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High entropy amorphous alloys (HE AMs) have attracted extensive interest lately due to their superior magnetocaloric properties. However, the critical behavior and mechanical properties have received less research, which restricts their applications. This work presented a comprehensive investigation of the magnetocaloric effect (MCE), critical behavior, and mechanical performance of quinary Gd20Dy20Er20Al20M20 (M = Fe, Co, Ni) HE AMs. All samples exhibited distinct spin glass-like behavior below TC and competitive MCE around hydrogen liquefaction temperature range. Excellent MCE was achieved by the HE AMs through a second-order phase transition from paramagnetic state to ferromagnetic state at 79 K for Fe, 41 K for Co, and 36 K for Ni. Among them, the maximum magnetic entropy change (-ΔSM)max of Gd20Dy20Er20Al20Co20 amorphous alloys was 9.59 J kg−1 K−1 under 0–5 T. Furthermore, RC and RCP of Gd20Dy20Er20Al20Fe20 amorphous alloys were respectively 519 J kg−1 and 613 J kg−1, larger than that of most RE-based amorphous alloys. For all samples, the critical behavior of the phase transition approached the mean field model, and this responded to the long-range ordering of the magnetic interaction. The bending plasticity of Gd20Dy20Er20Al20M20 (M = Fe, Co, Ni) HE AMs were 0.78, 1.03, 0.89, respectively. The adjustable Tc, large (-ΔSM), high RCP, and outstanding mechanical properties suggested Gd20Dy20Er20Al20M20 (M = Fe, Co, Ni) HE AMs may find utility as magnetic refrigerants in low-temperature applications.

ObjectiveAbnormal cognitive functioning is a core symptom of Major Depressive Disorder (MDD) and is strongly correlated with MDD prognosis. Current studies suggest that the occurrence of MDD may be related to oxidative stress-induced inflammation, hypothalamic-pituitary-adrenal axis disorders, diminished monoamine function and microbe-brain-gut axis, among other pathways. In recent years, the relationship between the immune-inflammatory response and MDD has been a hot topic of research, but how the relationship between immunoinflammation and cognitive function is manifested in MDD is still unclear. In this study, we examined cognitive function characteristics, serum inflammatory factors, brain-derived neurotrophic factor, and their correlations before and after pharmacological treatment(paroxetine hydrochloride tablets) in patients with first-episode major depressive disorder, aiming to identify objective biomarkers for cognitive function assessment.MethodsWe included 22 patients with first-episode major depressive disorder and 27 healthy volunteers from the community during the same period. The Hamilton Depression Scale-17 (HAMD-17) assessed the severity of depressive symptoms at baseline and after 8 weeks of treatment. The Repeatable Battery for the Assessment of Neuropsychological Status(RBANS) evaluated cognitive function, and serum samples were collected to determine levels of inflammatory and neurotrophic factors at these two time points. For healthy volunteers, only HAMD-17 scale scores, RBANS scale scores, and serum samples were taken at baseline. Spearman’s correlation analyzed the relationship between inflammatory factors, neurotrophic factors, and cognitive function. Multiple linear regression determined factors affecting cognitive function in first-time patients.ResultsBaseline findings indicated that patients’ IL-6 and TNF-α levels exceeded those of healthy individuals, while their IFN-α levels were below; their scores in language, attention, delayed memory, and the RBANS scale were also lower than healthy counterparts. Post-treatment, patients’ BDNF, IL-6, and TNF-α levels remained higher than those of healthy subjects, and their IFN-α levels were still lower; their language and attention scores were also inferior. Association analyses revealed an association between BDNF and visuospatial/constructional ability scores and language scores in patients with MDD at baseline, and a positive relationship between TNF-α and attention score. Multiple regression analysis indicated an association between TNF-α levels and attention scores in MDD patients at baseline.ConclusionsOur study concludes that TNF-α and BDNF correlate with cognitive function in MDD at baseline, and furthermore, TNF-α could potentially serve as an objective biomarker to support the assessment of attentional function at baseline.

An 8-week growth experiment was conducted to investigate the effects of different levels of crawfish shell meals (Procambarus clarkii, CSM) replacement of soybean meal (SM) on growth, feed utilization, antioxidant response, body color and muscle quality of Oujiang color common carp (3.0 ± 0.5 g, Cyprinus carpio var. Color), and to assess the suitable range of CSM replacement of soybean meal and its effects on fish. Three isonitrogenous and isolipidic experimental diets were formulated to replace SM by equal proportion (1:1, w: w) of CSM at 0, 25, or 50 % (designated as CSM0, CSM25, or CSM50, respectively). The results showed that weight gain (WG) as well as hepatic superoxide dismutase (SOD) activities were significantly (P < 0.05) higher in the CSM25 group compared to the CSM0 group. In addition, there were no significant (P > 0.05) differences in growth performance, feed utilization, skin color, and muscle texture parameters between CSM50 and CSM0 groups, except for the overall ash content, which was significantly (P < 0.05) higher in CSM50 than CSM0 group. Therefore, it was feasible to replace 50 % of SM with CSM in Oujiang color common carp diets without negative effects on serum biochemical indices, antioxidant and immune responses, skin color or muscle texture. These findings suggested that CSM could be a potential alternative protein source in diets of Oujiang color common carp.

