"Dictionary of immune responses" reveals the critical role of monocytes and the core target IRF7 in intervertebral disc degeneration.

Background: Intervertebral disc degeneration (IDD) is widely regarded as the primary contributor to low back pain(LBP). As an immune-privileged organ, upon the onset of IDD, various components of the nucleus pulposus (NP) are exposed to the host's immune system, accumulating cytokines. Cytokines facilitate intercellular communication within the immune system, induce immune cells polarisation, and exacerbate oxidative stress in IDD. Methods: Machine learning was used to identify crucial immune cells. Subsequently, Immune Response Enrichment Analysis (IREA) was conducted on the key immune cells to determine their cytokine responses and polarisation states in IDD. "CellChat" package facilitated the analysis of cell-cell communication. Differential gene expression analysis, PPI network, GO and KEGG pathway enrichment analysis, GSVA, co-expressed gene analysis and key gene-related networks were also performed to explore hub genes and their associated functions. Lastly, the differential expression and functions of key genes were validated through in vitro and in vivo experiments. Results: Through multiple machine learning methods, monocytes were identified as the crucial immune cells in IDD, exhibiting significant differentiation capacity. IREA revealed that monocytes in IDD polarize into an IFN-a1 and IFN-b enriched Mono-a state, potentially intensifying inflammation. Cell-cell communication analysis uncovered alteration in ANNEXIN pathway and a reduction in CXCL signaling between macrophages and monocytes, suggesting immune response dysregulation. Furthermore, ten algorithms identified three hub genes. Both experiments conducted in vitro and in vivo have conclusively shown that IRF7 serves as a crucial target for the treatment of IDD, and its knockdown alleviates IDD. Eight small-molecule drugs were predicted to have therapeutic potential for IDD. Conclusion: These findings offer a multidimensional understanding of the pathogenesis of IDD, pinpointing monocytes and key genes as potential diagnostic and therapeutic targets. They provide novel insights into potential diagnostic and therapeutic targets for IDD.

Tailoring efficient manganese bromide-based scintillator films with ethyl acetate assistance.

Metal halide scintillators serve as a compelling substitute for traditional scintillators in X-ray detection and imaging due to their low-temperature fabrication process, high light yield and mechanical flexibility. Nevertheless, the spatial resolution and photoluminescence quantum yield (PLQY) of these films are hindered by the agglomeration and uneven distribution of metal halides crystal particles during the fabrication process. We introduce a modified fabrication approach for metal halide scintillator films involving an additional step of ethyl acetate (EA) treatment, resulting in the preparation of a smooth EA-treated (Ph4P)2MnBr4/Polydimethylsiloxane film. The carbonyl groups within EA interact with elements of the (Ph4P)2MnBr4 microcrystals powder, ensuring uniform dispersion and preventing agglomeration. The EA-treated composite film demonstrates a remarkable PLQY of approximately 95% and an impressive spatial resolution of 14 lp/mm, with enhanced stability under harsh environments. These characteristics ensure its suitability as a high-performance X-ray imaging scintillator. .

Development and validation of a novel endoplasmic reticulum stress-related lncRNAs signature in osteosarcoma.

Osteosarcoma (OS) is a cancerous tumor, and its development is greatly influenced by long non-coding RNA (lncRNA). Endoplasmic reticulum stress (ERS) is an essential biological defense process in cells and contributes to the progression of tumors. However, the exact mechanisms remain elusive. This study aims to develop a signature of lncRNAs associated with ERS in OS. This signature will guide the prognosis prediction and the determination of appropriate treatment strategies. The UCSC Xena database collected transcriptional and clinical data of OS and muscle, after identifying ERS differentially expressed genes, we utilized correlation analysis to determine the endoplasmic reticulum stress lncRNAs (ERLs). The Least Absolute Shrinkage and Selection Operator (LASSO) and Cox regression analysis were utilized to develop an ERLs signature. To clarify the fundamental mechanisms controlling gene expression in low and high-risk groups, Gene Set Variation Analysis (GSVA) were conducted. In addition, the distinction between the two groups regarding drug sensitivity and immune-related activity was investigated to determine the immunotherapy effects. Utilizing RT-qPCR, the expression of model lncRNAs in OS cell lines was ascertained. The functional analysis of LINC02298 was carried out through in vitro experiments and pan-cancer analysis. This study successfully constructed an ERLs prognostic signature for OS, which comprised 5 lncRNAs (AC023157.3, AL031673.1, LINC02298, LINC02328, SNHG26). The risk signature predicted overall survival in patients with OS and was confirmed by assessing the validation and whole cohorts. Further, it was discovered that individuals classified as high-risk displayed suppressed immune activation, decreased infiltration of immune cells, and decreased responsiveness to immunotherapy. The RT-qPCR showed that the constructed risk prognosis model is reliable. Experimental validation has demonstrated that LINC02298 can promote OS cells' invasion, migration, and proliferation. In addition, LINC02298 exhibited significant differential expression in many types of cancer. Moreover, LINC02298 is an important biomarker in a variety of tumors. This study established a novel ERLs signature, which successfully predicted the prognosis of OS. The function of LINC02298 in OS was elucidated via in vitro experiments. Therefore, it offers new opportunities for predicting the clinical prognosis of OS and establishes the basis for targeted therapy in OS.

