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The progression of hepatocellular carcinoma (HCC) is influenced by disrupted metabolic processes, presenting challenges in prognostic outcomes. Hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality, is closely associated with metabolic reprogramming and stem cell-like properties in liver cancer stem cells (LCSCs). This study explored the potential molecular mechanisms by which tLyP-1-modified extracellular vesicles (EVs) delivering CTCF shRNA (tLyp-1-EV-shCTCF) regulate mitochondrial DNA methylation-induced glycolytic metabolic reprogramming and LCSC self-renewal. Through a series of methods, including Western blot, nanoparticle tracking analysis, and immunofluorescence, we demonstrated the successful delivery and internalization of tLyp-1-EV in HCC cells. Our results identified SALL3 as a critical factor underexpressed in HCC and LCSCs, while CTCF was overexpressed. Overexpression of SALL3 inhibited LCSC self-renewal and immune evasion by blocking the CTCF-DNMT3A interaction, thus repressing DNMT3A methyltransferase activity and subsequent mitochondrial DNA methylation-mediated glycolytic metabolic reprogramming. In vivo experiments further supported these findings, showing that tLyp-1-EV-shCTCF treatment significantly reduced tumor growth by upregulating SALL3 expression, thereby inhibiting glycolytic metabolic reprogramming and enhancing the immune response against HCC cells. This study provides novel insights into the role of SALL3 and mitochondrial DNA methylation in HCC progression, offering potential therapeutic targets for combating HCC and its stem cell-like properties.

Abstract Polymerized β-actin may provide a structural basis for chromatin accessibility and actin transport into the nucleus can guide mesenchymal stem cell (MSC) differentiation. Using MSC, we show that using CK666 to inhibit Arp2/3 directed secondary actin branching results in decreased nuclear actin structure, and significantly alters chromatin access measured with ATACseq at 24 h. The ATAC-seq results due to CK666 are distinct from those caused by cytochalasin D (CytoD), which enhances nuclear actin structure. In addition, nuclear visualization shows Arp2/3 inhibition decreases pericentric H3K9me3 marks. CytoD, alternatively, induces redistribution of H3K27me3 marks centrally. Such alterations in chromatin landscape are consistent with differential gene expression associated with distinctive differentiation patterns. Further, knockdown of the non-enzymatic monomeric actin binding protein, Arp4, leads to extensive chromatin unpacking, but only a modest increase in transcription, indicating an active role for actin-Arp4 in transcription. These data indicate that dynamic actin remodeling can regulate chromatin interactions.

Abstract Background Foreign bodies (FBs) are a common emergency in medical institutions, that can occur in any area and among people of any age, which are common public health problems. Understanding the epidemiological characteristics of FBs is crucial for their prevention and control. The purpose of this study was to analyze the epidemiological characteristics of FBs worldwide through the data from the Global Burden of Disease Study 2019 (GBD 2019). Methods We obtained data from the GBD 2019, which is an important public database to understand the disease burden of FBs. Joinpoint was used to analyze temporal trends in the incidence and death trends of FBs, which is widely used to study the long-term temporal trend of the burden of diseases. SaTScan was used to detect spatial-temporal clusters of pulmonary aspiration and foreign body in the airway (PAFBA), which is based on a Poisson model, scanning the number of people and diseases in the study area to obtain the spatial-temporal clusters of diseases. Results Globally, the age-standardized incidence rate (ASIR) and the age-standardized death rate (ASDR) of FBs in 2019 were 869.23/100,000 (679.92/100,000-1120.69/100,000) and 1.55/100,000 (1.41/100,000-1.67/100,000), respectively. The ASIR and ASDR showed downtrends with average annual percent changes (AAPCs) of -0.31% and − 1.47% from 1990 to 2019. Of note, the ASIR showed an uptrend during 2010–2019, especially in high, high-middle, and middle SDI regions. Stratified analysis by age group showed that ASIR increased in each age group in recent years. From 1990 to 2019, the ASDR in the over-70 age group showed an uptrend worldwide, especially in high and high-middle SDI regions. In different types of FBs, the ASDR of PAFBA was the highest. The death burden of PAFBA was mainly clustered in 82 countries during 1993–2007, such as Canada, Cuba, and Mexico. Conclusion The most important goal is to improve public awareness and emergency knowledge of FBs through publicity methods, such as the internet or offline activities, and to improve laws and regulations. Additionally, different age groups need different targeted measures, such as strengthening the care of children, caring for elderly individuals, improving necessary monitoring programs and reporting systems, conducting effective hazard assessments, and publicity and education activities.

