Concrete Aggregate-Gradation Effect and Strength-Criterion Modification for Fully Graded Hydraulic Concrete.

Utilization of large aggregates can promote energy conservation and emissions reductions, and large aggregates have been widely used in hydraulic concrete. The failure criterion for concrete material utilizing large aggregates forms the basis for constitutive models and structural design. However, the concrete failure criterion with respect to large aggregates has never been researched. To this end, the authors first conducted a series of triaxial compressive tests on concrete specimens with scaled aggregates. On this basis, several 3D mesoscopic numerical models were established with different aggregate gradations and used to simulate the triaxial compressive behaviors of hydraulic concrete after the models had been verified by experimental results. The results showed a pronounced aggregate-gradation effect on triaxial compressive behaviors, and concrete mixes with larger aggregates usually have higher compressive strength, especially under conditions of higher confinement. The normalized peak strength can increase by up to 23.49%. Finally, based on the available testing data, the strength criterion in different constitutive models is discussed and modified to allow more accurate simulation of the dynamic responses of and damage to fully graded concrete structures. This result can provide a theoretical basis on which construction entities can optimize the mix proportions of fully graded concrete and detect the failure modes of concrete structures.

MetalTrans: A Biological Language Model-Based Approach for Predicting Disease-Associated Mutations in Protein Metal-Binding Sites.

The critical importance of accurately predicting mutations in protein metal-binding sites for advancing drug discovery and enhancing disease diagnostic processes cannot be overstated. In response to this imperative, MetalTrans emerges as an accurate predictor for disease-associated mutations in protein metal-binding sites. The core innovation of MetalTrans lies in its seamless integration of multifeature splicing with the Transformer framework, a strategy that ensures exhaustive feature extraction. Central to MetalTrans's effectiveness is its deep feature combination strategy, which merges evolutionary-scale modeling amino acid embeddings with ProtTrans embeddings, thus shedding light on the biochemical properties of proteins. Employing the Transformer component, MetalTrans leverages the self-attention mechanism to delve into higher-level representations. Utilizing mutation site information for feature fusion not only enriches the feature set but also sidesteps the common pitfall of overestimation linked to protein sequence-based predictions. This nuanced approach to feature fusion is a key differentiator, enabling MetalTrans to outperform existing methods significantly, as evidenced by comparative analyses. Our evaluations across varied metal binding site data sets (specifically Zn, Ca, Mg, and Mix) underscore MetalTrans's superior performance, which achieved the average AUC values of 0.971, 0.965, 0.980, and 0.945 on multiple 5-fold cross-validation, respectively. Remarkably, against the multichannel convolutional neural network method on a benchmark independent test set, MetalTrans demonstrated unparalleled robustness and superiority, boasting the AUC score of 0.998 on multiple 5-fold cross-validation. Our comprehensive examination of the predicted outcomes further confirms the effectiveness of the model. The source codes, data sets, and prediction results for MetalTrans can be accessed for academic usage at https://github.com/EduardWang/MetalTrans.

Tremor Estimation and Removal in Robot-Assisted Surgery Using Improved Enhanced Band-Limited Multiple Fourier Linear Combiner.

BACKGROUND: During a robot-assisted minimally invasive surgery, hand tremors in a surgeon's manipulation of the master manipulator can cause vibrations of the slave surgical instruments. METHODS: This letter addresses this problem by proposing an improved Enhanced Band-Limited Multiple Linear Fourier Combiner (E-BMFLC) algorithm for filtering the physiological tremor signals of a surgeon's hand. The proposed method uses the amplitude of the input signal to adapt the learning rate and a dense division of the combiner bands for the higher amplitude bands of the tremor signals. RESULTS: By using the proposed improved E-BMFLC algorithm, the compensation accuracy can be improved by 4.5%-8.9%, as well as a spatial position error of less than 1 mm. CONCLUSION: The results show that among all filtering methods, the improved E-BMFLC filtering method has the highest number of successful experiments and the lowest experimental time.

Deep ultraviolet laser at 223.8†nm with adjustable repetition rate and narrow pulse width.

