Magnesium Ions Promote the Induction of Immunosuppressive Bone Microenvironment and Bone Repair through HIF-1α-TGF-ß Axis in Dendritic Cells.

The effect of immunoinflammation on bone repair during the recovery process of bone defects needs to be further explored. It is reported that Mg2+ can promote bone repair with immunoregulatory effect, but the underlying mechanism on adaptive immunity is still unclear. Here, by using chitosan and hyaluronic acid-coated Mg2+ (CSHA-Mg) in bone-deficient mice, it is shown that Mg2+ can inhibit the activation of CD4+ T cells and increase regulatory T cell formation by inducing immunosuppressive dendritic cells (imDCs). Mechanistically, Mg2+ initiates the activation of the MAPK signaling pathway through TRPM7 channels on DCs. This process subsequently induces the downstream HIF-1α expression, a transcription factor that amplifies TGF-ß production and inhibits the effective T cell function. In vivo, knock-out of HIF-1α in DCs or using a HIF-1α inhibitor PX-478 reverses inhibition of bone inflammation and repair promotion upon Mg2+-treatment. Moreover, roxadustat, which stabilizes HIF-1α protein expression, can significantly promote immunosuppression and bone repair in synergism with CSHA-Mg. Thus, the findings identify a key mechanism for DCs and its HIF-1α-TGF-ß axis in the induction of immunosuppressive bone microenvironment, providing potential targets for bone regeneration.

An FOF1-ATPase motor-embedded chromatophore as a nanorobot for overcoming biological barriers and targeting acidic tumor sites.

Despite the booming progress of anticancer nanomedicines in the past two decades, precise tumor-targetability and sufficient tumor-accumulation are less successful and still require further research. To tackle this challenge, herein we present a biomolecular motor (FOF1-ATPase)-embedded chromatophore as nanorobot to efficiently overcome biological barriers, and thoroughly investigate its chemotactic motility, tumor-accumulation ability and endocytosis. Chromatophores embedded with FOF1-ATPase motors were firstly extracted from Thermus thermophilus, then their properties were fully characterized. Specifically, two microfluidic platforms (laminar flow microchip and tumor microenvironment (TME) microchip) were designed and developed to fully investigate the motility, tumor-accumulation ability and endocytosis of the chromatophore nanorobot (CN). The results from the laminar flow microchip indicated that the obtained CN possessed the strongly positive chemotaxis towards protons. And the TME microchip experiments verified that the CN had a desirable tumor-accumulation ability. Cellular uptake experiments demonstrated that the CN efficiently promoted the endocytosis of the fluorescence DiO into the HT-29 cells. And the in vivo studies revealed that the intravenously administered CN exhibited vigorous tumor-targetability and accumulation ability as well as highly efficient antitumor efficacy. All the results suggested that FOF1-ATPase motors-embedded CN could be promising nanomachines with powerful self-propulsion for overcoming physiological barriers and tumor-targeted drug delivery. STATEMENT OF SIGNIFICANCE: In this study, we demonstrated that FOF1-ATPase-embedded chromatophore nanorobots exhibit a strong proton chemotaxis, which not only plays a key role in tumor-targetability and accumulation, but also promotes tumor tissue penetration and internalization. The results of in vitro and in vivo studies indicated that drug-loaded chromatophore nanorobots are capable to simultaneously accomplish tumor-targeting, accumulation, penetration and internalization for enhanced tumor therapy. Our study provides a fundamental basis for further study on FOF1-ATPase-embedded chromatophore as tumor-targeting drug delivery systems that have promising clinical applications. It offers a new and more efficient delivery vehicle for cancer related therapeutics.

Association between alcohol intake and bone mineral density: results from the NHANES 2005-2020 and two-sample Mendelian randomization.