Introduction: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood. Methods: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed by µCT, and volumetric BMAT was quantified via 9.4T MRI/advanced image analysis. Histomorphometry of adipocytes and osteoclasts, and qPCR were performed. Results: Body weight and visceral white adipose tissue accumulated in response to HFD started in adulthood. Trabecular bone parameters declined with advancing experimental age. BV/TV declined 22% in LFD (p = 0.0001) and 17% in HFD (p = 0.0022) by 24 weeks. HFD failed to appreciably alter BV/TV and had negligible impact on other microarchitecture parameters. Both dietary intervention and age accounted for variance in BMAT, with regional differences: distal femoral BMAT was more responsive to diet, while proximal femoral BMAT was more attenuated by age. BMAT increased 60% in the distal metaphysis in HFD at 18 and 24 weeks (p = 0.0011). BMAT in the proximal femoral diaphysis, unchanged by diet, decreased 45% due to age (p = 0.0002). Marrow adipocyte size via histomorphometry supported MRI quantification. Osteoclast number did not differ between groups. Tibial qPCR showed attenuation of some adipose, metabolism, and bone genes. A regulator of fatty acid β-oxidation, cytochrome C (CYCS), was 500% more abundant in HFD bone (p < 0.0001; diet effect). CYCS also increased due to age, but to a lesser extent. HFD mildly increased OCN, TRAP, and SOST. Conclusions: Long-term high fat feeding after skeletal maturity, despite upregulation of visceral adiposity, body weight, and BMAT, failed to attenuate bone microarchitecture. In adulthood, we found aging to be a more potent regulator of microarchitecture than diet-induced obesity.

Coating technologies are a commonly used way to protect metals against corrosion. However, with more and more severe service environments of materials, many protective coating systems often are not environmentally friendly or toxic as in the case of chromates. Based on the world's abundant ideal magnesium (Mg) and its alloy, the smart self-healing anticorrosive coating can autonomously restore the damaged part of the coating according to the environmental changes, strengthen the corrosion protection ability, and prolong its service life. This paper reviews the research progress of smart self-healing coatings on Mg alloys. These coatings mostly contain suitable corrosion inhibitors encapsulated into micro/nano containers. Moreover, the different self-healing mechanisms and functionalities of micro/nano containers are discussed. The micro/nano containers range from inorganic nanocontainers such as mesoporous nanoparticles (silica (SiO2), titanium dioxide (TiO2), etc.), over inorganic clays (halloysite, hydrotalcite-like, zeolite), to organic nanocontainers such as polymer microcapsules, nanofibers, chitosan (CS) and cyclodextrin (CD), as well as, carbon materials such as graphene and carbon nanotubes and hybrids such as metal organic frameworks. The functioning of micro/nano containers can be divided in two principal groups: autonomous (based on defect filling and corrosion inhibition) and non-autonomous (based on dynamic bonds and shape memory polymers). Moreover, multi functionalities and composite applications of various micro/nano containers are summarized. At present, significant progress has been made in the preparation methods and technologies of micro/nano containers. Achieving long-term self-healing properties of coatings sensing of coating failure and early warning after self-healing function failure can be expected as the main development direction of self-healing corrosion protection coatings in the future.

Water-based or waterborne polyurethane matting resins find extensive application in surface coating to diminish gloss, offering a pleasant tactile experience and a matte aesthetic. This review represents the inaugural effort to consolidate the recent advancements in waterborne polyurethane matting resins, encompassing both physical and chemical matting types. The exploration commences with an introduction to a range of innovative matting agents tailored for the formulation of physical matting waterborne polyurethane resins. Subsequently, a thorough analysis and discussion unfold, delving into the synthesis, characterization, and matting mechanisms of chemical matting waterborne polyurethane resins. This comprehensive discussion draws upon a decade of dedicated research work by our group, contributing fresh perspectives to the evolution of chemical matting techniques. In conclusion, the review not only addresses the current state but also outlines potential challenges and future trends. This forward-looking perspective is intended to offer guidance for the design and synthesis of innovative waterborne polyurethane matting resins.

