Search

In this paper, the hot deformation behavior of Ti65 alloy was investigated over the temperature range of 930–1110 °C with the strain rate of 0.001–1 s−1. According to the stress-strain curves, the constitutive equation was developed to describe the flow behavior of Ti65 alloy. The processing maps were constructed based on the dynastic materials model (DMM) and the perfect formability zone of Ti65 alloy is found under the temperature of 970–1020 °C and the strain rate of 0.001–0.1 s−1. In addition, a three-dimensional nonlinear transient thermo-mechanically coupled finite element model of the multi-dimensional forging (MDF) process of Ti65 alloy was developed. The effects of the forging temperature and forging speed, on the temperature rise, residual stress, and grain refinement were predicted. By analyzing the temperature and stress distribution, the optimum forging temperature and speed for Ti65 alloys were determined to be 1000 °C and 10 mm/s, respectively. Increasing the forging temperature or reducing the forging speed reduces the temperature rise and the maximum tensile stress, thus reducing the risk of cracking. Additionally, the equivalent strain increases as forging speed decreases. Simultaneously, the accumulated strain is more significant for the inside of the forgings. The results of this research are instructive for the optimization of the MDF process.

To address the problem of the low nitrogen (N) content of carbon materials prepared through the direct carbonization of food waste, soybean meal and egg whites with high N contents were selected to carry out carbonization experiments on food waste. At 220 °C, the effects of hydrothermal carbonization and microwave carbonization on the properties of supercapacitor electrode materials were investigated. The results show that food waste doped with soybean meal and egg whites could achieve good N doping. At a current density of 1 A·g−1, the specific capacitance of the doped carbon prepared by hydrothermal doping is as high as 220.00 F·g−1, which is much greater than that of the raw material prepared through the hydrothermal carbonization of food waste alone, indicating that the hydrothermal carbonization reactions of soybean meal, egg white, and food waste promote the electrochemical properties of the prepared carbon materials well. However, when a variety of raw materials are mixed for pyrolysis carbonization, different raw materials cannot be fully mixed in the pyrolysis process, and under the etching action of potassium hydroxide, severe local etching and local nonetching occur, resulting in a severe increase in the pore size distribution and deterioration of the electrochemical performance of the prepared carbon materials. At a current density of 1 A·g−1, the specific capacitance of these prepared carbon materials is 157.70 F·g−1, whereas it is only 62.00 F·g−1 at a high current density of 20 A·g−1. Therefore, this study suggests that the hydrothermal carbonization process is superior to the microwave pyrolysis carbonization process for preparing supercapacitor electrode materials with multiple samples doped with each other.

Background: osteoporosis is a skeletal disorder disease features low bone mass and poor bone architecture, which predisposes to increased risk of fracture. Copper death is a newly recognized form of cell death caused by excess copper ions, which presumably involve in various disease. Accordingly, we intended to investigate the molecular clusters related to the cuproptosis in osteoporosis and to construct a predictive model. Methods: we investigated the expression patterns of cuproptosis regulators and immune signatures in osteoporosis based on the GSE56815 dataset. Through analysis of 40 osteoporosis samples, we investigated molecular clustering on the basis of cuproptosis--related genes, together with the associated immune cell infiltration. The WGCNA algorithm was applied to detect cluster-specific differentially expressed genes. Afterwards, the optimum machine model was selected by calculating the performance of the support vector machine model, random forest model, eXtreme Gradient Boosting and generalized linear model. Nomogram, decision curve analysis, calibration curves, and the GSE7158 dataset was utilizing to confirm the prediction efficiency. Results: Differences between osteoporotic and non-osteoporotic controls confirm poorly adjusted copper death-related genes and triggered immune responses. In osteoporosis, two clusters of molecules in connection with copper death proliferation were outlined. The assessed levels of immune infiltration showed prominent heterogeneity between the different clusters. Cluster 2 was characterized by a raised immune score accompanied with relatively high levels of immune infiltration. The functional analysis we performed showed a close relationship between the different immune responses and specific differentially expressed genes in cluster 2. The random forest machine model showed the optimum discriminatory performance due to relatively low residuals and root mean square errors. Finally, a random forest model based on 5 genes was built, showing acceptable performance in an external validation dataset (AUC = 0.750). Calibration curve, Nomogram, and decision curve analyses also evinced fidelity in predicting subtypes of osteoporosis. Conclusion: Our study identifies the role of cuproptosis in OP and essentially illustrates the underlying molecular mechanisms that lead to OP heterogeneity.

