Circ_RPPH1 facilitates progression of breast cancer via miR-1296-5p/TRIM14 axis.

Circular RNA Ribonuclease P RNA Component H1 (circ_RPPH1) and microRNA (miRNA) miR-1296-5p play a crucial role in breast cancer (BC), but the molecular mechanism is vague. Evidence showed that miR-1296-5p can activate tripartite motif-containing 14 (TRIM14). Clinical indications of eighty BC patients were collected and the circ_RPPH1 expression was detected using real-time quantitative PCR. MCF-7 and MDA-MB-231 cells were transfected with overexpression or knockdown of circ_RPPH1, miR-1296-5p, or TRIM14. Cell counting kit-8, cell cloning formation, wound healing, Transwell, and flow cytometry assays were performed to investigate the malignant phenotype of BC. The dual-luciferase reporter gene analyses were applied to reveal the interaction between these target genes. Subcutaneous tumorigenic model mice were established with circ_RPPH1 overexpression MDA-MB-231 cells in vivo; the tumor weight and volume, levels of miR-1296-5 and TRIM14 mRNA were measured. Western blot and immunohistochemistry were used to detect TRIM14 in cells and mice. Circ_RPPH1 levels were notably higher in BC patients and have been found to promote cell proliferation, invasion, and migration of BC cells. Circ_RPPH1 altered cell cycle and hindered apoptosis. Circ_RPPH1 knockdown or miR-1296-5p overexpression inhibited the malignant phenotype of BC. Furthermore, miR-1296-5p knockdown reversed circ_RPPH1's promotion effects on BC. Interestingly, TRIM14 overexpression counteracts the inhibitory effects of miR-1296-5p overexpression and circ_RPPH1 silencing on BC. Moreover, in BC tumor-bearing mice, circ_RPPH1 overexpression led to increased TRIM14 expression and facilitated tumor growth. Circ_RPPH1 enhanced BC progression through miR-1296-5p/TRIM14 axis, indicating its potential as a biomarker and therapeutic target in BC.

TRIM58 downregulation maintains stemness via MYH9-GRK3-YAP axis activation in triple-negative breast cancer stem cells.

TRIM58 is a member of the TRIM protein family, which possess with E3 ubiquitin ligase activities. Studies have revealed that low expression of TRIM58 plays key roles, has been implicated in the tumor progression of tumor formation due to its reduced expression. However, its role in regulating the stemness of breast cancer stem cells (CSCs) remains unexplored. Here, we found that TRIM58 was underexpressed in TNBC tissues and cells compared to adjacent mucosa tissue, and its downregulation was significantly associated with shorter survival. Overexpression of TRIM58 reduced the proportion of CD44 + /CD24- cells, upregulated differentiation genes, and inhibited stemness-related gene expression in TNBC CSCs. In vitro and in vivo experiments revealed that TRIM58 overexpression in CSCs suppressed tumor sphere formation and tumorigenic capacity. Co-IP results indicated direct interaction between TRIM58 and MYH9, with TRIM58 inducing MYH9 degradation via ubiquitination in differentiated cells. Label-free quantitative proteomics identified GRK3 and Hippo-YAP as downstream targets and signaling pathways of MYH9. TIMER database analysis, immunohistochemistry, western blotting, DNA-protein pulldown experiments, and dual luciferase reporter assays demonstrated that MYH9 regulated GRK3 transcriptional activation in CSCs. In conclusion, elevated TRIM58 expression in CSCs downregulates MYH9 protein levels by promoting ubiquitin-mediated degradation, thereby inhibiting downstream GRK3 transcription, inactivating the YAP stemness pathway, and ultimately promoting CSC differentiation.

Assessing trends and burden of occupational exposure to asbestos in the United States: a comprehensive analysis from 1990 to 2019.