ObjectiveTo meet the efficient thermal management needs of electronic devices such as ships and underwater vehicles, this study focuses on the constructal design of a tree-shaped microchannel disc heat sink with wavy walls. MethodA design prototype of the heat sink with wavy walls is first proposed. Based on constructal theory, the amplitude and wavelength of the wavy walls are designed under the constraints of fixed heat sink volume and fixed microchannel volume by maximizing the comprehensive performance evaluation criteria (PEC) while considering both heat transfer and flow pressure drop. ResultsThe results show that the wavy walls increase the heat transfer surface areas and generate vortices in their cavities, effectively reducing the maximum temperature. When the inlet Reynolds number is fixed at 700, 900 or 1100 respectively, the maximum temperature is reduced by 13.5 K by increasing the amplitude of the wavy walls, while the pressure drop increases significantly; and the maximum temperature is reduced by 4.7 K by reducing the wavelength of the wavy walls, while the pressure drop increases slightly. There are optimal amplitudes that raise the comprehensive performance evaluation criteria to extreme values for given larger wavelengths, while the comprehensive performance evaluation criteria increase monotonously as the amplitude increases for given smaller wavelengths. ConclusionWavy walls can significantly improve the thermal performance of tree-shaped microchannel disc heat sinks, and the use of constructal design can realize optimal geometric constructs with optimal comprehensive performance evaluation criteria.

ObjectivesThis study seeks to improve the thermal management technology of electronic devices through constructal optimization design. MethodsFirst, the 3D flow and heat transfer numerical model of a hybrid microchannel heat sink is established, and the volume ratio and relative position of its single-sided internal fins are fixed. Constructal optimization is then performed, for which the height-to-width ratio h/w and spacing distribution of fins ε are taken as the design variables, and the minimization of the temperature gradient uniformity factor in the solid region of the heat sink is taken as the objective. The exhaustive method and genetic algorithm are subsequently performed. ResultsThe results show that both the exhaustive method and genetic algorithm can find the minimum value of the temperature gradient uniformity factor and corresponding optimal construct, and the temperature gradient uniformity is improved by up to 13.30% compared to that of the finless microchannel heat sink. The relative difference in the obtained minimum objective function value between the exhaustive method and ten genetic algorithm schemes is no more than 0.92%. ConclusionsThis study provides new optimization design results for the research and development of heat sinks for electronic devices.

Embedded liquid cooling is a preferred solution for dissipating the heat generated by high-power chips. The cooling capacity and pump power consumption of embedded liquid cooling heat sinks differ significantly between different structures. To achieve an accurate match between cooling capacity and heat dissipation requirements, the selection of a liquid-cooled heat sink should be carefully considered in conjunction with the heat dissipation needs of heat sources in real-world thermal management issues. Based on the manufacturing limitations on chip temperature and microchannel pressure, a composite performance index function was developed to assess the cooling capacity and cooling cost of the heat sink. This allowed for the establishment of an evaluation standard to determine the suitability of embedded liquid cooling and heat sink for the heat source. In this study, the suitability of four microchannel heat sinks with the same feature length and fin volume was evaluated under various thermal load conditions. The results show that the best-suited heat sink changes with variations in the thermal load of the chip. In the example, when the heat source was homogeneous at 100 W, the circular section pin fins have an optimal suitability of 0.928 for Re = 500. When the heat source was a heterogeneous heat source with a power of 100 W, the value of Θ was found to be 0.389. Additionally, the optimal suitability of drop section pin fins for Re = 971.5 was determined to be 0.862.

Abstract Background Clarkson disease (monoclonal gammopathy-associated idiopathic systemic capillary leak syndrome, ISCLS) is a rare idiopathic condition marked by transient, relapsing-remitting episodes of systemic microvascular hyper-permeability, which liberates plasma fluid and macromolecules into the peripheral tissues. This pathology manifests clinically as the abrupt onset of hypotensive shock, hemoconcentration, and hypoalbuminemia. Methods We analysed endothelial glycocalyx (eGCX)-related markers in plasma from patients with ISCLS during acute disease flares and convalescence by ELISA and comprehensive proteomic profiling. We evaluated eGCX-related components and gene expression in cultured endothelial cells using RNA-sequencing, real-time PCR, and fluorescence staining. Results Serum levels of eGCX-related core components including hyaluronic acid (HA) and the core proteoglycan soluble syndecan-1 (sCD138) were elevated at baseline and during acute ISCLS flares. Serial measurements demonstrated that sCD138 levels peaked during the recovery (post-leak) phase of the illness. Proteomic analysis of matched acute and convalescent ISCLS plasma revealed increased abundance of eGCX-related proteins, including glypicans, thrombospondin-1 (TSP-1), and eGCX-degrading enzymes in acute compared to remission plasma. Abundance of endothelial cell damage markers did not differ in acute and baseline plasma. Expression of several eGCX-related genes and surface carbohydrate content in endothelial cells from patients with ISCLS did not differ significantly from that observed in healthy control cells. Conclusions eGCX dysfunction, but not endothelial injury, may contribute to clinical symptoms of acute ISCLS. Serum levels of of eGCX components including sCD138 may be measured during acute episodes of ISCLS to monitor clinical status and therapeutic responses.

