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Abstract Aims We aim to explore the associations between serum tyrosine (Tyr) to threonine (Thr) ratio and chronic heart failure (HF) with reduced or mildly reduced ejection fraction (EF) (HFrEF or HFmrEF). Methods and results The study recruited 418 subjects (77.5% males, mean age 65.2 ± 12.5 years), including 318 HF subjects (HFrEF or HFmrEF) and 100 cardiovascular subjects without acute or chronic HF [including heart failure with preserved ejection fraction (HFpEF)] as controls. Serum levels of 21 kinds of amino acids (AAs) were measured by mass spectrometry. Logistic regression analysis was conducted to measuring the association between the AAs levels and the presence of HF. Event‐free survival was determined by Kaplan–Meier curves and differences in survival were assessed using log‐rank tests. Cox regression analysis was used to assess the prognostic value of AAs in HF. Receiver‐operating characteristic (ROC) curve was performed to further confirm regression analysis. Along with the control, HFmrEF, and HFrEF subjects, serum tyrosine (Tyr) gradually increased (64.43 ± 15.28 μmol/L vs. 71.79 ± 18.74 μmol/L vs. 77.32 ± 25.90 μmol/L, P

Abstract To elucidate the brain‐wide information interactions that vary and contribute to individual differences in schizophrenia (SCZ), an information‐resolved method is employed to construct individual synergistic and redundant interaction matrices based on regional pairwise BOLD time‐series from 538 SCZ and 540 normal controls (NC). This analysis reveals a stable pattern of regionally‐specific synergy dysfunction in SCZ. Furthermore, a hierarchical Bayesian model is applied to deconstruct the patterns of whole‐brain synergy dysfunction into three latent factors that explain symptom heterogeneity in SCZ. Factor 1 exhibits a significant positive correlation with Positive and Negative Syndrome Scale (PANSS) positive scores, while factor 3 demonstrates significant negative correlations with PANSS negative and general scores. By integrating the neuroimaging data with normative gene expression information, this study identifies that each of these three factors corresponded to a subset of the SCZ risk gene set. Finally, by combining data from NeuroSynth and open molecular imaging sources, along with a spatially heterogeneous mean‐field model, this study delineates three SCZ synergy factors corresponding to distinct symptom profiles and implicating unique cognitive, neurodynamic, and neurobiological mechanisms.

Abstract Smart windows effectively respond to the ever‐changing climatic conditions, offering a smart solution for low‐carbon buildings. However, current smart windows derived from chromic materials often have inferior solar modulation ability, or showcase high haze that obstructs outdoor views. Here, instead of developing new chromic materials, a new bistatic window is proposed for ultra‐high solar modulation and luminous transmission. The new developed window can reduce the indoor surface temperature for ≈11 °C, and reduce the building space cooling and heating energy consumption by 30% to 40%, providing significant energy‐related advances over traditional smart windows. In detail, the bistatic window exhibits excellent solar modulation ability (ΔTsol = 61%), high visible transmittance in both bleached (Tlum,bleached = 91%) and colored (Tlum,colored = 56%) states, low haze (< 1%), rapid switching response (switching time < 1 min), high color rendering index (CRI > 80), and long‐cyclic stability after 1000 cycles. With the advantages of facile fabrication and scalability, it is foreseen the developed bistatic window holds promising prospect for the next‐generation low‐carbon buildings, paving a new way for future advancements in the fields of smart windows.

Abstract Background With the advancement of whole‐genome sequencing (WGS) technology, massively parallel sequencing (MPS) remains the mainstream due to its accuracy, low cost, and high throughput. The development of the analytical pipeline corresponding to MPS has always been of great importance. Increasingly large population genomics studies, as a specific type of big data research, pose new challenges for analysis solutions. Results Here, we introduce ZBOLT, a comprehensive analysis system that incorporates both software and hardware advancements, making it an appropriate choice for large‐scale population genomic studies that require extensive data processing. In this study, we first evaluate ZBOLT's calling accuracy using the Genome in a Bottle (GIAB) benchmark dataset. Then we apply ZBOLT to a large‐scale population genomics study with 5,616 high sequencing depth samples totaling 1.16Pbp (base pair). As the results show, ZBOLT demonstrates exceptional efficiency and low energy consumption, processing 100Tbp per day and using 1kWh per 100Gbp sequenced sample. Conclusion This research serves as a valuable reference for analyzing sequencing data from large population cohorts and underscores the significant potential of ZBOLT in large‐scale population genomics studies.

