Integrating Bioinformatics and Experimental Validation to Identify Mitochondrial Permeability Transition-Driven Necrosis-Related lncRNAs that can Serve as Prognostic Biomarkers and Therapeutic Targets in Endometrial Carcinoma.

Endometrial carcinoma (EC) is a common malignant tumor in women with high mortality and relapse rates. Mitochondrial permeability transition (MPT)-driven necrosis is a novel form of programmed cell death. The MPT-driven necrosis related lncRNAs (MRLs) involved in EC development remain unclear. We aimed to predict the outcomes of patients with EC by constructing a novel prognostic model based on MRLs and explore potential molecular functions. A risk prognostic model was developed utilizing multi-Cox regression in conjunction with the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm, which was based on MRLs. The predictive efficacy of the model was evaluated through receiver operating characteristic (ROC) curve analysis, as well as nomogram and concordance index (C-index) assessments. Patients were categorized into high- and low-risk groups based on their median risk scores. Notably, the high-risk group exhibited significantly poorer overall survival (OS) outcomes. Gene ontology (GO) and Gene set enrichment analysis (GSEA) demonstrated that Hedgehog and cell cycle pathways were enriched in the high-risk group. Tumor Immune Dysfunction and Exclusion (TIDE) displayed that patients in the high-risk group showed a high likelihood of immune evasion and less effective immunotherapy. A significant disparity in immune function was also observed between two groups. Based on the nine-MRLs, drug sensitivity analysis identified several anticancer drugs with potential efficacy in prognosis. Meanwhile, the results demonstrated that OGFRP1 plays a carcinogenic role by affecting mitochondrial membrane permeability in EC. Therefore, the risk model constructed by nine MRLs could be used to predict the clinical outcomes and therapeutic responses in patients with EC effectively.

Application of a modified multifunctional short peptide in the treatment of periodontitis.

Periodontitis is a chronic inflammatory disease involving plaque biofilm as a pathogenic factor. Potassium ion plays an important role in cellular homeostasis; a large outflow of potassium may lead to local inflammation progression. In this work, the multifunctional short peptide molecule BmKTX-33 was designed by modifying the BmKTX, a Kv1.3 potassium channel inhibitor. This was to explore its antibacterial properties, capability of maintaining cell ion homeostasis, and bone-forming capacity. The results showed that BmKTX-33 had inhibitory effects on S. gordonii, F. nucleatum, and P. gingivalis. Moreover, BmKTX-33 also inhibited excessive potassium outflow in inflammatory environments. Finally, BmKTX-33 promoted MC3T3-E1 early osteogenesis while suppressing the NLRP3 inflammasome's production. In conclusion, BmKTX-33 not only has antibacterial properties, but also can inhibit the expression of NLRP3 inflammasome and play an anti-inflammatory role.

The vasculogenic mimicry, CD146+ and CD105+ microvessel density in the prognosis of endometrioid endometrial adenocarcinoma: a single-centre immunohistochemical study.

The microvessel compartment is crucial in the tumour microenvironment of endometrioid adenocarcinoma (EA). This study investigated the role of vasculogenic mimicry (VM), CD146, and CD105 microvessel density in the clinical prognosis of EA. A total of 188 EA cases were analyzed, with VM channels and microvessels detected using PAS/CD31, CD146, and CD105 staining. Mann-Whitney and Fisher exact tests were used to compare the study groups according to the evaluated criteria. ROC analysis included determination of the confidence interval (CI) and area under the ROC curve. The Mantel-Cox test was used to analyze progression-free survival. Multivariate Cox proportional hazard analysis was performed using stepwise regression. Results showed that VM channels and CD146 and CD105 microvessels were significantly higher (p < 0.0001) in cases with unfavourable prognosis. Univariate survival analysis highlighted the significant role of these factors in progression-free survival, while multivariate Cox analysis identified VM and CD146+ vessels as predictive factors. This study demonstrates, for the first time, that VM, CD146, and CD105-positive vessels are involved in EA prognosis, suggesting their potential as independent prognostic indicators and targets for antiangiogenic therapy. However, these findings require further validation through large-scale studies.