BACKGROUND: This study aimed to analyze the trends and burden of occupational exposure to asbestos in the United States (U.S.) from 1990 to 2019, focusing on mortality rates, geographic distribution, age and sex patterns, and causes of death. METHODS: Data on the number of deaths attributable to occupational exposure to asbestos were collected from 1990 to 2019 in the U.S. Joinpoint analysis was conducted to assess trends over time, and regression models were applied to calculate annual percentage changes (APC) and annual average percentage changes (AAPC). Geographic distribution was examined using mapping techniques. Age and sex patterns were analyzed, and causes of death were identified based on available data. RESULTS: From 1990 to 2019, the overall number of deaths due to occupational exposure to asbestos in the U.S. increased by 20.2%. However, age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALYs) rates (ASDR) exhibited a decline over the same period. Geographic analysis revealed differences in the number of deaths across states in 2019, with California reporting the highest number of fatalities. Age-specific mortality and DALYs showed an increase with age, peaking in older age groups. Tracheal, bronchus, and lung cancer were the leading causes of death attributed to asbestos exposure, with increasing trends observed over the past five years. CONCLUSION: The study highlights significant trends and burden in occupational exposure to asbestos in the U.S., including overall increases in mortality rates, declining ASMR and ASDR, geographic disparities, age and sex patterns, and shifts in causes of death. These findings underscore the importance of continued monitoring and preventive measures to mitigate the burden of asbestos-related diseases.

Optimizing metal part distortion in the material extrusion-thermal debinding-sintering process: An experimental and numerical study.

The thermal debinding-sintering process plays an essential role in the context of material extrusion-based additive manufacturing (AM) for producing parts using metal injection molding (MIM). During thermal debinding, metal parts often experience material distortion and porosity, which negatively impacts their mechanical properties. Slowing down the debinding speed is a common approach to mitigate material distortion and porosity. However, this leads to a significant increase in the debinding time. In this study, we carried out debinding-sintering experiments to optimize the distortion and porosity in metal parts. These metal parts were manufactured utilizing bronze/polylactide (PLA) blend filaments and placed in crucibles of different sizes (small, medium, and large), with different heating rates and holding times. The results revealed that the small crucible yielded higher porosity levels in the metal parts, which could be reduced from 23% to 12% by extending both the heating and holding times. In contrast, the medium crucible managed to reduce porosity to approximately 15% without requiring an extension of the processing time. The large crucible, on the other hand, couldn't achieve further porosity reduction due to challenges in reaching the desired temperature. To gain a deeper insight into temperature distribution during the debinding process, we performed numerical simulations using the computational fluid dynamics (CFD) technique and obtained temperature profiles within the kiln using the three crucibles. Ultimately, we carried out standard mechanical tests on the resulting metal parts and evaluated the thermal debinding procedure under various conditions. The approach we employed, combining experiments and numerical simulations, demonstrated significant promise for enhancing the quality of metal parts in the thermal debinding-sintering process.

Identification of cuproptosis-related miRNAs in triple-negative breast cancer and analysis of the miRNA-mRNA regulatory network.