Background This study aimed to explore predictive biomarkers of coronary collateralization in patients with chronic total occlusion. Methods and Results By using a microarray expression profiling program downloaded from the Gene Expression Omnibus database, weighted gene coexpression network analysis was constructed to analyze the relationship between potential modules and coronary collateralization and screen out the hub genes. Then, the hub gene was identified and validated in an independent cohort of patients (including 299 patients with good arteriogenic responders and 223 patients with poor arteriogenic responders). Weighted gene coexpression network analysis showed that SERPING1 in the light‐cyan module was the only gene that was highly correlated with both the gene module and the clinical traits. Serum levels of serpinG1 were significantly higher in patients with bad arteriogenic responders than in patients with good arteriogenic responders (472.53±197.16 versus 314.80±208.92 μg/mL; P

Background Myocardial infarction (MI) is characterized by the emergence of dead or dying cardiomyocytes and excessive immune cell infiltration after coronary vessel occlusion. However, the complex transcriptional profile, pathways, cellular interactome, and transcriptional regulators of immune subpopulations after MI remain elusive. Methods and Results Here, male C57BL/6 mice were subjected to MI surgery and monitored for 1 day and 7 days, or sham surgery for 7 days, then cardiac CD45‐positive immune cells were collected for single‐cell RNA sequencing to determine immune heterogeneity. A total of 30 135 CD45+ immune cells were partitioned into macrophages, monocytes, neutrophils, dendritic cells, and T or B cells for further analysis. We showed that macrophages enriched for Olr1 and differentially expressed Gpnmb represented 2 crucial ischemia‐associated macrophages with distinct proinflammatory and prophagocytic capabilities. In contrast to the proinflammatory subset of macrophages enriched for Olr1, Gpnmb‐positive macrophages exhibited higher phagocytosis and fatty acid oxidation preference, which could be abolished by etomoxir treatment. In addition to macrophages, MI triggered prompt recruitment of neutrophils into murine hearts, which constituted the sequential cell‐fate from naïve S100a4‐positive, to activated Sell‐high, to aging Icam1‐high neutrophils. In silico tools predicted that the excessively expanded neutrophils at 1 day were attributed to chemokine C‐C motif ligand/chemokine C‐X‐C motif ligand pathways, whereas CD80/inducible T‐cell costimulator (ICOS) signaling was responsible for the immunosuppressive response at day 7 after MI. Finally, the Fos/AP‐1 (activator protein 1) regulon was identified as the critical regulator of proinflammatory responses, which was significantly activated in patients with dilated cardiomyopathy and ischemic cardiomyopathy. We showed the enriched Fos/AP‐1 target gene loci in genome‐wide association study signals for coronary artery diseases and MI. Targeting Fos/AP‐1 with the selective inhibitor T5224 blunted leukocyte infiltration and alleviated cardiac dysfunction in the preclinical murine MI model. Conclusions Taken together, this single‐cell RNA sequencing data lay the groundwork for the understanding of immune cell heterogeneity and dynamics in murine ischemic hearts. Moreover, Fos/AP‐1 inhibition mitigates inflammatory responses and cardiac dysfunction, which might provide potential therapeutic benefits for heart failure intervention after MI.

Background Because of advances in medical treatments, a substantial proportion of patients with heart failure (HF) have experienced recovery of ejection fraction (EF), termed HF with recovered EF (HFrecEF). Insulin resistance (IR) is prevalent in HF and tightly related with prognosis. This study investigates the relationship between IR and the incidence of HFrecEF in patients who are nondiabetic. Methods and Results A total of 262 patients with HF with reduced EF (HFrEF) who were nondiabetic were consecutively enrolled. Patients were classified into HFrecEF (follow‐up EF>40% and ≥10% absolute increase) or otherwise persistent HFrEF based on repeat echocardiograms after 12 months. IR was estimated by an updated homeostasis model assessment for IR (HOMA2‐IR). The median HOMA2‐IR level was 1.05 (interquartile range [IQR], 0.67–1.63) in our cohort of patients with HF who were nondiabetic. During follow‐up, 121 (odds ratio [OR], 46.2% [95% CI 40.2–52.2]) patients developed HFrecEF. Compared with patients with HFrEF, patients with HFrecEF had significantly lower HOMA2‐IR levels (0.92 [IQR, 0.61–1.37] versus 1.14 [IQR, 0.75–1.78], P=0.007), especially in nonischemic HF. Log2‐transformed HOMA2‐IR was inversely correlated to improvements in EF (Pearson's r=−0.25, P

Objectives. To analyze and summarize the effect of SSA treatment on EAS due to p-NETs (EAS-p-NETs). Methods. Thirteen patients with EAS-p-NETs treated with SSAs at our center or described in the literature were included in this study. Clinical characteristics, laboratory data, imaging studies, histopathologic results, the effect of SSA treatment, and the prognosis of these EAS-p-NET patients were evaluated. Results. Four males and 9 females with an average age of 42.9 years were included in the study. The mean duration of follow-up was 38.8 ± 28.2 months. As one of the combined treatment measures, SSAs controlled the levels of ACTH and cortisol in 9 of the 13 patients (69.2%). Partial response was observed in 3 patients (23.1%), stable disease in 2 patients (15.4%), and progressive disease in 6 patients (46.2%). The median time to tumor progression was 24 months, and the median overall survival was 61 months. The side effects of SSA treatment included temporary mild abdominal pain, diarrhea, gallstones, and cholecystitis. Conclusions. As a supplemental therapy, SSA treatment led to clinical and biochemical improvement with a good safety profile in patients exhibiting EAS-p-NET with metastasis. However, tumor progression was inhibited by SSA treatment in only a few patients. Combined with other treatments, SSAs may improve the prognosis of patients with EAS-p-NETs.

