ANT2 functions as a translocon for mitochondrial cross-membrane translocation of RNAs.

Bidirectional transcription of mammalian mitochondrial DNA generates overlapping transcripts that are capable of forming double-stranded RNA (dsRNA) structures. Release of mitochondrial dsRNA into the cytosol activates the dsRNA-sensing immune signaling, which is a defense mechanism against microbial and viral attack and possibly cancer, but could cause autoimmune diseases when unchecked. A better understanding of the process is vital in therapeutic application of this defense mechanism and treatment of cognate human diseases. In addition to exporting dsRNAs, mitochondria also export and import a variety of non-coding RNAs. However, little is known about how these RNAs are transported across mitochondrial membranes. Here we provide direct evidence showing that adenine nucleotide translocase-2 (ANT2) functions as a mammalian RNA translocon in the mitochondrial inner membrane, independent of its ADP/ATP translocase activity. We also show that mitochondrial dsRNA efflux through ANT2 triggers innate immunity. Inhibiting this process alleviates inflammation in vivo, providing a potential therapeutic approach for treating autoimmune diseases.

A randomized trial of the inflammatory cytokines levels and the blood transfusion rate between miniaturized tubing group and conventional tubing group in congenital heart disease open heart surgeries.

INTRODUCTION: We aimed to compare the inflammatory cytokines levels of the miniaturized and conventional extracorporeal circuit system. The miniaturized extracorporeal circuit system may be fewer possible inflammation-induced or blood transfusion-related complications. METHODS: We performed a prospective randomized controlled trial (RCT) of 101 patients undergoing congenital heart surgery with CPB (cardiopulmonary bypass, weight ≤15 kg, age ≤2 years). Patients were divided into two different CPB groups randomly by random data form. Blood samples at five different time points and the ultrafiltration fluid before and after CPB were collected in all patients. IL-6, IL-8, and TNF alpha were respectively tested with Abcam ELISA kit. RESULTS: The IL-6 level of blood serum in two groups had no statistical differences between the two groups at all time points. The IL-8 level of blood serum in two groups had no statistical differences right after anesthesia and 5 min after CPB. However, IL-8 level was significantly higher in conventional extracorporeal circuit group than that in miniaturized extracorporeal circuit group at 6 h, 12 h and 24 h after CPB. Blood serum TNF alpha in conventional extracorporeal circuit group was significantly higher at 6 h after CPB than that in miniaturized extracorporeal circuit group. No statistical differences in TNF alpha were found between two groups right after anesthesia and at 5 min after CPB, 12 h and 24 h after CPB. In ultrafiltration fluid, no statistical differences were found in IL-6, IL-8 nor TNF alpha between two groups in all time. No statistical differences were found in ICU (intensive care unit) stay and mechanical ventilation time between the two groups. The blood transfusion rate was significantly lower in miniaturized extracorporeal circuit group. CONCLUSION: Implementing the miniaturized extracorporeal circuit system could decrease the inflammatory cytokines at a certain level. The blood transfusion rate is significantly lower in miniaturized extracorporeal circuit group This indicates the miniaturized extracorporeal circuit system might be a safer CPB strategy with fewer possible inflammation-induced or blood transfusion-related complications.

Emerging multiple function of B-RAFs in plants.

Recent studies have revealed that B-subgroup rapidly accelerated fibrosarcoma (RAF) kinases have pivotal roles in hormone signaling and stress responses across a wide range of organisms. In this forum, I explore their evolution and diverse signaling pathways, highlighting the significance of B-RAF kinases in plant growth and plant-environment interactions while discussing open questions for future research.

Noncoding RNA Terc-53 and hyaluronan receptor Hmmr regulate ageing in mice.

One of the basic questions in the ageing field is whether there is fundamental difference between the ageing of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-ageing Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at early age was observed, indicating its involvement in normal ageing of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal ageing. AAV-delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan (Stern 2017). These findings demonstrate the complexity of ageing in mammals, and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.