Design of Auto-Adaptive Drug Delivery System for Effective Delivery of Peptide Drugs to Overcoming Mucus and Epithelial Barriers.

Oral administration of peptide represents a promising delivery route, however, it is hindered by the harsh gastrointestinal environment, leading to low in vivo absorption. In this study, auto-adaptive protein corona-AT 1002-cationic liposomes (Pc-AT-CLs) are constructed with the characteristic of hydrophilic and electrically neutral surface properties for the encapsulation of liraglutide. BSA protein corona is used to coat AT-CLs reducing the adherence of mucus, and may fall off after penetrating the mucus layer. Transmucus transport experiment demonstrated that the mucus penetration amount of Pc-AT-CLs are 1.45 times that of AT-CLs. After penetrating the mucus layer, AT-CLs complete transmembrane transport by the dual action of AT and cationic surface properties. Transmembrane transport experiment demonstrated that the apparent permeability coefficient (Papp) of AT-CLs is 2.03 times that of CLs. In vivo tests demonstrated that Pc-AT-CLs exhibited a significant hypoglycemic effect and enhanced the relative bioavailability comparing to free liraglutide. Pc-AT-CLs protect liraglutide from degradation, facilitate its absorption, and ultimately improve its oral bioavailability.

Characterization of Flavor Compounds in Chinese Indigenous Sheep Breeds Using Gas Chromatography-Ion Mobility Spectrometry and Chemometrics.

This study analyzed the flavor compounds in the meat of four indigenous breeds of Chinese sheep through the use of gas chromatography-ion mobility spectrometry (GC-IMS). GC-IMS provided information on the characteristics and strength of 71 volatile flavor compounds (monomers and dimers), with aldehydes, alcohols and ketones being the most abundant in all types of sheep meat. The compounds with higher intensity peaks in the sheep meat were aldehydes (n-nonanal, octanal, heptanal, 3-methylbutanal, and hexanal), alcohols (1-octen-3-ol, hexanol, and pentanol), ketones (3-hydroxy-2-butanon, 2-butanone, and 2-propanone), esters (methyl benzoate), and thiazole (trimethylthiazole). The volatile flavor components in the meat of the different breeds of sheep obtained via GC-IMS were further differentiated using principal component analysis. In addition, orthogonal partial least squares discriminant analysis (OPLS-DA) and variable importance on projection (VIP) were used to determine the characteristic flavor compounds in the meats of different breeds of sheep, and 21 differentially volatile components were screened out based on having a VIP above 1. These results indicate that GC-IMS combined with multivariate analysis is a convenient and powerful method for characterizing and discriminating sheep meat.

Soybean Yield Simulation and Sustainability Assessment Based on the DSSAT-CROPGRO-Soybean Model.

In order to ensure national grain and oil security, it is imperative to expand the soybean planting area in the Xinjiang region. However, the scarcity of water resources in southern Xinjiang, the relatively backward soybean planting technology, and the lack of a supporting irrigation system have negatively impacted soybean planting and yield. In 2022 and 2023, we conducted an experiment which included three irrigation amounts of 27 mm, 36 mm, and 45 mm and analyzed the changes in dry mass and yield. Additionally, we simulated the potential yield using the corrected DSSAT-CROPGRO-Soybean model and biomass based on the meteorological data from 1994 to 2023. The results demonstrated that the model was capable of accurately predicting soybean emergence (the relative root mean square error (nRMSE) = 0, the absolute relative error (ARE) = 0), flowering (nRMSE = 0, ARE = 2.78%), maturity (nRMSE = 0, ARE = 3.21%). The model demonstrated high levels of accuracy in predicting soybean biomass (R2 = 0.98, nRMSE = 20.50%, ARE = 20.63%), 0-80 cm soil water storage (R2 = 0.64, nRMSE = 7.78%, ARE = 3.24%), and yield (R2 = 0.81, nRMSE = 10.83%, ARE = 8.79%). The biomass of soybean plants increases with the increase in irrigation amount. The highest biomass of 63 mm is 9379.19 kg·hm-2. When the irrigation yield is 36-45 mm (p < 0.05), the maximum yield can reach 4984.73 kg·hm-2; the maximum efficiency of soybean irrigation water was 33-36 mm. In light of the impact of soybean yield and irrigation water use efficiency, the optimal irrigation amount for soybean cultivation in southern Xinjiang is estimated to be between 36 and 42 mm. The simulation results provide a theoretical foundation for soybean cultivation in southern Xinjiang.