Introduction: The close association between cuproptosis and tumor immunity in triple-negative breast cancer (TNBC) allows its monitoring for predicting the prognosis of patients with TNBC. Nevertheless, the biological function and prognostic value of cuproptosis-related miRNAs and their target genes have not been reported. Purpose: To construct the miRNA and mRNA-based risk models associated with cuproptosis for patients with TNBC. Methods: Comparison of expression levels for genes associated with cuproptosis was executed between patients in the normal individuals and the TCGA-TNBC cohort. Conducting differential analysis resulted in the identification of differentially expressed miRNA (DE-miRNAs) and differentially expressed genes (DEGs) between the TNBC and Control samples. Screening for prognostic miRNAs and biomarkers involved employing univariate Cox analysis and least absolute shrinkage and selection operator regression analyses. These methods were utilized to construct risk models aimed at predicting the survival of patients with TNBC. Based on the median value of risk scores, patients were then stratified into low- and high-risk groups. Functional enrichment analysis was employed to explore the potential function and pathways of prognostic genes. Additionally, independent prognostic analysis was performed through univariate and multivariate Cox regression. Immune infiltration analysis was performed to examine disparities in the infiltration of immune cells between the two risk groups. Finally, the prognostic gene expression was mined in key cell types of TNBC. Results: We obtained 5213 DEGs and 204 DE-miRNAs related to cuproptosis between TNBC and Control samples. Five prognostic miRNAs (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were closely associated with TNBC. Significant differences in the functions of prognostic genes between the two risk groups were observed, encompassing adipogenesis, inflammatory response, and hormone metabolic process. The prognostic gene regulatory network revealed that miR200C-3p regulated ZFPM2 and CFL2, and miR-1277-3p regulated BMP2 and RORA. A nomogram was created based on riskScore, cancer status, and pathologic stage to predict 1/3/5-year survival of patients with TNBC. Immune infiltration analysis indicated that the immune microenvironment may be associated with the progression of TNBC. Interestingly, prognostic genes exhibited higher expression levels in T cells, fibroblasts, endothelial cells, and monocytes compared to other cells. Conclusions: Five prognostic miRNA (miR-203a-3p, miR-1277-3p, miR-135b-5p, miR-200c-3p, and miR-592) and three biomarkers (DENND5B, IGF1R, and MEF2C) were significantly associated with TNBC, it provides new therapeutic targets for the treatment and prognosis of TNBC.

Mechanistic insights and catalytic enhancement of phenolic wastewater supercritical water gasification: A combined experiment and density functional theory study.

Supercritical water gasification technology provides a favorable technology to achieve pollution elimination and resource utilization of phenolic wastewater. In this study, the reaction mechanism of phenolic wastewater supercritical water gasification was investigated using a combination of experimental and computational methods. Five reaction channels were identified to elucidate the underlying pathway of phenol decomposition. Importantly, the rate-determining step was found to be the dearomatization reaction. By integrating computational and experimental analyses, it was found that phenol decomposition via the path with the lowest energy barrier generates cyclopentadiene, featuring a dearomatization barrier of 70.97 kcal/mol. Additionally, supercritical water plays a catalytic role in the dearomatization process by facilitating proton transfer. Based on the obtained reaction pathway, alkali salts (Na2CO3 and K2CO3) are employed as a catalyst to diminish the energy barrier of the rate-determining step to 40.00 kcal/mol and 37.14 kcal/mol. Alkali salts catalysis significantly improved carbon conversion and pollutant removal from phenolic wastewater, increasing CGE from 58.44% to 93.55% and COD removal efficiency from 94.11% to 99.79%. Overall, this study provides a comprehensive understanding of the decomposition mechanism of phenolic wastewater in supercritical water.

Noninvasive neuromodulation protects against doxorubicin-induced cardiotoxicity and inhibits tumor growth.

Doxorubicin (Dox) poses a considerable threat to patients owing to its cardiotoxicity, thus limiting its clinical utility. Optimal cardioprotective intervention strategies are needed to suppress tumor growth but also minimize cardiac side effects. Here, we showed that tragus vagus nerve stimulation (tVNS) improved the imbalanced autonomic tone, ameliorated impaired cardiac function and fibrosis, attenuated myocyte apoptosis, and mitochondrial dysfunction compared to those in the Dox group. The beneficial effects were attenuated by methyllycaconitine citrate (MLA). The transcript profile revealed that there were 312 differentially expressed genes and the protection of tVNS and retardation of MLA were related to inflammatory response and NADPH oxidase activity. In addition, tVNS synergizing with Dox inhibited tumor growth and lung metastasis and promoted apoptosis of tumor cells in an anti-tumor immunity manner. These results indicated that non-invasive neuromodulation can play a dual role in preventing Dox-induced cardiotoxicity and suppressing tumor growth through inflammation and oxidative stress.

Megafossils of Betulaceae from the Oligocene of Qaidam Basin and their paleoenvironmental and phytogeographic implications.

