Human umbilical cord mesenchymal stem cells promote steroid-induced osteonecrosis of the femoral head repair by improving microvascular endothelial cell function.

Recently, there has been growing interest in using cell therapy through core decompression (CD) to treat osteonecrosis of the femoral head (ONFH). Our study aimed to investigate the effectiveness and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in treating steroid-induced ONFH. We constructed a steroid-induced ONFH rabbit model as well as dexamethasone (Dex)-treated bone microvascular endothelial cells (BMECs) model of human femoral head. We injected hUCMSCs into the rabbit femoral head via CD. The effects of hUCMSCs on steroid-induced ONFH rabbit model and Dex-treated BMECs were evaluated via micro-CT, microangiography, histology, immunohistochemistry, wound healing, tube formation, and western blotting assay. Furthermore, we conducted single-cell RNA sequencing (scRNA-seq) to examine the characteristics of endothelial cells, the activation of signaling pathways, and inter-cellular communication in ONFH. Our data reveal that hUCMSCs improved the femoral head microstructure and bone repair and promoted angiogenesis in the steroid-induced ONFH rabbit model. Importantly, hUCMSCs improved the migration ability and angioplasty of Dex-treated BMECs by secreting COL6A2 to activate FAK/PI3K/AKT signaling pathway via integrin α1ß1.

Sequencing, Analysis and Organization of the Complete Genome of a Novel Baculovirus Calliteara abietis Nucleopolyhedrovirus (CaabNPV).

Baculoviridae, a virus family characterized by a single large double stranded DNA, encompasses the majority of viral bioinsecticides, representing a highly promising and environmentally friendly pesticide approach to insect control. This study focuses on the characterization of a baculovirus isolated from larvae of Calliteara abietis (Erebidae, Lymantriidae) collected in Mongolian pinaceae forests. This new isolate was called Calliteara abietis nucleopolyhedrovirus (CaabNPV). CaabNPV exhibits an irregular polyhedron shape, and significant variation in the diameter of its occlusion bodies (OBs) was observed. Nucleotide distance calculations confirmed CaabNPV as a novel baculovirus. The CaabNPV genome spans 177,161 bp with a G+C content of 45.12% and harbors 150 potential open reading frames (ORFs), including 38 core genes. A comprehensive genomic analysis categorizes CaabNPV within Group II alphabaculovirus, revealing a close phylogenetic relationship with Alphabaculovirus orleucostigmae (OrleNPV). Additionally, repeat sequence analysis identified three highly repetitive sequences consisting of 112 bp repeat units, known as homologous regions (hrs). This research contributes valuable insights into CaabNPV's phylogenetic placement, genomic structure, and its potential applications in insect biocontrol.

Nanocomposites based on nanoceria regulate the immune microenvironment for the treatment of polycystic ovary syndrome.

The immune system is closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). Macrophages are one of the important immune cell types in the ovarian proinflammatory microenvironment, and ameliorate the inflammatory status mainly through M2 phenotype polarization during PCOS. Current therapeutic approaches lack efficacy and immunomodulatory capacity, and a new therapeutic method is needed to prevent inflammation and alleviate PCOS. Here, octahedral nanoceria nanoparticles with powerful antioxidative ability were bonded to the anti-inflammatory drug resveratrol (CeO2@RSV), which demonstrates a crucial strategy that involves anti-inflammatory and antioxidative efficacy, thereby facilitating the proliferation of granulosa cells during PCOS. Notably, our nanoparticles were demonstrated to possess potent therapeutic efficacy via anti-inflammatory activities and effectively alleviated endocrine dysfunction, inflammation and ovarian injury in a dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Collectively, this study revealed the tremendous potential of the newly developed nanoparticles in ameliorating the proinflammatory microenvironment and promoting the function of granulosa cells, representing the first attempt to treat PCOS by using CeO2@RSV nanoparticles and providing new insights in combating clinical PCOS.

Identification and validation of long noncoding RNA AC083900.1 and RP11-283C24.1 for prediction of progression of osteosarcoma.