The current art image classification methods have low recall and accuracy rate issues . To improve the classification performance of art images, a new adaptive classification method is designed employing multi-scale convolutional neural networks (CNNs). Firstly, the multi-scale Retinex algorithm with color recovery is used to complete the enhancement processing of art images. Then the extreme pixel ratio is utilized to evaluate the image quality and obtain the art image that can be analyzed. Afterward, edge detection technology is implemented to extract the key features in the image and use them as initial values of the item to be trained in the classification model. Finally, a multi-scale convolutional neural network (CNN) is constructed by using extended convolutions, and the characteristics of each level network are set. The decision fusion method based on maximum output probability is employed to calculate different subclassifies’ probabilities and determine the final category of an input image to realize the art image adaptive classification. The experimental results show that the proposed method can effectively improve the recall rate and precision rate of art images and obtain reliable image classification results.

Fish gut health is influenced by various factors, with the environment being a significant one. S. sinensis is a key aquaculture species in China, yet research on the impact of different aquaculture systems on its intestinal health remains limited. This study aims to explore the changes in intestinal morphology and gut microbiota of S. sinensis under two aquaculture systems. The juveniles of S. sinensis were divided into two groups and cultured in traditional ponds (CT) and an in-pond tank culture system (JY), with equal amounts of feed provided daily over a 72-day experimental period. The results showed no significant differences in growth performance metrics, including the specific growth rate, weight gain rate, hepatosomatic index, and viscerosomatic index between the two groups. In terms of intestinal morphology, the JY group villus width was significantly wider than the CT group, and the number of goblet cells in the CT group was significantly higher than that of the JY group (p < 0.05), which suggested that the fish in the JY group may have better intestinal nutrient absorption capacity, while the water quality in the CT group may be worse. The 16S rRNA gene sequencing analysis of the gut microbiota showed that the JY group had a significantly higher Shannon index compared to the CT group (p < 0.05), indicating greater species richness and evenness. Principal Coordinates Analysis (PCoA) revealed a distinct clustering of gut microbiota between the two groups. At the phylum level, the relative abundance of Fusobacteriota was significantly higher in the CT group, whereas Bacteroidota and Proteobacteria were significantly higher in the JY group (p < 0.05). Furthermore, KEGG pathway predictions indicated differences in the potential metabolic capabilities of the gut microbiota between the two groups (p < 0.05). Overall, this study is the first to conduct a comparative analysis of the growth performance, intestinal tissue morphology, and gut microbiota of S. sinensis under two different aquaculture systems, which has valuable implications for the further optimization of aquaculture practices.

The shear mechanical behavior of soils in the slip zone under cyclic loading is of great importance for the stability analysis of landslides. In this paper, an experimental device is developed to study the nonlinear deformation mechanism of soil in sliding zone under cyclic load. Based on field tests and model tests, the change of shear strength parameters of the soil in the slip zone with cyclic loading parameters was investigated. Based on the deformation characteristics of slip zone soils under cyclic dynamic loading, the unsteady creep transient model based on fractional derivative is established, and three deformation types of sliding zone soil are described: stable, critical and destructive. The Levenberg-Marquardt (LM) algorithm is used to fit the nonlinear curves, and the applicability of the model is also verified. This research method provides a test apparatus and a method for studying the deformation characteristics of slip zone soils under cumulative loading.

Abstract Förster resonance energy transfer (FRET) has demonstrated its potential to enhance the light energy utilization ratio of perovskite solar cells by interacting with metal‐organic frameworks (MOFs) and perovskite layers. However, comprehensive investigations into how MOF design and synthesis impact FRET in perovskite systems are scarce. In this work, nanoscale HIAM‐type Zr‐MOF (HIAM‐4023, HIAM‐4024, and HIAM‐4025) is meticulously tailored to evaluate FRET's existence and its influence on the perovskite photoactive layer. Through precise adjustments of amino groups and acceptor units in the organic linker, HIAM‐MOFs are synthesized with the same topology, but distinct photoluminescence (PL) emission properties. Significant FRET is observed between HIAM‐4023/HIAM‐4024 and the perovskite, confirmed by spectral overlap, fluorescence lifetime decay, and calculated distances between HIAM‐4023/HIAM‐4024 and the perovskite. Conversely, the spectral overlap between the PL emission of HIAM‐4025 and the perovskite's absorption spectrum is relatively minimal, impeding the energy transfer from HIAM‐4025 to the perovskite. Therefore, the HIAM‐4023/HIAM‐4024‐assisted perovskite devices exhibit enhanced EQE via FRET processes, whereas the HIAM‐4025 demonstrates comparable EQE to the pristine. Ultimately, the HIAM‐4023‐assisted perovskite device achieves an enhanced power conversion efficiency (PCE) of 24.22% compared with pristine devices (PCE of 22.06%) and remarkable long‐term stability under ambient conditions and continuous light illumination.