"Three birds, one stone" strategy of NIR-responsive CO/H2S dual-gas Nanogenerator for efficient treatment of osteoporosis.

Osteoporosis (OP), the most prevalent bone degenerative disease, has become a significant public health challenge globally. Current therapies primarily target inhibiting osteoclast activity or stimulating osteoblast activation, but their effectiveness remains suboptimal. This paper introduced a "three birds, one stone" therapeutic approach for osteoporosis, employing upconversion nanoparticles (UCNPs) to create a dual-gas storage nanoplatform (UZPA-CP) targeting bone tissues, capable of concurrently generating carbon monoxide (CO) and hydrogen sulfide (H2S). Through the precise modulation of 808 nm near-infrared (NIR) light, the platform could effectively control the release of CO and H2S in the OP microenvironment, and realize the effective combination of promoting osteogenesis, inhibiting osteoclast activity, and improving the immune microenvironment to achieve the therapeutic effect of OP. High-throughput sequencing results further confirmed the remarkable effectiveness of the nanoplatform in inhibiting apoptosis, modulating inflammatory response, inhibiting osteoclast differentiation and regulating multiple immune signaling pathways. The gas storage nanoplatform not only optimized the OP microenvironment with the assistance of NIR, but also restored the balance between osteoblasts and osteoclasts. This comprehensive therapeutic strategy focused on improving the bone microenvironment, promoting osteogenesis and inhibiting osteoclast activity provides an ideal new solution for the treatment of metabolic bone diseases.

A dynamic regulome of shoot-apical-meristem-related homeobox transcription factors modulates plant architecture in maize.

BACKGROUND: The shoot apical meristem (SAM), from which all above-ground tissues of plants are derived, is critical to plant morphology and development. In maize (Zea mays), loss-of-function mutant studies have identified several SAM-related genes, most encoding homeobox transcription factors (TFs), located upstream of hierarchical networks of hundreds of genes. RESULTS: Here, we collect 46 transcriptome and 16 translatome datasets across 62 different tissues or stages from the maize inbred line B73. We construct a dynamic regulome for 27 members of three SAM-related homeobox subfamilies (KNOX, WOX, and ZF-HD) through machine-learning models for the detection of TF targets across different tissues and stages by combining tsCUT&Tag, ATAC-seq, and expression profiling. This dynamic regulome demonstrates the distinct binding specificity and co-factors for these homeobox subfamilies, indicative of functional divergence between and within them. Furthermore, we assemble a SAM dynamic regulome, illustrating potential functional mechanisms associated with plant architecture. Lastly, we generate a wox13a mutant that provides evidence that WOX13A directly regulates Gn1 expression to modulate plant height, validating the regulome of SAM-related homeobox genes. CONCLUSIONS: The SAM-related homeobox transcription-factor regulome presents an unprecedented opportunity to dissect the molecular mechanisms governing SAM maintenance and development, thereby advancing our understanding of maize growth and shoot architecture.

Synthetic approaches and clinical application of representative small-molecule inhibitors of phosphodiesterase.

Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors.

From lab to clinic: The discovery and optimization journey of PI3K inhibitors.