BACKGROUND: The role of cuproptosis, an emerging cell death pathway that makes a remarkable contribution to tumor progression, remains elusive in osteosarcoma (OS), in addition to its regulator, including long-no-coding RNAs (lncRNAs) that are also a critical factor for fueling OS. METHODS: Transcriptome and clinical data from 70 normal human bone tissue samples and 84 frozen clinical osteosarcoma samples were included in this study. Cuproptosis-associated lncRNAs (CRlncs) were identified through differential expression and co-expression analyses. Univariate Cox regression was performed to screen for prognostic lncRNAs, then we used least absolute shrinkage and selection operator regression to distinguish prognosis-related CRlncs (AC083900.1 and RP11-283C24.1) for modeling the CRlncs prognostic signature (CLPS) by multivariate Cox regression using the stepwise method. CLPS performance was tested by independent prognostic analyses, survival curve and receiver operating characteristic (ROC) curve. In addition, the molecular and immune mechanisms that underlie the unfavorable prognosis of CLPS-identified high-risk group were elucidated. RESULT: AC083900.1 and RP11-283C24.1 have been identified as the most important CRlncs for OS progression (hazard ratio: 3.498 and 2.724, respectively), and the derived CLPS demonstrated outstanding performance for the prediction of OS prognosis (AUC of 0.799 and 0.778 in the training and test sets, both adj-p < 0.05 in survival curve). As was anticipated, CLPS also outperformed a recent clinical prognostic approach that only achieved an AUC of 0.682 [metastasis]. It is notable that AC083900.1 progressed OS metastasis, evidenced by its high expression in metastatic OS, its high correlation to metastasis-related genes, and its high AUC of 0.683 for the prediction of metastasis. Mechanistically, AC083900.1 and RP11-283C24.1 dysregulated many critical biological processes regarding humoral immune response, immunoglobulin complex, etc.; while reducing the infiltration of many cytotoxic immune cells (B-cells, TIL, neutrophils, etc.). It is encouraging that BMS-509744 and KIN001-135 demonstrated high therapeutic implications for CLPS-identified high-risk OS, and the low-risk counterpart was sensitive to SB-216763. Quantitative RT-PCR analysis showed that both AC083900.1 and RP11-283C24.1 were significantly upregulated in different osteosarcoma cell lines. CONCLUSION: This study elucidated the roles and mechanisms of AC083900.1 and RP11-283C24.1 in the development of OS, fostering a reliable prognostic approach and treatment for OS patients.

Probing the Potential of Defense Response-Associated Genes for Predicting the Progression, Prognosis, and Immune Microenvironment of Osteosarcoma.

BACKGROUND: The defense response is a type of self-protective response of the body that protects it from damage by pathogenic factors. Although these reactions make important contributions to the occurrence and development of tumors, the role they play in osteosarcoma (OS), particularly in the immune microenvironment, remains unpredictable. METHODS: This study included the clinical information and transcriptomic data of 84 osteosarcoma samples and the microarray data of 12 mesenchymal stem cell samples and 84 osteosarcoma samples. We obtained 129 differentially expressed genes related to the defense response (DRGs) by taking the intersection of differentially expressed genes with genes involved in the defense response pathway, and prognostic genes were screened using univariate Cox regression. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression and multivariate Cox regression were then used to establish a DRG prognostic signature (DGPS) via the stepwise method. DGPS performance was examined using independent prognostic analysis, survival curves, and receiver operating characteristic (ROC) curves. In addition, the molecular and immune mechanisms of adverse prognosis in high-risk populations identified by DGPS were elucidated. The results were well verified by experiments. RESULT: BNIP3, PTGIS, and ZYX were identified as the most important DRGs for OS progression (hazard ratios of 2.044, 1.485, and 0.189, respectively). DGPS demonstrated outstanding performance in the prediction of OS prognosis (area under the curve (AUC) values of 0.842 and 0.787 in the training and test sets, respectively, adj-p < 0.05 in the survival curve). DGPS also performed better than a recent clinical prognostic approach with an AUC value of only 0.674 [metastasis], which was certified in the subsequent experimental results. These three genes regulate several key biological processes, including immune receptor activity and T cell activation, and they also reduce the infiltration of some immune cells, such as B cells, CD8+ T cells, and macrophages. Encouragingly, we found that DGPS was associated with sensitivity to chemotherapeutic drugs including JNK Inhibitor VIII, TGX221, MP470, and SB52334. Finally, we verified the effect of BNIP3 on apoptosis, proliferation, and migration of osteosarcoma cells through experiments. CONCLUSIONS: This study elucidated the role and mechanism of BNIP3, PTGIS, and ZYX in OS progression and was well verified by the experimental results, enabling reliable prognostic means and treatment strategies to be proposed for OS patients.