Abstract Background Two cycles of neoadjuvant PD-1 blockade plus chemotherapy induced favorable pathological response and tolerant toxicity in patients with locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 25% of patients relapsed within 1 year after surgery, indicating that a short course of treatment may not be sufficient. Therefore, exploring the effects of intensive treatment is needed for optimal clinical outcomes. Methods Locally advanced ESCC patients were administered three cycles of camrelizumab plus nab-paclitaxel and capecitabine, followed by thoracoscopic esophagectomy. The primary endpoint was pathologic response. Secondary endpoints included safety, feasibility, radiologic response, survival outcomes, and immunologic/genomic correlates of efficacy. Results Forty-seven patients were enrolled in the study. Forty-two patients received surgery, and R0 resection was achieved in all cases. The complete and major pathological response rates were 33.3% and 64.3%, respectively, and the objective response rate was 80.0%. Three cycles of treatment significantly improved T down-staging compared to two cycles (P = 0.03). The most common treatment-related adverse events were grades 1–2, and no surgical delay was reported. With a median follow-up of 24.3 months, the 1-year disease-free survival and overall survival rates were both 97.6%, and the 2-year disease-free survival and overall survival rates were 92.3% and 97.6%, respectively. Three patients experienced disease recurrence or metastasis ranging from 12.5 to 25.8 months after surgery, and one patient died 6 months after surgery due to cardiovascular disease. Neither programmed death-ligand 1 expression nor tumor mutational burden was associated with pathological response. An increased infiltration of CD56 dim natural killer cells in the pretreatment tumor was correlated with better pathological response in the primary tumor. Conclusions It seems probable that intensive cycles of neoadjuvant camrelizumab plus nab-paclitaxel and capecitabine increased tumor regression and improved survival outcomes. Randomized controlled trials with larger sample sizes and longer follow-up periods are needed to validate these findings. Trial registration Chinese Clinical Trial Registry, ChiCTR2000029807, Registered February 14, 2020, https://www.chictr.org.cn/showproj.aspx?proj=49459 .

The Yangtze River Delta (YRD) bears the vital task of driving the growth of China's equipment manufacturing industry (EMI) intelligence as an advanced region. Fostering the transformation and upgrading of the EMI in the YRD and constructing a modern production mode is vital to developing and reforming China's manufacturing industry. This paper uses industrial robot data to assess the level of intelligence (LoI) in the EMI from 2016 to 2019. The OLS (ordinary least squares) model is used for the measurements, and the MQ (the modified contribution index) is used to estimate the degree of contribution from a host of variables. It is identified that the LoI is on the rise. However, excluding railways, aerospace, shipbuilding, and other transportation equipment manufacturing, the LoI is significantly higher than in other subsectors. It is also identified that technological innovation ability, human capital density, and enterprise cost pressure govern the industry's LoI. Moreover, while there is a difference in the main influencing factors in LoI within different industries, R&D investment, technological innovation ability, and enterprise cost pressure have the most significant impact across most equipment manufacturing sub-industries.

Abstract Background Rare disease is a general term for a disease that affects a small number of people but recognized as a global public health priority. Governments worldwide are paying more and more attention to the academical research and drug investment of rare diseases. The conduct of rare disease clinical trials is still difficult, despite the promotion of government policies and the awakening of social consciousness. In this article, we outlined the characteristics and obstacles of clinical trials of rare diseases in China and expected to provide reference for subsequent clinical trials in this field. Results In recent years, China has made some progress in clinical trials of rare diseases in the past 10 years. There were 481 clinical trials on rare diseases in total, covering more than 10 rare diseases with high incidence. Clinical trial applications on rare diseases for a total of 481 were submitted and with an average annual growth rate of 28.2% from 2013 to 2022. The number of clinical trial application for rare diseases in 2016 dramatically increased by 80% compared to 2015 due to the policy document issued by China for clinical research in rare diseases in 2015. Besides, about 70% of applications registering for clinical trials could recruit subjects as expected. Despite this, the number of clinical trials of rare diseases in China was less compared with the United States, Europe and Japan, and the types of infant drugs were limited to biological products and chemical drugs lacking other new treatments. Conclusions Efforts have been made in recent years to develop clinical research on rare diseases in China. The number of clinical trials for rare diseases in China was growing steadily every year, which was inseparable from the support of the country, society and rare disease patients. Still, there was a large gap between China and other developed countries in this field and this merit further investigation.

The last few decades have witnessed an advancement in our understanding of multiple cancer cell pathways related to metabolic reprogramming. One of the most important cancer hallmarks, including aerobic glycolysis (the Warburg effect), the central carbon pathway, and multiple-branch metabolic pathway remodeling, enables tumor growth, progression, and metastasis. Phosphoenolpyruvate carboxykinase 1 (PCK1), a key rate-limiting enzyme in gluconeogenesis, catalyzes the conversion of oxaloacetate to phosphoenolpyruvate. PCK1 expression in gluconeogenic tissues is tightly regulated during fasting. In tumor cells, PCK1 is regulated in a cell-autonomous manner rather than by hormones or nutrients in the extracellular environment. Interestingly, PCK1 has an anti-oncogenic role in gluconeogenic organs (the liver and kidneys), but a tumor-promoting role in cancers arising from non-gluconeogenic organs. Recent studies have revealed that PCK1 has metabolic and non-metabolic roles in multiple signaling networks linking metabolic and oncogenic pathways. Aberrant PCK1 expression results in the activation of oncogenic pathways, accompanied by metabolic reprogramming, to maintain tumorigenesis. In this review, we summarize the mechanisms underlying PCK1 expression and regulation, and clarify the crosstalk between aberrant PCK1 expression, metabolic rewiring, and signaling pathway activation. In addition, we highlight the clinical relevance of PCK1 and its value as a putative cancer therapeutic target.