PI3K inhibitors have emerged as promising therapeutic agents due to their critical role in various cellular processes, particularly in cancer, where the PI3K pathway is frequently dysregulated. This review explores the evolutionary path of PI3K inhibitors from laboratory discovery to clinical application. The journey begins with early laboratory investigations into PI3K signaling and inhibitor development, highlighting fundamental discoveries that laid the foundation for subsequent advancements. Optimization strategies, including medicinal chemistry approaches and structural modifications, are scrutinized for their contributions to enhancing inhibitor potency, selectivity, and pharmacokinetic properties. The translation from preclinical studies to clinical trials is examined, emphasizing pivotal trials that evaluated efficacy and safety profiles. Challenges encountered during clinical development are critically assessed. Finally, the review discusses ongoing research directions and prospects for PI3K inhibitors, underscoring these agents' continuous evolution and therapeutic potential.

Minimally Invasive versus Traditional Surgery: Efficacy of PELD and PLIF in Treating Pyogenic Spondylodiscitis.

BACKGROUND Pyogenic spondylodiscitis is infection of the intervertebral disc or discs and the adjacent vertebrae. This retrospective study aimed to compare the effectiveness of percutaneous endoscopic lumbar debridement (PELD) versus posterior lumbar interbody fusion (PLIF) in 40 patients with pyogenic spondylodiscitis (PSD). MATERIAL AND METHODS Medical records of patients who underwent PELD (n=18) or PLIF (n=22) for PSD between 2018 and 2023 were reviewed. The recorded outcomes encompassed surgical duration, intraoperative blood loss, Oswestry Disability Index (ODI) measurements, Visual Analog Scale (VAS) assessments, C-reactive protein (CRP) levels, duration of hospitalization, erythrocyte sedimentation rate (ESR), American Spinal Injury Association (ASIA) grading, lumbar sagittal parameters, and the incidence of complications. RESULTS The PELD group had shorter surgical duration, less intraoperative blood loss, and shorter length of hospital stay compared to the PLIF group (P<0.01). At the last follow-up, both groups had significant improvement in ESR, CRP levels, and ASIA classification (P<0.001), but there was no significant difference between the 2 groups (P>0.05). The PELD group had lower ODI and VAS ratings at 1 month and 3 months, respectively (P<0.01). The PLIF group had significant improvements in intervertebral space height and lumbar lordosis angle (P<0.01). CONCLUSIONS Both PLIF and PELD surgical approaches demonstrate adequate clinical efficacy in the treatment of monosegmental PSD. PLIF can better ensure more spinal stability than PELD, but PELD offers advantages such as reduced minimal surgical trauma, shorter operative duration, and faster recovery after surgery.

Detection Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by metagenomic next-generation sequencing test: a case report.

BACKGROUND: Andersen's lesion (AL) is a rare complication of ankylosing spondylitis (AS), characterized by nonneoplastic bone destruction, typically manifested as bone destruction and sclerosis in the vertebral body and/or intervertebral disc area. At present, there is no consensus on the pathology and etiology of AL. Repeated trauma, inflammation in essence and part of the natural history of Ankylosing spondylitis itself are the most widely recognized theories of the etiology of AL. However, positive bacteria cultured in bone biopsy of Andersen's lesion (AL) in Ankylosing spondylitis patients are extremely rare. Herein, we report a rare case of detecting Ewingella americana from a patient with Andersson lesion in ankylosing spondylitis by Metagenomic Next-Generation Sequencing (mNGS) Test. CASE PRESENTATION: This case involved a 39-year-old male with a history of AS for 11 years, who developed AL (T11/12) in the thoracic vertebrae. After sufficient preoperative preparation, we successfully performed one-stage posterior approach corrective surgery and collected bone biopsies samples for examination. Cultured bacteria were not found, and pathological histology indicated infiltration of inflammatory cells. However, it is worth noting that we discovered a gram-negative bacterium, the Ewingella americana, through mNGS testing. Further histopathological examination suggests chronic inflammatory cell infiltration. After one-stage posterior approach corrective surgery, the patient's condition significantly improved. At the 6-month follow-up, the pain significantly decreased, and the patient returned to normal life. CONCLUSION: We detected Ewinia americana in the bone biopsies of Andersson lesion (AL) in ankylosing spondylitis patient by mNGS.