Intelligent Song Recognition via a Hollow-Microstructure-Based, Ultrasensitive Artificial Eardrum.

Artificial ears with intelligence, which can sensitively detect sound-a variant of pressure-and generate consciousness and logical decision-making abilities, hold great promise to transform life. However, despite the emerging flexible sensors for sound detection, most success is limited to very simple phonemes, such as a couple of letters or words, probably due to the lack of device sensitivity and capability. Herein, the construction of ultrasensitive artificial eardrums enabling intelligent song recognition is reported. This strategy employs novel geometric engineering of sensing units in the soft microstructure array (to significantly reduce effective modulus) along with complex song recognition exploration leveraging machine learning algorithms. Unprecedented pressure sensitivity (6.9 × 103 kPa-1) is demonstrated in a sensor with a hollow pyramid architecture with porous slants. The integrated device exhibits unparalleled (exceeding by 1-2 orders of magnitude compared with reported benchmark samples) sound detection sensitivity, and can accurately identify 100% (for training set) and 97.7% (for test set) of a database of the segments from 77 songs varying in language, style, and singer. Overall, the results highlight the outstanding performance of the hollow-microstructure-based sensor, indicating its potential applications in human-machine interaction and wearable acoustical technologies.

Radiomics of multi-parametric MRI for the prediction of lung metastasis in soft-tissue sarcoma: a feasibility study.

PURPOSE: To investigate the value of multi-parametric MRI-based radiomics for preoperative prediction of lung metastases from soft tissue sarcoma (STS). METHODS: In total, 122 patients with clinicopathologically confirmed STS who underwent pretreatment T1-weighted contrast-enhanced (T1-CE) and T2-weighted fat-suppressed (T2FS) MRI scans were enrolled between Jul. 2017 and Mar. 2021. Radiomics signatures were established by calculating and selecting radiomics features from the two sequences. Clinical independent predictors were evaluated by statistical analysis. The radiomics nomogram was constructed from margin and radiomics features by multivariable logistic regression. Finally, the study used receiver operating characteristic (ROC) and calibration curves to evaluate performance of radiomics models. Decision curve analyses (DCA) were performed to evaluate clinical usefulness of the models. RESULTS: The margin was considered as an independent predictor (p < 0.05). A total of 4 MRI features were selected and used to develop the radiomics signature. By incorporating the margin and radiomics signature, the developed nomogram showed the best prediction performance in the training (AUCs, margin vs. radiomics signature vs. nomogram, 0.609 vs. 0.909 vs. 0.910) and validation (AUCs, margin vs. radiomics signature vs. nomogram, 0.666 vs. 0.841 vs. 0.894) cohorts. DCA indicated potential usefulness of the nomogram model. CONCLUSIONS: This feasibility study evaluated predictive values of multi-parametric MRI for the prediction of lung metastasis, and proposed a nomogram model to potentially facilitate the individualized treatment decision-making for STSs.

Bacterial community structure and metabolomic profiles of yak milk and cattle-yak milk during refrigeration in Gannan region: Analysis of interspecific differences in milk spoilage.

The bacterial community dynamics and metabolomic profiles in raw yak (Y) milk and cattle-yak (CY) milk during refrigeration at 4 °C were investigated, followed by the elucidation of interspecific differences in milk storage. Bacterial communities and succession patterns were significantly different between the two milk types during refrigeration, with Lactococcus and Pseudomonas being the key distinguishing genera. Moreover, higher network complexity and tighter interactions were observed for the microbial community in CY milk than in Y milk. Furthermore, 7 proteases and 1 lipase potentially contributed to milk spoilage. The metabolomic profiles significantly differed between the milk types during refrigeration. Extended storage time decreased the relative abundances of organic nitrogen compounds and lipids and lipid-like molecules, with a concomitant increase in organic acids and derivatives, particularly in Y milk. Moreover, 9 metabolites, whose levels gradually increased with storage time, were strongly correlated with psychrophiles and thus considered potential markers of deterioration in plateau-characteristic milk. These findings offer a theoretical foundation for augmenting the quality and safety of plateau-characteristic milk and its derivatives, while also helping us understand the microbial and metabolic dynamics in raw milk under extreme environments.