Abstract Mixed‐dimensional engineering of perovskite material has been demonstrated as a facile and promising strategy to improve both photovoltaic performance and long‐term stability of perovskite solar cells (PSCs). In this study, we report an in‐plane preferred orientation of 1D perovskite induced by an ionic liquid (IL) of 1‐(3‐cyanopropyl)‐3‐methylimidazolium chloride (CPMIMCl) for the first time via sequential deposition approach, leading to a mixed dimensional perovskite thin films. The generated one‐dimensional (1D) CPMIMPbI3 with in‐plane orientation resides at the grain boundaries of three‐dimensional (3D) perovskite can be appreciably observed from the morphology level, leading to creation of high‐quality films with large grain size with more efficient defect passivation. Moreover, the dispersion of IL in the bulk phase of perovskite material allows for the formation of 1D perovskite for multiple level passivation to inhibit non‐radiative recombination and optimize carrier transport. This IL engineering strategy not only yields a mixed‐dimensional perovskite heterostructure with in‐plane orientation 1D perovskite nano‐rods but also significantly improves the opto‐electronic property with suppressed trap states. As a result, the CPMIMCl‐treated PSCs show an enhanced photovoltaic performance with a champion power conversion efficiency (PCE) up to 24.13%. More importantly, benefiting from the hydrophobicity of formed 1D perovskite and defects suppression, the corresponding PSC demonstrates an excellent long‐term stability and maintain 97.1% of its pristine PCE at 25°C under 50% RH condition over 1000 h. This research provides an innovative perspective for employing the low dimensional engineering to optimize the performance and stability of photovoltaic devices.

Deciphering the crosstalk between metabolic reprogramming and epigenetic regulation is a promising strategy for cancer therapy. In this study, we discovered that the gluconeogenic enzyme PCK1 fueled the generation of S-adenosylmethionine (SAM) through the serine synthesis pathway. The methyltransferase SUV39H1 catalyzed SAM, which served as a methyl donor to support H3K9me3 modification, leading to the suppression of the oncogene S100A11. Mechanistically, PCK1 deficiency–induced oncogenic activation of S100A11 was due to its interaction with AKT1, which upregulated PI3K/AKT signaling. Intriguingly, the progression of hepatocellular carcinoma (HCC) driven by PCK1 deficiency was suppressed by SAM supplement or S100A11 KO in vivo and in vitro. These findings reveal the availability of the key metabolite SAM as a bridge connecting the gluconeogenic enzyme PCK1 and H3K9 trimethylation in attenuating HCC progression, thus suggesting a potential therapeutic strategy against HCC.

Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B’s anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.

Enhancing the efficiency of quantum emitters is essential for exploring new functionalities. Here the authors show Si cuboids that sustain bound states in the continuum enable the injection of dense electron-hole plasma and provide high quantum efficiency.

IntroductionAlcohol is the main legal drug in the world, and excessive consumption of alcohol seriously damages the morphological structure and function of various organs. The insufficiency of an essential enzyme in ethanol metabolism, aldehyde dehydrogenase-2 (ALDH2), will aggravate the alcohol-induced brain injury. The effect of ALDH2 after chronic alcohol exposure on global lipid profiling of the brain remains unclear.MethodsIn this study, ALDH2*2 knock-in mice were fed the Lieber-DeCarli liquid diet containing ethanol for 8 weeks. Blood alcohol and acetaldehyde levels were examined, and the mice were tested through novel object recognition and the Y-maze test to evaluate cognitive impairment toward the end of the study. The lipidome profiling of cerebral cortex samples was investigated using a lipidomics method based on ultra-high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOFMS).Results and DiscussionCompared with similarly treated wild-type (WT) mice, ALDH2*2 mice exhibited poor cognitive performance, though the result did not achieve statistical significance. The lipidomics results indicated that 74 differential lipid species were selected in WT mice, of which 57 species were up-regulated, and 17 were down-regulated. Moreover, 99 differential lipids were identified in ALDH2*2 mice, of which 73 were up-regulated, and 26 were down-regulated. For ALDH2*2 mice, the number of changed significantly glycerophospholipids (GPs) subtypes was lower than that of WT mice. Interestingly, compared with WT mice, a lower proportion of polyunsaturated fatty acids (PUFAs) was found in ALDH2*2 mice. Collectively, the results provide clear evidence for a lipidomic signature of marked changes in the cerebral cortex of ALDH2*2 mice after chronic alcohol exposure.Highlights• The cerebral cortex of heterozygous ALDH2*2 mice showed more significant changes in lipidome profiles after chronic alcohol exposure than wild-type mice.• Most lipids were significantly up-regulated in both groups of mice, whereas the increase in TAG was restricted to WT mice.• For ALDH2*2 mice, GPs substances changed significantly, and SHexCer and SM subclasses in sphingolipids also deserved attention.

DNA methylation mediated by DNA methyltransferase is an important epigenetic process that regulates gene expression in mammals, which plays a key role in silencing certain genes, such as tumor suppressor genes, in cancer, and it has become a promising therapeutic target for cancer treatment. Similar to other epigenetic targets, DNA methyltransferase can also be modulated by chemical agents. Four agents have already been approved to treat hematological cancers. In order to promote the development of a DNA methyltransferase inhibitor as an anti-tumor agent, in the current review, we discuss the relationship between DNA methylation and tumor, the anti-tumor mechanism, the research progress and pharmacological properties of DNA methyltransferase inhibitors, and the future research trend of DNA methyltransferase inhibitors.