We presented the first, to our knowledge, demonstration of an ultraviolet (UV) laser at 223.8 nm by six-harmonic generation of an electro-optic Q-switched cavity dumping 1342 nm Nd:YVO4 laser. It offers high power, constant short pulse duration, and adjustable pulse repetition rate. The pulse duration is independent of the pump power and repetition rate compared to classical Q-switched oscillators. The output efficiency of the UV laser is optimized by adjusting the focusing lens. With the incident pump power of 30 W, an maximum average output power of 249 mW was obtained at 13 kHz. The pulse width maintained 3.4-3.5 ns from 5 to 20 kHz. The maximum pulse energy of 28.1 µJ was obtained at 5 kHz, and the corresponding peak power was up to 8.1 kW.

Osteostaticytes: A novel osteoclast subset couples bone resorption and bone formation.

Background: Osteomyelitis (OM) is an inflammatory condition of bone characterized by cortical bone devascularization and necrosis. Dysregulation of bone remodelling is triggered by OM. Bone remodelling is precisely coordinated by bone resorption and formation via a reversal phase. However, the cellular and molecular mechanisms underlying bone remodelling failure after osteomyelitis remain elusive. Methods: To elucidate the cellular and molecular mechanism underlying bone healing after osteomyelitis, we employed single-cell RNA sequencing (scRNA-seq) to depict the atlas of human cortical bone in normal, infected and reconstructed states. Dimensionality reduction by t-stochastic neighbourhood embedding (t-SNE) and graph-based clustering were applied to analyse the detailed clusters of osteoclast lineages. After trajectory analysis of osteoclast lineages over pseudotime, real-time PCR and immunofluorescence (IF) staining were applied to identify marker gene expression of various osteoclast lineages in the osteoclast induction model and human bone sections, respectively. The potential function and communication of osteoclasts were analysed via gene set enrichment analysis (GSEA) and CellChat. The chemotactic ability of mesenchymal stem cells (MSCs) and osteoclast lineage cells in various differentiation states was determined by transwell assays and coculture assays. The effects of various osteoclast lineages on the osteogenic differentiation potential of MSCs were also determined by using this coculture system. A normal mouse tibia fracture model and an osteomyelitis-related tibia fracture model were generated via injection of luciferase-labelled Staphylococcus aureus to verify the relationships between a novel osteoclast lineage and MSCs. Then, the infection was detected by a bioluminescence imaging system. Finally, immunofluorescence staining was used to detect the expression of markers of MSCs and novel osteoclast lineages in different remodelling phases in normal and infected bone remodelling models. Results: In this study, we constructed a cell atlas encompassing normal, infected, and reconstructed cortical bone. Then, we identified a novel subset at the earlier stage of the osteoclast lineage that exhibited increased expression of IDO1, CCL3, and CCL4. These IDO1highCCL3highCCL4high cells, termed osteostaticytes (OSCs), were further regarded as the reservoir of osteoclasts in the reversal phase. Notably, OSCs exhibited the highest chemotactic activity, surpassing other lineage subsets. We also discovered that cells at the earlier stage of the osteoclast lineage play a significant role in recruiting mesenchymal stem cells (MSCs). Finally, the data revealed that OSCs might be positively related to the occurrence of bone MSCs and the contribution of bone remodelling. Conclusion: Collectively, our findings revealed a novel stage (OSC) within the osteoclast lineage, potentially representing elusive bone reversal cells due to its increased chemotactic ability towards MSCs and potential contribution to bone remodelling. This study provides valuable insights into the intricate mechanisms of the reversal phase during bone remodelling and unveils potential therapeutic strategies for diseases associated with bone uncoupling. Translational potential of this article: This study identified a new subset, referred to as IDO1(plus symbol) CCL3(plus symbol) CCL4(plus symbol) osteostaticytes which displayed the highest chemotactic activity among all osteoclast lineages and may serve as reversal cells in bone remodelling. These findings offer new insights and insights for understanding bone reversal-related diseases and may serve as novel therapeutic targets for conditions such as osteomyelitis and delayed bone healing.

Enhanced choroid plexus segmentation with 3D UX-Net and its association with disease progression in multiple sclerosis.