Effect of obstructive sleep apnea on semen quality.

BACKGROUND: Obstructive sleep apnea (OSA) has several notable complications such as hypertension and diabetes. Studies have also shown that OSA is associated with erectile dysfunction and reduced androgen levels. However, the effect of OSA on semen quality remains poorly studied. METHODS: Men attending a tertiary reproductive center for semen analysis were tested with a portable sleep breathing monitor. Patients were divided into four groups based on their apnea hypopnea index: none, mild, moderate, and severe obstructive sleep apnea. Differences between groups were assessed using χ2, and associations were tested with multiple regression analysis. RESULTS: We included a total of 175 male subjects with a mean age of 32.2 ± 3.6 years. There were significant differences between groups in progressive sperm motility (%) (43 ± 16, 42 ± 17, 36 ± 18, 29 ± 18, respectively; p = 0.002), total motility (%) (59 ± 19, 59 ± 20, 49 ± 21, 42 ± 20, respectively; p = 0.010), and vitality (%) (80 ± 10, 81 ± 11, 79 ± 8, 72 ± 19, respectively; p = 0.039). Asthenospermia (progressive motility < 35%) was significantly more common in subjects with OSA (χ2 = 5.195, p = 0.023). In multiple regression models, after adjusting for age and body mass index, apnea hypopnea index remained negatively and significantly associated with progressive motility, total motility, and vitality. CONCLUSIONS: OSA is an independent risk factor for sperm motility and vitality, and further investigation is now needed to determine if continuous positive pressure ventilation or other therapies can improve semen quality in these patients.

Establishment of a rapid detection method for plutella xylostella granulovirus based on qPCR.

Plutella xylostella granulovirus (PlxyGV) biopesticide is an effective tool to control the long-term damage of Plutella xylostella (Linnaeus) to cruciferous vegetables. In China, PlxyGV can be produced on a large scale using host insects, and its products have been registered in 2008. In experiments and biopesticide production, the routine enumeration method of PlxyGV virus particles is to use the Petroff-Hausser counting chamber in dark field microscope. However, the accuracy and repeatability of granulovirus (GV) counting are affected due to the small particle size of GV occlusion bodies (OBs), the limitations of optical microscope, the judgment of different operators, host impurities, the addition of biological products. This limits the convenience of its production, product quality, trading and field application. Here we use PlxyGV as an example, the method based on Real-time fluorescence quantitative PCR (qPCR) was optimized from two aspects of sample treatment and specific primers design, which improved the repeatability and accuracy of absolute quantitative OBs of GV. This study provides basic information for accurate quantitative PlxyGV by qPCR method.

Gastrodin alleviates rat chondrocyte senescence and mitochondrial dysfunction through Sirt3.

Several researchers have focused on understanding the pathogenesis and treatment strategies for osteoarthritis (OA). Gastrodin (GAS) is a potential anti-inflammatory agent. In this study, we constructed an in vitro OA chondrocyte model by treating chondrocytes with IL-1ß. Next, we determined the expression of aging-related markers and mitochondrial functions in chondrocytes treated with GAS. Further, we constructed a "drug-component-target-pathway-disease" interactive network and determined the effect of GAS on the functions and pathways related to OA. Finally, we constructed the OA rat model by removing the medial meniscus of the right knee and transection of the anterior cruciate ligament. The results revealed that GAS reduced senescence and improved mitochondrial functions in OA chondrocytes. We used network pharmacology and bioinformatics to screen for key molecules Sirt3 and the PI3K-AKT pathway involved in regulating the effect of GAS on OA. Further studies showed an increase in SIRT3 expression and reduced chondrocyte aging, mitochondrial damage, and the phosphorylation of the PI3K-AKT pathway. The results showed that GAS ameliorates pathological changes related to aging, increases SIRT3 expression, and protects the ECM in the OA rat model. These results were consistent with our bioinformatics results and previous studies. In summary, GAS slows down the aging of chondrocytes and mitochondrial damage in OA by regulating the phosphorylation of the PI3K-AKT pathway via SIRT3.