Abstract Suicide is one of the top 20 leading causes of death worldwide. With the rapid spreading of coronavirus disease 2019 (COVID‐19) crisis around the world, suicide cases induced by the COVID‐19 pandemic have been reported in many countries. Individuals with suspected and confirmed COVID‐19 infection, frontline healthcare workers, bereaved families, elders, children, and adolescents are vulnerable populations who might be at elevated suicide risk. In this micro‐review, a systematic search through PubMed was performed for a comprehensive investigation of suicide risk factors during the pandemic. On this basis, we put forward considerations and advice for preventing pandemic related suicide, including staying socially connected through online platform or apps during period of quarantine, reducing unemployment, dispelling rumors and misinformation in time, and maintaining evidenced‐based management of psychiatric symptoms. More importantly, early detection and timely intervention of individuals with psychiatric disorders and suicide behaviors will be effective to reduce the number of suicides, with specific measurements of using validated scales to perform regular suicide risk screening, improving the availability of mental health services, and providing appropriate and evidence‐based interventions for individuals in demand. Policy makers, psychiatrists, psychologists, and other healthcare professionals need to collaborate to control the possible suicide events during the COVID‐19 pandemic and future possible crisis.

Abstract Graphene films, fabricated by chemical vapor deposition (CVD) method, have exhibited superiorities in high crystallinity, thickness controllability, and large‐scale uniformity. However, most synthesized graphene films are substrate‐dependent, and usually fragile for practical application. Herein, a freestanding graphene film is prepared based on the CVD route. By using the etchable fabric substrate, a large‐scale papyraceous freestanding graphene fabric film (FS‐GFF) is obtained. The electrical conductivity of FS‐GFF can be modulated from 50 to 2800 Ω sq−1 by tailoring the graphene layer thickness. Moreover, the FS‐GFF can be further attached to various shaped objects by a simple rewetting manipulation with negligible changes of electric conductivity. Based on the advanced fabric structure, excellent electrical property, and high infrared emissivity, the FS‐GFF is thus assembled into a flexible device with tunable infrared emissivity, which can achieve the adaptive camouflage ability in complicated backgrounds. This work provides an infusive insight into the fabrication of large‐scale freestanding graphene fabric films, while promoting the exploration on the flexible infrared camouflage textiles.

Rice quality has received more attention, so monitoring and analysis are of great significance to rice quality. General quality indexes of rice in southern China from 2011 to 2020 were determined, including processing quality (brown rice yield, milled rice recovery, head rice yield), appearance quality (grain length, length-width ratio, chalky rice percentage, chalkiness degree, transparency), and cooking quality (alkali spreading value, gel consistency, amylose). Principal component analysis was used to distinguish the regional quality of southern rice. The results showed that amylose and chalkiness were the main contributory quality indexes of rice in South China, the upper reaches of the Yangtze River, and the middle and lower reaches of the Yangtze River. In the past decade, the total high-quality rate of rice in the South has improved. The random forest was used to determine the important influence index of rice quality. The results showed that chalkiness degree, alkali spreading value, and gel consistency were important indexes affecting the quality of southern rice, and random forest could be used as an effective approach for continuous monitoring and analysis of rice quality.

In the process of Earth-Moon transfer orbit, many parameters are involved and the degree of influence varies among the parameters. How to accurately distinguish the influence relationship between different parameters is of great significance to engineering missions. Based on Sobol sequence sampling method and Sobol global sensitivity analysis method, a calculation process of global sensitivity analysis is proposed in this paper for high-fidelity Earth-Moon transfer orbit. A numerical simulation method is used to verify that the Sobol sequence sampling method has better convergence and higher precision than other sampling methods and has better adaptability in global sensitivity analysis. The effects of different state parameters and the combination of different parameters on the perilune parameters of Earth-Moon transfer orbit are given by simulation examples, which verifies the effectiveness and feasibility of the calculation process proposed in this paper. Simulation results show that the radial position and tangential velocity at the trans-lunar injection point are the main sensitivity parameters, and the other parameters have little effect on the results. The sensitivity of the orbital elements at the trans-lunar injection point to the perilune parameters is different and needs to be determined according to the specific parameters. The results of this study can provide important reference for future Earth-Moon transfer orbit design and related engineering missions.