BACKGROUND: The choroid plexus (CP) is suggested to be closely associated with the neuroinflammation of multiple sclerosis (MS). Segmentation based on deep learning (DL) could facilitate rapid and reproducible volume assessment of the CP, which is crucial for elucidating its role in MS. PURPOSE: To develop a reliable DL model for the automatic segmentation of CP, and further validate its clinical significance in MS. METHODS: The 3D UX-Net model (3D U-Net used for comparison) was trained and validated on T1-weighted MRI from a cohort of 216 relapsing-remitting MS (RRMS) patients and 75 healthy subjects. Among these, 53 RRMS with baseline and 2-year follow-up scans formed an internal test set (dataset1b). Another 58 RRMS from multi-center data served as an external test set (dataset2). Dice coefficient was computed to assess segmentation performance. Compare the correlation of CP volume obtained through automatic and manual segmentation with clinical outcomes in MS. Disability and cognitive function of patients were assessed using the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT). RESULTS: The 3D UX-Net model achieved Dice coefficients of 0.875 ± 0.030 and 0.870 ± 0.044 for CP segmentation on dataset1b and dataset2, respectively, outperforming 3D U-Net's scores of 0.809 ± 0.098 and 0.601 ± 0.226. Furthermore, CP volumes segmented by the 3D UX-Net model aligned consistently with clinical outcomes compared to manual segmentation. In dataset1b, both manual and automatic segmentation revealed a significant positive correlation between normalized CP volume (nCPV) and EDSS scores at baseline (manual: r = 0.285, p = 0.045; automatic: r = 0.287, p = 0.044) and a negative correlation with SDMT scores (manual: r = -0.331, p = 0.020; automatic: r = -0.329, p = 0.021). In dataset2, similar correlations were found with EDSS scores (manual: r = 0.337, p = 0.021; automatic: r = 0.346, p = 0.017). Meanwhile, in dataset1b, both manual and automatic segmentation revealed a significant increase in nCPV from baseline to follow-up (p < 0.05). The increase of nCPV was more pronounced in patients with disability worsened than stable patients (manual: p = 0.023; automatic: p = 0.018). Patients receiving disease-modifying therapy (DMT) exhibited a significantly lower nCPV increase than untreated patients (manual: p = 0.004; automatic: p = 0.004). CONCLUSION: The 3D UX-Net model demonstrated strong segmentation performance for the CP, and the automatic segmented CP can be directly used in MS clinical practice. CP volume can serve as a surrogate imaging biomarker for monitoring disease progression and DMT response in MS patients.

Effect of desflurane maintenance on postoperative sleep quality in patients undergoing elective breast surgery: A non-inferiority randomized controlled trial.

BACKGROUND: Postoperative sleep disturbance (PSD) is prevalent in perioperative patients，and has significant impact on postoperative recovery and prognosis. The aim of this study was to investigate the effect of desflurane maintenance on postoperative sleep quality, in order to optimize patients' perioperative sleep management. METHOD: A total of 118 patients undergoing elective breast surgery were randomized to receive either desflurane-based volatile anesthesia (desflurane group) or propofol-based total intravenous anesthesia (propofol group) for anesthesia maintenance. The primary outcome was the quality of sleep, which was assessed by the Pittsburgh Sleep Quality Index (PSQI) on 3 days after operation (POD3). Secondary outcomes were PSQI on postoperative day 7 (POD7) and 30 (POD30), and postoperative anxiety, depression, and pain score, as well as objective sleep parameters including total sleep time (TST), WASO (Wakefulness after sleep onset), REM (Rapid eye movement) and NREM (Non-rapid Eye Movement) measured by Fitbit Charge 2TM during the initial 3 postoperative days. RESULTS: The global PSQI scores on POD3 in the desflurane group was non-inferior to that in the propofol group [mean (SD) 8.47 (3.46) vs. 7.65 (3.16); mean difference (95 % CI) 0.82 (-0.43, 2.07); p < 0.001 for non-inferiority]. There were no significant differences in PSQI scores on POD3 and POD7. In addition, the score of anxiety, depression, and pain on the 3rd, 7th, and 30th day after surgery have no significant differences between the propofol and the desflurane group, respectively. The postoperative NREM was higher in the desflurane group than that in the propofol group. CONCLUSION: The effects of desflurane-based volatile anesthesia maintenance on postoperative sleep quality is not inferior to that of propofol-based total intravenous anesthesia, and these two drugs may have different effects on the sleep structure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04805775.