We used the data from the NHANES cross-sectional study among 14,113 participants and indicated a positive correlation between alcohol intake frequency and bone mineral density in different body sites. Mendelian randomization was conducted, and no causal relationship is significant between these two variables. The study can provide some suggestions on the daily consumption of alcohol for osteoporosis patients. PURPOSE: The effect of alcohol intake on bone mineral density (BMD) remains unclear. This study explored the association and causality between alcohol intake and BMD. METHODS: Based on the 2005-2020 National Health and Nutrition Examination Survey including 14,113 participants, we conducted co-variate-adjusted multilinear regression analyses to explore the association between alcohol intake levels and spine or femur BMD. To evaluate the causal association between alcohol intake frequency and bone mineral density, the inverse variance weighted approach of two-sample Mendelian randomization (MR) was used with genetic data from the Medical Research Council Integrative Epidemiology Unit (462,346 cases) for alcohol intake frequency and the Genetic Factors for Osteoporosis Consortium (28,496 cases) for lumbar spine and femur neck BMD (32,735 cases). RESULTS: Compared with non-drinkers, total femur BMDs but not total spine BMD increased with daily alcohol intake in males (ß = 3.63*10-2 for mild drinkers, ß = 4.21*10-2 for moderate drinkers, and ß = 4.26*10-2 for heavy drinkers). By contrast, the higher total spine BMD in females was related to higher alcohol intake levels (ß = 2.15*10-2 for mild drinkers, ß = 2.59*10-2 for moderate drinkers, and ß = 3.88*10-2 for heavy drinkers). Regarding the two-sample MR results, no causal relationship was observed between alcohol intake frequency and lumbar spine BMD (odds ratio [OR] = 1.016, P = 0.789) or femur neck BMD (OR = 1.048, P = 0.333). CONCLUSION: This study suggests a positive association between alcohol intake frequency and BMD, although the causal relationship was not significant.

Dual-energy computed tomography in a multiparametric regression model for diagnosing lymph node metastases in pancreatic ductal adenocarcinoma.

OBJECTIVE: To investigate the diagnostic value of dual-energy computed tomography (DECT) quantitative parameters in the identification of regional lymph node metastasis in pancreatic ductal adenocarcinoma (PDAC). METHODS: This retrospective diagnostic study assessed 145 patients with pathologically confirmed pancreatic ductal adenocarcinoma from August 2016-October 2020. Quantitative parameters for targeted lymph nodes were measured using DECT, and all parameters were compared between benign and metastatic lymph nodes to determine their diagnostic value. A logistic regression model was constructed; the receiver operator characteristics curve was plotted; the area under the curve (AUC) was calculated to evaluate the diagnostic efficacy of each energy DECT parameter; and the DeLong test was used to compare AUC differences. Model evaluation was used for correlation analysis of each DECT parameter. RESULTS: Statistical differences in benign and metastatic lymph nodes were found for several parameters. Venous phase iodine density had the highest diagnostic efficacy as a single parameter, with AUC 0.949 [95% confidence interval (CI):0.915-0.972, threshold: 3.95], sensitivity 79.80%, specificity 96.00%, and accuracy 87.44%. Regression models with multiple parameters had the highest diagnostic efficacy, with AUC 0.992 (95% CI: 0.967-0.999), sensitivity 95.96%, specificity 96%, and accuracy 94.97%, which was higher than that for a single DECT parameter, and the difference was statistically significant. CONCLUSION: Among all DECT parameters for regional lymph node metastasis in PDAC, venous phase iodine density has the highest diagnostic efficacy as a single parameter, which is convenient for use in clinical settings, whereas a multiparametric regression model has higher diagnostic value compared with the single-parameter model.

Correlation between lesion location and dysphagia characteristics in post-stroke patients.