8-oxoguanine DNA Glycosylase (OGG1) may be a Diagnostic Indicator of Diminished Ovarian Reserve (DOR).

BACKGROUND: Oxidative/antioxidant imbalance is considered a causal cause of diminished ovarian reserve (DOR). 8-oxyguanine DNA glycosylase (OGG1) has been reported to act as an antioxidant by binding non-catalytically to oxidation-induced DNA damage in the promoter region. OBJECTIVE: This study aimed to evaluate serum OGG1 concentrations in patients with or without DOR and to explore the clinical value of OGG1 as a novel diagnostic indicator for DOR. METHODS: Sixty-four women with DOR and seventy-eight women with normal ovarian reserve (NOR) from the reproductive medical center of Renmin Hospital of Wuhan University were included. Enzyme-linked immunosorbent assay (ELISA) kits were used to determine serum OGG1 levels in patients on 2-5 days of the menstrual cycle. Data regarding the enrolled patients were also obtained from the database of the hospital, including age, body mass index (BMI), anti-Müllerian hormone (AMH), etc. Results: OGG1 levels were increased in the DOR group (2.08 ± 0.70 vs 1.46 ± 0.47 nmol/L, P < 0.001) and negatively correlated with AMH levels (Spearman r = -0.586, P < 0.001). After adjusting for age and BMI, a negative association between OGG1 and AMH remained (ß = -0.619, P < 0.001). ROC curve analysis showed that a cut-off value of 1.765 nmol/L had an appropriate sensitivity (81.30%) and specificity (76.90%) for discriminating individuals with and without DOR, with the area under the curve (95% CI) of 0.870 (0.814 to 0.926), P < 0.001. CONCLUSION: We determined that serum OGG1 levels might be suggested as a new diagnostic indicator for DOR.

Ensemble deep learning enhanced with self-attention for predicting immunotherapeutic responses to cancers.

Introduction: Despite the many benefits immunotherapy has brought to patients with different cancers, its clinical applications and improvements are still hindered by drug resistance. Fostering a reliable approach to identifying sufferers who are sensitive to certain immunotherapeutic agents is of great clinical relevance. Methods: We propose an ELISE (Ensemble Learning for Immunotherapeutic Response Evaluation) pipeline to generate a robust and highly accurate approach to predicting individual responses to immunotherapies. ELISE employed iterative univariable logistic regression to select genetic features of patients, using Monte Carlo Tree Search (MCTS) to tune hyperparameters. In each trial, ELISE selected multiple models for integration based on add or concatenate stacking strategies, including deep neural network, automatic feature interaction learning via self-attentive neural networks, deep factorization machine, compressed interaction network, and linear neural network, then adopted the best trial to generate a final approach. SHapley Additive exPlanations (SHAP) algorithm was applied to interpret ELISE, which was then validated in an independent test set. Result: Regarding prediction of responses to atezolizumab within esophageal adenocarcinoma (EAC) patients, ELISE demonstrated a superior accuracy (Area Under Curve [AUC] = 100.00%). AC005786.3 (Mean [|SHAP value|] = 0.0097) was distinguished as the most valuable contributor to ELISE output, followed by SNORD3D (0.0092), RN7SKP72 (0.0081), EREG (0.0069), IGHV4-80 (0.0063), and MIR4526 (0.0063). Mechanistically, immunoglobulin complex, immunoglobulin production, adaptive immune response, antigen binding and others, were downregulated in ELISE-neg EAC subtypes and resulted in unfavorable responses. More encouragingly, ELISE could be extended to accurately estimate the responsiveness of various immunotherapeutic agents against other cancers, including PD1/PD-L1 suppressor against metastatic urothelial cancer (AUC = 88.86%), and MAGE-A3 immunotherapy against metastatic melanoma (AUC = 100.00%). Discussion: This study presented deep insights into integrating ensemble deep learning with self-attention as a mechanism for predicting immunotherapy responses to human cancers, highlighting ELISE as a potential tool to generate reliable approaches to individualized treatment.

Procyanidin B2 ameliorates the progression of osteoarthritis: An in vitro and in vivo study.