Plasma-generated RONS in liquid transferred into cryo-microneedles patch for skin treatment of melanoma.

Malignant melanoma is the most lethal form of skin cancer. As a promising anti-cancer agent, plasma-activated water (PAW) rich in reactive oxygen and nitrogen species (RONS) has shown significant potential for melanoma treatment. However, rapid decay of RONS and inefficient delivery of PAW in conventional injection methods limit its practical applications. To address this issue, here we report a new approach for the production of plasma-activated cryo-microneedles (PA-CMNs) patches using custom-designed plasma devices and processes. Our innovation is to incorporate PAW into the PA-CMNs that are fabricated using a fast cryogenic micro-molding method. It is demonstrated that PA-CMNs can be easily inserted into skin to release RONS and slow the decay of RONS thereby prolonging their bioactivity and effectiveness. The new insights into the effective melanoma treatment suggest that the rich mixture of RONS within PA-CMNs prepared by custom-developed hybrid plasma-assisted configuration induces both ferroptosis and apoptosis to selectively kill tumor cells. A significant inhibition of subcutaneous A375 melanoma growth was observed in PA-CMNs-treated tumor-bearing nude mice without any signs of systemic toxicity. The new approach based on PA-CMNs may potentially open new avenues for a broader range of disease treatments.

Upscaling the production of sterile male mosquitoes with an automated pupa sex sorter.

Effective mosquito population suppression has been repeatedly demonstrated in field trials through the release of male mosquitoes to induce sterile mating with wild females using the incompatible insect technique (IIT), the sterile insect technique (SIT), or their combination. However, upscaling these techniques requires a highly efficient and scalable approach for the sex separation of mass-reared mosquitoes to minimize the unintentional release of females, which can lead to either population replacement or biting nuisance, a major bottleneck up to now. Here, we report the successful development of an automated mosquito pupa sex sorter that can effectively separate large numbers of males from females for population suppression of Aedes aegypti, A. albopictus, and Culex quinquefasciatus. The male production capacity of the automated sex sorter was increased by ~17-fold compared with manual sex separation with the Fay-Morlan sorter and enabled one person to separate 16 million males per week. With ~0.5% female contamination, the produced males exhibited high flight ability and mating performance. The field trial demonstrates that the quality of A. albopictus males produced using the automated sex sorter is suitable for inducing population suppression. These results indicate that the automated sex sorter offers the potential to upscale IIT and SIT against mosquito vectors for disease control.

Effect of Lacticaseibacillus casei LC2W Supplementation on Glucose Metabolism and Gut Microbiota in Subjects at High Risk of Metabolic Syndrome: A Randomized, Double-blinded, Placebo-controlled Clinical Trial.

Metabolic syndrome (MetS) is a global epidemic complex and will cause serious metabolic comorbidities without treatment. A prevention strategy for MetS development has been proposed to modulate gut microbiota by probiotic administration to improve intestinal dysbiosis and benefit the host. Lacticaseibacillus casei LC2W has exhibited positive effects in preventing colitis and anti-hypertension in vivo. However, the effect of L. casei LC2W on subjects at high risk of MetS is unknown. Here, a randomized, double-blinded, placebo-controlled study was conducted on 60 subjects with high risk of MetS, and the hypoglycemic and hypolipidemic activity and possible pathways of L. casei LC2W were inferred from the correlation analysis with gut microbiome composition, function, and clinical phenotypic indicators. The results showed that oral administration of L. casei LC2W could exert significant benefits on weight control, glucose and lipid metabolism, inflammatory and oxidative stress parameters, and SCFA production, as well as modulate the composition of gut microbiota. The relative abundance of Lacticaseibacillus, Bifidobacterium, Dorea, and Blautia was enriched, and their interaction with other gut microbes was strengthened by oral administration of L. casei LC2W, which was beneficial in ameliorating gut inflammation, promoting glucose and lipids degradation pathways, thus alleviated MetS. The present study confirmed the prevention effects of L. casei LC2W towards MetS from aspects of clinical outcomes and microflora modulation, providing an alternative strategy for people at high risk of MetS.Trial registration: The study was proactively registered in ClinicalTrial.gov with the registration number of ChiCTR2000031833 on April 09, 2020.