OBJECTIVE: To assess the correlation between lesion location and swallowing function characteristics in post-stroke dysphagia (PSD) patients. MATERIALS AND METHODS: We enrolled 133 PSD. The patients were divided into supratentorial and infratentorial stroke groups. We compared the measurements in the videofluoroscopic swallowing study (VFSS) with 3ml and 5 ml of diluted and thickened barium liquid data between supratentorial and brainstem stroke groups. We further compared the difference of VFSS measurements between patients with left hemispheric or right hemispheric lesions (further divided into unilateral hemispheric cortical and subcortical subgroups) and brianstem leison stroke group.To explore the lesion location's effect on different bolus volume, the VFSS measurements of 3ml and 5ml in each subgroups were compared respectively. The measurements of VFSS included the oral transit time, soft palate elevation duration, hyoid bone movement duration (HMD), UES opening duration, pharyngeal transit duration (PTD), stage of ansition duration, and laryngeal closure duration (LCD), the upper esophageal sphincter opening (UESO), hyoid bone superior horizontal displacement, and hyoid bone anterior horizontal displacement. General swallowing function was assessed using the Penetration Aspiration Scale (PAS) and Functional Oral Intake Scale (FOIS). We performed the paired t-test, Spearman's correlation, and Kruskal-Wallis test analysis to characterize the parameters among the groups. RESULTS: Fifty-eight patients were assessed in the final analysis. The HMD (p = 0.019), PTD (p = 0.048) and LCD (p = 0.013) were significantly different between the supratentorial and brainstem lesion groups in 5ml volume. The HMD was significantly different (p = 0.045) between the left cortical and brainstem lesion groups. Significant differences in the HMD (p = 0.037) and LCD (p = 0.032) between the left subcortical and brainstem lesion groups were found in 5ml volume bolus. There was no group different when taking the 3ml volume bolus. Regarding the relationship between food bolus volume and swallowing functions, only the UESO demonstrated a significant difference in the subcortical lesion of the right hemisphere (p = 0.0032) compared the 3 ml and 5 ml volume bolus. The PTD demonstrated a moderate correlation with the PAS scores (r = 0.38, p = 0.0044). The HMD (r = 0.32, p = 0.018) and LCD (r = 0.29, p = 0.039) demonstrated weak correlations with the PAS scores. We did not identify any correlation between the VFSS parameters and FOIS scores in each subgroup level. CONCLUSION: The PSD with brainstem lesion shows more sever dysfunction in the pharyngeal phases. The left hemisphere was engaged in both the oral and pharyngeal phases. Lesions in the bilateral cortical, subcortical, and brainstem regions may impair sensory input.

Mycorrhizal mediation of soil carbon in permafrost regions depends on soil nutrient stoichiometry and physical protection.

Mycorrhizal associations are considered as one of the key drivers for soil carbon (C) accumulation and stability. However, how mycorrhizal associations influence soil organic C (SOC) and its fractions (i.e., particulate organic C [POC] and mineral-associated organic C [MAOC]) remain unclear. In this study, we examined effects of plant mycorrhizal associations with arbuscular mycorrhiza (AM), ectomycorrhiza (ECM), and their mixture (Mixed) on SOC and its fractions as well as soil stoichiometric ratios across 800-km transect in permafrost regions. Our results showed that soil with only ECM-associated trees had significantly higher SOC and POC compared to only AM-associated tree species, while soil in Mixed plots with both AM- and ECM- associated trees tend to be somewhat in the middle. Using structural equation models, we found that mycorrhizal association significantly influenced SOC and its fraction (i.e., POC, MAOC) indirectly through soil stoichiometric ratios (C:N, C:P, and N:P). These results suggest that selecting ECM tree species, characterized by a "slow cycling" nutrient uptake strategy, can effectively enhance accumulation of SOC and its fractions in permafrost forest ecosystems. Our findings provide novel insights for quantitatively assessing the influence of mycorrhiza-associated tree species on the management of soil C pool and biogeochemical cycling.

Alcohol use disorder and time perception: The mediating role of attention and working memory.

Alcohol use disorder (AUD) has been associated with attentional deficits and impairments of working memory. Meanwhile, attention and working memory are critical for time perception. However, it remains unclear how time perception alters in AUD patients and how attention and working memory affect their time perception. The current study aims to clarify the time perception characteristics of AUD patients and the cognitive mechanisms underlying their time perception dysfunction. Thirty-one patients (three of them were excluded) with AUD and thirty-one matched controls completed the Time Bisection Task, Attention Network Test and Digital Span Backward Test to assess their abilities in time perception, attention network and working memory, respectively. The results showed that, after controlling for anxiety, depression, and impulsivity, AUD patients had a lower proportion of 'long' responses at intervals of 600, 750, 900, 1050 and 1200 ms. Furthermore, they displayed higher subjective equivalence points and higher Weber ratios compared to controls. Moreover, AUD patients showed impaired alerting and executive control networks as well as reduced working memory resources. Only working memory resources mediated the impact of AUD on time perception. In conclusion, our findings suggested that the duration underestimation in AUD patients is predominantly caused by working memory deficits.

Dual-Energy Computed Tomography in Detecting and Predicting Lymph Node Metastasis in Malignant Tumor Patients: A Comprehensive Review.

The accurate and timely assessment of lymph node involvement is paramount in the management of patients with malignant tumors, owing to its direct correlation with cancer staging, therapeutic strategy formulation, and prognostication. Dual-energy computed tomography (DECT), as a burgeoning imaging modality, has shown promising results in the diagnosis and prediction of preoperative metastatic lymph nodes in recent years. This article aims to explore the application of DECT in identifying metastatic lymph nodes (LNs) across various cancer types, including but not limited to thyroid carcinoma (focusing on papillary thyroid carcinoma), lung cancer, and colorectal cancer. Through this narrative review, we aim to elucidate the clinical relevance and utility of DECT in the detection and predictive assessment of lymph node metastasis in malignant tumors, thereby contributing to the broader academic discourse in oncologic radiology and diagnostic precision.