Understanding the paleoenvironment and phytogeographical history of the Tibetan Plateau, China relies on discovering new plant fossils. The Qaidam Basin has long been regarded as an ideal 'field laboratory' to investigate the paleoclimate and paleobiological evolution of the northern Tibetan Plateau. However, fossil angiosperms from the Qaidam Basin are rare, and our knowledge of its paleovegetation is poor. Here, we report fossil leaves and fruits of Betulaceae found from the Oligocene Shangganchaigou Formation of northwestern Qaidam Basin (Huatugou area). Comparative morphological analysis led us to assign the fruits to the Betula subgenus Betula and the leaves to Carpinus grandis. These findings, together with other reported fossil plants from the same locality, reveal a close floristic linkage between the Qaidam Basin and Europe during the Oligocene. The northern pathway of this floristic exchange may have crossed through the Qaidam Basin during the late Paleogene. This floristic linkage may have been facilitated by the continuous narrowing of the Turgai Strait and stronger westerlies, which transported moisture and provided favorable climatic conditions. Indeed, fossil plants collected from the Qaidam Basin suggest that during the Oligocene this region had warm and humid deciduous broad-leaf forest, which differs from the region's modern vegetation and indicates that the Qaidam Basin may have been a suitable region for these plants to flourish and spread during the Oligocene.

An experimental and thermodynamic equilibrium investigation of heavy metals transformation in supercritical water gasification of oily sludge.

Supercritical water gasification (SCWG) is an advanced and highly efficient method for treating oily sludge. However, it is crucial to consider the transformation characteristics of heavy metals (HMs) during the SCWG process to prevent potential secondary pollution. This work studied the transformation and distribution characteristics of Cu, Cr and Zn after SCWG of oily sludge in a batch reactor at temperatures ranging from 550 to 700 °C. Additionally, thermodynamic equilibrium analysis was conducted to assess the distribution of HMs based on the minimization of Gibbs free energy. Experimental results indicated that higher temperatures led to the conversion of HMs into more stable forms, effectively immobilizing them within solid products. Furthermore, the addition of Na2CO3 enhanced this process and contributed to a reduction in HMs pollution in the effluent. Thermodynamic equilibrium results were consistent with our experimental data, indicating that the molar fraction of stable HMs forms followed the order: Cr > Cu > Zn. Besides, it is worth noting that Na2CO3 had a limited impact on the distribution of Cu and Cr. However, it played a significant role in inhibiting the formation of silicate Zn at lower temperatures, promoting the decomposition of ZnO*Al2O3 into unstable Zn. This may explain the higher presence of unstable Zn when Na2CO3 was introduced. In summary, this study offers valuable insights into the transformation characteristics of heavy metals and strategies for pollution control during SCWG of oily sludge.

Dual-engineered cartilage-targeting extracellular vesicles derived from mesenchymal stem cells enhance osteoarthritis treatment via miR-223/NLRP3/pyroptosis axis: Toward a precision therapy.

Osteoarthritis (OA) is the most common disabling joint disease with no effective disease modifying drugs. Extracellular vesicles released by several types of mesenchymal stem cells could promote cartilage repair and ameliorate OA pathology in animal models, representing a novel therapeutic strategy. In this study, we demonstrated that extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUC-EVs) could maintain chondrocyte homeostasis and alleviate OA, and further revealed a novel molecular mechanism of this therapeutic effect. miR-223, which could directly bind with the 3'UTR of NLRP3 mRNA, was found to be a key miRNA for hUC-EVs to exert beneficial effects on inflammation inhibiting and cartilage protecting. For enhancing the effect on mitigating osteoarthritis, exogenous miR-223 was loaded into hUC-EVs by electroporation, and a collagen II-targeting peptide (WYRGRL) was modified onto the surface of hUC-EVs by genetic engineering to achieve a more targeted and efficient RNA delivery to the cartilage. The dual-engineered EVs showed a maximal effect on inhibiting the NLRP3 inflammasome activation and chondrocyte pyroptosis, and offered excellent results for the treatment of OA. This study provides a novel theoretical basis and a promising therapeutic strategy for the application of engineered extracellular vesicles in OA treatment.

Experimental study on supercritical water gasification of oily sludge using a continuous two-step method.