Abstract Background Lung cancer associated with cystic airspaces, especially solitary multicystic lesion lung cancer, is a rare disease (a rare imaging performance of non-small cell lung cancer). It is difficult to diagnose owing to the lack of a clear definition; therefore, diagnosis of these neoplastic lesions remains challenging. Case presentation We outlined two cases of elderly Chinese men who were admitted to the hospital with a solitary multicystic lesion of the lung and subsequent surgical resection, confirming a diagnosis of adenocarcinoma. Conclusions For solitary pulmonary cystic airspaces (especially solitary multicystic lung lesions), it is important to properly recognise their imaging features. Due to the possibility of malignancies, timely surgery is an effective treatment strategy for early diagnosis.

Generally, wavefronts are measured using angle-based sensors like the Shack-Hartmann sensor. Here, the authors present an angle-sensitive device that uses flat optics integrated on a focal plane array for compact wavefront sensing with improved resolution.

Summary: To overcome the increased risk of SARS-CoV-2 reinfection or post-vaccination infection caused by the Omicron variant, Omicron-specific vaccines were considered a potential strategy. We reported the increased magnitude and breadth of antibody response against VOCs elicited by post-vaccination Delta and Omicron infection, compared to WT infection without vaccination. Then, in mouse models, three doses of Omicron-RBD immunization elicited comparable neutralizing antibody (NAb) titers with three doses of WT-RBD immunization, but the neutralizing activity was not cross-active. By contrast, a heterologous Omicron-RBD booster following two doses of WT-RBD immunization increased the NAb titers against Omicron by 9-folds than the homologous WT-RBD booster. Moreover, it retains neutralization against both WT and current VOCs. Results suggest that Omicron-specific subunit booster shows its advantages in the immune protection from both WT and current VOCs and that SARS-CoV-2 vaccines including two or more virus lineages might improve the NAb response.

Febuxostat is a urate-lowering medication for the treatment of patients with gout. This study was performed to elucidate the effects and underlying mechanisms of febuxostat on neuronal injury induced by intracerebral hemorrhage (ICH) in mice. The results showed that the administration of febuxostat improved neurological severity scores and blood–brain barrier (BBB) permeability. Moreover, febuxostat attenuated neuronal cell death and cytokine levels compared with the ICH group. Next, we conducted a transcriptome analysis of the neuroprotective effects of febuxostat. The overlapping significant differentially expressed genes (DEGs) were identified. Gene ontology (GO) analysis revealed that the overlapping significant DEGs were most enriched in five items. The intersecting DEGs of the aforementioned five pathways were Wisp1, Wnt7b, Frzb, and Pitx2. In addition, GO terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that DEGs were mainly involved in the wnt signaling pathway. Furthermore, the expression of Wisp1 and Wnt7b in the perihematomal region at 72 h post-ICH was observed. The results showed that both Wisp1 and Wnt7b were increased in the ICH group and were decreased by the administration of febuxostat. Taken together, the study showed that febuxostat protected against secondary brain injury after ICH and the Wnt7b-Wisp1 pathway was closely related to neuroprotective effects.

Phosphoenolpyruvate carboxykinase 1 (PCK1), a step limiting enzyme of gluconeogenesis, is downregulated in hepatocellular carcinoma (HCC). Overexpression of PCK1 has been shown to suppress hepatoma cell growth, but the underlying mechanism remains unclear. We used recombinant adenovirus overexpressing PCK1 or GFP in Huh7 cells, and the differentially expressed genes (DEGs) were identified by RNA-Seq. 180 were upregulated by PCK1 overexpression, whereas 316 were downregulated. Pathway analysis illustrated that PCK1 was closely correlated with Wnt signaling pathway and TGF-beta signaling pathway. Hence, Wnt signaling pathway and its downstream component, FZD2, FZD6, FZD7 and β-catenin were confirmed by qRT-PCR and Western blot. In vivo we also observed that PCK1 had restrained tumor growth as a result of decreasing expression of β-catenin. Whole-transcriptomic profile analysis discovered that overexpression of PCK1 downregulates several oncogenic signaling pathways in HCC, providing potential therapeutic targets for improving HCC therapy. Keywords: Hepatocellular carcinoma cells, Oncogene, Phosphoenolpyruvate carboxylase kinase1 (PCK1), RNA sequencing, Wnt signaling pathway