Printed circuit heat exchangers (PCHEs) are widely used as recuperators in the supercritical carbon dioxide (S-CO2) Brayton cycle design. The variation of heat sources will have a great impact on the heat transfer effect of the recuperator. It is of interest to study the fast calculation of flow and heat transfer performance of PCHEs under different operating conditions to obtain the optimal comprehensive performance and provide guidance for the operation control strategy analysis. Herein, a fast calculation method is established through a one-dimensional model of a PCHE based on Modelica. The effects of working medium mass flow rate and inlet temperature on the flow and heat transfer process are analyzed from the three aspects of heat transfer rate, flow pressure drop, and comprehensive performance, and the mass flow rate matching optimization is realized. The results show that increased mass flow rate increases heat transfer rate and flow pressure drop. The efficiency evaluation coefficient (EEC) has a maximum value at which the mass flow rate values of the cold and hot channels are best matched, and the comprehensive performance is optimal. When the mass flow rate of the heat channel is 4.8 g/s, the maximum EEC is 1.42, corresponding to the mass flow rate of the cold channel, 4.2 g/s. Compared with the design condition, the heat transfer rate increases by 62.1%, and the total pump power increases by 14.2%. When the cold channel inlet temperature increases, EEC decreases rapidly, whereas EEC increases when the hot channel inlet temperature increases. The conclusions can provide theoretical support for the design and operation of PCHEs.

BackgroundsThe widespread coronavirus disease 2019 (COVID-19) outbreak impacted the mental health of infected patients admitted to Fangcang shelter hospital a large-scale, temporary structure converted from existing public venues to isolate patients with mild or moderate symptoms of COVID-19 infection.ObjectiveThis study aimed to investigate the risk factors of the infected patients from a new pharmacological perspective based on psychiatric drug consumption rather than questionnaires for the first time.MethodsWe summarised the medical information and analysed the prevalence proportion, characteristics, and the related risk factors of omicron variants infected patients in the Fangcang Shelter Hospital of the National Exhibition and Convention Center (Shanghai) from 9 April 2022 to 31 May 2022.ResultsIn this study, 6,218 individuals at 3.57% of all admitted patients in the Fangcang shelter were collected suffering from mental health problems in severe conditions including schizophrenia, depression, insomnia, and anxiety who needed psychiatric drug intervention. In the group, 97.44% experienced their first prescription of psychiatric drugs and had no diagnosed historical psychiatric diseases. Further analysis indicated that female sex, no vaccination, older age, longer hospitalization time, and more comorbidities were independent risk factors for the drug-intervened patients.ConclusionThis is the first study to analyse the mental health problems of omicron variants infected patients hospitalised in Fangcang shelter hospitals. The research demonstrated the necessity of potential mental and psychological service development in Fangcang shelters during the COVID-19 pandemic and other public emergency responses.

Graphene oxide has a strong tendency to agglomerate in polymers that are only hydrogen bonded acceptors due to the strong hydrogen bonding and van der Waals forces between its lamellae, which greatly limits its application. In this work, Silica (SiO2) was introduced on the surface of graphene oxide (GO) by hydrolysis of tetraethoxysilane (TEOS). Graphene oxide-silica/polylactic acid (PLA) composites with different grafting ratios were prepared by melt blending. The results by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray photoelectron spectrometry (XPS) show that the silica is grafted on the GO surface in the form of covalent bonds. Other test results show that regulating the amount of TEOS addition could effectively control the grafting rate. The performance test shows that grafting SiO2 on the GO surface can increase the layer spacing of graphene oxide flakes and thus improve its melt dispersion. It also slows down or improves the performance degradation caused by the severe agglomeration of graphene oxide. At the grafting rate of 45.65%, GO is well exfoliated and well dispersed in PLA in the form of monolayers resulting in a substantial improvement in crystalline properties, mechanical properties, and barrier properties. This work solves the problem of severe agglomeration of GO in polymers that are only hydrogen bond acceptors by modifying GO, and provides guidance for the melt processing of graphene oxide and polymers that are only hydrogen bond acceptors.