Benign glomus tumor of prostate: a case report.

Glomus tumor (GT) is a neoplastic lesion of mesenchymal origin arising from the neuromyoarterial canal or glomus body. Although most GT occur in the peripheral soft tissue and extremities, these tumors can grow anywhere in the body. Here, we describe an uncommon case of GT involving the prostate.

RAB17 promotes endometrial cancer progression by inhibiting TFRC-dependent ferroptosis.

Studies have indicated that RAB17 expression levels are associated with tumor malignancy, and RAB17 is more highly expressed in endometrial cancer (EC) tissues than in peritumoral tissues. However, the roles and potential mechanisms of RAB17 in EC remain undefined. The present study confirmed that the expression of RAB17 facilitates EC progression by suppressing cellular ferroptosis-like alterations. Mechanistically, RAB17 attenuated ferroptosis in EC cells by inhibiting transferrin receptor (TFRC) protein expression in a ubiquitin proteasome-dependent manner. Because EC is a blood-deprived tumor with a poor energy supply, the relationship between RAB17 and hypoglycemia was investigated. RAB17 expression was increased in EC cells incubated in low-glucose medium. Moreover, low-glucose medium limited EC cell ferroptosis and promoted EC progression through the RAB17-TFRC axis. The in vitro results were corroborated by in vivo studies and clinical data. Overall, the present study revealed that increased RAB17 promotes the survival of EC cells during glucose deprivation by inhibiting the onset of TFRC-dependent ferroptosis.

The hepatoprotective effect of sodium butyrate on hepatic inflammatory injury mediated by the NLRP3 inflammatory pathway in subchronic fluoride-exposed mice.

BACKGROUND: Excessive subchronic fluoride exposure can cause severe damage to detoxification organs, including the liver. Sodium butyrate has anti-inflammatory, antitumor, antioxidant and immunomodulatory properties. However, relatively few studies have investigated the effects of sodium butyrate on liver injury caused by subchronic fluoride exposure. The purpose of this research was to investigate the effect and mechanism of sodium butyrate on fluoride-induced hepatic inflammatory injury via the expression of nod-like receptor protein 3 (NLRP3). METHODS: Mice were subjected to randomization into four groups, control group (C), fluorosis group (F), sodium butyrate alone group (S), and treatment group (Y). The mice in groups F and F + S drank 100 mg/L sodium fluoride-containing distilled water freely every day. After fluoride exposure lasted for 3 months, the mice in group S and F + S were gavaged with sodium butyrate daily at a concentration of 1000 mg/kg. Following the treatment regimen, liver specimens were collected for analysis. The mRNA and protein expression levels of inflammatory factors and NLRP3 and its downstream gene were measured by RT-qPCR and western blotting. RESULTS: The histological hematoxylin and eosin (H&E) staining of liver showed that the subchronic fluoride-exposed group were chronic inflammation. The liver of treatment group were less vacuolar degeneration and inflammatory infiltration. The results of the biochemical assay showed that the subchronic fluoride-exposed group were liver injury. In addition, the detection of oxidative stress indicators showed that chronic subchronic fluoride exposure could lead to an increase in the level of oxidative stress in the liver, and the treatment alleviated this increase. RT-qPCR results showed that compared with those in the control group, the mRNA levels of the inflammatory factors TNF-α, IL-6 and IL-1ß, the NLRP3 inflammasome and its downstream factors NLRP3, caspase-1, gasdermin D (GSDMD) and IL-18 increased in the liver tissue of mice in the subchronic fluoride-exposed group. Sodium butyrate released inflammatory factors during subchronic fluoride exposure and inhibited the protein expression of activated NLRP3 to a certain extent. CONCLUSIONS: Sodium butyrate may play a protective role by antagonizing the production of activated inflammasomes and their downstream inflammatory factors in the livers of subchronic fluoride-exposed mice.