Supercritical water gasification (SCWG) technology can convert oily sludge into hydrogen-rich gas. To achieve high gasification efficiency of oily sludge with a high oil concentration under mild conditions, a two-step method involving a desorption process and a catalytic gasification process using Raney-Ni catalyst was investigated. High oil removal efficiency (99.57%) and carbon gasification efficiency (93.87%) were achieved. The lowest wastewater total organic carbon, oil content, and carbon content in the solid residues were 4.88 ppm, 0.08% and 0.88%, respectively, using a gasification temperature of 600 °C, treatment concentration of 1.11 wt%, gasification time of 70.7 s, and the optimal desorption temperature of 390 °C. The main organic carbon component in the solid residues was cellulose, which is environmentally safe. As the treatment concentration increased, the two-step method outperformed the single-step method. The mechanism for the two-step SCWG of oily sludge was revealed. In the first step, supercritical water is used in the desorption unit to achieve a high oil removal efficiency with few liquid products generated. In the second step, the Raney-Ni catalyst promotes efficient gasification of high-concentration oil at a low temperature. This research provides valuable insights into the effective SCWG of oily sludge at a low temperature.

FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma.

BACKGROUND: This research aimed to investigate the roles of fanconi anemia complementation group D2 (FANCD2) on the regulation of ferroptosis in osteosarcoma progression. METHODS: The function of FANCD2 on cell viability, invasion, migration, and tumor growth were explored. FANCD2 and pathway-related genes were determined by western blot. Ferroptosis-associated markers were determined, including lipid peroxidation, labile iron pool (LIP), ferrous iron (Fe2+), and ferroptosis-related genes. RESULTS: FANCD2 expression was increased in osteosarcoma cells. FANCD2 knockdown reduced cell viability, invasion, and migration of osteosarcoma cells. FANCD2 knockdown regulated ferroptosis-related gene expression, and distinctly increased the levels of LIP, Fe2+, and lipid peroxidation, and these effects were reversed by a ferroptosis inhibitor Fer-1. In addition, JAK2 and STAT3 expression were reduced by silencing of FANCD2, and STAT3 activator (colivelin) distinctly reversed tumor suppressor effects of FANCD2 silencing on osteosarcoma development. CONCLUSION: These findings suggested that FANCD2 silencing could suppress osteosarcoma cell viability, migration, invasion, and tumor growth, and induced ferroptosis by regulating the JAK2/STAT3 axis. These findings may provide novel therapeutic ideas for clinical treatment of osteosarcoma.

Effects of pulsed field ablation on autonomic nervous system in paroxysmal atrial fibrillation: A pilot study.

BACKGROUND: Vagal responses and phrenic activation are commonly observed during pulsed field ablation (PFA). However, whether the vagal responses and phrenic activations are nerve damage or a neurological stress response due to electrical stimulation is unclear. OBJECTIVE: The purpose of this study was to evaluate the effect of a PFA system for performing pulmonary vein isolation on the autonomic nervous system. METHODS: Patients with paroxysmal atrial fibrillation (AF) who underwent PFA between August 2021 and November 2021 were included. Nerve injury biomarkers and heart rate variability were obtained preablation and postablation. Patients were scheduled to undergo magnetic resonance imaging and diffusion-weighted imaging to evaluate cerebral microembolus formation postablation. RESULTS: Acute electrical isolation was achieved in 100% of pulmonary veins (n = 72) in the 18 patients. Mean total procedural time was 64.1 ± 18.2 minutes, and mean fluoroscopy time was 12.3 ± 3.5 minutes. Serum nerve injury biomarkers did not show any changes preablation and immediately postablation and 24 hours after ablation (all P >.05). Preablation and 30-day postablation heart rate variability did not differ (all P >.05). Postablation diffusion-weighted imaging revealed no acute cerebral microembolus events. Moreover, there were no other procedure-related complications. The 8-month Kaplan-Meier estimate of freedom from arrhythmia was 83% ± 9%. CONCLUSION: PFA does not induce nerve injury during pulmonary vein isolation for paroxysmal AF.