When the dense pin-fins array distributed uniformly is used to dissipate the non-uniform heat source, it is easy to generate excessive cooling at the non-hot spot, which leads to unnecessary heat dissipation loss. In this study, a three-dimensional model of a multi-core chip-microchannel heat sink is established. Fin layout in the chip-microchannel is optimized under the conditions of non-uniform power-partition chip based on constructal theory. The total volume of fins in a channel is selected as the constraint condition. A genetic algorithm is used to seek the optimal construct. Comparing the optimal fin layout with the dense pin-fins array, the results demonstrate that the maximum temperature can be reduced by 6.75 K when Re number is 750, and the total pressure loss can be reduced by 54.1% when Re number is 750. Namely, under the condition of non-uniform heat source, the fins with a certain total volume were distributed reasonably, which can maintain the optimal balance of heat dissipation capacity and heat dissipation cost, so that the accurate and efficient thermal design is realized, and the better comprehensive benefits are obtained.

Background We explored the relationship between the platelet-lymphocyte ratio (PLR), the prognostic nutritional index (PNI), the lactate dehydrogenase-albumin ratio (LDH/albumin ratio; LAR), the controlling nutritional status (CONUT) score, and the long-term survival of colon cancer patients. Methods We conducted a retrospective analysis of the clinical data and follow-up materials of 126 patients with colon cancer who underwent surgical treatment in the Department of Gastrointestinal Surgery of Jiangnan University Affiliated Hospital from June 2012 to December 2015. The receiver operating characteristic curve (ROC) was used to distinguish the high ratio group from the low ratio group. The Kaplan Meier method was used to draw the survival curve in our survival analysis. The log rank test was used for the univariate analysis and the Cox multivariate regression analysis was used to analyze the correlation between preoperative PLR, PNI, LAR, conut scores, and overall survival (OS) and progression free survival (PFS) of patients with colon cancer. Results The median follow-up time was 72 months. The OS rates at 3 and 5 years were 83.3% and 78.5%, respectively. The PFS rates at 3 and 5 years were 79.3% and 77.6%, respectively. The 3-year and 5-year OS rates in the low LAR group (≤4.91) were 90.9% and 87.1%, respectively, and were 56.0% and 44.0% in the high LAR group (>4.91) respectively. Univariate and multivariate analyses showed that the LAR value was correlated with OS and PFS (P < 0.05). Conclusion A high preoperative LAR is an independent predictor of the prognosis of colon cancer patients.

Exercise, typically beneficial for skeletal health, has not yet been studied in lipodystrophy, a condition characterized by paucity of white adipose tissue, with eventual diabetes, and steatosis. We applied a mouse model of global deficiency of Bscl2 (SEIPIN), required for lipid droplet formation. Male twelve-week-old B6 knockouts (KO) and wild type (WT) littermates were assigned six-weeks of voluntary, running exercise (E) versus non-exercise (N=5-8). KO weighed 14% less than WT (p=0.01) and exhibited an absence of epididymal adipose tissue; KO liver Plin1 via qPCR was 9-fold that of WT (p=0.04), consistent with steatosis. Bone marrow adipose tissue (BMAT), unlike white adipose, was measurable, although 40.5% lower in KO vs WT (p=0.0003) via 9.4T MRI/advanced image analysis. SEIPIN ablation’s most notable effect marrow adiposity was in the proximal femoral diaphysis (-56% KO vs WT, p=0.005), with relative preservation in KO-distal-femur. Bone via μCT was preserved in SEIPIN KO, though some quality parameters were attenuated. Running distance, speed, and time were comparable in KO and WT. Exercise reduced weight (-24% WT-E vs WT p

Two new integrated models with heat source–heat sink are established, in which isothermal liquid cooling channels with triangle or square sections are, respectively, embedded in a cylindrical heating body with uniform heat production. Based on constructal theory, under the conditions of a fixed cylinder cross-sectional area and the proportion of channels, taking the dimensionless maximum temperature and the dimensionless entransy equivalent thermal resistance (EETR) as the optimization goals, the influences of distribution of liquid cooling channels on the heat dissipation capacity of integrated models are studied with the number and the center distance of liquid cooling channels as design variables, and the optimal constructs with different proportions of channels are obtained. The results show that when the proportion of channels, cross-sectional area and the number of liquid cooling channels are given, there is an optimal center distance to make the overall heat dissipation performance of the integrated model reach its best, but the optimal center distances for the two indicators are different. The dimensionless maximum temperature and the dimensionless EETR decrease when the proportion of channels increases, but the optimal dimensionless center distances are almost the same for different proportions of channels. The dimensionless maximum temperature with the triangular cross-section is lower than that with the square cross-section under the conditions of constant cross-sectional area and dimensionless center distance, which is the same as the case for the dimensionless EETR. The results can furnish the theoretical guidelines for the thermal design of cylindrical devices needing efficient cooling.