Machine learning algorithm-based biomarker exploration and validation of mitochondria-related diagnostic genes in osteoarthritis.

The role of mitochondria in the pathogenesis of osteoarthritis (OA) is significant. In this study, we aimed to identify diagnostic signature genes associated with OA from a set of mitochondria-related genes (MRGs). First, the gene expression profiles of OA cartilage GSE114007 and GSE57218 were obtained from the Gene Expression Omnibus. And the limma method was used to detect differentially expressed genes (DEGs). Second, the biological functions of the DEGs in OA were investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Wayne plots were employed to visualize the differentially expressed mitochondrial genes (MDEGs) in OA. Subsequently, the LASSO and SVM-RFE algorithms were employed to elucidate potential OA signature genes within the set of MDEGs. As a result, GRPEL and MTFP1 were identified as signature genes. Notably, GRPEL1 exhibited low expression levels in OA samples from both experimental and test group datasets, demonstrating high diagnostic efficacy. Furthermore, RT-qPCR analysis confirmed the reduced expression of Grpel1 in an in vitro OA model. Lastly, ssGSEA analysis revealed alterations in the infiltration abundance of several immune cells in OA cartilage tissue, which exhibited correlation with GRPEL1 expression. Altogether, this study has revealed that GRPEL1 functions as a novel and significant diagnostic indicator for OA by employing two machine learning methodologies. Furthermore, these findings provide fresh perspectives on potential targeted therapeutic interventions in the future.

Pressure Strategy To Improve H Atomic Utilization via Optimized Decomposition Pathway in Solid Hydrazine Borane.

Hydrazine borane (N2H4BH3, HB), a typical B-N-H compound with very high hydrogen content (15.4 wt %), is regarded as an efficient hydrogen storage material. However, during the pyrolysis at ambient pressure, solid HB decomposes, losing ∼30 wt %, which is rationalized by the evolution of hydrazine (N2H4). Here, high pressure is introduced as an analogous catalyst role that enable to optimize the decomposition pathway of solid HB. This approach improves the H atomic utilization to over 95%. Energy-dispersive spectroscopy (EDS) analysis indicates that pressure inhibits the production of N2H4, in-situ high-pressure-high-temperature Raman and in-situ high-pressure Infrared (IR) spectra, Density functional theory (DFT) calculation, and Hirshfeld analysis reveal that this inhibition is a consequence of pressure-enhanced dihydrogen and BN bonds. The superior hydrogen release properties of HB under high pressure make it a candidate for use in the synthesis of superconductor CeH9 as a hydrogen source.

Lightweight Single-Stage Ship Object Detection Algorithm for Unmanned Surface Vessels Based on Improved YOLOv5.

Object detection is applied extensively in various domains, including industrial manufacturing, road traffic management, warehousing and logistics, and healthcare. In ship object detection tasks, detection networks are frequently deployed on devices with limited computational resources, e.g., unmanned surface vessels. This creates a need to balance accuracy with a low parameter count and low computational load. This paper proposes an improved object detection network based on YOLOv5. To reduce the model parameter count and computational load, we utilize an enhanced ShuffleNetV2 network as the backbone. In addition, a split-DLKA module is devised and implemented in the small object detection layer to improve detection accuracy. Finally, we introduce the WIOUv3 loss function to minimize the impact of low-quality samples on the model. Experiments conducted on the SeaShips dataset demonstrate that the proposed method reduces parameters by 71% and computational load by 58% compared to YOLOv5s. In addition, the proposed method increases the mAP@0.5 and mAP@0.5:0.95 values by 3.9% and 3.3%, respectively. Thus, the proposed method exhibits excellent performance in both real-time processing and accuracy.

Cellular, Structural Basis, and Recent Progress for Targeting Murine Double Minute X (MDMX) in Tumors.

Murine double minute X (MDMX) is an oncoprotein that mainly has a negative regulatory effect on the tumor suppressor p53 to induce tumorigenesis. As MDMX is highly expressed in various types of tumor cells, targeting and inhibiting MDMX are becoming a promising strategy for treating cancers. However, the high degree of structural homology between MDMX and its homologous protein murine double minute 2 (MDM2) is a great challenge for the development of MDMX-targeted therapies. This review introduces the structure, distribution, and regulation of the MDMX, summarizes the structural features and structure-activity relationships (SARs) of MDMX ligands, and focuses on the differences between MDMX and MDM2 in these aspects. Our purpose of this work is to propose potential strategies to achieve the specific targeting of MDMX.