Abstract Bladder cancer is the second most prevalent urological malignancy. It's a big contributor to cancer-related deaths throughout the globe. Researchers discovered that the hedgehog signaling (HhS) pathway contributed to the onset and spread of many different kinds of cancer. Nevertheless, the present understanding of the function of HhS in the bladder cancer molecular landscape is incomplete. Raw data were gotten from the IMvigor210, the Gene Expression Omnibus, and The Cancer Genome Atlas databases. Bioinformatics was used to examine the HhS score of each sample, and the enrichment of differentially expressed genes (DEGs), differentiation characteristics, immunological infiltration, and metabolic activity. The HhS prognostic signature was developed with significant assistance from the least absolute shrinkage and selection operator regression and Cox regression. An HhS-related nomogram was developed to assist in the prediction of patients’ survival probability. We found that HhS was linked to poor prognosis in bladder cancer, and its activation was linked to the Basal subtype of bladder cancer. Bladder cancer with high HhS activity has higher glycolysis, nucleotide metabolism, amino acid metabolism, and other cancer-promoting metabolic activities. Furthermore, HhS mediates an immunosuppressive microenvironment in bladder cancer on the basis that HhS negatively correlates with the CD8 + T cells and correlates positively with immune checkpoints and T cell exhaustion scores. Finally, an HhS-related signature was developed for predicting the prognosis of patients with bladder cancer. Targeting HhS may be a potential therapy choice for bladder cancer.

Macrolide antibiotics are widely used antibacterial agents that are associated with autophagy inhibition. This study aimed to investigate the association between macrolide antibi-otics and malignant tumors, as well as the effect on autophagy, reactive oxygen species (ROS) accumulation and integrated stress response (ISR). The meta-analysis indicated a modestly higher risk of cancer in macrolide antibiotic ever-users com-pared to non-users. Further experiments showed that macro-lides block autophagic flux by inhibiting lysosomal acidification. Additionally, azithromycin, a representative macrolide antibi-otic, induced the accumulation of ROS, and stimulated the ISR and the activation of transcription factor EB (TFEB) and TFE3 in a ROS-dependent manner. Finally, animal experiments confirmed that azithromycin promoted tumor progression in vivo, which could be receded by N-acetylcysteine, an inhibitor of ROS and ISR. Overall, this study reveals the potential role of macrolide antibiotics in malignant progression and highlights the need for further investigation into their effects.

The tumor-adipose microenvironment (TAME) is a universal microecosystem, that is characterized by the dysfunction of lipid metabolism, such as excessive free fatty acids (FFAs). Macrophages are the most abundant immune cell type within TAME, although their diversity in the TAME is not clear. We first reveal that infiltration of M2-like macrophages in the TAME is associated with poor survival in breast cancer. To explore lipid-associated alterations in the TAME, we also detected the levels of FFAs transporters including fatty acid binding proteins (FABPs) and fatty acid transport protein 1 (FATP1). The results indicated that expression of fatty acid transporters in the TAME is tightly linked to the function of macrophages and predicts survival in breast cancer. To explore the impact of FFAs transporters on the function of macrophages, we performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. Consequently, we identified a special subpopulation of macrophages defined as lipid-associated macrophages (LAMs), highly expressed macrophage markers (CD163, SPP1 and C1QC), genes involved in lipid metabolism (FABP3, FABP4, FABP5, LPL and LIPA) and some lipid receptors (LGALS3 and TREM2). Functionally, LAMs were characterized by a canonical functional signature of M2-like macrophages, lipid accumulation and enhancing phagocytosis, and they were mostly distributed in tumor-adipose junctional regions. Finally, the allograft cancer mouse models confirmed that LAMs depletion in the TAME synergizes the antitumorigenic effects of anti-PD1 therapy. In summary, we defined a novel subtype of macrophages in the TAME, that has unique features and clinical outcomes.