Genome-wide identification of WRKY transcription factors in Casuarina equisetifolia and the function analysis of CeqWRKY11 in response to NaCl/NaHCO3 stresses.

BACKGROUND: Casuarina equisetifolia (C. equisetifolia) is a woody species with many excellent features. It has natural resistance against drought, salt and saline-alkali stresses. WRKY transcription factors (TFs) play significant roles in plant response to abiotic stresses, therefore, molecular characterization of WRKY gene family under abiotic stresses holds great significance for improvement of forest trees through molecular biological tools. At present, WRKY TFs from C. equisetifolia have not been thoroughly studied with respect to their role in salt and saline-alkali stresses response. The current study was conducted to bridge the same knowledge gap. RESULTS: A total of 64 WRKYs were identified in C. equisetifolia and divided into three major groups i.e. group I, II and III, consisting of 10, 42 and 12 WRKY members, respectively. The WRKY members in group II were further divided into 5 subgroups according to their homology with Arabidopsis counterparts. WRKYs belonging to the same group exhibited higher similarities in gene structure and the presence of conserved motifs. Promoter analysis data showed the presence of various response elements, especially those related to hormone signaling and abiotic stresses, such as ABRE (ABA), TGACG (MeJA), W-box ((C/T) TGAC (T/C)) and TC-rich motif. Tissue specific expression data showed that CeqWRKYs were mainly expressed in root under normal growth conditions. Furthermore, most of the CeqWRKYs were up-regulated by NaCl and NaHCO3 stresses with few of WRKYs showing early responsiveness to both stresses while few others exhibiting late response. Although the expressions of CeqWRKYs were also induced by cold stress, the response was delayed compared with other stresses. Transgenic C. equisetifolia plants overexpressing CeqWRKY11 displayed lower electrolyte leakage, higher chlorophyll content, and enhanced tolerance to both stresses. The higher expression of abiotic stress related genes, especially CeqHKT1 and CeqPOD7, in overexpression lines points to the maintenance of optimum Na+/K+ ratio, and ROS scavenging as possible key molecular mechanisms underlying salt stress tolerance. CONCLUSIONS: Our results show that CeqWRKYs might be key regulators of NaCl and NaHCO3 stresses response in C. equisetifolia. In addition, positive correlation of CeqWRKY11 expression with increased stress tolerance in C. equisetifolia encourages further research on other WRKY family members through functional genomic tools. The best candidates could be incorporated in other woody plant species for improving stress tolerance.

Molecular characterization of Golgi apparatus-related genes indicates prognosis and immune infiltration in osteosarcoma.

BACKGROUND: The Golgi apparatus (GA) is crucial for protein synthesis and modification, and regulates various cellular processes. Dysregulation of GA can lead to pathological conditions like neoplastic growth. GA-related genes (GARGs) mutations are commonly found in cancer, contributing to tumor metastasis. However, the expression and prognostic significance of GARGs in osteosarcoma are yet to be understood. METHODS: Gene expression and clinical data of osteosarcoma patients were obtained from the TARGET and GEO databases. A consensus clustering analysis identified distinct molecular subtypes based on GARGs. Discrepancies in biological processes and immunological features among the subtypes were explored using GSVA, ssGSEA, and Metascape analysis. A GARGs signature was constructed using Cox regression. The prognostic value of the GARGs signature in osteosarcoma was evaluated using Kaplan-Meier curves and a nomogram. RESULTS: Two GARG subtypes were identified, with Cluster A showing better prognosis, immunogenicity, and immune cell infiltration than Cluster B. A novel risk model of 3 GARGs was established using the TARGET dataset and validated with independent datasets. High-risk patients had poorer overall survival, and the GARGs signature independently predicted osteosarcoma prognosis. Combining risk scores and clinical characteristics in a nomogram improved prediction performance. Additionally, we discovered Stanniocalcin-2 (STC2) as a significant prognostic gene highly expressed in osteosarcoma and potential disease biomarker. CONCLUSIONS: Our study revealed that patients with osteosarcoma can be divided into two GARGs subgroups. Furthermore, we have developed a GARGs prognostic signature that can accurately forecast the prognosis of osteosarcoma patients.