Using the pedicle screw-U rod system for the treatment of double-level lumbar spondylolysis and isthmic spondylolisthesis.

Objective: The aim of this study was to evaluate the efficacy of the pedicle screw-U rod system in treating double-level lumbar spondylolysis with or without spondylolisthesis. Methods: A retrospective study was conducted. Twenty-six patients were included in this study and followed up at 3, 6, and 12 months. Patients without spondylolisthesis were treated with double U-shaped rods (group I), and patients with spondylolisthesis were treated with a lengthened U-shaped rod (group II). Japanese Orthopedic Association (JOA) scores, Oswestry disability index (ODI) scores, disc range of motion (ROM), intervertebral space height of fixed levels and adjacent levels, and grading the degeneration of adjacent segmental intervertebral discs were evaluated preoperatively and postoperatively. Results: JOA and ODI scores improved significantly at 3 months both in groups I and II. The average bone grafting healing time was 6.1 ± 3.1 months for group I and 6 ± 2.8 months for group II. The intervertebral space heights of L4/L5 and L5/S1 were improved significantly at the final follow-up (p < 0.05 for both groups). Surgical segmental and adjacent segmental ROM had no significant change at the final follow-up, in comparison with data preoperatively (p > 0.05). No significant changes of intervertebral space height (L3/L4) and grading of intervertebral disc degeneration were noted before and after surgery (p = 0.141 and 0.484, respectively). Conclusions: The pedicle screw-U rod system provided advantages of being easy in repairing symptomatic double-level lumbar spondylolysis. This technique improved disabilities of patients, preserved the lumbar spine ROM, and delayed the degeneration of adjacent segments.

Dancr-BRG1 regulates Nfatc1 transcription and Pgc1ß-dependent metabolic shifts in osteoclastogenesis.

Long non-coding RNA (lncRNA) serves as a vital regulator of bone metabolism, but its role in pathologically overactive osteoclast differentiation remains elusive. Here, we identify lncRNA Dancr (Differentiation Antagonizing Non-protein Coding RNA) as a critical suppressor of osteoclastogenesis and bone resorption, which is down-regulated in response to estrogen deficiency. Global or osteoclast-specific Dancr Knockout mice display significant trabecular bone deterioration and enhanced osteoclast activity, but minimal alteration of bone formation. Moreover, the bone-targeted delivery of Dancr by Adeno-associated viral remarkably attenuates ovariectomy-induced osteopenia in mice. Mechanistically, Dancr establishes a direct interaction with Brahma-related gene 1 to prevent its binding and preserve H3K27me3 enrichment at the nuclear factor of activated T cells 1 and proliferator-activated receptor gamma coactivator 1-beta promoters, thereby maintaining appropriate expression of osteoclastic genes and metabolic programs during osteoclastogenesis. These results demonstrate that Dancr is a key molecule maintaining proper osteoclast differentiation and bone homeostasis under physiological conditions, and Dancr overexpression constitutes a potential strategy for treating osteoporosis.

3D-printed dosage forms for oral administration: a review.

Oral administration is the most commonly used form of treatment due to its advantages, including high patient compliance, convenient administration, and minimal preparation required. However, the traditional preparation process of oral solid preparation has many defects. Although continuous manufacturing line that combined all the unit operations has been developed and preliminarily applied in the pharmaceutical industry, most of the currently used manufacturing processes are still complicated and discontinuous. As a result, these complex production steps will lead to low production efficiency and high quality control risk of the final product. Additionally, the large-scale production mode is inappropriate for the personalized medicines, which commonly is customized with small amount. Several attractive techniques, such as hot-melt extrusion, fluidized bed pelletizing and spray drying, could effectively shorten the process flow, but still, they have inherent limitations that are challenging to address. As a novel manufacturing technique, 3D printing could greatly reduce or eliminate these disadvantages mentioned above, and could realize a desirable continuous production for small-scale personalized manufacturing. In recent years, due to the participation of 3D printing, the development of printed drugs has progressed by leaps and bounds, especially in the design of oral drug dosage forms. This review attempts to summarize the new development of 3D printing technology in oral preparation and also discusses their advantages and disadvantages as well as potential applications.