Emotional labour in nursing research: A bibliometric analysis.

AIM: This study aims to conduct a comprehensive bibliometric analysis to explore the trajectory and thematic developments of emotional labour research in nursing. DESIGN: Utilizing descriptive and bibliometric analysis techniques. METHODS: The data analysis and graphical presentation were conducted using the Bibliometrix Package in R software. DATA SOURCES: The Web of Science Core Collection (WoSCC) database was searched on October 20, 2023. RESULTS: From 1992 to 2023, 842 authors published relevant articles, yielding 779 author keywords. There has been a general upward trend in the number of articles published over the past 30 years, with an annual growth rate of 11.71%. Keyword co-occurrence cluster analysis revealed the main focus areas of research on emotional labour antecedents and consequences, regulatory modalities, training and education, as well as research methods and application scenarios. CONCLUSION: Emotional labour significantly influences nursing staff's well-being and patient care outcomes. Effective management and education regarding emotional labour are crucial for enhancing nursing staff performance and patient care quality. Future research should focus on long-term effects, training efficacy, regulatory strategies across clinical settings, and innovative approaches to address current challenges. IMPACT: This study provides valuable insights into the unique trajectory and thematic developments of emotional labour research in nursing. The findings underscore the importance of addressing emotional labour in nursing practice and education to improve patient care outcomes and nursing staff well-being. REPORTING METHOD: Adherence to recognized bibliometric reporting methods, following relevant EQUATOR guidelines. NO PATIENT OR PUBLIC CONTRIBUTION: This study is based solely on existing literature and did not involve patients or the public in its design, conduct, analysis, interpretation, or preparation.

Adolescents High in Callous-Unemotional Traits are Prone to be Bystanders: The Roles of Moral Disengagement, Moral Identity, and Perceived Social Support.

Bystanders are the most common role that adolescents play in bullying episodes, they have considerable influence on the formation of the victim's experience and the perpetrator's behavior. Based on the social-cognitive model, the current study examined the mediating role of moral disengagement in the association between callous-unemotional traits and bystander behavior and the moderating roles of moral identity and perceived social support. Participants included 2,286 Chinese adolescents aged 11-16 years (49.3% boys; Mage = 13.46, SDage = 0.93). The study showed callous-unemotional traits were significantly and positively associated with bystander behavior and this relation was partially mediated by moral disengagement. Moral identity moderated the relation between callous-unemotional traits and moral disengagement as well as callous-unemotional traits and bystander behavior. Perceived social support moderated in the direct and indirect associations between callous-unemotional traits and bystander behavior via moral disengagement. The relation between callous-unemotional traits and moral disengagement and the relation between callous-unemotional traits and bystander behavior became weaker for adolescents with high perceived social support. Surprisingly, the relation between moral disengagement and bystander behavior became stronger for adolescents with a high level of perceived social support. The results supported two specific patterns of perceived social support: stress-buffering and reverse stress-buffering. The present study contributes to our understanding of the key mechanisms underlying the association between callous-unemotional traits and adolescents' bystander behavior.

Improvement in Tol2 transposon for efficient large-cargo capacity transgene applications in cultured cells and zebrafish ( Danio rerio).

Most viruses and transposons serve as effective carriers for the introduction of foreign DNA up to 11 kb into vertebrate genomes. However, their activity markedly diminishes with payloads exceeding 11 kb. Expanding the payload capacity of transposons could facilitate more sophisticated cargo designs, improving the regulation of expression and minimizing mutagenic risks associated with molecular therapeutics, metabolic engineering, and transgenic animal production. In this study, we improved the Tol2 transposon by increasing protein expression levels using a translational enhancer ( QBI SP163, ST) and enhanced the nuclear targeting ability using the nuclear localization protein H2B (SHT). The modified Tol2 and ST transposon efficiently integrated large DNA cargos into human cell cultures (H1299), comparable to the well-established super PiggyBac system. Furthermore, mRNA from ST and SHT showed a significant increase in transgene delivery efficiency of large DNA payloads (8 kb, 14 kb, and 24 kb) into zebrafish ( Danio rerio). This study presents a modified Tol2 transposon as an enhanced nonviral vector for the delivery of large DNA payloads in transgenic applications.