Reorganization of structural brain networks in Parkinson's disease with postural instability/gait difficulty.

The Postural Instability/Gait Difficulty (PIGD) subtype of Parkinson's disease (PD) has a faster disease progression, a higher risk of cognitive and motor decline, yet the alterations of structural topological organization remain unknown. Diffusion Tensor Imaging (DTI) and 3D-TI scanning were conducted on 31 PD patients with PIGD (PD-PIGD), 30 PD patients without PIGD (PD-non-PIGD) and 35 Healthy Controls (HCs). Structural networks were constructed using DTI brain white matter fiber tractography. A graph theory approach was applied to characterize the topological properties of complex structural networks, and the relationships between significantly different network metrics and motor deficits were analyzed within the PD-PIGD group. PD-PIGD patients exhibited increased shortest path length compared with PD-non-PIGD and HCs (P < 0.05, respectively). Additionally, PD-PIGD patients exhibited decreased nodal properties, mainly in the cerebellar vermis, prefrontal cortex, paracentral lobule, and visual regions. Notably, the degree centrality of the cerebellar vermis was negatively correlated with the PIGD score (r = -0.390; P = 0.030) and Unified Parkinson's Disease Rating Scale Part III score (r = -0.436; P = 0.014) in PD-PIGD patients. Furthermore, network-based statistical analysis revealed decreased structural connectivity between the prefrontal lobe, putamen, supplementary motor area, insula, and cingulate gyrus in PD-PIGD patients. Our findings demonstrated that PD-PIGD patients existed abnormal structural connectomes in the cerebellar vermis, frontal-parietal cortex and visual regions. These topological differences can provide a topological perspective for understanding the potential pathophysiological mechanisms of PIGD in PD.

Modified Percutaneous Endoscopic Interlaminar Discectomy through the Near-spinous Process Approach for L4/5 Disc Herniation: A Retrospective Clinical Study.

OBJECTIVE: Compared with traditional open surgery, percutaneous endoscopic lumbar discectomy (PELD) has the advantages of less trauma, faster recovery, and less postoperative pain, so it has been widely used in the field of spinal surgery. However, it still has the defect of intraoperative fluoroscopy occurrences, complications, and even the risk of damage to the spinal cord and nerve. This study aims to compare the clinical efficacy of modified percutaneous endoscopic interlaminar discectomy (MPEID) with percutaneous endoscopic transforaminal discectomy (PETD) in treating L4/5 lumbar disc herniation (LDH) and to evaluate the effectiveness and safety of MPEID. METHODS: Thirty-four L4/5 LDH patients treated at the Second Affiliated Hospital of Nanchang University from June 2020 to June 2021 were studied retrospectively. Seventeen underwent MPEID and seventeen PETD. Variables analyzed included demographics, operative duration, intraoperative fluoroscopy occurrences, and surgical outcomes. Effectiveness was evaluated using the visual analogue scale (VAS), Oswestry disability index (ODI), and modified MacNab criteria. Lumbar Magnetic Resonance Imaging (MRI) was used to assess radiological outcomes. A paired t-test was performed to compare intragroup pre- and postoperative clinical data, VAS, and ODI scores. RESULTS: The average operative time in PETD group was 91.65 ± 14.04 min, and the average operative time in MPEID group was 65.41 ± 12.61 min (p < 0.001). In PETD group, the fluoroscopy occurrences averaged 9.71 ± 1.05 times, with fluoroscopy occurrences averaging 6.47 ± 1.00 times (p < 0.001) in MPEID group. At 12 months follow-up, the clinical effect showed significant improvement in both two groups. The MPEID group showed a decrease in average VAS-back score from 5.41 ± 2.18 to 1.76 ± 1.09 (p < 0.001) and VAS-leg score from 6.53 ± 1.66 to 0.82 ± 0.64 (p < 0.001). The ODI scores decreased from 51.35 ± 10.65 to 11.71 ± 2.91 (p < 0.001). In the PETD group, the VAS-back score decreased from 4.94 ± 1.98 to 2.06 ± 1.25 (p < 0.001), VAS-leg score from 7.12 ± 1.73 to 1.12 ± 0.60 (p < 0.001), and ODI scores from 48.00 ± 11.62 to 12.24 ± 2.56 (p < 0.001). According to the modified MacNab criteria, MPEID had 15 excellent and two good results; PETD had 12 excellent and 5 good (p = 0.23). No nerve root injuries, dural tears, or significant complications were reported. CONCLUSION: MPEID and PETD effectively treat L4/5 LDH, with MPEID showing shorter operative times and fewer fluoroscopies. Furthermore, the MPEID group can provide excellent clinical efficacy as the PETD group in the short term.