Efficacy and safety of short-term edaravone or nerve growth factor add-on therapy for alcohol-related brain damage: A multi-centre randomised control trial.

AIMS: To measure the therapeutic effect of an anti-oxidant, edaravone (EDV), or neurotrophic treatment with nerve growth factor (NGF) as an add-on treatment for alcohol-related brain damage (ARBD). DESIGN: Multi-centre, randomised, single-blinded, comparative clinical trial. SETTING AND PARTICIPANTS: One hundred and twenty-two inpatients recruited from seven hospitals in different regions of China, all diagnosed with ARBD and aged 18 to 65 years old; among them, only two were female. INTERVENTION AND COMPARATOR: Patients were randomly assigned to receive one of three treatments for 2 weeks: 40 patients, treatment as usual (TAU: a combination of intramuscular injections of thiamine, intravenous infusions of other B vitamins with vitamin C and oral medication with vitamin E per day); 40, EDV add-on treatment to TAU (intravenous infusion with 30 mg of EDV twice per day); and 42, NGF add-on treatment to TAU (intramuscular injection of 20 µg of NGF per day). The patients underwent follow-up for 24 weeks. MEASUREMENTS: The primary outcome was the composite score of executive cognitive function in the 2nd week after treatment, which was measured as the mean of the Z scores of the assessments, including the digit symbol substitute test (DSST), digit span memory test-forward (DST-F), digit span memory test-reverse (DST-R) and space span memory test (SSMT). The secondary outcomes were the composite scores at later follow-ups, the score for each component of cognitive function, global cognitive function measured by the Montreal Cognitive Assessment (MoCA), craving for alcohol and the safety of the therapies. FINDINGS: EDV add-on treatment improved the composite score of executive cognitive function better than TAU in the 2nd week (adjusted mean difference: 0.24, 95% confidence interval 0.06 to 0.41; P = 0.008), but NGF add-on treatment did not (adjusted mean difference: 0.07, 95% confidence interval -0.09 to 0.24; P = 0.502). During the follow-up to 24 weeks, EDV add-on treatment improved the composite score of executive cognitive function and DST-R score better than TAU (both P < 0.01). Craving for alcohol was relieved in all three groups. No severe adverse events were observed. CONCLUSION: The short-term addition of edaravone to supplementary therapy treatment for alcohol-related brain damage (ARBD) improved executive cognitive function in patients with ARBD.

Bacterial Cellulose-Based Bandages with Integrated Antibacteria and Electrical Stimulation for Advanced Wound Management.

Bandages for daily wounds are the most common medical supplies, but there are still ingrained defects in their appearance, comfort, functions, as well as environmental pollution. Here, novel bandages based on bacterial cellulose (BC) membrane for wound monitoring and advanced wound management are developed. The BC membrane is combined with silver nanowires (AgNWs) by using vacuum filtration method to achieve transparent, ultrathin (≈7 µm), breathable (389.98-547.79 g m-2  d-1 ), and sandwich-structured BC/AgNWs bandages with superior mechanical properties (108.45-202.35 MPa), antibacterial activities against Escherichia coli and Staphylococcus aureus, biocompatibility, and conductivity (9.8 × 103 -2.0 × 105  S m-1 ). Significantly, the BC/AgNWs bandage is used in the electrical stimulation (direct current, 600  microamperes for 1 h every other day) treatment of full-thickness skin defect in rats, which obviously promotes wound healing by increasing the secretion of vascular endothelial growth factor (VEGF). The BC bandage is used for monitoring wounds and achieve a high accuracy of 94.7% in classifying wound healing stages of hemostasis, inflammation, proliferation, and remodeling, by using a convolutional neural network. The outcomes of this study not only provide two BC-based bandages as multifunctional wound management, but also demonstrate a new strategy for the development of the next generation of smart bandage.

Evaluation of lumbar paraspinal muscles degeneration and fatty infiltration in dynamic sagittal imbalance based on magnetic resonance imaging.