This paper is mainly aimed at 0.28 + 6 × 0.26 steel cords and 0.26 + 6 × 0.24 steel cords under different lay length conditions through the ABAQUS finite element analysis software to limit the tensile performance of the steel cord and the stress field distribution during the tensile loading. Based on the finite meta-analysis, in this experiment, the tensile simulation of the same kind of steel cord at the twist lay length of 5 mm, 7 mm, 9 mm, 11 mm, 13 mm, and 15 mm was carried out under the condition of 2 mm/s. The results show that, under certain conditions of other process conditions, with the increase of the twisting distance of the steel cord strands, the strength of the steel cord increases, the deformability decreases, the stress concentration decreases, and the spinning loss decreases. The spinning loss formula is modified to reduce the calculation error.

A direct abort orbit design method is presented for direct abort missions in the Earth-Moon transfer phase of crewed lunar exploration missions. First, according to the demand of an emergency rescue in the Earth-Moon transfer phase, two direct abort orbit schemes are introduced. Then, a serial orbit design method is proposed for a high-fidelity direct abort orbit. An analytical model is established for the calculation of initial values, and the optimization design is performed in the high-fidelity orbit model to determine a single-impulse abort orbit. A hybrid optimization design process is proposed to generate a two-impulse abort orbit. The results of simulation examples verify the validity and feasibility of the proposed direct abort orbit design method. Finally, extensive simulations are carried out to analyze the characteristics of abort impulse and abort return time and reveal the general rules of direct abort orbits. The research conclusions can provide a reference for the design of emergency rescue schemes in future crewed lunar exploration missions.

Changes of precipitates, dynamic recrystallization, texture, and properties at room temperature in the as-extruded AZ alloys (Al = 0, 3, 6, 8, wt.%) with 0.3% La addition were systematically investigated in this work. The analysis results suggest that new Mg12La with lamellar-structure precipitates in AZ01-0.3La alloy and new Al11La3 with needlelike structure precipitates in AZ-0.3La alloy with 3%–8% Al. Crashed Mg17Al12 could decrease the recrystallization temperature. Proper-sized Mg12La and Al11La3 could promote the dynamic recrystallization nucleation, leading to the reduction of grains in the as-extruded AZ-0.3La alloy, except for 6% Al. At room temperature, the strength of as-extruded AZ-0.3La alloys increases as Al increases, and the elongation first increases and then decreases, while the elongation is greater than 20% with 3%–8% Al. Due to the refined average grain size of 12.2 μm, the scattered and wakened 0002 base texture, the as-extruded AZ31-0.3La shows the best comprehensive tensile property compared with other AZ-0.3La alloys and AZ alloys, of which the Rp0.2 is 162 MPa, the Rm is 252 MPa, and the A is 21.7%.

Purpose. To analyze the visual prognosis of macular buckling in patients with high myopia foveoschisis (FS) and to identify factors that predict the final visual outcome. Methods. We retrospectively included 155 eyes of 155 patients who underwent foveoschisis-related macular buckling. Best-corrected visual acuity (BCVA) and coexisting macular pathologies were assessed as a measure of surgical outcome, and multivariate linear regression was performed to identify factors affecting final visual prognosis. Results. The mean preoperative BCVA was 1.19 ± 0.55 logMAR (20/308), while the mean postoperative BCVA was 0.82 ± 0.51 logMAR (20/133) (P

Abstract Background Health behaviors including smoking cessation, physical activity (PA), and alcohol moderation are key aspects of cancer survivorship. Immigrants may have unique survivorship needs. We evaluated whether immigrant cancer survivors had health behaviors and perceptions that were distinct from native‐born cancer survivors. Methods Adult cancer patients from Princess Margaret Cancer Centre were surveyed on their smoking, PA, and alcohol habits and perceptions of the effects of these behaviors on quality of life (QoL), 5‐year survival, and fatigue. Multivariable models evaluated the association of immigration status and region‐of‐origin on behaviors and perceptions. Results Of the 784 patients, 39% self‐identified as immigrants. Median time of survey was 24 months after histological diagnosis. At baseline, immigrants had trends toward not meeting Canadian PA guidelines or being ever‐drinkers; patients from non‐Western countries were less likely to smoke (aORcurrent = 0.46, aORex‐smoker = 0.47, P = 0.02), drink alcohol (aORcurrent = 0.22, aORex‐drinker = 0.52, P