IRF8 maintains mononuclear phagocyte and neutrophil function in acute kidney injury.

Immune cells are key players in acute tissue injury and inflammation, including acute kidney injury (AKI). Their development, differentiation, activation status, and functions are mediated by a variety of transcription factors, such as interferon regulatory factor 8 (IRF8) and IRF4. We speculated that IRF8 has a pathophysiologic impact on renal immune cells in AKI and found that IRF8 is highly expressed in blood type 1 conventional dendritic cells (cDC1s), monocytes, monocyte-derived dendritic cells (moDCs) and kidney biopsies from patients with AKI. In a mouse model of ischemia‒reperfusion injury (IRI)-induced AKI, Irf8 -/- mice displayed increased tubular cell necrosis and worsened kidney dysfunction associated with the recruitment of a substantial amount of monocytes and neutrophils but defective renal infiltration of cDC1s and moDCs. Mechanistically, global Irf8 deficiency impaired moDC and cDC1 maturation and activation, as well as cDC1 proliferation, antigen uptake, and trafficking to lymphoid organs for T-cell priming in ischemic AKI. Moreover, compared with Irf8 +/+ mice, Irf8 -/- mice exhibited increased neutrophil recruitment and neutrophil extracellular trap (NET) formation following AKI. IRF8 primarily regulates cDC1 and indirectly neutrophil functions, and thereby protects mice from kidney injury and inflammation following IRI. Our results demonstrate that IRF8 plays a predominant immunoregulatory role in cDC1 function and therefore represents a potential therapeutic target in AKI.

Parental and Adolescents' Anxiety during the COVID-19 Outbreak in Rural China: The role of Parent-child Communication.

Purpose: It has been suggested that the intergenerational transmission of anxiety may be an important contributor to the high prevalence of anxiety in adolescents. The objectives of this study are to examine whether and how parental anxiety is related to adolescent's anxiety and to explore the associations of parental anxiety and parent-child communication with adolescents' anxiety across different grades. Methods: The current survey was conducted online from February 8th to February 27th, 2020.The questionnaires were distributed and retrieved through a web-based platform. A total of 6196 Chinese rural adolescents from grade seven to twelve (age ranging from 11 to 18 years old) were included. Results: In this study, parental anxiety was significantly associated with higher adolescent anxiety (ß = 0.14, p < 0.001) and this association was statically strongest at grade twelve. Besides, children with problematic parent-child communication related to COVID-19 reported elevated anxiety (ß = 0.05, p < 0.01). In contrast, effective parent-child communication about COVID-19 mitigated the level of anxiety transmitted from parent to child (ß = -0.04, p < 0.05). Conclusions: During the COVID-19 epidemic, parents' anxiety was related to adolescents' anxiety. In addition, parent-child communication plays a moderating role in the above relationship. These findings emphasize the importance of implementing more psycho-education programs that specifically target parents' emotion regulation and effective communication abilities to ameliorate the psychopathological symptoms of parents and their children. Supplementary Information: The online version contains supplementary material available at 10.1007/s40653-023-00609-y.

Clinical characteristics and outcomes associated with culture-negative status in limb osteomyelitis patients.