Fenton-like Reaction Inspired "·OH Catalyzed" Osteogenic Process for the Treatment of Osteoporosis.

Inspired by the Fenton-like reaction, this work combines copper peroxide (CP) nanoparticles with black phosphorus (BP) nanosheets to form a hydroxyl radical (·OH)-centered "catalytic" osteogenic system. CP-produced ·OH interacts with BP to rapidly produce a large amount of phosphate ions, thus accelerating self-mineralization and promoting bone formation. In turn, BP not only exerts anti-inflammatory effects, thereby providing a favorable microenvironment for bone formation, but also offsets the potential toxicity of CP induced by reactive oxygen species (ROS). Together with copper ions (Cu2+), phosphate ions are also released as a byproduct of this process, which can contribute to the comprehensive promotion of osteogenesis.

Spectrum-effect relationship study between ultra-high-performance liquid chromatography fingerprints and anti-hepatoma effect in vitro of Cnidii Fructus.

Cnidii Fructus, derived from the dried ripe fruit of Cnidium monnieri (L.) Cuss, has the effect of warming kidneys and invigorating Yang. This study established the spectrum-effect relationships between ultra-high-performance liquid chromatography (UHPLC) fingerprints and the antitumor activities of Cnidii Fructus on human hepatocellular carcinoma (HepG2) cells. In UHPLC fingerprints, 19 common peaks were obtained, and 17 batches of herbs had similarity >0.948. In Cell Counting Kit-8 (CCK-8) test, 17 batches of Cnidii Fructus extract significantly inhibited the proliferation of HepG2 cells to different degrees, showing different half-maximal inhibitory concentration (IC50) values. Furthermore, gray correlation analysis, Pearson's analysis, and orthogonal partial least squares discriminant analysis were performed to screen out eight components. The analysis of mass spectrum data and a comparison with standards revealed that the eight components were methoxsalen, isopimpinellin, osthenol, imperatorin, osthole, ricinoleic acid, linoleic acid, and oleic acid. The verification experiments by testing single compounds indicated that these eight compounds were the major anti-hepatoma compounds in Cnidii Fructus. This work provides a model combining UHPLC fingerprints and antitumor activities to study the spectrum-effect relationships of Cnidii Fructus, which can be used to determine the principal components responsible for the bioactivity.

Delivery of paclitaxel by carboxymethyl chitosan-functionalized dendritic fibrous nano-silica: Fabrication, characterization, controlled release performance and pharmacokinetics.

In this study, carboxymethyl chitosan (CMCS) with excellent biocompatibility was used as the "gatekeeper" to design and fabricate a pH-responsive drug delivery system (CMCS-DFNS) as paclitaxel carriers. Characterization results showed that CMCS-DFNS was successfully prepared and the nanocarriers displayed excellent drug loading efficiency of 19.8 %, and the results of the adsorption mechanism revealed that the adsorption of PTX was consistent with the Freundlich isotherm and pseudo-second-order kinetic model. Furthermore, the pH-responsive controlled release behavior at different pH (pH = 7.4, 6.5, and 5.0) was evaluated, and the results demonstrated that the cumulative release at pH 5.0 was 58.8 %, which was 2.7 times higher than that at pH 7.4, suggesting that the carrier exhibited a good pH sensitivity. The results of in vitro cellular experiments further indicated that CMCS-DFNS significantly improved the drug uptake efficiency in breast cancer MCF-7 cells. Importantly, the results of in vivo and cellular pharmacokinetic revealed that CMCS-DFNS can improve the circulation time and enhance the relative bioavailability of paclitaxel. Therefore, the fabricated pH-responsive drug delivery system has potential applications in the delivery of anti-tumor drugs, and provides a new delivery pathway for other compounds with low bioavailability.