Emergency logistics is one of the important measures to solve the unconventional sudden disaster. The research on the distribution design of emergency logistics project has an important supporting role for the whole emergency rescue system. Therefore, it is necessary to analyze and plan the emergency logistics project scientifically in order to better serve the emergency rescue system. In view of the defect that the current emergency logistics model cannot completely describe the whole emergency logistics process, this paper proposes a new emergency logistics distribution model by using GERT random network. From the perspective of system, this model fully considers the possible situation in the process of emergency material transportation and puts forward the corresponding countermeasures, so as to improve the transportation efficiency of rescue materials in the actual disaster relief activities to speed up disaster relief. Based on the properties of moment generating function and the calculation method of Mason formula, this paper fully considers the success probability, risk probability, delivery time, and other factors of the distribution route and puts forward the transshipment scheme of each logistics site to the disaster sites. After that, the effectiveness of GERT stochastic network in the process of emergency distribution is verified by an example of a logistics distribution route, which provides decision-making basis for relevant departments. Compared with the literature, this paper uses GERT network model to intuitively and clearly express the overall process of emergency material distribution, breaks through the thinking mode of simply choosing the distribution path in the distribution process, combines with the dynamic changes of the distribution environment, and comprehensively considers the timeliness and traffic capacity of emergency material distribution in sudden disasters, so as to provide reference for emergency management in complex and random situations for decision-making reference.

With the rapid development of the service industry, the service supply chain has become one of the most popular areas. With the logistics service supply chain being an important branch of the service supply chain, we should pay attention to the role of logistics service supply chain in enterprises. How to evaluate the logistics service supply chain comprehensively and rationally has become an important task for related enterprises to solve urgently. This paper, through extensive literature analysis and research on logistics service supply chain projects, established an indicator system composed of 18 secondary indicators from three perspectives of customer satisfaction, logistics service capabilities, and co-development ability, using the analytic hierarchy process (AHP) to determine the weight of each index and matter-element analysis to establish a logistics service supply chain performance evaluation model. At the end of the paper, the performance of S logistics enterprise is evaluated. The result turns out to be good, which is consistent with the actual situation, indicating that the evaluation system and method are effective and reliable.

Due to the fact that steel reinforcement is vulnerable to corrosion, FRP bars with light weight, high strength, and excellent durability have become a good substitute for ordinary steel bars. FRP bars have high tensile strength, but their compressive strength is relatively low and often neglected, so the application of FRP bars in compression members has been restricted. This paper proposes a new pultrusion-winding-pultrusion method to improve the compressive ability of FRP bars. A hoop FRP layer is winded on the outer surface of the pultruded FRP core, and a longitudinal pultruded layer and ribs are also added on the outermost surface. In this paper, mechanical properties of this novel FRP bar with hoop winding layer are investigated. First, monotonic tensile and compressive tests on traditional and novel GFRP bars were conducted. Then, cyclic tension-compression loading tests were also carried out on the two types of GFRP bars. Test results showed that the compressive ultimate bearing capacities of GFRP bars with winding layers were 10∼20 kN greater than those of the traditional GFRP bars, and the compressive ductility of the novel GFRP bars was also improved. Furthermore, the tensile stress-strain behaviors of both GFRP bars were linear-elastic and the added winding layer did not greatly influence the tensile properties of the GFRP bars. Moreover, for the cyclic loading test, the compressive ultimate load of GFRP bars was 80%∼90% of that under monotonic compressive test, and the tensile ultimate load was 45%∼65% of that under monotonic tensile test. Compared with the GFRP bar without winding layer, the overall stiffness of the novel GFRP bar was greater than that of the traditional one and the ultimate load of the novel GFRP bar was also greater. In addition, seeing that the residual displacement of the novel GFRP bar was greater than that of the traditional GFRP bar, winding hoop fibers on the outer surface of the core is a useful way to improve the energy dissipation capacity of the GFRP bar.

Flexibility is an important indicator to consider the uncertain information processing ability of the supply chain comprehensively. It is a powerful way to improve the efficiency and quality of supply chain operation by evaluating the level of supply chain flexibility effectively. The traditional method is used to decompose the supply chain flexibility evaluation indicators from the perspective of system structure or cost saving, but these indicators cannot truly describe the dynamics of the supply chain operation. Otherwise, supply chain flexibility evaluation is a typical multiobjective evaluation; there are some incompatibilities between these flexible evaluation indicators, and the common evaluation methods are difficult to deal with such contradictions. In this paper, the dynamic characteristics of supply chain operation are considered, and the evaluation system of supply chain flexibility is designed from the perspective of operation efficiency. The matter-element analysis theory is used to create the comprehensive appraisal model of supply chain flexibility. The matter-element matrix solves the uncertainty and incompatibility of the evaluated factors used to assess supply chain flexibility. The paper evaluates the performance of four autoservice companies and concludes that the evaluation grades of the four companies are in line with the reality, indicating that the evaluation system and the method are effective and credible.