OBJECTIVE: Osteoarthritis (OA) is characterized by cartilage degeneration and inflammation. Procyanidin B2 (PCB2), a natural flavonoid compound, exhibits potential anti-inflammatory and anti-oxidative effects against several diseases. However, its curative effects on OA remain unclear. PURPOSE: Herein, we explored the anti-arthritic effects of PCB2 on OA onset and progress and its potential mechanism. METHODS: CCK-8 assays and EdU staining were used to assess the cytotoxic effects and cell proliferation activity of PCB2. Flow cytometry was used to detect apoptosis in chondrocytes. ELISA, qPCR, and western blotting, were applied to explore the expression of apoptosis and senescence-associated secretion phenotype (SASP) factors. The Nrf2/NF-κB signaling cascade was explored using immunofluorescence and western blotting. Additionally, we silenced the Nrf2 gene using siRNAs to verify its function in PCB2 regulation of senescence and apoptosis phenotypes. Safranin O-Fast Green (SO) and immunohistochemical staining were used to explore the effects of PCB2 on OA model rats. RESULTS: PCB2 dampened interleukin (IL)-1ß-triggered expression of SASP factors in vitro. Additionally, PCB2 diminished IL-1ß-triggered destruction of the extracellular matrix (ECM) via downregulating the expression of MMPs, while upregulating the expression of collagen II and aggrecan. In addition, PCB2 treatment reduced IL-1ß-induced apoptosis of chondrocytes. Mechanistically, PCB2 could attenuated chondrocyte senescence in vitro via the Nrf2/NF-κB pathway. Moreover, PCB2 exhibited anti-apoptotic properties via the Nrf2/BAX/Bcl-2 pathway. PCB2 alleviated knee cartilage degeneration in an OA rat model. CONCLUSIONS: Our results suggest that PCB2 may be used as a therapeutic agent for OA.

Dissecting the effect of sphingolipid metabolism gene in progression and microenvironment of osteosarcoma to develop a prognostic signature.

Sphingolipid metabolism (SM) fuels tumorigenesis and the malignant progression of osteosarcoma (OS), which leads to an unfavorable prognosis. Elucidating the molecular mechanisms underlying SM in osteosarcoma and developing a SM-based prognostic signature could be beneficial in the clinical setting. This study included 88 frozen OS samples to recognize the vital SM-relevant genes in the development of OS utilizing univariate Cox regression. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was conducted on the SM- relevant genes to minimize the risk of overfitting. The prognostic signature was generate utilizing the multivariable Cox regression analysis and was verified in the validation cohort. Moreover, cellular and molecular mechanisms associated with SM have an unfavorable prognosis for OS patients and have been widely studied. Resultantly, an SM-based prognostic risk model was established according to critical prognostic genes (CBS, GLB1, and HACD1), which had an excellent ability to predict the prognosis of OS patients (AUC for the train cohort was 0.887 and AUC for validation cohort was 0.737). The high-risk OS patients identified based on this prognostic signature had significantly poor immune microenvironment, indicated by significantly low immune score (mean=216.290 ± 662.463), reduced infiltrations of 25 immune cells, including NK cells (LogFC= -0.3597), CD8+T cells ((LogFC=-0.2346), Cytolytic activity ((LogFC=-0.1998), etc. The immunosuppressive microenvironment could be due to dysregulated SM of glycolipids. Further, a nomogram was constructed by integrating the SM-based prognostic signature and clinical paraments to facilitate clinical application. The nomogram could accurately predict the prognosis of OS invalids. Collectively, this study clarified the function of SM in the development of OS and helped develop a tool for risk stratification based on SM-related genes with application in clinical settings. The results of our study will aid in identifying high-risk patients and provide individualized treatments.

A novel inflammation-associated prognostic signature for clear cell renal cell carcinoma.