Association between problematic social networking use and anxiety symptoms: a systematic review and meta-analysis.

A growing number of studies have reported that problematic social networking use (PSNU) is strongly associated with anxiety symptoms. However, due to the presence of multiple anxiety subtypes, existing research findings on the extent of this association vary widely, leading to a lack of consensus. The current meta-analysis aimed to summarize studies exploring the relationship between PSNU levels and anxiety symptoms, including generalized anxiety, social anxiety, attachment anxiety, and fear of missing out. 209 studies with a total of 172 articles were included in the meta-analysis, involving 252,337 participants from 28 countries. The results showed a moderately positive association between PSNU and generalized anxiety (GA), social anxiety (SA), attachment anxiety (AA), and fear of missing out (FoMO) respectively (GA: r = 0.388, 95% CI [0.362, 0.413]; SA: r = 0.437, 95% CI [0.395, 0.478]; AA: r = 0.345, 95% CI [0.286, 0.402]; FoMO: r = 0.496, 95% CI [0.461, 0.529]), and there were different regulatory factors between PSNU and different anxiety subtypes. This study provides the first comprehensive estimate of the association of PSNU with multiple anxiety subtypes, which vary by time of measurement, region, gender, and measurement tool.

Screening and diagnosis of cardiovascular disease using artificial intelligence-enabled cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.

Molecular mechanism of the influence of related genes expression in synovium tissue around shoulder joint of secondary frozen shoulder model rats on angiogenesis.

The study aimed to explore the pathogenesis of secondary frozen shoulder and its influence on synovium tissue and angiogenesis by constructing a rat secondary frozen shoulder model along with transforming growth factor. 40 healthy male rats aged 8 weeks were divided into Sham group (n=10, no modeling treatment), Control group (n=10, modeling treatment), Low group (n=10, modeling treatment, and 10 mL/d transforming growth factor), and High group (n=10, modeling treatment, and 20 mL/d transforming growth factor). Hematoxylin and Eosin (HE) method was used for histological detection, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical staining method were adopted to detect the expression of Matrix metalloproteinase-14 (MMP-14), mitogen-activated protein kinase (p38MAPK), and Vascular endothelial growth factor (VEGF). Compared with Sham group, the range of abduction and external rotation of rat glenohumeral joint in Control group, Low group, and High group was significantly reduced, and High group had the smallest range. Compared with the Sham group, the synovium in the Control group, the Low group, and the High group had obvious hyperplasia, and the blood vessels were significantly increased. Immunohistochemical staining and RT-PCR results showed that compared with Sham group, MMP-14, p38 MAPK, and VEGF in Control group, Low group, and High group all increased significantly, among which High group increased most. The secondary frozen shoulder is mainly manifested as synovial hyperplasia and increased blood vessels, which are related to the induction of MMP-14, p38 MAPK, and VEGF by transforming growth factor, which reveals the pathogenesis of secondary frozen shoulder to a certain extent, and lays a foundation for subsequent clinical treatment of secondary frozen shoulder.

Investigation of the underlying mechanism of Buyang Huanwu decoction in ischemic stroke by integrating systems pharmacology-proteomics and in vivo experiments.