Abstract Background & Aims There is limited evidence on the efficacy and safety of nucleos(t) ide analogues (NAs) in the treatment of HBV-ACLF. Our objective was to evaluate the outcomes among TAF, TDF and ETV, three first-line antivirals against chronic hepatitis B, in patients with HBV-ACLF. Methods Patients with HBV-related ACLF were recruited and received daily TAF (25 mg/d), TDF (300 mg/d) and ETV (0.5 mg/d). They were prospectively followed-up. The primary endpoint was overall survival at week 12 and week 48, the secondary endpoints were virological response and biochemical response. Results Forty gender and age matched eligible subjects were recruited and divided into three groups: TAF group, TDF group and ETV group. By week 48, 8 (80%) patients in TAF group, 6 (60%) patients in TDF group and 17 (85%) patients in ETV group survived without liver transplantation (P = 0.251). After 4 weeks of NAs treatment, all three groups showed paralleling reduction of HBV DNA levels. All three groups presented similar biochemical responses at week 4, patients treated with TAF showed a priority in total bilirubin reduction, albumin and cholesterol maintenance. Additionally, although there was no significant difference in changes of serum urea, serum creatinine, serum cystatin C and estimated GFR among the three groups by treatment week 4, TDF showed unfavorable renal safety even in short -term treatment. The treatment using NAs was well-tolerated and there was no serious drug-related adverse event reported. Conclusions TAF, TDF and ETV are of similar efficacy and safety in short-term and long-term treatment of HBV-ACLF. Trial registration This study is ongoing and is registered with ClinicalTrials.gov , NCT03640728 (05/02/2019).

To explore the cooling effect of phase change materials (PCM) on asphalt pavement, a numerical model of the coupled heat transfer process of a typical monolithic subgrade of the G7 Expressway in the eastern Tianshan mountain area was developed. Three types of paraffin materials (OP55E, OP52E, OP47E) were mixed in a 4:3:3 volume ratio and blended into the asphalt upper layer and overall asphalt layer at volume ratios of 5%, 10%, 15% and 20%. The cooling effect of different PCM addition schemes was simulated and analyzed, and the frequency and duration of asphalt pavement high temperature operation status were also measured. The results showed that: (1) Th addition of PCM in the asphalt layer can effectively reduce the frequency of pavement high temperature rutting damage. The number of days and average daily duration of high temperature on the road surface were both reduced. (2) The cooling effect was positively correlated with the PCM volume mixing ratio, and the temperature drop of the pavement also increased with the increase of the PCM blending ratio. As the PCM mixing ratio increased from 5% to 20%, the initial 75 °C pavement cooled by 1.49 °C and 4.66 °C, respectively, and the number of days and hours of pavement temperature over 70 °C decreased to 4 days and 3.3 h, respectively. (3) The cooling effect of the asphalt upper layer PCM scheme was greater at a small mixing ratio (5%), whereas the performance of the overall asphalt layer PCM blended scheme was effectively promoted by increasing the equivalent heat capacity of system under the large mixing ratio (20%).

Abstract Background Neurodevelopmental disorders (NDDs) are a group of disorders with high genetic and phenotypic heterogeneities. The 16p11.2 microdeletion has been implicated as an important genetic risk factor for NDDs. Methods Multiple genetic tests were used to detect the 16p11.2 microdeletion from 918 Chinese children with NDDs. Targeted sequencing of genes in the 16p11.2 interval was performed in all carriers of the 16p11.2 microdeletion, and whole‐genome expression profiling analysis was performed for the patient carriers and normal carriers in their intra‐family. Results Three patients carrying the 16p11.2 microdeletion were screened out, indicating a frequency of 0.33% for the 16p11.2 microdeletion in this cohort. We reviewed the neurodevelopmental trajectories of the 16p11.2 microdeletion carriers from childhood to puberty and confirmed that this microdeletion was associated with abnormal neurodevelopment, with varied neurodevelopmental phenotypes. A differential PRRT2 genotype (rs10204, T>C) was identified between patients and normal carriers of the 16p11.2 microdeletion. Moreover, the determination of differential whole‐genome expression profiling demonstrated the destruction of the top‐ranked network in neurogenesis and accounted for observation of abnormal neurodevelopmental phenotypes in the 16p11.2 microdeletion carriers. Conclusions We have provided the frequency of the 16p11.2 microdeletion in a Chinese pediatric NDD cohort with a variable NDD phenotype from childhood to puberty, which is useful for Chinese geneticists/pediatricians to conduct the 16p11.2 microdeletion testing in children with NDDs.