Clear cell renal cell carcinoma (ccRCC) are typically situated in a complex inflammatory and immune microenvironment, which has been reported to contribute to the unfavorable prognosis of patients with ccRCC. There would be beneficial clinical implications for elucidating the roles of its molecular characteristics in the inflammatory microenvironment. This is because it would facilitate the development of reliable biomarkers for pre-stratification prior to the designation of individualized treatment strategies. In the present study, RNA-sequencing data from 607 patients were retrospectively analyzed to elucidate the profile of inflammatory molecules. Based on this, an inflammatory prognostic signature (IPS) was developed and further validated using clinical ccRCC samples. Subsequently, the associated mechanisms in terms of the immune microenvironment and molecular pathways were then investigated. This proposed IPS was found to exhibit superior accuracy compared with the criterion of a good prognostic model for the prediction of patient prognosis from ccRCC [area under the receiver operating characteristic curve (AUC)=0.811] in addition to being an independent factor for prognostic risk stratification [hazard ratio: 11.73 (95% CI, 26.98-5.10); log-rank test, P<0.001]. Pathologically, ccRCC cells identified as high-risk according to their IPS presented with a more malignant tumor structure, including voluminous eosinophilic cytoplasm, acinar/lamellar/tubular growth patterns and atypic nuclei. High-risk ccRCC also exhibited higher infiltration levels by four types of immune cells, including T regulatory cells, but lower infiltration levels by mast cells. Pathways associated with immune-inflammation interaction, including the IL-17 pathway, were found to be upregulated in IPS-identified high-risk ccRCC. Furthermore, by combining the IPS with clinical factors, an integrated prognostic index was developed and validated for increasing the accuracy of patient risk-stratification for ccRCC (AUC=0.911). In conclusion, the complex regulatory mechanisms and molecular characteristics involved in ccRCC-inflammation interaction, coupled with their prognostic potential, were systematically elucidated in the present study. This may have important implications in furthering the understanding into the molecular mechanisms underlying this ccRCC-inflammation interaction, which can in turn be exploited for identifying high-risk patients with ccRCC prior to designing their clinical treatment strategy.

Salidroside alleviates oxidative stress and apoptosis via AMPK/Nrf2 pathway in DHT-induced human granulosa cell line KGN.

In the past few years, emerging evidence established persistent oxidative stress to be a key player in the pathogenesis of polycystic ovary syndrome (PCOS). Particularly, it damages the function of granulosa cells, and thus hinders the development of follicles. The present study aimed to explore and establish the protective effects of salidroside on dihydrotestosterone (DHT)-induced Granulosa-like tumor cell line (KGN), mediated via antioxidant mechanisms. The study assessed the positive effects of salidroside on DHT-induced apoptosis, reactive oxygen species (ROS) accumulation, damage of antioxidant capacity, and mitochondrial membrane potential depolarization. Interestingly, salidroside partly reversed DHT mediated effects, via stimulation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and the downstream antioxidant proteins heme oxygenase-1(HO-1) and quinine oxidoreductase 1(NQO1). Additionally, the knockdown of Nrf2 partly moderated the antioxidant and anti-apoptosis effects of salidroside in DHT-treated KGN cells. Mechanistically, AMP-activated protein kinase (AMPK) was identified to be the upstream signaling involved in salidroside-induced Nrf2 activation, as silencing of AMPK partly prevented the upregulation of Nrf2 and the downstream proteins HO-1 and NQO1. Altogether, the present study is the first to effectively demonstrate the inhibitory effect of salidroside on DHT-stimulated oxidative stress and apoptosis in KGN cells, which was dependent on Nrf2 activation that involved AMPK.

The Effect of Individual Musculoskeletal Conditions on Depression: Updated Insights From an Irish Longitudinal Study on Aging.