Experimental study on alkali catalytic gasification of oily sludge in supercritical water with a continuous reactor.

Realizing the harmless resource utilization of oily sludge is urgent for petroleum industry and of great significance for environmental management. The treatment of oily sludge was investigated using supercritical water gasification (SCWG) with a continuous fluidized bed reactor. The effect of operating parameters on gasification efficiency and gas yield without catalyst was tested, and then the influences of catalyst type (K2CO3 and Na2CO3) and concentrations (1-8 wt%) were systematically studied. The results indicated that a medium mass flow ratio and low feedstock concentration were beneficial for gas production. Alkali catalyst improved carbon gasification efficiency (CE) prominently, and Na2CO3 showed better performance due to its better stability. A maximum CE of 95.87% was achieved when 5 wt% Na2CO3 was added at 650 °C, 23 MPa with 5 wt% oily sludge concentration. Besides, according to XRD patterns of solid residues, Na2CO3 was more stable than K2CO3 during SCWG. SEM-EDX results also revealed that more K was migrated into solid residues than Na. The analysis of pore structure demonstrated that alkali catalyst promoted the evolution of pore structure, resulting in higher specific surface areas and total pore volumes. Na2CO3 has a more substantial destructive effect on solid matrix, causing the matrix structure to collapse and inhibiting pore structure development. The FTIR spectra of solid products exhibited a lower content of carbohydrates and aromatic structures than the initial oily sludge. NH4-N results demonstrated that SCWG was a potential green treatment process for oily sludge. This work can not only give an insight into the reaction mechanism of alkali catalytic gasification of oily sludge, but also help to guide the optimal design of reactor and the regulation of operating parameters.

ATBF1 is a potential diagnostic marker of histological grade and functions via WNT5A in breast cancer.

BACKGROUND: Histological grade has been demonstrated to be an important factor of breast cancer outcome and is associated with cell differentiation and is currently being evaluated via H&E-stained sections. Molecular biomarkers are essential to improve the accuracy of histological grading. ATBF1, a large transcription factor, has been considered a tumor suppressor gene with frequent mutations or deletions in multiple cancers. In breast cancer, ATBF1 was reported to function in cell differentiation and mammary development. However, its role in the clinic has rarely been reported. METHODS: Breast cancer tissues (BCTs) and adjacent noncancerous tissues (ANCTs) were collected to analyze the expression of ATBF1 at the mRNA and protein levels. Three anti-ATBF1 antibodies recognizing independent peptides of ATBF1 (N-terminal end, middle region and C-terminal end) were applied for IHC staining. Small interfering RNA (siRNA) was used to silence ATBF1 expression and to investigate the roles of ATBF1 in MCF7 cells. Microarrays were introduced to analyze the differentially expressed genes, enriched GO terms and KEGG terms regulated by ATBF1 and its potential downstream genes, which were further confirmed in vitro and in clinical samples. RESULTS: The expression of ATBF1 was reduced in BCTs at both the mRNA and protein levels compared with that in ANCTs. ATBF1 protein was predominantly localized in the nucleus of ANCTs but in the cytoplasm of BCTs. Both the mRNA and protein levels of ATBF1 were significantly correlated with histological grade. Consistently, knockdown of ATBF1 increased stemness marker expression and reduced differentiation markers in vitro. Further analysis identified WNT5A as an essential downstream gene of ATBF1 in breast cancer cells. Treatment of WNT5A disrupted cell proliferation induced by ATBF1 silencing. In BCTs, a significant correlation was observed between the expression of WNT5A and ATBF1. CONCLUSION: The results indicated that ATBF1 expression might be a useful diagnostic marker associated with histological grade and breast cancer malignancy. WNT5A and its signaling pathway are novel mechanisms by which ATBF1 contributes to breast cancer tumorigenesis.

Analysis of Factors Influencing the Decision-Making Behavior of Beef Cattle Farmers: An Empirical Analysis Based on Logit-ISM Model.