More and more evidences proved that deltamethrin (Del) exposure induced adverse effects and damaged immune function to the aquatic animals in the parasite killing process with increasing insecticide application. However, little is currently known of the negative effect on mucosal immunity, especially in gills tissue. Therefore, this study was aimed to reveal the tissue injury and immunotoxicity in the gill of gibel carp following acute deltamethrin exposure. The LC50 of deltamethrin on gibel carp at 96 h was determined to be 6.194 μg/L, and then juvenile gibel carp (Carassius auratus gibelio) (8.8 ± 1.0 g) were exposed to four Del exposure groups (0.61, 1.22, 2.44, and 4.88 μg/L) for 12 h and 24 h. We measured the lysozyme (LYZ) contents and myeloperoxidase (MPO) activities and found that with increased concentration of Del exposure, the LYZ contents were found to increase in the 1.22 μg/L Del group initially significantly and then gradually significantly decrease in the 4.88 μg/L Del group. And the activities of MPO were significantly lifted in a dose-dependent manner. The histological analysis showed that Del exposure caused serious desquamation and necrosis in the surface of epithelial cells, accompanied by interlamellar cellular mass degenerative. In addition, the mucous cells were significantly decreased in the high Del concentration group (2.44 μg/L and 4.88 μg/L Del group) by AB-PAS staining. Additionally, totally 2857 DEGs (including 1624 up-regulated and 1233 down-regulated genes) were identified between the control group and 4.88 μg/L Del exposure group using transcriptional analysis. Among these, some genes involved in innate immune molecules, complement activation, apoptosis-related molecules, cytokine, and adaptive immune molecules, were also down-regulated. Importantly, we found immune system process and tumor necrosis factor receptor (superfamily) binding pathways were downregulated based on the GO and KEGG enrichment analysis. Meanwhile, we detected the expression of pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-8), anti-inflammatory cytokines (TGF-β), LYZ, IgM, and Hsp70 in the gills tissue at 12 h and 24 h after Del exposure, which were consistent with our sequencing results. Collectively, these results demonstrated that the gills injury and immunotoxicity were induced by Del exposure and provided novel insight for explaining to some extent why Del-exposure fish are more susceptible to concurrent or secondary viral or bacterial infections.

Improving the efficacy of anticancer drugs is especially challenging. Estrogen is a sex hormone that not only promotes the development of female secondary sexual characteristics, but also supports many important physiological functions. Interestingly, estrogen has shown to be vital for the activity of some anticancer drugs, such as adriamycin, cisplatin, olaparib, trastuzumab, bevacizumab, tamoxifen, cyclophosphamide, methotrexate, and paclitaxel. Although there are many reasons for the differences in therapeutic effects among cancer patients, estrogen status is undoubtedly a very important factor. In view of the importance of the crosstalk between estrogen signaling and drug therapy for cancer, this review summarizes the effects of estrogen on the targets, metabolism and resistance of anticancer drugs and describes the related pathways and underlying mechanisms. Here, an analysis of the close relationship between estrogen and cancer drug therapy was conducted to clarify the effects of estrogen on the therapeutic efficacy of anticancer drugs to facilitate the future development of specific drug treatment strategies to achieve optimal outcomes.

Anthropogenic and extreme climate disasters cause ecological changes in natural rivers and lakes, increasing the risk of starvation in yellowcheek (Elopichthys bambusa). Therefore, the impact of starvation on the metabolism and wild population of yellowcheek should be explored. In this study, we used transcriptome sequencing technology to analyze the effects of short (8 d) and long-term (28 d) starvation on the liver transcriptome, growth, and serum indicators of yellowcheek. Our results showed that short-term starvation significantly reduced the visceral weight and viscera index of yellowcheek. Long-term starvation significantly reduced the body weight and Fulton’s condition factor, and it maintained significant reductions in visceral weight and viscera index. These results indicate that glycogen is the preferred energy source, rather than muscle protein, under starvation. Short-term starvation limited N-glycan and fatty acid biosynthesis, fatty acid elongation in the endoplasmic reticulum in the liver, and upregulated fatty acid degradation. However, long-term starvation alleviated the reduction in N-glycan and fatty acid biosynthesis caused by early starvation, and it significantly reduced fatty acid elongation in the mitochondria, as well as fatty acid degradation. These results provide important experiment information for assessing the starvation levels and nutritional status of wild yellowcheek.

In order to find out the key factor affecting the stability of coke pusher, the structural deformation and vibration mode parameters of the coke pusher are obtained by thermal-structural coupling simulation and thermal-modal coupling simulation, and the vibration signals in the process of coke pushing are collected for time-domain analysis and time-frequency analysis. The results show that the coke pusher vibrates after being affected by the friction, and the vibration frequencies are close to the natural frequencies; that is, the friction has a great influence on the stability of the coke pushing rod. In addition, affected by the friction, the deformation of the bottom of coke pusher is the largest, resulting in unstable contact between the bottom of coke pusher and the ground of carbonization chamber, which is very easy to cause vibration.

All-dielectric optical antenna with multiple Mie modes and lower inherent ohmic loss can achieve high efficiency of light manipulation. However, the silicon-based optical antenna is not reconfigurable for specific scenarios. The refractive index of optical phase-change materials can be reconfigured under stimulus, and this singular behavior makes it a good candidate for making reconfigurable passive optical devices. Here, the optical radiation characteristics of the V-shaped phase-change antenna are investigated theoretically. The results show that with increasing crystallinity, the maximum radiation direction of the V-shaped phase-change antenna can be continuously deflected by 90°. The exact multipole decomposition analysis reveals that the modulus and interference phase difference of the main multipole moments change with the crystallinity, resulting in a continuous deflection of the maximum radiation direction. Thus, the power ratio in the two vertical radiation directions can be monotonically reversed from −12 to 7 dB between 20% and 80% crystallinity. The V-shaped phase-change antenna exhibits the potential to act as the basic structural unit to construct a reconfigurable passive spatial angular power splitter or wavelength multiplexer. The mechanism analysis of radiation directivity involving the modulus and interference phase difference of the multipole moments will provide a reference for the design and optimization of the phase-change antenna.