Emergency events are full of large number of uncertain information. The existence of these uncertain information leads to less research on emergency logistics involving transshipment scenarios. In this paper, a new emergency transport model is proposed, which simulates the scenario of emergency transport from the logistics center to each disaster site and between each disaster site. The single-valued neutrosophic set (SVNS) is applied to transform the emergency transshipment problem into a multiattribute decision-making problem in ambiguous and uncertain environments. Technology for order preference by similarity to ideal solution (TOPSIS) is extended to the single-valued neutrosophic environment to rank and optimize the alternative transshipment routes. Firstly, the attribute weight is determined by using the entropy weight method; secondly, the scoring function of the single-valued neutrosophic fuzzy number is defined; thirdly, the TOPSIS method is used to rank the decision-making; finally, the feasibility and rationality of the proposed method are verified by an emergency operation example.

Mesenchymal stem cells (MSCs) are being widely investigated for the development of novel therapeutic approaches for different cancers, including breast cancer, the leading form of cancer in women. Our previous study showed that the factors secreted by human umbilical cord MSCs (hUCMSCs) induced pyroptosis in the breast cancer cell line MCF7 and our RNA sequencing studies revealed an increase in the expression of the pyroptosis-related gene caspase-4 (CASP4) and nucleotide-binding, leucine-rich repeat pyrin domain-containing protein 1 (NLRP1) in pyroptotic MCF7 cells. Cellular pyroptosis can occur via the canonical pathway (involving caspase-1 and NLRP1) or the noncanonical pathway (involving caspase-4). In this study, we first confirmed that the inflammasome complex formed by NLRP1 and ASC is involved in MCF7 cell pyroptosis induced by hUCMSC-CM. Further, we investigated the role of CASP4 and NLRP1 in MCF7 cell pyroptosis induced by hUCMSC-secreted factors using shRNA-mediated transfection of CASP4 or NLRP1 in MCF7 cells. Cytotoxicity analyses revealed that neither CASP4 knockdown nor NLRP1 knockdown could inhibit the hUCMSC-CM-induced pyroptosis in MCF7 cells. Gene and protein expression analysis showed that hUCMSC-CM induced pyroptosis mainly via the canonical pathway in CASP4 knockdown MCF7 cells but mainly via the noncanonical pathway in NLRP1 knockdown MCF7 cells. Our study provides a foundation for further studies aimed at elucidating the precise mechanism underlying hUCMSC-induced pyroptosis in breast cancer cells and aid the identification of potential therapeutic targets for breast cancer.

Background The pathophysiological process of calcific aortic valve disease (CAVD) is similar to that of atherosclerosis. Leptin accelerates the process of atherosclerosis. We sought to examine the relationship between leptin and CAVD. Methods and Results Serum leptin was measured in 397 consecutive patients undergoing standard transthoracic echocardiography and Doppler flow imaging. Multiple logistic regression analyses were used to assess the association between leptin and CAVD. Western blotting was performed to detect the expression of phosphorylated and total extracellular signal‐regulated kinase. Serum leptin (median) was higher in 200 patients with CAVD than that in 197 non‐CAVD controls (20.07 versus 9.03 ng/mL; P

Background Few reports have addressed the mechanism by which microRNA miR‐10b‐5p regulates post–myocardial infarction (post‐MI) cardiomyocyte apoptosis under hypoxic conditions. Methods and Results C57BL/6 mice underwent surgical ligation of the left anterior descending artery to create an MI or ischemia/reperfusion animal model. The expression of miR‐10b‐5p, PTEN (phosphatase and tensin homolog), and HIF‐1α (hypoxia‐inducible factor 1α) was detected in infarct border zone tissues at various time points. After precordial injections of the negative control or miR‐10b‐5p, overexpression lentiviruses were made in the areas surrounding the MI sites at 1 week, and myocardial infarct size, cardiac function, and cardiomyocyte apoptosis were examined. A miR‐10b‐5p mimic was transfected into primary mouse cardiomyocytes to analyze its effects on cardiomyocyte apoptosis and PTEN expression. Meanwhile, PTEN as a target of miR‐10b‐5p was verified via luciferase reporter gene assays. Cotransfection of miR‐10b‐5 and PTEN verified the relationship between miR‐10b‐5 and PTEN. Under hypoxic stress, the expression of HIF‐1α and miR‐10b‐5p was examined. The results showed that miR‐10b‐5p expression was markedly reduced in the infarct border zone. Overexpression of miR‐10b‐5p in the murine model of MI significantly reduced MI size, improved cardiac function, and inhibited apoptosis. Overexpression of miR‐10b‐5p in vitro antagonized hypoxia‐induced cardiomyocyte apoptosis and specifically inhibited the expression of the apoptosis‐related gene PTEN, but overexpression of PTEN weakened these effects. We also found that hypoxia‐induced accumulation of HIF‐1α resulted in decreased expression of miR‐10b‐5p. Interfering with the activation of the HIF‐1α signaling pathway promoted Pri‐miR‐10b and miR‐10b‐5p expression and inhibited PTEN expression. Conclusions MicroRNA miR‐10b‐5p antagonizes hypoxia‐induced cardiomyocyte apoptosis, indicating that miR‐10b‐5p may serve as a potential future clinical target for the treatment of MI.