Identification of CXCL16 as a diagnostic biomarker for obesity and intervertebral disc degeneration based on machine learning.

Intervertebral disc degeneration (IDD) is the primary cause of neck and back pain. Obesity has been established as a significant risk factor for IDD. The objective of this study was to explore the molecular mechanisms affecting obesity and IDD by identifying the overlapping crosstalk genes associated with both conditions. The identification of specific diagnostic biomarkers for obesity and IDD would have crucial clinical implications. We obtained gene expression profiles of GSE70362 and GSE152991 from the Gene Expression Omnibus, followed by their analysis using two machine learning algorithms, least absolute shrinkage and selection operator and support vector machine-recursive feature elimination, which enabled the identification of C-X-C motif chemokine ligand 16 (CXCL16) as a shared diagnostic biomarker for obesity and IDD. Additionally, gene set variant analysis was used to explore the potential mechanism of CXCL16 in these diseases, and CXCL16 was found to affect IDD through its effect on fatty acid metabolism. Furthermore, correlation analysis between CXCL16 and immune cells demonstrated that CXCL16 negatively regulated T helper 17 cells to promote IDD. Finally, independent external datasets (GSE124272 and GSE59034) were used to verify the diagnostic efficacy of CXCL16. In conclusion, a common diagnostic biomarker for obesity and IDD, CXCL16, was identified using a machine learning algorithm. This study provides a new perspective for exploring the possible mechanisms by which obesity impacts the development of IDD.

Evaluation of Safety and Efficacy of Preoperative Coronal MRI-Guided Minimally Invasive Surgery for Cervical Spondylotic Radiculopathy.

BACKGROUND Key-hole surgery is a minimally invasive technique that has shown promise in various surgical procedures. This study aimed to assess the clinical effectiveness of preoperative coronal MRI-assisted key-hole surgery for the treatment of patients with cervical spondylotic radiculopathy (CSR). MATERIAL AND METHODS A total of 30 patients diagnosed with CSR and undergoing key-hole surgery with CMRI assistance were included in the study. Various parameters, including surgical segments, incision length, disease duration, operative time, intraoperative fluoroscopy times, intraoperative blood loss, complications, and length of hospitalization, were recorded. Precise measurements of Cobb angles and intervertebral space height were taken before and after the surgical procedure. Surgical outcomes were evaluated using modified Macnab criteria, visual analogue scale (VAS), Japanese Orthopaedic Association Scores (JOA), and neck disability index (NDI). RESULTS The average duration of disease was 6.47±3.29 months, with an average incision length of 1.94±0.15 cm and operative time of 57.83±4.34 minutes. The average intraoperative blood loss was 33.70±9.28 ml, with an average of 3.50±0.73 intraoperative fluoroscopies. The average duration of hospitalization was 4.10±1.27 days. Preoperative and postoperative measurements showed no statistically significant difference in C2-C7 Cobb angles and intervertebral space height. However, there were significant improvements in postoperative VAS, NDI, and JOA scores compared to preoperative scores. The surgical effectiveness rate was 100%, with a high rate of good and excellent outcomes. CONCLUSIONS The findings of this study suggest that preoperative CMRI-assisted key-hole surgery for single-segment CSR is a safe and effective treatment option with low complication rates. The clinical benefits include high security and good outcomes. Further research and larger studies are warranted to validate these findings.

Identification of mitochondrial-related signature and molecular subtype for the prognosis of osteosarcoma.

Mitochondria play a vital role in osteosarcoma. Therefore, the purpose of this study was to investigate the potential role of mitochondrial-related genes (MRGs) in osteosarcoma. Based on 92 differentially expressed MRGs, osteosarcoma samples were divided into two subtypes using the nonnegative matrix factorization (NMF). Ultimately, a univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox analysis were performed to construct a prognostic risk model. The single-sample gene set enrichment analysis assessed the immune infiltration characteristics of osteosarcoma patients. Finally, we identified an osteosarcoma biomarker, malonyl-CoA decarboxylase (MLYCD), which showed downregulation. Osteosarcoma cells proliferation, migration, and invasion were effectively inhibited by the overexpression of MLYCD. Our findings will help us to further understand the molecular mechanisms of osteosarcoma and contribute to the discovery of new diagnostic biomarkers and therapeutic targets.