Few longitudinal studies have systematically investigated whether or how individual musculoskeletal conditions (IMCs) convey risks for negative psychological health outcomes, and approaches to assess such risk in the older population are lacking. In this Irish nationally representative longitudinal prospective study of 6,715 individuals aged 50 and above, machine learning algorithms and various models, including mediation models, were employed to elaborate the underlying mechanisms of IMCs leading to depression and to develop an IMC-induced negative psychological risk (IMCPR) classification approach. Resultantly, arthritis [odds ratio (95% confidence interval): 2.233 (1.700-2.927)], osteoporosis [1.681 (1.133-2.421)], and musculoskeletal chronic pain [MCP, 2.404 (1.838-3.151)] were found to increase the risk of depression after 2 years, while fracture and joint replacement did not. Interestingly, mediation models further demonstrated that arthritis per se did not increase the risk of depression; such risk was augmented only when arthritis-induced restrictions of activities (ARA) existed [proportion of mediation: 316.3% (ARA of usual), 213.3% (ARA of social and leisure), and 251.3% (ARA of sleep)]. The random forest algorithm attested that osteoarthritis, not rheumatoid arthritis, contributed the most to depressive symptoms. Moreover, bone mineral density was negatively associated with depressive symptoms. Systemic pain contributed the most to the increased risk of depression, followed by back, knee, hip, and foot pain (mean Gini-Index: 3.778, 2.442, 1.980, 1.438, and 0.879, respectively). Based on the aforementioned findings, the IMCPR classification approach was developed using an interpretable machine learning model, which stratifies participants into three grades. Among the IMCPR grades, patients with a grade of "severe" had higher odds of depression than those with a "mild" [odds ratio (95% confidence interval): 4.055 (2.907-5.498)] or "moderate" [3.584 (2.101-5.883)] grade. Females with a "severe" grade had higher odds of depression by 334.0% relative to those with a "mild" grade, while males had a relative risk of 258.4%. In conclusion, the present data provide systematic insights into the IMC-induced depression risk and updated the related clinical knowledge. Furthermore, the IMCPR classification approach could be used as an effective tool to evaluate this risk.

Do eye diseases increase the risk of arthritis in the elderly population?

There are very few longitudinal studies which have previously conducted an investigation into whether eye diseases are a risk for arthritis, and how this occurs. The study employed a variety of machine-learning algorithms, including random forest for investigating the risks, and to elucidate these underlying mechanisms by focusing on five aspects containing 389 characterized variables (mental health and wellbeing; physical health; disability, functional impairment and helpers; health behavior; and health measures). The study population included 8,423 individuals. Cataracts, glaucoma, and other eye diseases increase the likelihood of arthritis after two years by 131.8% (odds ratio (OR)=2.318, 95% confidence interval: 1.748 to 3.038), 123.1% (OR=2.231, 1.306 to 3.626), and 91.1% (OR=1.911, 1.501 to 2.415). Random forest corroborated that cataract contributes the most to arthritis risks after two years, followed by other eye diseases and glaucoma (mean Gini-index: 5.20, 2.11, 1.31). It is of note that the potential mechanisms of cataract-induced arthritis risk were elucidated extensively. The control domains of life quality, negative aging self-perceptions, mobility (steadiness, physical limitations, and muscle strength) and memory impairments, and sleep quality mediated the relationship between cataracts and arthritis significantly. Furthermore, different eye diseases affected osteoarthritis, rheumatoid arthritis, and other arthritis to varying degrees. Eye diseases increased the risk of arthritis, whereby cataracts were the most significant. Interventions which target these discovered mechanisms may be the preferred levers for reducing cataract-related arthritis risk.

Associations between fear of falling and activity restriction and late life depression in the elderly population: Findings from the Irish longitudinal study on ageing (TILDA).

BACKGROUND: The effect of Fear of Falling (FOF) and fear-related Activity Restriction (AR) on Late Life Depression (LLD) remains unstudied in older adults. In this study, we aimed to clarify associations between FOF, AR and the prevalence and incidence of LLD in a large cohort of community-dwelling older adults. METHODS: In this prospective study, participants (n = 4230; 52.1% female) aged ≥50 years completed the survey on whether they had FOF and AR at baseline. In addition, the Centre for Epidemiological Studies Depression (CESD) scale was used to evaluate LLD at baseline and after 2 years of follow-up. Moreover, LLD was defined by a CES-D score ≥ 16, at follow-up. RESULTS: The results showed that the prevalence and incidence of LLD were 6.9% (n = 293) and 4.2% (n = 167), respectively. In addition, most of the respondents with LLD were female (64.9% vs 55.4%) and 50-59 years of age (50.9% vs 42.8%, all P < 0.05). Analysis of data from Wave 1 and 2 using logistic regression also demonstrated that the levels of FOF/AR was associated with 82.2% and 62.7% higher odds of prevalence [OR = 1.822, 95%CI: 1.272-2.612] and incidence [OR = 1.627, 95%CI: 1.085-2.440] of LLD, respectively in the fully adjusted models. CONCLUSION: FOF and AR may be associated with the prevalence and incidence of LLD. Additionally, the study highlighted the importance of assessing LLD in older adults with FOF and AR.

