autophagy and molecules related to the adenosine 5'-monophosphate-activated protein kinase (AMPK)-transient receptor potential mucolipin 1 (TRPML1)-calcineurin signalling pathway. KEY RESULTS: The outcomes revealed that BF-30 enhanced I/R-injured island skin flap viability. Autophagy, oxidative stress, pyroptosis and apoptosis were related to the BF-30 capability to enhance I/R-injured flap survival. Improved autophagy flux and tolerance to oxidative stress promoted the inhibition of apoptosis and pyroptosis in vascular endothelial cells. Activation of TFEB increased autophagy and inhibited endothelial cell oxidative stress in I/R-injured flaps. A reduction in TFEB level led to a loss of the protective effect of BF-30, by reducing autophagy flux and increasing the accumulation of reactive oxygen species (ROS) in endothelial cells. Additionally, BF-30 modulated TFEB activity via the AMPK-TRPML1-calcineurin signalling pathway. CONCLUSION AND IMPLICATIONS: BF-30 promotes I/R-injured skin flap survival by TFEB-mediated up-regulation of autophagy and inhibition of oxidative stress, which may have possible clinical applications.

Monotonic trends of soil microbiomes, metagenomic and metabolomic functioning across ecosystems along water gradients in the Altai region, northwestern China.

To investigate microbial communities and their contributions to carbon and nutrient cycling along water gradients can enhance our comprehension of climate change impacts on ecosystem services. Thus, we conducted an assessment of microbial communities, metagenomic functions, and metabolomic profiles within four ecosystems, i.e., desert grassland (DG), shrub-steppe (SS), forest (FO), and marsh (MA) in the Altai region of Xinjiang, China. Our results showed that soil total carbon (TC), total nitrogen, NH4+, and NO3- increased, but pH decreased with soil water gradients. Microbial abundances and richness also increased with soil moisture except the abundances of fungi and protists being lowest in MA. A shift in microbial community composition is evident along the soil moisture gradient, with Proteobacteria, Basidiomycota, and Evosea proliferating but a decline in Actinobacteria and Cercozoa. The ß-diversity of microbiomes, metagenomic, and metabolomic functioning were correlated with soil moisture gradients and have significant associations with specific soil factors of TC, NH4+, and pH. Metagenomic functions associated with carbohydrate and DNA metabolisms, as well as phages, prophages, TE, plasmids functions diminished with moisture, whereas the genes involved in nitrogen and potassium metabolism, along with certain biological interactions and environmental information processing functions, demonstrated an augmentation. Additionally, MA harbored the most abundant metabolomics dominated by lipids and lipid-like molecules and organic oxygen compounds, except certain metabolites showing decline trends along water gradients, such as N'-Hydroxymethylnorcotinine and 5-Hydroxyenterolactone. Thus, our study suggests that future ecosystem succession facilitated by changes in rainfall patterns will significantly alter soil microbial taxa, functional potential, and metabolite fractions.

An update on the advances in the field of nanostructured drug delivery systems for a variety of orthopedic applications.

Nanotechnology has made significant progress in various fields, including medicine, in recent times. The application of nanotechnology in drug delivery has sparked a lot of research interest, especially due to its potential to revolutionize the field. Researchers have been working on developing nanomaterials with distinctive characteristics that can be utilized in the improvement of drug delivery systems (DDS) for the local, targeted, and sustained release of drugs. This approach has shown great potential in managing diseases more effectively with reduced toxicity. In the medical field of orthopedics, the use of nanotechnology is also being explored, and there is extensive research being conducted to determine its potential benefits in treatment, diagnostics, and research. Specifically, nanophase drug delivery is a promising technique that has demonstrated the capability of delivering medications on a nanoscale for various orthopedic applications. In this article, we will explore current advancements in the area of nanostructured DDS for orthopedic use.

APOBEC3A suppresses cervical cancer via apoptosis.

Background: Family members of Apolipoprotein B mRNA-editing enzyme catalytic 3 (APOBEC3) play critical roles in cancer evolution and development. However, the role of APOBEC3A in cervical cancer remains to be clarified. Methods: We used bioinformatics to investigate APOBEC3A expression and outcomes using The Cancer Genome Atlas (TCGA)-cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) dataset, GTEx, and GSE7803. Immunohistochemistry was then used to identify APOBEC3A's expression pattern. We performed Cell Counting Kit-8, wound-healing, Transwell, and flow cytometry assays to measure proliferation, migration, invasion, and apoptosis, respectively, using the SiHa and HeLa cell lines transfected with APOBEC3A. BALB/c nude mice were used to investigate the effects of APOBEC3A in vivo. The phosphorylated gamma-H2AX staining assay was applied to measure DNA damage. RNA sequencing (RNA-Seq) was applied to explore APOBEC3A-related signaling pathways. Results: APOBEC3A was more significantly expressed in cancer tissues than in adjacent normal tissues. Higher expression of APOBEC3A was associated with better outcomes in TCGA-CESC and GTEx. Immunohistochemistry showed that the expression of APOBEC3A was significantly higher in cancer tissues than in normal tissues. Transfection experiments showed that APOBEC3A inhibited proliferation, upregulated S-phase cells, inhibited migration and invasion, induced DNA damage, and promoted apoptosis. Overexpression of APOBEC3A inhibited tumor formation in the mouse model. RNA-seq analysis showed that ectopic expression of APOBEC3A inhibited several cancer-associated signaling pathways. Conclusions: APOBEC3A is significantly upregulated in cervical cancer, and higher expression of APOBEC3A is associated with better outcomes. APOBEC3A is a tumor suppressor whose overexpression induces apoptosis in cervical cancer.

Tumor Microenvironment Composition and Related Therapy in Hepatocellular Carcinoma.

Globally, primary liver cancer is the third leading cause of cancer death, and hepatocellular carcinoma (HCC) accounts for 75%-95%. The tumor microenvironment (TME), composed of the extracellular matrix, helper cells, immune cells, cytokines, chemokines, and growth factors, promotes the immune escape, invasion, and metastasis of HCC. Tumor metastasis and postoperative recurrence are the main threats to the long-term prognosis of HCC. TME-related therapies are increasingly recognized as effective treatments. Molecular-targeted therapy, immunotherapy, and their combined therapy are the main approaches. Immunotherapy, represented by immune checkpoint inhibitors (ICIs), and targeted therapy, highlighted by tyrosine kinase inhibitors (TKIs), have greatly improved the prognosis of HCC. This review focuses on the TME compositions and emerging therapeutic approaches to TME in HCC.