Edge devices (EDs) carry limited energy, but 6th generation mobile networks (6G) communication will consume more energy. The unmanned aerial vehicle (UAV)-aided wireless communication network can provide communication links to EDs without a signal. However, with the time-lag system, the EDs cannot dynamically adjust the emission energy because the dynamic UAV coordinates cannot be accurately acquired. In addition, the fixed emission energy makes the EDs have poor endurance. To address this challenge, in this paper, we propose a deep learning-based energy optimization algorithm (DEO) to dynamically adjust the emission energy of the ED so that the received energy of the mobile relay UAV is, as much as possible, equal to the sensitivity of the receiver. Specifically, the edge server provides the computing platform and uses deep learning (DL) to predict the location information of the relay UAV in dynamic scenarios. Then, the ED emission energy is adjusted according to the predicted position. It enables the ED to communicate reliably with the mobile relay UAV at minimum energy. We analyze the performance of a variety of predictive networks under different time-delay systems through experiments. The results show that the Weighted Mean Absolute Percentage Error (WMAPE) of this algorithm is 0.54%, 0.80% and 1.15% under the effect of a communication delay of 0.4 s, 0.6 s and 0.8 s, respectively.

BackgroundInadequate accuracy of ultrasound-guided core needle biopsy (US-CNB) urges further improvement for the diagnosis and management of lymphoma to meet with the practitioners’ increased reliance on this mini-invasive approach.MethodsData related to US-CNB of the deep-sited dominant lesions suspicious of lymphoma detected by computer tomography or positron-emission tomography/computer tomography for eligibility assessment of three prospective clinical trials were collected in advance. A retrospective analysis of the prospective data collection was performed, in which Viable-targeting US-CNB that Color Doppler flow imaging (CDFI) and/or contrast enhanced ultrasound (CEUS) were employed to select viable area for biopsy target compared with Routine US-CNB that routine procedure of evaluation and guidance using gray-scale ultrasound with CDFI in terms of the yield of clinically actionable diagnosis and safety, and determinants for the successful US-CNB that established an actionable diagnosis were explored. The establishment of final diagnosis was based on surgical pathology or medical response to therapy with follow-up at least 6 months.ResultsA total of 245 patients underwent Routine US-CNB (N = 120) or Viable-targeting US-CNB (N = 125), of which 91 (91/120, 75.8%) and 112 (112/125, 89.6%) were revealed with actionable diagnoses, respectively (p = 0.004, OR 0.846, 95% CI: 0.753–0.952). And 239 patients established final diagnoses. Diagnostic yields of actionable diagnosis according to the final diagnoses were 78.4% (91/116) and 91.1% (112/123) (p = 0.006, OR 0.554, 95% CI: 0.333–0.920), 82.6% (90/109) and 92.5% (111/120) for malignancy, 84.0% (84/100) and 91.8% (101/110) for lymphoma, 85.1% (80/94) and 92.3% (96/104) for Non-Hodgkin Lymphoma, 66.7% (4/6) and 83.3% (5/6) for Hodgkin Lymphoma in Routine and Viable-targeting CNB groups, respectively. No major complications were observed. Dominant lesions with actionable diagnosis in US-CNB were with higher FDG-avid Standardized Uptake Value. Binomial logistic regression revealed that actionable diagnosis of US-CNB was correlated with group and ancillary studies.ConclusionViable-Targeting US-CNB was superior to routine US-CNB in term of the yield of actionable diagnosis for deep-sited dominant lesions suspicious of lymphoma, which demonstrated a potential to be the initial approach in this setting.

Pushing coke is an important process in coke oven production. In the process of pushing coke, under the three-body contact state of steel, coke powder, and refractory brick, coke powder plays an important role in lubrication. In this article, a study on the macro- and micro-behavior and mechanism of coke powder lubrication is carried out through tribological tests. The results show that in the process of sliding friction, coke powder plays a role of lubrication through forming a powder layer and shearing occurred inside the powder layer. The load keeps at 5 MPa, under the lower velocity, the powder layer is thinner and delamination occurred in local position. While under the higher velocity, the coke powder can form a compact and complete powder layer and exhibit better lubrication characteristics. However, when the velocity increases to 0.52 m/s, the continuous powder layer is not formed, so the friction coefficient is higher, the frictional surface wears seriously and results in vibration to occur. The velocity keeps at 0.40 m/s, and the powder layer inclines to deteriorate under higher load. When the load increases to 20 MPa, a part of the powder layer is damaged, and severe wear occurs on the surface.