Aims: This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients. Methods: A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts. Results: Of these patients, 264 (25.2%) had negative cultures. Patients with a culture-negative compared with a culture-positive status were more likely to have the following characteristics: younger age (≤ 40 years) (113/264 (42.8%) vs 257/783 (32.8%); p = 0.004), a haematogenous aetiology (75/264 (28.4%) vs 150/783 (19.2%); p = 0.002), Cierny-Mader host A (79/264 (29.9%) vs 142/783 (18.1%); p < 0.001), antibiotic use before sampling (34/264 (12.9%) vs 41/783 (5.2%); p＜0.001), fewer taken samples (n＜3) (48/264 (18.2%) vs 60/783 (7.7%); p＜0.001), and less frequent presentation with a sinus (156/264 (59.1%) vs 665/783 (84.9%); p < 0.001). After initial treatments of first-debridement and antimicrobial, infection eradication was inferior in culture-positive osteomyelitis patients, with a 2.24-fold increase (odds ratio 2.24 (95% confidence interval 1.42 to 3.52)) in the redebridement rate following multivariate analysis. No statistically significant differences were found in long-term recurrence and complications within the two-year follow-up. Conclusion: We identified several factors being associated with the culture-negative result in osteomyelitis patients. In addition, the data also indicate that culture negativity is a positive prognostic factor in early infection eradication. These results constitute the basis of optimizing clinical management and patient consultations.

Targeting delivery of a novel TGF-ß type I receptor-mimicking peptide to activated hepatic stellate cells for liver fibrosis therapy via inhibiting the TGF-ß1/Smad and p38 MAPK signaling pathways.

Excessive transforming growth factor ß1 (TGF-ß1) secreted by activated hepatic stellate cells (aHSCs) aggravates liver fibrosis via over-activation of TGF-ß1-mediated signaling pathways in a TGF-ß type I receptor (TßRI) dependent manner. TßRI with the C-terminal valine truncated (RIPΔ), as a novel TßRI-mimicking peptide, is an appealing anti-fibrotic candidate by competitive binding of TGF-ß1 to block TGF-ß1 signal transduction. Platelet-derived growth factor receptor ß (PDGFßR) is highly expressed on the surface of aHSCs in liver fibrosis. Herein, we designed a novel RIPΔ variant Z-RIPΔ (PDGFßR-specific affibody ZPDGFßR fused to the N-terminus of RIPΔ) for liver fibrosis therapy, and expect to improve the anti-liver fibrosis efficacy by specifically inhibiting the TGF-ß1 activity in aHSCs. Target peptide Z-RIPΔ was prepared in Escherichia coli by SUMO fusion system. Moreover, Z-RIPΔ specifically bound to TGF-ß1-activated aHSCs, inhibited cell proliferation and migration, and reduced the expression of fibrosis markers (α-SMA and FN) and TGF-ß1 pathway-related effectors (p-Smad2/3 and p-p38) in vitro. Furthermore, Z-RIPΔ specifically targeted the fibrotic liver, alleviated the liver histopathology, mitigated the fibrosis responses, and blocked TGF-ß1-mediated Smad and p38 MAPK cascades. More importantly, Z-RIPΔ exhibited a higher fibrotic liver-targeting capacity and stronger anti-fibrotic effects than its parent RIPΔ. Besides, Z-RIPΔ showed no obvious toxicity effects in treating both an in vitro cell model and an in vivo mouse model of liver fibrosis. In conclusion, Z-RIPΔ represents a promising targeted candidate for liver fibrosis therapy.

CST2 promotes cell proliferation and regulates cell cycle by activating Wnt-ß-catenin signalling pathway in serous ovarian cancer.

BACKGROUND: Cystatin SA (CST2) plays multiple roles in different types of malignant tumours; however, its role in serous ovarian cancer (SOC) remains unclear. Therefore, we aimed to investigate the expression levels, survival outcomes, immune cell infiltration, proliferation, cell cycle, and underlying molecular mechanisms associated with the CST2 signature in SOC. METHODS: The Cancer Genome Atlas database was used to acquire clinical information and CST2 expression profiles from patients with SOC. Wilcoxon rank-sum tests were used to compare CST2 expression levels between SOC and normal ovarian tissues. A prognostic assessment of CST2 was conducted using Cox regression analysis and the Kaplan-Meier method. Differentially expressed genes were identified using functional enrichment analysis. Immune cell infiltration was examined using a single-sample gene set enrichment analysis. Cell cycle characteristics and proliferation were assessed using a colony formation assay, flow cytometry, and a cell counting kit-8 assay. Western blots and quantitative reverse transcription PCR analyses were employed to examine CST2 expressions and related genes involved in the cell cycle and the Wnt-ß-catenin signalling pathway. RESULTS: Our findings revealed significant upregulation of CST2 in SOC, and elevated CST2 expression was correlated with advanced clinicopathological characteristics and unfavourable prognoses. Pathway enrichment analysis highlighted the association between the cell cycle and the Wnt signalling pathway. Moreover, increased CST2 levels were positively correlated with immune cell infiltration. Functionally, CST2 played vital roles in promoting cell proliferation, orchestrating the G1-to-S phase transition, and driving malignant SOC progression through activating the Wnt-ß-catenin signalling pathway. CONCLUSIONS: The elevated expression of CST2 may be related to the occurrence and progression of SOC by activating the Wnt-ß-catenin pathway. Additionally, our findings suggest that CST2 is a promising novel biomarker with potential applications in therapeutic, prognostic, and diagnostic strategies for SOC.