Buyang Huanwu Decoction (BHD) has been effective in treating ischemic stroke (IS). However, its mechanism of action remains unclear. The study intended to explore the potential mechanism of BHD against IS using systems pharmacology, proteomics, and animal experiments. The active components of BHD were identified from UPLC-Q-TOF-MS and literature mining. Systems pharmacology and proteomics were employed to investigate the underlying mechanism of BHD against IS. The AutoDock tool was used for molecular docking. A middle cerebral artery occlusion (MCAO) model rat was utilized to explore the therapeutic benefits of BHD. The rats were divided into sham, model, BHD (5, 10, 20 g/kg, ig) groups. The neurological scores, pathological section characteristics, brain infarct volumes, inflammatory cytokines, and signaling pathways were investigated in vivo experiments. The results of systems pharmacology showed that 13 active compounds and 112 common targets were screened in BHD. The docking results suggested that the active compounds in BHD had a high affinity for the key targets. In vivo experiments demonstrated that BHD exhibited neuroprotective benefits by lowering the neurological score, the volume of the cerebral infarct, the release of inflammatory cytokines, and reducing neuroinflammatory damage in MCAO rats. Furthermore, BHD decreased TNF-α and CD38 levels while increasing ATP2B2, PDE1A, CaMK4, p-PI3K, and p-AKT. Combined with systems pharmacology and proteomic studies, we confirmed that PI3K-Akt and calcium signaling pathways are the key mechanisms for BHD against IS. Furthermore, this study demonstrated the feasibility of combining proteomics with systems pharmacology to study the mechanism of herbal medicine.

Synthesis, Characterization, and Properties of Heat-Resistant Energetic Materials Based on C-C Bridged Dinitropyrazole Energetic Materials.

Polycyclic energetic materials make up a distinctive class of conjugated structures that consist of two or more rings. In this work, 1,3-bis(3,5-dinitro-1H-pyrazol-4-yl)-4,6-dinitrobenzene (BDPD) was synthesized and investigated in detail as a polycyclic heat-resistant energetic molecule that can be deprotonated by bases to obtain its anionic (3-5) salts. All compounds were thoroughly characterized by 1H and 13C NMR, infrared spectroscopy, high-resolution mass spectrometry, and elemental analysis. The structural features of BDPD and its salts were investigated by single-crystal X-ray diffraction and analyzed by different kinds of computing software, like Multiwfn, Gaussian 09W, and so on. In addition, their thermal decomposition temperatures were evaluated by differential scanning calorimetry to be 319.8-329.0 °C, revealing that they possessed high thermal stabilities. The results of impact sensitivity and friction sensitivity analysis confirm that these energetic compounds were insensitive. The detonation properties of neutral compound BDPD and all its nonmetallic salts were calculated by the EXPLO5 v6.05.04 program. The results revealed that their detonation performances were higher than those of the widely used heat-resistant explosive 2,2',4,4',6,6'-hexanitrostilbene (HNS). Combining the above results, it is reasonable to suggest that these compounds have the potential to be heat-resistant energetic materials.

Liposome Nanomedicine Based on Tumor Cell Lysate Mitigates the Progression of Lynch Syndrome-Associated Colon Cancer.

Treatment with immune checkpoint inhibitors (ICIs) has shown efficacy in some patients with Lynch syndrome-associated colon cancer, but some patients still do not benefit from it. In this study, we adopted a combination strategy of tumor vaccines and ICIs to maximize the benefits of immunotherapy. Here, we obtained tumor-antigen-containing cell lysate (TCL) by lysing MC38Mlh1 KD cells and prepared liposome nanoparticles (Lipo-PEG) with a typical spherical morphology by thin-film hydration. Anti-PD-L1 was coupled to the liposome surface by the amidation reaction. As observed, anti-PD-L1/TCL@Lipo-PEG was not significantly toxic to mouse intestinal epithelial cells (MODE-K) in the safe concentration range and did not cause hemolysis of mouse red blood cells. In addition, anti-PD-L1/TCL@Lipo-PEG reduced immune escape from colon cancer cells (MC38Mlh1 KD) by the anti-PD-L1 antibody, restored the killing function of CD8+ T cells, and targeted more tumor antigens to bone marrow-derived dendritic cells (BMDCs), which also expressed PD-L1, to stimulate BMDC antigen presentation. In syngeneic transplanted Lynch syndrome-associated colon cancer mice, the combination of anti-PD-L1 and TCL provided better cancer suppression than monoimmunotherapy, and the cancer suppression effect of anti-PD-L1/TCL@Lipo-PEG treatment was even better than that of the free drug. Meanwhile anti-PD-L1/TCL@Lipo-PEG enhanced the immunosuppressive tumor microenvironment. In vivo fluorescence imaging and H&E staining showed that the nanomedicine was mainly retained in the tumor site and had no significant toxic side effects on other major organs. The anti-PD-L1/TCL@Lipo-PEG prepared in this study has high efficacy and good biosafety in alleviating the progression of Lynch syndrome-associated colon cancer, and it is expected to be a therapeutic candidate for Lynch syndrome-associated colon cancer.