Machine-intelligence for developing a potent signature to predict ovarian response to tailor assisted reproduction technology.

The prediction of poor ovarian response (POR) for stratified interference is a critical clinical issue that has received an increasing amount of recent concern. Anthropogenic diagnostic modes remain too simple for the handling of actual clinical complexity. Therefore, this study conducted extensive selection using models that were derived from a variety of machine learning algorithms, including random forest (RF), decision trees, eXtreme Gradient Boosting (XGBoost), support vector machine (SVM), and artificial neural networks (ANN) for the development of two models called the COS pre-launch model (CPLM) and the hCG pre-trigger model (HPTM) to assess POR based on different requirements. The results demonstrated that CPLM constructed using ANN achieved the highest AUC result of all the algorithms in COS pre-launch (AUC=0.859, C-index=0.87, good calibration), and HPTL constructed using random forest was found to be the most effective in hCG pre-trigger (AUC=0.903, C-index=0.90, good calibration). It is notable that CPLM and HPTM exhibited better performance than common clinical characteristics (0.895 [CPLM], and 0.903 [HPTM] in comparison to 0.824 [anti-Müllerian hormone (AMH)], and 0.799 [antral follicle count (AFC)]). Furthermore, variable importance figure elucidated the values of AMH, AFC, and E2 level and follicle number on hCG day, which provides important theoretical guidance and experimental data for further application. Generally, the CPLM and HPTM can offer effective POR prediction for patients who are receiving assisted reproduction technology (ART), and has great potential for guiding the clinical treatment of infertility.

Association between CT-Quantified Body Composition and Recurrence, Survival in Nonmetastasis Colorectal Cancer Patients Underwent Regular Chemotherapy after Surgery.

BACKGROUND: Body mass index, measured at colorectal cancer (CRC) diagnosis has been associated with recurrence and survival outcomes. Computed tomography- (CT-) defined body compositions accurately reflect body mass, but there was no consistent perspective on the influence of visceral adipose tissue (VAT) and skeletal muscle mass (SM) on the prognosis of nonmetastasis CRC, especially in the patients underwent surgery and regularly standard chemotherapy. METHODS: We investigated the associations of CT-quantified body composition (VAT and SM) with CRC patients successively underwent surgery and regular 8-12 of periods standard chemotherapy. All of the CT images were obtained at the level of the L3/4 spinal level. The prognostic value of the body compositions was analyzed using the Cox regression model, and precise clinical nomograms were established. RESULTS: In XELOX-treated patients, progression-free survival (PFS) (P = 0.025) and overall survival (OS) (P = 0.032) were lower in the high-SM than in the low-SM group. The univariate analysis demonstrated that compared with low-SM patients, patients with high-SM showed a strikingly poor prognosis in both OS (P = 0.0512) and PFS in the T4 subgroup (P = 0.0417), while contrary to the T2-3 subgroup. CONCLUSIONS: CT-quantified body compositions have a significant influence on CRC patients successively underwent curative resection and regularly standard chemotherapy with the endpoints of 1-year, 3-year, and 5-year both OS and PFS. Patients with high-SM showed a strikingly poor prognosis in OS and PFS in the T4 subgroup; however, the prognosis role of body composition was opposite in T2-3 patients.

Novel multifunctional adenine-modified chitosan dressings for promoting wound healing.

Wound healing is a dynamic and intricate process, and newly dressings are urgently needed to promote wound healing over the multiple stages. Herein, two water-soluble adenine-modified chitosan (CS-A) derivatives were synthesized in aqueous solutions and freeze-dried to obtain porous sponge-like dressings. The novel derivatives displayed antibacterial activities against S. aureus and E. coli. Moreover, CS-A derivatives demonstrated excellent hemocompatibility and cytocompatibility, as well as promoted the proliferation of the wound cells by shortening the G1 phase and improving DNA duplication efficiency. The ability of CS-A sponges to promote wound healing was studied in a full-thickness skin defect model. The histological analysis and immunohistochemical staining showed that the wounds treated with CS-A sponges displayed fewer inflammatory cells, and faster regeneration of epithelial tissue, collagen deposition and neovascularization. Therefore, CS-A derivatives have potential application in wound dressings and provide new ideas for the design of multifunctional biomaterials.