The beef cattle industry is an important part of herbivorous animal husbandry and an important industry to enrich the dietary structure of residents and promote the income of farmers and herdsmen. The cow is an important foundation to support the healthy development of the beef cattle industry, which is related to the stability of cattle sources and the sustainable development of the industry. However, in recent years, the shortage of cows in our country has led to the shortage of cattle resources and the high price of calves, which has restricted the further development of our beef cattle industry. In order to explore the factors that affect the decision-making behavior behind cow breeding and to find the right policy to mobilize the enthusiasm for cow breeding, based on the field survey of five provinces (cities and regions), including Inner Mongolia Autonomous Region and Ningxia Hui Autonomous Region, this paper conducts an empirical analysis through the Logit ISM model. The results show that market expectation is the surface factor that directly affects the decision-making behavior of cow breeding. The influencing factors of the middle layer are policy propaganda, policy subsidies, breeding years, and feeding methods. The deep root factors are the age of the breeder, the amount of loan, and whether to plant feed crops. Based on this, this paper proposes that we should actively promote the importance of cow breeding, strengthen policy support for cow breeding, formulate scientific and reasonable subsidy policies for cows, innovate financial support methods to solve the problem of fund shortage of farmers, and develop forage resources and reduce the breeding cost of cows.

Prediction of major adverse cardiovascular events in patients with acute coronary syndrome: Development and validation of a non-invasive nomogram model based on autonomic nervous system assessment.

Background: Disruption of the autonomic nervous system (ANS) can lead to acute coronary syndrome (ACS). We developed a nomogram model using heart rate variability (HRV) and other data to predict major adverse cardiovascular events (MACEs) following emergency coronary angiography in patients with ACS. Methods: ACS patients admitted from January 2018 to June 2020 were examined. Holter monitors were used to collect HRV data for 24 h. Coronary angiograms, clinical data, and MACEs were recorded. A nomogram was developed using the results of Cox regression analysis. Results: There were 439 patients in a development cohort and 241 in a validation cohort, and the mean follow-up time was 22.80 months. The nomogram considered low-frequency/high-frequency ratio, age, diabetes, previous myocardial infarction, and current smoking. The area-under-the-curve (AUC) values for 1-year MACE-free survival were 0.790 (95% CI: 0.702-0.877) in the development cohort and 0.894 (95% CI: 0.820-0.967) in the external validation cohort. The AUCs for 2-year MACE-free survival were 0.802 (95% CI: 0.739-0.866) in the development cohort and 0.798 (95% CI: 0.693-0.902) in the external validation cohort. Development and validation were adequately calibrated and their predictions correlated with the observed outcome. Decision curve analysis (DCA) showed the model had good discriminative ability in predicting MACEs. Conclusion: Our validated nomogram was based on non-invasive ANS assessment and traditional risk factors, and indicated reliable prediction of MACEs in patients with ACS. This approach has potential for use as a method for non-invasive monitoring of health that enables provision of individualized treatment strategies.

YB-1 promotes cell proliferation and metastasis by targeting cell-intrinsic PD-1/PD-L1 pathway in breast cancer.

Programmed cell death 1 (PD-1) suppresses T effector functions by inhibiting signaling downstream of the T cell receptor and helping tumor cells escape the immune response. However, the effect and mechanism of cell-intrinsic PD-1 in cancer cells are still unknown. Here, we found that PD-1 is aberrantly upregulated in TNBC patients and cell lines. Cell-intrinsic PD-1 in TNBC cells significantly facilitated tumor growth and metastasis in vitro and in vivo. Further studies indicated that PD-1 effect on TNBC cell growth depends on the cell-intrinsic-PD-1/PD-L1 pathway independent of adaptive immunity. In addition, we further found that the activation of cell-intrinsic PD-1/PD-L1 pathway in TNBC cells is regulated by the gene expression regulator YB-1. Mechanistically, the results of protein degradation analysis, mRNA translationally active analysis, CLICK chemistry and L-azidohomoalanine (AHA) incorporation assays, immunoprecipitation assay and Dual-Luciferase reporter assay showed that YB-1 promotes PD-1 expression through the translational activation pathway. We provide in vitro and in vivo evidence that silencing YB-1 expression in TNBC cells inhibits cell proliferation, tumorigenesis, and metastasis. However, this inhibition can be rescued by simultaneous exogenous expression of PD-1 and PD-L1 proteins. In conclusion, our results identify TNBC cell-intrinsic functions of the PD-1/PD-L1 axis in tumor growth and metastasis; and revealed PD-1/PD-L1 is a critical effector of YB-1-mediated TNBC proliferation and metastasis in vitro and in vivo.