A three-dimensional convective heat transfer model of a microchannel pin-fin hybrid heat sink was established. Considering the non-uniform heat generation of 3D stacked chips, the splitting distance of pin-fins was optimized by minimizing the maximum heat sink temperature under different heat fluxes in the hotspot, the Reynolds numbers at the entrance of the microchannel, and the proportions of the pin-fin volume. The average pressure drop and the performance evaluation criteria were considered to be the performance indexes to analyze the influence of each parameter on the flow performance and comprehensive performance, respectively. The results showed that the maximum temperature of the hybrid heat sink attained a minimum value with an increase in the splitting distance. The average pressure drop in the center passage of the microchannel first increased and then decreased. Furthermore, the optimal value could not be simultaneously obtained with the maximum temperature. Therefore, it should be comprehensively considered in the optimization design. The heat flux in the hotspot was positively correlated with the maximum heat sink temperature. However, it had no effect on the flow pressure drop. When the Reynolds number and the pin-fin diameter increased, the maximum heat sink temperature decreased and the average pressure drop of the microchannel increased. The comprehensive performance of the hybrid heat sink was not good at small Reynolds numbers, but it significantly improved as the Reynolds number gradually increased. Choosing a bigger pin-fin diameter and the corresponding optimal value of the splitting distance in a given Reynolds number would further improve the comprehensive performance of a hybrid heat sink.

The multi-scale line-to-line vascular channels (LVCs) widely exist in nature because of their excellent transmission characteristics. In this paper, models of LVCs with turbulent convection heat transfer are established. Based on constructal theory and the entropy generation minimization principle, the constructal optimizations of LVCs with any order are conducted by taking the angles at bifurcations as the optimization variables. The heat flux on the channel wall per unit length is fixed and uniform. The areas occupied by vasculature and the total volumes of channels are fixed. The analytical expressions of the optimal angles, dimensionless total entropy generation rate and entropy generation number (EGN) of LVCs with any order versus dimensionless mass flow rate are obtained, respectively. The results indicate that the dimensionless total entropy generation rate of LVCs with any order can be significantly decreased by optimizing the angles of LVCs, which is significantly more when the order of LVCs is higher. As the dimensionless mass flow rate increases, the optimal angles of LVCs with any order remain unchanged first, then the optimal angles at the entrance (root) increase, and the other optimal angles decrease continuously and finally tend to the respective stable values. The optimal angles of LVCs continue to increase from the entrance to the outlet (crown), i.e., the LVCs with a certain order gradually spread out from the root to the crown. The dimensionless total entropy generation rate and EGN of LVCs first decrease and then increase with the growth of the dimensionless mass flow rate. There is optimal dimensionless mass flow rate, making the dimensionless total entropy generation rate and the EGN reach their respective minimums. The results obtained herein can provide some new theoretical guidelines of thermal design and management for the practical applications of LVCs.

A numerical simulation model of embedded liquid microchannels for cooling 3D multi-core chips is established. For the thermal management problem when the operating power of a chip changes dynamically, an intelligent method combining BP neural network and genetic algorithm is used for distribution optimization of coolant flow under the condition with a fixed total mass flow rate. Firstly, a sample point dataset containing temperature field information is obtained by numerical calculation of convective heat transfer, and the constructed BP neural network is trained using these data. The “working condition–flow distribution–temperature” mapping relationship is predicted by the BP neural network. The genetic algorithm is further used to optimize the optimal flow distribution strategy to adapt to the dynamic change of power. Compared with the commonly used uniform flow distribution method, the intelligently optimized nonuniform flow distribution method can further reduce the temperature of the chip and improve the temperature uniformity of the chip.