PURPOSE: To explore degeneration and fatty infiltration (FI) of lumbar paraspinal muscles in patients with dynamic sagittal imbalance (DSI) and the relationship between lumbar paraspinal muscles degeneration, fatty infiltration and severity of the disease. METHODS: We recruited 41 DSI patients and selected 22 lumbar spinal stenosis (LSS) patients without osphyalgia as controls. All patients received magnetic resonance imaging (MRI) scan and DSI patients also received pre-walk and post-walk X-rays. DSI patients were divided into 2 subgroups according to their symptom improvement after conservative treatment. We calculated rmCSA and FI of the lumbar paraspinal muscles. The rmCSA and FI between DSI and control and between DSI subgroups were compared by t test. The regression analysis was used to explore the risk factors influencing disease severity. Receiver operating characteristic (ROC) curves and area under curves (AUCs) were used to evaluate the severity of the disease. RESULTS: In comparison of rmCSA and FI between DSI and control, there are significant differences of most muscles. In comparison of rmCSA between two subgroups, there are significant differences of most muscles, while in comparison of FI, only muscles in L4 segment have significant different. In logistic regression analysis, total rmCSA and total FI are risk factors influencing disease severity. ROC curves shows that total rmCSA and total FI both achieve an AUC greater than 0.7. CONCLUSION: Compared with control, DSI patients have degeneration and fatty infiltration of the lumbar paraspinal muscles. The degeneration and fatty infiltration are risk factors influencing disease severity. The total rmCSA and total FI can be used as an indicator to determine whether a patient has severe DSI.

Bioinformatics and system biology analysis revealed the crosstalk between COVID-19 and osteoarthritis.

BACKGROUND: The global coronavirus disease 2019 (COVID-19) outbreak has significantly impacted public health. Moreover, there has been an association between the incidence and severity of osteoarthritis (OA) and the onset of COVID-19. However, the optimal diagnosis and treatment strategies for patients with both diseases remain uncertain. Bioinformatics is a novel approach that may help find the common pathology between COVID-19 and OA. METHODS: Differentially expressed genes (DEGs) were screened by R package "limma." Functional enrichment analyses were performed to find key biological functions. Protein-protein interaction (PPI) network was constructed by STRING database and then Cytoscape was used to select hub genes. External data sets and OA mouse model validated and identified the hub genes in both mRNA and protein levels. Related transcriptional factors (TF) and microRNAs (miRNAs) were predicted with miRTarBase and JASPR database. Candidate drugs were obtained from Drug Signatures database. The immune infiltration levels of COVID-19 and OA were evaluated by CIBERSORT and scRNA-seq. RESULTS: A total of 74 common DEGs were identified between COVID-19 and OA. Receiver operating characteristic curves validated the effective diagnostic values (area under curve > 0.7) of four hub genes (matrix metalloproteinases 9, ATF3, CCL4, and RELA) in both the training and validation data sets of COVID-19 and OA. Quantitative polymerase chain reaction and Western Blot showed significantly higher hub gene expression in OA mice than in healthy controls. A total of 84 miRNAs and 28 TFs were identified to regulate the process of hub gene expression. The top 10 potential drugs were screened including "Simvastatin," "Hydrocortisone," and "Troglitazone" which have been proven by Food and Drug Administration. Correlated with hub gene expression, Macrophage M0 was highly expressed while Natural killer cells and Mast cells were low in both COVID-19 and OA. CONCLUSION: Four hub genes, disease-related miRNAs, TFs, drugs, and immune infiltration help to understand the pathogenesis and perform further studies, providing a potential therapy target for COVID-19 and OA.

Causal effects of gut microbiota on scoliosis: A bidirectional two-sample mendelian randomization study.

Background: Recent studies have shown altered gut microbiome composition in patients with scoliosis. However, the causal effect of gut microbiota on scoliosis remains unknown. Methods: A Mendelian randomization (MR) study was conducted to quantify the impact of 191 gut microbiome taxa's instrumental variables from the MibioGen Genome-wide association study (GWAS) on scoliosis risk using data from the FinnGen GWAS (1168 cases and 16,4682 controls). Inverse variance weighted (IVW) was the main method, and MR results were verified by sensitive analysis. Results: Bilophila, Eubacterium (eligens group), Prevotella9, and Ruminococcus2 were discovered to have a protective effect on the risk of scoliosis. Ruminococcaceae UCG009, Catenibacterium, Coprococcus2, Eubacterium (ventriosum group), Lachnospiraceae (FCS020 group), Ruminiclostridium6, and Mollicutes RF9 may increase the occurrence of scoliosis. Heterogeneity (P > 0.05) and pleiotropy (P > 0.05) analysis confirmed the robustness of the MR results. Conclusion: Our study identified four protective bacteria taxa on scoliosis and seven microbiota that may increase scoliosis occurrence. Further MR analysis is required to corroborate our findings, using a more sophisticated technique to obtain estimates with less bias and greater precision or GWAS summary data with more gut microbiome and scoliosis patients.