Based on the Ritz method, this paper focused on the free vibration of functionally graded (FG) spherical torus with uniform variable thickness along axial direction under different boundary conditions. The first-order shear deformation theory (FSDT) is employed to formulate the analytical model. The method involves partitioning of the spherical torus structure into proper shell segments in order to satisfy the computing requirement of high-order vibration responses according to the domain decomposition method. The two adjacent segments are connected by using the penalty method, where penalty parameters are defined by the artificial springs; the continuity condition and different boundary conditions can be obtained by assigning the appropriate values of springs. The displacement functions’ components are double mixed series, in which Fourier series and unified Jacobi polynomials, respectively, represent displacement function along circumferential direction and axial direction. Then the Ritz method is used to obtain final solutions. The numerical results obtained by the proposed method show great agreement with previously published literatures and those from the finite element program ABAQUS. The effects of boundary conditions and geometric parameters on the vibration responses of the structure are also presented. The most novelty of this paper is to generalize the selection of admissible displacement functions by using Jacobi polynomial.

Purpose. To investigate the demographic characteristics, etiology, and comorbidities of Cushing’s syndrome (CS) patients at a large medical center in China. Methods. Records on CS patients discharged from 2008 to 2017 were retrieved from the hospital discharge abstract database (DAD) using ICD-10 codes. Demographic characteristics, etiology, and comorbidity data were analyzed. Results. Cushing’s disease (CD) accounted for 63.0% of CS patients, followed by adrenocortical adenoma (ACA) (20.9%), primary bilateral macronodular adrenal hyperplasia (BMAH) (6.2%), ectopic ACTH syndrome (EAS) (5.9%), primary pigmented nodular adrenocortical disease (PPNAD) (1.8%), and adrenocortical carcinoma (ACC) (1.0%). CD, ACA, ACC, and PPNAD presented marked preponderances in women (4.1 : 1, 10.5 : 1, 4.3 : 1, and 2.3 : 1, respectively), while BMAH (59.8%) and EAS (51.0%) showed slightly higher preponderances in men. CD patients were younger than ACA and EAS patients (36.1±12.9 years vs. 39.4±12.7 years and 36.1±12.9 years vs. 41.0±15.8, P

BackgroundRenal dysfunction, commonly associated with cardiac dysfunction, has predictive value for adverse long‐term outcomes in heart failure (HF). We previously identified a novel renal biomarker, interleukin‐34 (IL‐34), elevated in HF patients and associated with kidney dysfunction and coronary artery disease during HF. However, the prognostic value of IL‐34 in HF remains unclear, so that the present study aimed to determine it. Methods and ResultsThis prospective, observational study included 510 consecutive HF patients with their serum IL‐34 as well as other variables measured at baseline, and they were followed up for 2 years. The primary end point was a composite of cardiovascular death or a first HF hospitalization, with cardiovascular death, HF hospitalization, and all‐cause mortality as secondary outcomes. There was a significant and gradual increase in risk as IL‐34 increased, determined by log‐rank tests with Kaplan–Meier curves. Serum IL‐34 was also a significant prognostic predictor of the primary end point (1.301 [1.115–1.518]; P=0.001), cardiovascular death (1.347 [1.096–1.655]; P=0.005), HF hospitalization (1.234 [1.018–1.494]; P=0.032), and all‐cause mortality (1.343 [1.115–1.618]; P=0.002) in HF as per SD increase in the log IL‐34 level after adjusting for age, sex, traditional risk factors, and N‐terminal pro‐brain natriuretic peptide. Especially, IL‐34 had a more‐significant prognostic value in HF patients with kidney impairment than those without. ConclusionsIL‐34 is a significant predictor of cardiovascular death, HF hospitalization, and all‐cause mortality in chronic HF, especially when concomitant with renal dysfunction. Serum IL‐34 measurement may provide new insights linking kidney impairment to poor HF outcomes beyond other renal markers.

This study aims to evaluate the efficacy of ketorolac with local anesthesia compared to local anesthesia alone for perioperative pain control in day care retinal detachment surgery. The randomized controlled trial included 59 eyes of 59 participants for retinal detachment surgery who were randomly assigned (1 : 1) into the ketorolac (K) group and control (C) group. All participants underwent conventional local anesthesia while patients in the K group received an extra administration of preoperative ketorolac. Participants in the K group had a statistically significantly lower intraoperative NRS score (median 1.0 versus 3.0, P=0.003), lower postoperative NRS score (median 0 versus 1.0, P=0.035), fewer proportion of rescue analgesic requirement (10% versus 34.5%, P=0.023), and lower incidence of postoperative nausea and vomiting (13.3% versus 41.4%, P=0.015) compared to the C group. Intraocular pressure (IOP) changes (△IOP) were significantly reduced in the K group (median 1.9 versus 3.0, P=0.038) compared to the C group 24 hours postoperatively. In conclusion, the combination of local anesthesia with ketorolac provides better pain control in retinal detachment surgery compared to local anesthesia alone. The beneficial effect of ketorolac with local anesthesia may contribute to a wider-spread adoption of day care retinal detachment surgery. This trial is registered with ClinicalTrials.gov NCT02729285.