ABSTRACT Use of the selective estrogen receptor modulator Tamoxifen (TAM) is a mainstay to induce conditional expression of Cre recombinase in transgenic laboratory mice. To excise β‐cateninfl/fl in 28‐day‐old male and female Prrx1‐CreER/β‐cateninfl/fl mice (C57BL/6), we utilized TAM at 150 mg/kg; despite β‐catenin knockout in MSC, we found a significant increase in trabecular and cortical bone volume in all genders. Because TAM was similarly anabolic in KO and control mice, we investigated a dose effect on bone formation by treating wild‐type mice (WT C57BL/6, 4 weeks) with TAM (total dose 0, 20, 40, 200 mg/kg via four injections). TAM increased bone in a dose‐dependent manner analyzed by micro–computed tomography (μCT), which showed that, compared to control, 20 mg/kg TAM increased femoral bone volume fraction (bone volume/total volume [BV/TV]) (21.6% ± 1.5% to 33% ± 2.5%; 153%, p

A model of rectangular microchannel heat sink (MCHS) with porous medium (PM) is developed. Aspect ratio of heat sink (HS) cell and length-width ratio of HS are optimized by numerical simulation method for entropy generation minimization (EGM) according to constructal theory. The effects of inlet Reynolds number (Re) of coolant, heat flux on bottom, porosity and volume proportion of PM on dimensionless entropy generation rate (DEGR) are analyzed. From the results, there are optimal aspect ratios to minimize DEGR. Given the initial condition, DEGR is 33.10% lower than its initial value after the aspect ratio is optimized. With the increase of Re, the optimal aspect ratio declines, and the minimum DEGR drops as well. DEGR gets larger and the optimal aspect ratio remains constant with the increasing of heat flux on bottom. For the different volume proportion of PM, the optimal aspect ratios are diverse, but the minimum DEGR almost stays unchanged. The twice minimized DEGR, which results from aspect ratio and length-width ratio optimized simultaneously, is 10.70% lower than the once minimized DEGR. For a rectangular bottom, a lower DEGR can be reached by choosing the proper direction of fluid flow.

A heat dissipation model of discrete elliptical cylinders with heat generation on a thermal conduction pedestal cooled by forced convection is established. Constructal design is conducted numerically by taking the distributions of thermal conductivity and heat generating intensity as design variables, the dimensionless entropy generation rate (DEGR) as performance indicator. The optimal designs for discrete elliptical cylinders with heat generating are obtained respectively, i.e., there are optimal distributions of heat generating intensity with its fixed total amount of heat sources, and there are optimal distributions of thermal conductivity with its fixed total amount of heat sources. These optimums for minimum DEGRs are different at different Reynolds numbers of airflow. The heat generating intensity can be decreased one by one appropriately in the fluid flow direction to achieve the best effect. When the Reynolds number of airflow is smaller, the thermal conductivity of heat source can be increased one by one appropriately in the fluid flow direction to achieve the best effect; when the Reynolds number of airflow is larger, the thermal conductivity of each heat source should be equalized to achieve the best effect. The results can give thermal design guidelines for the practical heat generating devices with different materials and heat generating intensities.

A heat conduction model with an arrow-shaped high thermal conductivity channel (ASHTCC) in a square heat generation body (SHGB) is established in this paper. By taking the minimum maximum temperature difference (MMTD) as the optimization goal, constructal designs of the ASHTCC are conducted based on single, two, and three degrees of freedom optimizations under the condition of fixed ASHTCC material. The outcomes illustrate that the heat conduction performance (HCP) of the SHGB is better when the structure of the ASHTCC tends to be flat. Increasing the thermal conductivity ratio and area fraction of the ASHTCC material can improve the HCP of the SHGB. In the discussed numerical examples, the MMTD obtained by three degrees of freedom optimization are reduced by 8.42% and 4.40%, respectively, compared with those obtained by single and two degrees of freedom optimizations. Therefore, three degrees of freedom optimization can further improve the HCP of the SHGB. Compared the HCPs of the SHGBs with ASHTCC and the T-shaped one, the MMTD of the former is reduced by 13.0%. Thus, the structure of the ASHTCC is proven to be superior to that of the T-shaped one. The optimization results gained in this paper have reference values for the optimal structure designs for the heat dissipations of various electronic devices.

A heat conduction model in a radial-pattern disc by considering non-uniform heat generation (NUHG) is established in this paper. A series of high conductivity channels (HCCs) are attached on the rim of the disc and extended to its center. Constructal optimizations of the discs with constant and variable cross-sectional HCCs are carried out, respectively, and their maximum temperature differences (MTDs) are minimized based on analytical method and finite element method. Besides, the influences of the NUHG coefficient, HCC number and width coefficient on the optimal results are studied. The results indicate that the deviation of the optimal constructs obtained from the analytical method and finite element method are comparatively slight. When the NUHG coefficient is equal to 10, the minimum MTD of the disc with 25 constant cross-sectional HCCs is specifically reduced by 48.8% compared to that with 10 HCCs. As a result, the heat conduction performance (HCP) of the disc can be efficiently improved by properly increasing the number of HCCs. The minimum MTD of the disc with variable cross-sectional HCC is decreased by 15.0% when the width coefficient is changed from 1 to 4. Therefore, the geometry of variable cross-sectional HCC can be applied in the constructal design of the disc to a better heat transfer performance. The constructal results obtained by investigating the non-uniform heat generating case in this paper can contribute to the design of practical electronic device to a better heat transfer performance.