Serous ovarian cancer is a type of gynecological malignant tumour with high mortality rates. Understanding this disease is crucial for improving treatments and enhancing patient survival. In our study, we investigated a protein called CST2 and its role in serous ovarian cancer. We found that CST2 levels vary among patients and are associated with the progression of cancer and the prognosis of the patient, which could be valuable for future diagnosis and treatment strategies. However, further research is needed to validate these findings. Despite its limitations, our findings suggest that CST2 holds promise as a potential biomarker for detecting serous ovarian cancer and as a therapeutic target in the management of patients with this type of cancer.

Retracted: Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Rongfeng Zhang, Jianwei Liu, Shengpeng Yu, Dong Sun, Xiaohua Wang, Jingshu Fu, Jie Shen, Zhao Xie. Osteoprotegerin (OPG) Promotes Recruitment of Endothelial Progenitor Cells (EPCs) via CXCR4 Signaling Pathway to Improve Bone Defect Repair. Med Sci Monit, 2019; 25: 5572-5579. DOI: 10.12659/MSM.916838.

Construction of an Early Risk Prediction Model for Type 2 Diabetic Peripheral Neuropathy Based on Random Forest.

Diabetic peripheral neuropathy is a major cause of disability and death in the later stages of diabetes. A retrospective chart review was performed using a hospital-based electronic medical record database to identify 1020 patients who met the criteria. The objective of this study was to explore and analyze the early risk factors for peripheral neuropathy in patients with type 2 diabetes, even in the absence of specific clinical symptoms or signs. Finally, the random forest algorithm was used to rank the influencing factors and construct a predictive model, and then the model performance was evaluated. Logistic regression analysis revealed that vitamin D plays a crucial protective role in preventing diabetic peripheral neuropathy. The top three risk factors with significant contributions to the model in the random forest algorithm eigenvalue ranking were glycosylated hemoglobin, disease duration, and vitamin D. The areas under the receiver operating characteristic curve of the model ware 0.90. The accuracy, precision, specificity, and sensitivity were 0.85, 0.83, 0.92, and 0.71, respectively. The predictive model, which is based on the random forest algorithm, is intended to support clinical decision-making by healthcare professionals and help them target timely interventions to key factors in early diabetic peripheral neuropathy.

Targeted delivery of type I TGF-ß receptor-mimicking peptide to fibrotic kidney for improving kidney fibrosis therapy via enhancing the inhibition of TGF-ß1/Smad and p38 MAPK pathways.

Renal fibrosis is a representative pathological feature of various chronic kidney diseases, and efficient treatment is needed. Interstitial myofibroblasts are a key driver of kidney fibrosis, which is dependent on the binding of TGF-ß1 to type I TGF-ß receptor (TßRI) and TGF-ß1-related signaling pathways. Therefore, attenuating TGF-ß1 activity by competing with TGF-ß1 in myofibroblasts is an ideal strategy for treating kidney fibrosis. Recently, a novel TßRI-mimicking peptide RIPΔ demonstrated a high affinity for TGF-ß1. Thus, it could be speculated that RIPΔ may be used for anti-fibrosis therapy. Platelet-derived growth factor ß receptor (PDGFßR) is highly expressed in fibrotic kidney. In this study, we found that target peptide Z-RIPΔ, which is RIPΔ modified with PDGFßR-specific affibody ZPDGFßR, was specifically and highly taken up by TGF-ß1-activated NIH3T3 fibroblasts. Moreover, Z-RIPΔ effectively inhibited the myofibroblast proliferation, migration and fibrosis response in vitro. In vivo and ex vivo experiments showed that Z-RIPΔ specifically targeted fibrotic kidney, improved the damaged renal function, and ameliorated kidney histopathology and renal fibrosis in UUO mice. Mechanistic studies showed that Z-RIPΔ hold the stronger inhibition of the TGF-ß1/Smad and TGF-ß1/p38 pathways than unmodified RIPΔ in vitro and in vivo. Furthermore, systemic administration of Z-RIPΔ to UUO mice led to minimal toxicity to major organs. Taken together, RIPΔ modified with ZPDGFßR increased its therapeutic efficacy and reduced its systemic toxicity, making it a potential candidate for targeted therapy for kidney fibrosis.