Abstract Background Neuronal ceroid lipofuscinoses (NCLs) are one of the most frequent childhood-onset neurodegenerative pathologies characterized by seizures, progressive cognitive decline, motor impairment and loss of vision. For the past two decades, more than 430 variants in 13 candidate genes have been identified in the affected patients. Most of the variants were almost exclusively reported in Western patients, and very little clinical and genetic information was available for Chinese patients. Case presentation We report a Chinese boy whose clinical phenotypes were suspected to be NCL, including intractable epilepsy, cognitive and motor decline and progressive vision loss. Using targeted next-generation sequencing, two novel null variants in CLN8 (c.298C > T, p.Gln100Ter; c.551G > A, p.Trp184Ter) were detected in this patient in trans model. These two variants were interpreted as pathogenic according to the variant guidelines of the American College of Medical Genetics and Genomics. Conclusions This is the first case report of NCL due to CLN8 variants in China. Our findings expand the variant diversity of CLN8 and demonstrate the tremendous diagnosis value of targeted next-generation sequencing for pediatric NCLs.

Neuropsychological studies indicate that new-onset childhood absence epilepsy (CAE) is associated with deficits in attention and executive functioning. However, the contribution of these deficits to impaired academic performance remains unclear. We aimed to examine whether attention and executive functioning deficits account for the academic difficulties prevalent in patients with new-onset CAE. We analyzed cognitive performance in several domains, including language, mathematics, psychomotor speed, spatial ability, memory, general intelligence, attention, and executive functioning, in 35 children with new-onset CAE and 33 control participants. Patients with new-onset CAE exhibited deficits in mathematics, general intelligence, attention, and executive functioning. Furthermore, attention deficits, as measured by a visual tracing task, accounted for impaired arithmetic performance in the new-onset CAE group. Therefore, attention deficits, rather than impaired general intelligence or executive functioning, may be responsible for arithmetic performance deficits in patients with new-onset CAE.

To improve the productivity, the resource utilization and reduce the production cost of flexible job shops, this paper designs an improved two-layer optimization algorithm for the dual-resource scheduling optimization problem of flexible job shop considering workpiece batching. Firstly, a mathematical model is established to minimize the maximum completion time. Secondly, an improved two-layer optimization algorithm is designed: the outer layer algorithm uses an improved PSO (Particle Swarm Optimization) to solve the workpiece batching problem, and the inner layer algorithm uses an improved GA (Genetic Algorithm) to solve the dual-resource scheduling problem. Then, a rescheduling method is designed to solve the task disturbance problem, represented by machine failures, occurring in the workshop production process. Finally, the superiority and effectiveness of the improved two-layer optimization algorithm are verified by two typical cases. The case results show that the improved twolayer optimization algorithm increases the average productivity by 7.44% compared to the ordinary two-layer optimization algorithm. By setting the different numbers of AGVs (Automated Guided Vehicles) and analyzing the impact on the production cycle of the whole order, this paper uses two indicators, the maximum completion time decreasing rate and the average AGV load time, to obtain the optimal number of AGVs, which saves the cost of production while ensuring the production efficiency. This research combines the solved problem with the real production process, which improves the productivity and reduces the production cost of the flexible job shop, and provides new ideas for the subsequent research. [ABSTRACT FROM AUTHOR]

With the rapid development of intelligent manufacturing and the changes in market demand, the current manufacturing industry presents the characteristics of multi-varieties, small batches, customization, and a short production cycle, with the whole production process having certain flexibility. In this paper, a mathematical model is established with the minimum production cycle as the optimization objective for the dual-resource batch scheduling of the flexible job shop, and an improved nested optimization algorithm is designed to solve the problem. The outer layer batch optimization problem is solved by the improved simulated annealing algorithm. The inner double resource scheduling problem is solved by the improved adaptive genetic algorithm, the double coding scheme, and the decoding scheme of Automated Guided Vehicle (AGV) scheduling based on the scheduling rules. The time consumption of collision-free paths is solved with the path planning algorithm which uses the Dijkstra algorithm based on a time window. Finally, the effectiveness of the algorithm is verified by actual cases, and the influence of AGV with different configurations on workshop production efficiency is analyzed. [ABSTRACT FROM AUTHOR]