The correlations between parental warmth and children's approaches to learning: a moderated mediation model of self-efficacy and teacher-child closeness.

Researchers have increasingly considered approaches to learning (ATL) a key indicator of school readiness. Our study purposed to examine the impacts of parental warmth on children's approaches to learning, and the mediating role of self-efficacy, as well as the moderating role of teacher-child closeness in this relationship. Using a whole-group sampling method, 414 Chinese children aged 5-6 years participated this research together with their parents and teachers. Parents of those children were asked to fill out in person questionnaires on parental warmth, children's approaches to learning, and self-efficacy. Children's teachers completed the questionnaire regarding teacher-child closeness. Results indicated that children with high parental warmth were more likely to get high approaches to learning and their self-efficacy played a partial mediating role in this link. In addition, teacher-child closeness moderated the correlation between parental warmth and children's self-efficacy. Specifically, the association between parental warmth and children's self-efficacy was stronger for children with high teacher-child closeness than those with low teacher-child closeness. The results extend our understanding of how parental warmth affects children's approaches to learning, revealing that strategies that could enhance self-efficacy would be effective in improving children's approaches to learning.

Effect of Sulfate Attack on the Expansion Behavior of Cement-Treated Aggregates.

The expansion induced by sulfate attack on cement-treated aggregates (SACA) is a well-known problem that can be solved. It causes obvious heaves in road bases and railway subgrades. In this paper, the effects of the sodium sulfate content, cement content, degree of compaction, sulfate types, attack types, aluminum ion supply, concentration of curing sulfate solution, and temperature on the expansion behavior induced by SACA were investigated over 60 days in the laboratory. Based on the Sobol sensitivity analysis method, the influence of the sensitivity of each factor on the expansion was quantitatively analyzed, and the dominant factor of expansion was proposed. Results show that sulfate content is the domain factor of expansion that is induced by SACA, and it presents a logarithmic function relationship with strain. The 0.5% sodium sulfate content is the minimum sulfate content which causes the expansion that is induced by SACA. When the sulfate content is less than 1%, the expansion induced by SACA is minor. When the sulfate content is between 1% and 3%, the expansion behavior is expressed in four stages as follows: rapid strain increase, followed by a short stagnation period, then a significant strain increase and, finally, constant strain. When the sulfate content is greater than 5%, there are two stages comprising the expansion behavior as follows: the rapid strain increases and constant strain occurs. Greater sulfate content, greater degree of compaction, and lower temperature have positive effects on the expansion induced by SACA. The cement content does not have a consistent effect on expansion behavior. Compared with a sodium sulfate attack, both the reaction rate and expansion of cement-treated aggregates that are attacked by gypsum are smaller, and the attack period is also longer. When the sulfate content is greater than 1%, the addition of kaolin promotes the progression of the expansion induced by SACA. A small amount of water is sufficient for the demand for the sulfate attack. When the sulfate content is at a certain level, the expansion induced by SACA that is under external attack is much smaller than the expansion that is under internal attack. This study is expected to serve as a reference for future research on the mechanics of SACA, and it attempts to provide theoretical support for amending expansions that are induced by SACA.

An integrated method for compensating and correcting nonlinear error in five-axis machining utilizing cutter contacting point data.