BackgroundCyanate has recently gained attention for its role in the pathogenesis of vascular injury. Nonetheless, the effect of cyanate on angiogenesis remains unclear. Methods and ResultsIn this study, we demonstrated that oral administration of cyanate impaired blood perfusion recovery in a mouse hind‐limb ischemia model. A reduction in blood perfusion recovery at day 21 was observed in the ischemic tissue of cyanate‐treated mice. Likewise, there were fewer capillaries in the ischemic hind‐limb tissue of cyanate‐exposed mice. Our in vitro study showed that cyanate, together with its carbamylated products, inhibited the migration, proliferation, and tube‐formation abilities of endothelial cells. Further research revealed that cyanate regulated angiogenesis partly by interrupting the vascular endothelial growth factor receptor 2/phosphatidylinositol 3‐kinase/Akt pathway. The serum concentrations of homocitrulline, a marker of cyanate exposure, were determined in 117 patients with stable angina and chronic total occlusion. Consistent with the antiangiogenic role of cyanate, homocitrulline levels were increased in patients with poor coronary collateralization (n=58) compared with those with high collateralization (n=59; 21.09±13.08 versus 15.54±9.02 ng/mL, P=0.009). In addition, elevated homocitrulline concentration was a strong predictor of poor coronary collateral growth. ConclusionsImpaired angiogenesis induced by cyanate might contribute to poor coronary collateral growth.

The aim of this study was to evaluate the efficacy of two botulinum toxin A (BoNT-A) injection patterns with or without the medial lower eyelid (MLE) in treating benign essential blepharospasm (BEB) and influencing lacrimal drainage. Two different injection patterns of BoNT-A were randomly applied to 98 eyes of 49 BEB patients: MLE Group received a full injection pattern of 5 sites and non-MLE Group received a MLE waived injection pattern of 4 sites. Tear breakup time (BUT), Schirmer I test, lagophthalmos height, and lower lid tear meniscus height (TMH) were measured and Jankovic Rating Scale (JRS) was surveyed before injection and at 1 week, 1 month, and 3 months after injection. The symptom of BEB was relieved in both groups as suggested by JRS scores at all time points after injection, and MLE Group came up with a better JRS score at 3 months. The increases of Schirmer I test value and TMH in MLE Group were higher than those in non-MLE Group at 1 week after injection. This study shows that the MLE-involved full injection pattern is a better choice for patients with BEB. It has longer-lasting effects in relieving BEB symptoms and better efficacy in reducing lacrimal drainage. Clinical Trials registration number is NCT02327728.

The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

To predict the service life of polystyrene (PS) under an aggressive environment, the nondimensional expression Z was established from a data set of multiple properties of PS by principal component analysis (PCA). In this study, PS specimens were exposed to the tropical environment on Xisha Islands in China for two years. Chromatic aberration, gloss, tensile strength, elongation at break, flexural strength, and impact strength were tested to evaluate the aging behavior of PS. Based on different needs of industries, each of the multiple properties could be used to evaluate the service life of PS. However, selecting a single performance variation will inevitably hide some information about the entire aging process. Therefore, finding a comprehensive measure representing the overall aging performance of PS can be highly significant. Herein, PCA was applied to obtain a specific property (Z) which can represent all properties of PS. Z of PS degradation showed a slight decrease for the initial two months of exposure after which it increased rapidly in the next eight months. Subsequently, a slower increase of Z value was observed. From the three different stages shown as Z value increases, three stages have been identified for PS service life.

ON patients with AQP4-Ab seropositivity tend to be predominantly female and young and have worse visual acuity and more severe damage to their visual fields compared with AQP4-Ab seronegativity.

This paper presents a modeling and computational study on particle erosion in curved ducts. It is found that the average erosion rates per impact range from to mm3/g under current conditions. For each doubled inlet velocity, the increases of erosion rates per impact are 2–14 times. The erosion rate per impact varies with particle diameter with “√” shape through bends, which is similar to the particle deposition behavior in duct flows. The erosion rate curves per injected particle show the shapes of a 90-degree anticlockwise rotated “S” and a wide open “V,” respectively, for three larger and smaller inlet velocities. The average erosion rates per injected particle are 1.4–18.9 times those rates per impact due to huge amounts of impacting, especially for those depositing particles. It is obvious that the erosion rate distribution per impact is similar to a “fingerprint” with five clear stripes and a lower “cloud” along the bend deflection angle for the three largest particles; yet, for other smaller particles, the erosion rate distributions are much like an entire “cloud.”