Neurological and metabolic related pathophysiologies and treatment of comorbid diabetes with depression.

BACKGROUND: The comorbidity between diabetes mellitus and depression was revealed, and diabetes mellitus increased the prevalence of depressive disorder, which ranked 13th in the leading causes of disability-adjusted life-years. Insulin resistance, which is common in diabetes mellitus, has increased the risk of depressive symptoms in both humans and animals. However, the mechanisms behind the comorbidity are multi-factorial and complicated. There is still no causal chain to explain the comorbidity exactly. Moreover, Selective serotonin reuptake inhibitors, insulin and metformin, which are recommended for treating diabetes mellitus-induced depression, were found to be a risk factor in some complications of diabetes. AIMS: Given these problems, many researchers made remarkable efforts to analyze diabetes complicating depression from different aspects, including insulin resistance, stress and Hypothalamic-Pituitary-Adrenal axis, neurological system, oxidative stress, and inflammation. Drug therapy, such as Hydrogen Sulfide, Cannabidiol, Ascorbic Acid and Hesperidin, are conducive to alleviating diabetes mellitus and depression. Here, we reviewed the exact pathophysiology underlying the comorbidity between depressive disorder and diabetes mellitus and drug therapy. METHODS: The review refers to the available literature in PubMed and Web of Science, searching critical terms related to diabetes mellitus, depression and drug therapy. RESULTS: In this review, we found that brain structure and function, neurogenesis, brain-derived neurotrophic factor and glucose and lipid metabolism were involved in the pathophysiology of the comorbidity. Obesity might lead to diabetes mellitus and depression through reduced adiponectin and increased leptin and resistin. In addition, drug therapy displayed in this review could expand the region of potential therapy. CONCLUSIONS: The review summarizes the mechanisms underlying the comorbidity. It also overviews drug therapy with anti-diabetic and anti-depressant effects.

From imaging to clinical outcome: dual-region CT radiomics predicting FOXM1 expression and prognosis in hepatocellular carcinoma.

Background: Liver cancer, especially hepatocellular carcinoma (HCC), remains a significant global health challenge. Traditional prognostic indicators for HCC often fall short in providing comprehensive insights for individualized treatment. The integration of genomics and radiomics offers a promising avenue for enhancing the precision of HCC diagnosis and prognosis. Methods: From the Cancer Genome Atlas (TCGA) database, we categorized mRNA of HCC patients by Forkhead Box M1 (FOXM1) expression and performed univariate and multivariate studies to pinpoint autonomous HCC risk factors. We deployed subgroup, correlation, and interaction analyses to probe FOXM1's link with clinicopathological elements. The connection between FOXM1 and immune cells was evaluated using the CIBERSORTx database. The functions of FOXM1 were investigated through analyses of Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). After filtering through TCGA and the Cancer Imaging Archive (TCIA) database, we employed dual-region computed tomography (CT) radiomics technology to noninvasively predict the mRNA expression of FOXM1 in HCC tissues. Radiomic features were extracted from both tumoral and peritumoral regions, and a radiomics score (RS) was derived. The performance and robustness of the constructed models were evaluated using 10-fold cross-validation. A radiomics nomogram was developed by incorporating RS and clinical variables from the TCGA database. The models' discriminative abilities were assessed using metrics such as the area under the curve (AUC) of the receiver operating characteristic curves (ROC) and precision-recall (PR) curves. Results: Our findings emphasized the overexpression of FOXM1 as a determinant of poor prognosis in HCC and illustrated its impact on immune cell infiltration. After selecting arterial phase CT, we chose 7 whole-tumor features and 3 features covering both the tumor and its surroundings to create WT and WP models for FOXM1 prediction. The WT model showed strong predictive capabilities for FOXM1 expression by PR curve. Conversely, the WP model did not demonstrate the good predictive ability. In our study, the radiomics score (RS) was derived from whole-tumor regions on CT images. The RS was significantly associated with FOXM1 expression, with an AUC of 0.918 in the training cohort and 0.837 in the validation cohort. Furthermore, the RS was correlated with oxidative stress genes and was integrated with clinical variables to develop a nomogram, which demonstrated good calibration and discrimination in predicting 12-, 36-, and 60-month survival probabilities. Additionally, bioinformatics analysis revealed FOXM1's potential role in shaping the immune microenvironment, with its expression linked to immune cell infiltration. Conclusion: This study highlights the potential of integrating FOXM1 expression and radiomics in understanding HCC's complexity. Our approach offers a new perspective in utilizing radiomics for non-invasive tumor characterization and suggests its potential in providing insights into molecular profiles. Further research is needed to validate these findings and explore their clinical implications in HCC management.