In current five-axis computer numerical control (CNC) machining, the use of minute linear path segments as an approximation for the ideal cutter contacting (CC) point trajectory is still prevalent. However, introducing rotation axes leads to a deviation of the actual CC point trajectory from the ideal, resulting in nonlinear errors. An integrated method is proposed in this paper for compensating and correcting both the contour error, associated with the approximation of the part surface by the ideal CC point trajectory and the nonlinear error of the CC point trajectory based on the information in the CC point data. By analyzing the spatial relationship between the tool posture and the CC point path during the five-axis linear interpolation process, two adjacent machining tool positions containing CC point data information are selected as the starting and ending points of the five-axis linear interpolation machining. The ideal tool center point and the actual CC point are calculated during the interpolation process, as well as the distance and the unit vector in the perpendicular direction between the actual CC point and the ideal CC point trajectory segment. In the comprehensive error compensation and correction phase, the obtained unit vectors are used as direction vectors for error compensation, and the tool center point during interpolation is first compensated and corrected. This ensures the actual CC point and the contour curve are on the same plane. The compensation direction for contour error is calculated using the start/end tool axis vectors and the ideal CC point trajectory vectors. The size of the contour error approximating the contour curve is calculated through the chord error. A second compensation and correction are applied to the tool center point for interpolation, ultimately achieving comprehensive compensation and correction of nonlinear errors. The data calculations were conducted in the MATLAB environment using actual machining data. After compensation and correction, the contour error was reduced by 76%, the nonlinear error of the CC point trajectory decreased to below 0.88 µm, and the comprehensive nonlinear error of the CC point trajectory was reduced from 19 to 1.5 µm, a reduction of 93%. This demonstrates significant practical value in enhancing the accuracy of five-axis CNC machining. Through actual machining verification, after using the method described in this paper, the average surface roughness decreased from 1.133 to 0.220 µm, and the maximum surface roughness decreased from 6.667 to 1.240 µm. This significantly demonstrates that the compensation and correction method proposed in this paper can significantly improve the surface quality of machined parts.

Ultralow-Loading Ruthenium-Iridium Fuel Cell Catalysts Dispersed on Zn-N Species-Doped Carbon.

Developing low-loading platinum-group-metal (PGM) catalysts is one of the key challenges in commercializing anion-exchange-membrane-fuel-cells (AEMFCs), especially for hydrogen oxidation reaction (HOR). Here, ruthenium-iridium nanoparticles being deposited on a Zn-N species-doped carbon carrier (Ru6Ir/Zn-N-C) are synthesized and used as an anodic catalyst for AEMFCs. Ru6Ir/Zn-N-C shows extremely high mass activity (5.87 A mgPGM -1) and exchange current density (0.92 mA cm-2), which is 15.1 and 3.9 times that of commercial Pt/C, respectively. Based on the Ru6Ir/Zn-N-C AEMFCs achieve a peak power density of 1.50 W cm-2, surpassing the state-of-the-art commercial PtRu catalysts and the power ratio of the normalized loading is 14.01 W mgPGM anode -1 or 5.89 W mgPGM -1 after decreasing the anode loading (87.49 µg cm-2) or the total PGM loading (0.111 mg cm-2), satisfying the US Department of Energy's PGM loading target. Moreover, the solvent and solute isotope separation method is used for the first time to reveal the kinetic process of HOR, which shows the reaction is influenced by the adsorption of H2O and OH-. The improvement of the hydrogen bond network connectivity of the electric double layer by adjusting the interfacial H2O structure together with the optimized HBE and OHBE is proposed to be responsible for the high HOR activity of Ru6Ir/Zn-N-C.

A Retrospective Study of Biological Risk Factors Associated with Primary Knee Osteoarthritis and the Development of a Nomogram Model.