Idiopathic systemic capillary leak syndrome (SCLS) is a rare and potentially fatal vascular disorder characterized by reversible bouts of hypotension and edema resulting from fluid and solute escape into soft tissues. Although spikes in permeability-inducing factors have been linked to acute SCLS flares, whether or not they act on an inherently dysfunctional endothelium is unknown. To assess the contribution of endothelial-intrinsic mechanisms in SCLS, we derived blood-outgrowth endothelial cells (BOEC) from patients and healthy controls and examined gene expression patterns. Ednra, encoding Endothelin receptor A (ETA)-the target of Endothelin 1 (ET-1)-was significantly increased in SCLS BOEC compared to healthy controls. Although vasoconstriction mediated by ET-1 through ETA activation on vascular smooth muscle cells has been well characterized, the expression and function of ETA receptors in endothelial cells (ECs) has not been described. To determine the role of ETA and its ligand ET-1 in SCLS, if any, we examined ET-1 levels in SCLS sera and functional effects of endothelial ETA expression. ETA overexpression in EAhy926 endothelioma cells led to ET-1-induced hyper-permeability through canonical mechanisms. Serum ET-1 levels were elevated in acute SCLS sera compared to remission and healthy control sera, suggesting a possible role for ET-1 and ETA in SCLS pathogenesis. However, although ET-1 alone did not induce hyper-permeability of patient-derived BOEC, an SCLS-related mediator (CXCL10) increased Edrna quantities in BOEC, suggesting a link between SCLS and endothelial ETA expression. These results demonstrate that ET-1 triggers classical mechanisms of vascular barrier dysfunction in ECs through ETA. Further studies of the ET-1-ETA axis in SCLS and in more common plasma leakage syndromes including sepsis and filovirus infection would advance our understanding of vascular integrity mechanisms and potentially uncover new treatment strategies.

Combining modern thermodynamics theory branches, including finite time thermodynamics or entropy generation minimization, constructal theory and entransy theory, with metallurgical process engineering, this paper provides a new exploration on generalized thermodynamic optimization theory for iron and steel production processes. The theoretical core is to thermodynamically optimize performances of elemental packages, working procedure modules, functional subsystems, and whole process of iron and steel production processes with real finite-resource and/or finite-size constraints with various irreversibilities toward saving energy, decreasing consumption, reducing emission and increasing yield, and to achieve the comprehensive coordination among the material flow, energy flow and environment of the hierarchical process systems. A series of application cases of the theory are reviewed. It can provide a new angle of view for the iron and steel production processes from thermodynamics, and can also provide some guidelines for other process industries.

Exercise prevents marrow mesenchymal stem cell (MSC) adipogenesis, reversing trends that accompany aging and osteoporosis. Mechanical input, the in-vitro analogue to exercise, limits PPARγ expression and adipogenesis in MSC. We considered whether C/EBPβ might be mechanoresponsive as it is upstream to PPARγ, and also is known to upregulate endoplasmic reticulum (ER) stress. MSC (C3H10T1/2 pluripotent cells as well as mouse marrow-derived MSC) were cultured in adipogenic media and a daily mechanical strain regimen was applied. We demonstrate herein that mechanical strain represses C/EBPβ mRNA (0.6-fold ±0.07, p

PPARγ and PPARδ agonists represent unique classes of drugs that act through their ability to modulate gene transcription associated with intermediary metabolism, differentiation, tumor suppression, and in some instances proliferation and cell adhesion. PPARγ agonists are used by millions of people each year to treat type 2 diabetes but may also find additional utility as relatively nontoxic potentiators of chemotherapy. PPARδ agonists produce complex actions as shown by their tumor promoting effects in rodents and their cholesterol-lowering action in dyslipidemias. There is now emerging evidence that PPARs regulate tumor suppressor genes and developmental pathways associated with transformation and cell fate determination. This review discusses the role of PPARγ and PPARδ agonists as modulators of these processes.