Uncovering specific taxonomic and functional alteration of gut microbiota in chronic kidney disease through 16S rRNA data.

Introduction: Chronic kidney disease (CKD) is worldwide healthcare burden with growing incidence and death rate. Emerging evidence demonstrated the compositional and functional differences of gut microbiota in patients with CKD. As such, gut microbial features can be developed as diagnostic biomarkers and potential therapeutic target for CKD. Methods: To eliminate the outcome bias arising from factors such as geographical distribution, sequencing platform, and data analysis techniques, we conducted a comprehensive analysis of the microbial differences between patients with CKD and healthy individuals based on multiple samples worldwide. A total of 980 samples from six references across three nations were incorporated from the PubMed, Web of Science, and GMrepo databases. The obtained 16S rRNA microbiome data were subjected to DADA2 processing, QIIME2 and PICRUSt2 analyses. Results: The gut microbiota of patients with CKD differs significantly from that of healthy controls (HC), with a substantial decrease in the microbial diversity among the CKD group. Moreover, a significantly reduced abundance of bacteria Faecalibacterium prausnitzii (F. prausnitzii) was detected in the CKD group through linear discriminant analysis effect size (LEfSe) analysis, which may be associated with the alleviating effects against CKD. Notably, we identified CKD-depleted F. prausnitzii demonstrated a significant negative correlation with three pathways based on predictive functional analysis, suggesting its potential role in regulating systemic acidbase disturbance and pro-oxidant metabolism. Discussion: Our findings demonstrated notable alterations of gut microbiota in CKD patients. Specific gut-beneficial microbiota, especially F. prausnitzii, may be developed as a preventive and therapeutic tool for CKD clinical management.

Cross-sectional and longitudinal evaluation of white matter microstructure damage and cognitive correlations by automated fibre quantification in relapsing-remitting multiple sclerosis patients.

The purpose of this study was to characterize whole-brain white matter (WM) fibre tracts by automated fibre quantification (AFQ), capture subtle changes cross-sectionally and longitudinally in relapsing-remitting multiple sclerosis (RRMS) patients and explore correlations between these changes and cognitive performance A total of 114 RRMS patients and 71 healthy controls (HCs) were enrolled and follow-up investigations were conducted on 46 RRMS patients. Fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD), and radial diffusivity (RD) at each node along the 20 WM fibre tracts identified by AFQ were investigated cross-sectionally and longitudinally in entire and pointwise manners. Partial correlation analyses were performed between the abnormal metrics and cognitive performance. At baseline, compared with HCs, patients with RRMS showed a widespread decrease in FA and increases in MD, AD, and RD among tracts. In the pointwise comparisons, more detailed abnormalities were localized to specific positions. At follow-up, although there was no significant difference in the entire WM fibre tract, there was a reduction in FA in the posterior portion of the right superior longitudinal fasciculus (R_SLF) and elevations in MD and AD in the anterior and posterior portions of the right arcuate fasciculus (R_AF) in the pointwise analysis. Furthermore, the altered metrics were widely correlated with cognitive performance in RRMS patients. RRMS patients exhibited widespread WM microstructure alterations at baseline and alterations in certain regions at follow-up, and the altered metrics were widely correlated with cognitive performance in RRMS patients, which will enhance our understanding of WM microstructure damage and its cognitive correlation in RRMS patients.