Abstract Background Altered glucose metabolism endows tumor cells with metabolic flexibility for biosynthesis requirements. Phosphoenolpyruvate carboxykinase 1 (PCK1), a key enzyme in the gluconeogenesis pathway, is downregulated in hepatocellular carcinoma (HCC) and predicts poor prognosis. Overexpression of PCK1 has been shown to suppress liver tumor growth, but the underlying mechanism remains unclear. Methods mRNA and protein expression patterns of PCK1, AMPK, pAMPK, and the CDK/Rb/E2F pathway were determined using qRT-PCR and western blotting. Cell proliferation ability and cell cycle were assessed by MTS assay and flow cytometric analysis. The effect of PCK1 on tumor growth was examined in xenograft implantation models. Results Both gain and loss-of-function experiments demonstrated that PCK1 deficiency promotes hepatoma cell proliferation through inactivation of AMPK, suppression of p27Kip1 expression, and stimulation of the CDK/Rb/E2F pathway, thereby accelerating cell cycle transition from the G1 to S phase under glucose-starved conditions. Overexpression of PCK1 reduced cellular ATP levels and enhanced AMPK phosphorylation and p27Kip1 expression but decreased Rb phosphorylation, leading to cell cycle arrest at G1. AMPK knockdown significantly reversed G1-phase arrest and growth inhibition of PCK1-expressing SK-Hep1 cells. In addition, the AMPK activator metformin remarkably suppressed the growth of PCK1-knockout PLC/PRF/5 cells and inhibited tumor growth in an orthotropic HCC mouse model. Conclusion This study revealed that PCK1 negatively regulates cell cycle progression and hepatoma cell proliferation via the AMPK/p27Kip1 axis and supports a potential therapeutic and protective effect of metformin on HCC.

Enzymes function as biocatalysts and are extensively exploited in industrial applications. Immobilization of enzymes using support materials has been shown to improve enzyme properties, including stability and functionality in extreme conditions and recyclability in biocatalytic processing. This review focuses on the recent advances utilizing the design space of in vivo self-assembled polyhydroxyalkanoate (PHA) particles as biocatalyst immobilization scaffolds. Self-assembly of biologically active enzyme-coated PHA particles is a one-step in vivo production process, which avoids the costly and laborious in vitro chemical cross-linking of purified enzymes to separately produced support materials. The homogeneous orientation of enzymes densely coating PHA particles enhances the accessibility of catalytic sites, improving enzyme function. The PHA particle technology has been developed into a remarkable scaffolding platform for the design of cost-effective designer biocatalysts amenable toward robust industrial bioprocessing. In this review, the PHA particle technology will be compared to other biological supramolecular assembly-based technologies suitable for in vivo enzyme immobilization. Recent progress in the fabrication of biological particulate scaffolds using enzymes of industrial interest will be summarized. Additionally, we outline innovative approaches to overcome limitations of in vivo assembled PHA particles to enable fine-tuned immobilization of multiple enzymes to enhance performance in multi-step cascade reactions, such as those used in continuous flow bioprocessing.

As an indirect semiconductor, silicon shows notoriously inefficient luminescence. Here, the authors utilize the Mie resonances in silicon nanoparticles to demonstrate visible white-light emission, both from free-standing spheres and particles etched on a silicon-on-insulator substrate.

Objective: To study the effects of regenerated tissue extracts after liver injury on the proliferation, differentiation, migration and invasion of SK-HEP1 cells. Methods: Regenerated tissue extracts after liver injury were used to induce SK-HEP1 cells after enrichment, their effects on the proliferation, differentiation, migration and invasion of SK-HEP1 cells were observed through in vitro cell culture, MTT, flow cytometry and transwell assays. Results: In response to the action of regenerated tissue extracts after liver injury, SK-HEP1 cells were blocked in G0/G1 phase, their growth rate was distinctly reduced. The number of SK-HEP1- fj colonies decreased. The migration ability of SK-HEP1 cells showed a decreased trend on day 7 and day 11 after induction. SK-HEPl’s invasion ability clearly decreased on days 7 and 11 after induction, especially on day 7. Conclusions: To a certain extent, regenerated tissue extracts after liver injury can inhibit the proliferation, differentiation, migration and invasion of hepatoma cells, showing an important potential of being a differentiating agent for the treatment of liver cancer.

Bioengineered polyhydroxyalkanoate (PHA) spheres assembled in engineered bacteria are showing promising potential in protein immobilization for high-value applications. Here, we have designed innovative streamlined approaches to add functional proteins from complex mixtures (e.g., without prior purification) to bioengineered PHA spheres directly harnessing the specificity of the SpyTag/SpyCatcher mediated protein ligation. Escherichia coli was engineered to assemble PHA spheres displaying the SpyCatcher domain while simultaneously producing a SpyTagged target protein, which was in vivo specifically ligated to the PHA spheres. To further demonstrate the specificity of this ligation reaction, we incubated isolated SpyCatcher-coated PHA spheres with cell lysates containing SpyTagged target protein, which also resulted in specific ligation mediating surface functionalization. An even cruder approach was used by lysing a mixture of cells, either producing PHA spheres or target protein, which resulted in specific surface functionalization suggesting that ligation between the SpyCatcher-coated PHA spheres and the SpyTagged target proteins is highly specific. To expand the design space of this general modular approach toward programmable multifunctionalization, e.g., one-pot construction of immobilized multienzyme cascade systems on PHA spheres, we designed various recombinant bimodular PHA spheres utilizing alternative Tag/Catcher pairs (e.g., SnoopTag/SnoopCatcher and SdyTag/SdyCatcher systems). One of our bimodular PHA spheres resulted in simultaneous multifunctionalization of plain PHA spheres in one-step with two differently tagged proteins under in vitro and ex vivo reaction conditions while remaining functional. Our bimodular PHA spheres also showed high orthogonality with the non-target peptide tag and exhibited decent robustness against repeated freeze-thaw treatment. We demonstrated the utility of these approaches by using a fluorescent protein, a monomeric amylase, and a dimeric organophosphate hydrolase as target proteins. We established a versatile toolbox for dynamic functionalization of PHA spheres for biomedical and industrial applications.