Design and Research of the Grasping Force Feedback Mechanism of Flexible Surgical Robots.

BACKGROUND: Robot-assisted microsurgery (RAMS) is gradually becoming the preferred method for some delicate surgical procedures. However, the lack of haptic feedback reduces the safety of the surgery. Surgeons are unable to feel the grasping force between surgical instruments and the patient's tissues, which can easily lead to grasping failure or tissue damage. METHODS: This paper proposes a tendon-driven grasping force feedback mechanism, consisting of a follower hand and a leader hand, to address the lack of grasping force feedback in flexible surgical robots. Considering the friction in the tendon transmission process, a grasping force estimation model is established for the follower hand. The admittance control model is designed for force/position control of the leader hand. RESULTS: Through experimental validation, it has been confirmed that the grasping force sensing range of the follower hand is 0.5-5 N, with a sensing accuracy of 0.3 N. The leader hand is capable of providing feedback forces in the range of 0-5 N, with a static force accuracy of 0.1 N. CONCLUSIONS: The designed mechanism and control strategy can provide the grasping force feedback function. Future work will focus on improving force feedback performance. TRIAL REGISTRATION: This research has no clinical trials.

Intensified electrochemiluminescence and photoluminescence via supramolecular anion recognition interactions.

Herein, intensified electrochemiluminescence (ECL) and photoluminescence (PL) via supramolecular anion recognition interactions are demonstrated. A bisindolylpyrrole derivative with a structure containing two indole groups and 2-hexyl-pyrrolo[3,4-c]pyrrole-1,3(2H,5H)-dione, BIPPD, was designed and synthesized de novo to induce the enhanced ECL and PL emission based on hydrogen bonding interactions with the dihydrogen phosphate anion. Remarkably, the ECL quantum efficiency and PL quantum yield were discovered to increase up to 5.5-fold and 1.5-fold, respectively, via this anion coordination. Dopant PF6 - was found not to form hydrogen bonds, while HSO4 - doping does slightly with the receptor molecule. There was no enhancement in either ECL or PL in both scenarios, revealing great recognition selectivity of the synthesized BIPPD. Mechanistic studies via 1H NMR, ECL, and PL spectra illustrated that the ECL processes varied in the presence and absence of H2PO4 - doping, thus leading to the understanding of enhanced efficiency. The bisindolylpyrrole derivative will find applications in supramolecular and analytical chemistry via controlled hydrogen bonding interactions.

Construction of immobilized laccase hydrogels via sodium alginate-dopamine/polyethylene glycol and its efficient degradation of dyeing wastewater.

Laccases with highly catalytic properties have been widely used in developing green applications for water remediation. However, the poor stability and low reutilization rate of free laccase make it difficult to be applied practically. Hence, in this study, an immobilized laccase was prepared using dopamine (DA) functionalized sodium alginate (SA)/polyethylene glycol (PEG) composite hydrogels to realize the recyclability of the laccase. The SA/PEG composite hydrogels, as the protective carrier for laccase, exhibited excellent catalytic stability in various interfering environments. After 30 days, Lac@SA-PDA/PEG beads could remain 70.23 % of the initial activity, as the residual activity of free laccase was only 12.35 %. When free laccase and Lac@SA-PDA/PEG beads were used for decolorization of Reactive Blue 19 (RB-19,100 mg/L), the degradation rate of Lac@SA-PDA/PEG is 6.88 times higher than free laccase. More importantly, the SA-PDA/PEG composite hydrogel exhibited a high reutilization rate, which after six cycles, Lac@SA-PDA/PEG beads retained 90.23 % of its initial activity. Besides, the degradation effect of Lac@SA-PDA/PEG on different dyes was analyzed. In addition, the conjectured degradation pathways of RB-19 by laccase were analyzed. The work showed that immobilized laccase has tremendous potential for the treatment of dyestuff wastewater.