Aim: A high percentage of the elderly suffer from knee osteoarthritis (KOA), which imposes a certain economic burden on them and on society as a whole. The purpose of this study is to examine the risk of KOA and to develop a KOA nomogram model that can timely intervene in this disease to decrease patient psychological burdens. Methods: Data was collected from patients with KOA and without KOA at our hospital from February 2021 to February 2023. Initially, a comparison was conducted between the variables, identifying statistical differences between the two groups. Subsequently, the risk of KOA was evaluated using the Least Absolute Shrinkage and Selection Operator method and multivariate logistic regression to determine the most effective predictive index and develop a prediction model. The examination of the disease risk prediction model in KOA includes the corresponding nomogram, which encompasses various potential predictors. The assessment of disease risk entails the application of various metrics, including the consistency index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, the calibration chart, the GiViTi calibration band, and the model for predicting KOA. Furthermore, the potential clinical significance of the model is explored through decision curve analysis (DCA) and clinical influence curve analysis. Results: The study included a total of 582 patients, consisting of 392 patients with KOA and 190 patients without KOA. The nomogram utilized age, haematocrit, platelet count, apolipoprotein a1, potassium, magnesium, hydroxybutyrate dehydrogenase, creatine kinase, and estimated glomerular filtration rate as predictors. The C index, AUC, calibration plot, Giviti calibration band, DCA and clinical influence KOA indicated the ability of nomogram model to differentiate KOA. Conclusion: Using nomogram based on disease risk, high-risk KOA can be identified directly without imaging.

Inhibition of miR-146b-5p alleviates isoprenaline-induced cardiac hypertrophy via regulating DFCP1.

Pathological cardiac hypertrophy often precedes heart failure due to various stimuli, yet effective clinical interventions remain limited. Recently, microRNAs (miRNAs) have been identified as critical regulators of cardiovascular development. In this study, we investigated the role of miR-146b-5p and its underlying mechanisms of action in cardiac hypertrophy. Isoprenaline (ISO) treatment induced significant hypertrophy and markedly enhanced the expression of miR-146b-5p in cultured neonatal rat cardiomyocytes and hearts of C57BL/6 mice. Transfection with the miR-146b-5p mimic led to cardiomyocyte hypertrophy accompanied by autophagy inhibition. Conversely, miR-146b-5p inhibition significantly alleviated ISO-induced autophagy depression, thereby mitigating cardiac hypertrophy both in vitro and in vivo. Our results showed that the autophagy-related mediator double FYVE domain-containing protein 1 (DFCP1) is a target of miR-146b-5p. MiR-146b-5p blocked autophagic flux in cardiomyocytes by suppressing DFCP1, thus contributing to hypertrophy. These findings revealed that miR-146b-5p is a potential regulator of autophagy associated with the onset of cardiac hypertrophy, suggesting a possible therapeutic strategy involving the inhibition of miR-146b-5p.

Tumor-associated macrophage-induced circMRCKα encodes a peptide to promote glycolysis and progression in hepatocellular carcinoma.

The tumor-associated macrophages (TAMs) play multifaceted roles in the progression of hepatocellular carcinoma (HCC). However, the involvement of circular RNAs in the interplay between TAMs and HCC remains unclear. Based on Transwell co-culturing and circular RNA sequencing, this study revealed that TAMs enhanced tumor glycolysis and progression by upregulating circMRCKα in HCC cells. Patients with HCC who exhibited elevated circMRCKα levels presented significantly reduced overall survival and greater cumulative recurrence. Notably, we identified a novel functional peptide of 227 amino acids named circMRCKα-227aa, encoded by circMRCKα. Mechanistically, circMRCKα-227aa bound to USP22 and enhanced its protein level to obstruct HIF-1α degradation via the ubiquitin-proteasome pathway, thereby augmenting HCC glycolysis and progression. In clinical HCC samples, a positive correlation was observed between the expression of circMRCKα and the number of infiltrating CD68+ TAMs and expression of USP22. Furthermore, circMRCKα emerged as an independent prognostic risk factor both individually and in conjunction with CD68+ TAMs and USP22. This study illustrated that circMRCKα-227aa, a novel TAM-induced peptide, promotes tumor glycolysis and progression via USP22 binding and HIF-1α upregulation, suggesting that circMRCKα and TAMs could be combined as therapeutic targets in HCC.