Mapping the intellectual structure and landscape of nano-drug delivery systems in colorectal cancer.

Background: Colorectal cancer (CRC) is a prevalent malignancy affecting the digestive tract, and its incidence has been steadily rising over the years. Surgery remains the primary treatment modality for advanced colorectal cancer, complemented by chemotherapy. The development of drug resistance to chemotherapy is a significant contributor to treatment failure in colorectal cancer. Nanodrug delivery systems (NDDS) can significantly improve the delivery and efficacy of antitumor drugs in multiple ways. However, there is a lack of visualization of NDDS research structures and research hotspots in the field of colorectal cancer, and the elaboration of potential research areas remains to be discovered. Objective: To comprehensively explore the current research status and development trend of NDDS in CRC research. Methods: Bibliometric analysis of articles and reviews on NDDS for CRC published between 2002 and 2022 using tools including CiteSpace, VOSviewer, R-bibliometrix, and Microsoft Excel was performed. Results: A total of 1866 publications authored by 9,870 individuals affiliated with 6,126 institutions across 293 countries/regions were included in the analysis. These publications appeared in 456 journals. Abnous Khalil has the highest number of publications in this field. The most published journals are the International Journal of Nanomedicine, International Journal of Pharmaceutics, and Biomaterials. Notably, the Journal of Controlled Release has the highest citation count and the third-highest H-index. Thematic analysis identified "inflammatory bowel disease"," "oral drug delivery," and "ulcerative colitis" as areas requiring further development. Keyword analysis revealed that "ulcerative colitis," "exosomes," and "as1411"have emerged as keywords within the last 2 years. These emerging keywords may become the focal points of future research. Conclusion: Our findings reveal the current research landscape and intellectual structure of NDDS in CRC research which helps researchers understand the research trends and hot spots in this field.

Identification of ROCK1 as a novel biomarker for postmenopausal osteoporosis and pan-cancer analysis.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a prevalent bone disorder with significant global impact. The elevated risk of osteoporotic fracture in elderly women poses a substantial burden on individuals and society. Unfortunately, the current lack of dependable diagnostic markers and precise therapeutic targets for PMOP remains a major challenge. METHODS: PMOP-related datasets GSE7429, GSE56814, GSE56815, and GSE147287, were downloaded from the GEO database. The DEGs were identified by "limma" packages. WGCNA and Machine Learning were used to choose key module genes highly related to PMOP. GSEA, DO, GO, and KEGG enrichment analysis was performed on all DEGs and the selected key hub genes. The PPI network was constructed through the GeneMANIA database. ROC curves and AUC values validated the diagnostic values of the hub genes in both training and validation datasets. xCell immune infiltration and single-cell analysis identified the hub genes' function on immune reaction in PMOP. Pan-cancer analysis revealed the role of the hub genes in cancers. RESULTS: A total of 1278 DEGs were identified between PMOP patients and the healthy controls. The purple module and cyan module were selected as the key modules and 112 common genes were selected after combining the DEGs and module genes. Five Machine Learning algorithms screened three hub genes (KCNJ2, HIPK1, and ROCK1), and a PPI network was constructed for the hub genes. ROC curves validate the diagnostic values of ROCK1 in both the training (AUC = 0.73) and validation datasets of PMOP (AUC = 0.81). GSEA was performed for the low-ROCK1 patients, and the top enriched field included protein binding and immune reaction. DCs and NKT cells were highly expressed in PMOP. Pan-cancer analysis showed a correlation between low ROCK1 expression and SKCM as well as renal tumors (KIRP, KICH, and KIRC). CONCLUSIONS: ROCK1 was significantly associated with the pathogenesis and immune infiltration of PMOP, and influenced cancer development, progression, and prognosis, which provided a potential therapy target for PMOP and tumors. However, further laboratory and clinical evidence is required before the clinical application of ROCK1 as a therapeutic target.