Experimental Study on Metal Parts under Variable 3D Printing and Sintering Orientations Using Bronze/PLA Hybrid Filament Coupled with Fused Filament Fabrication.

Producing metal parts from Fused Filament Fabrication (FFF) 3D printing coupled with a metal/polymer hybrid filament, considering the advantages of high-performance and low cost, has generated considerable research interest recently. This paper addresses the studied relationship between variable printing/sintering directions and the properties of the sintered metal parts. It was shown that the printing directions played a significant role in determining the properties of final products, such as shrinkage, tensile stress, and porosity. The shrinkage in the layer direction because of anisotropic behavior is more minor than in the other dimensions. The microstructural analysis indicated that the printing directions had influenced the form and position of porosity on the produced metal parts. Most porosities occurred on the surfaces printed parallel to the printing bed. Furthermore, the sintering orientations had no possible benefits for dimension shrinkage, weight shrinkage, density, and porosity position of produced metal parts. However, the sintering direction "upright" resulted in parting lines inside the sintered tensile samples and made them fragile. The best printing-sintering combination was "on-edge-flat".

Role of Perforating Artery Pedicled Neurotrophic Flap in the Treatment of Compound Tissue Defect of Tibia Using the Ilizarov Technique.

OBJECTIVE: To describe our experience with the combined use of pedicled neurotrophic flap and distraction osteogenesis in the management of complex lower extremity injuries with composite bone and soft tissue defects and assess the functional and cosmetic results of this method. METHODS: A pedicled flap with a marked perforator artery was applied for soft tissue coverage after radical debridement and temporary external fixation. In the second stage, the Ilizarov external fixator was used in place of the temporary external fixator for reconstruction of the segmental bone defect by distraction osteogenesis. Twenty-five patients (16 men and nine women; mean age, 39.2 years) were treated by using this combined technique between 2008 and 2016. All cases were graded initially as Gustilo-Anderson grade IIIB open fractures. The soft tissue defect after radical debridement ranged from 9 cm × 5 cm to 14 cm × 11 cm, and the average size of segmental defect was 5.2 (Range, 2.5-8.5) cm. Seventeen of these patients had a history of local infection. The bone structure and function were evaluated by two independent evaluators using Paley's criteria. RESULTS: Twenty-five patients were followed up for an average of 28.96 (Range, 15-48) months. The distally based sural neurovascular flap was applied in 13 patients, and the greater saphenous neurocutaneous perforator flap in 12 patients. The flap area ranged from 10 cm × 5 cm to 14 cm × 12 cm. Sufficient coverage of soft tissue defect was achieved in all cases. All flaps survived completely without complications. The bone defects were corrected by a mean lengthening of 6.94 (Range, 4.5-9.5) cm. The residual discrepancy was <1 cm in all cases, which was not clinically significant. The function was evaluated as excellent in 12 patients and good in 13 patients. Bone results were graded as excellent in 18 patients and good in seven patients. Complications during treatment included pain, pin tract infections, ankle midfoot joint stiffness, and docking site nonunion. No recurrence of infection was observed in infected patients. All cases achieved successful limb salvage and satisfactory function recovery without recurrence of infection. CONCLUSIONS: The combined technique of a perforator artery pedicled neurotrophic flap and distraction osteogenesis is an effective alternative approach in the salvage treatment of massively traumatized and chronically infected lower extremities.