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BackgroundOne of the primary reasons for tumor invasion and metastasis is anoikis resistance. Biochemical recurrence (BCR) of prostate cancer (PCa) serves as a harbinger of its distant metastasis. However, the role of anoikis in PCa biochemical recurrence has not been fully elucidated.MethodsDifferential expression analysis was used to identify anoikis-related genes based on the TCGA and GeneCards databases. Prognostic models were constructed utilizing LASSO regression, univariate and multivariate Cox regression analyses. Moreover, Gene Expression Omnibus datasets (GSE70770 and GSE46602) were applied as validation cohorts. Gene Ontology, KEGG and GSVA were utilized to explore biological pathways and molecular mechanisms. Further, immune profiles were assessed using CIBERSORT, ssGSEA, and TIDE, while anti-cancer drugs sensitivity was analyzed by GDSC database. In addition, gene expressions in the model were examined using online databases (Human Protein Atlas and Tumor Immune Single-Cell Hub).Results113 differentially expressed anoikis-related genes were found. Four genes (EEF1A2, RET, FOSL1, PCA3) were selected for constructing a prognostic model. Using the findings from the Cox regression analysis, we grouped patients into groups of high and low risk. The high-risk group exhibited a poorer prognosis, with a maximum AUC of 0.897. Moreover, larger percentage of immune infiltration of memory B cells, CD8 Tcells, neutrophils, and M1 macrophages were observed in the high-risk group than those in the low-risk group, whereas the percentage of activated mast cells and dendritic cells in the high-risk group were lower. An increased TIDE score was founded in the high-risk group, suggesting reduced effectiveness of ICI therapy. Additionally, the IC50 results for chemotherapy drugs indicated that the low-risk group was more sensitive to most of the drugs. Finally, the genes EEF1A2, RET, and FOSL1 were expressed in PCa cases based on HPA website. The TISCH database suggested that these four ARGs might contribute to the tumor microenvironment of PCa.ConclusionWe created a risk model utilizing four ARGs that effectively predicts the risk of BCR in PCa patients. This study lays the groundwork for risk stratification and predicting survival outcomes in PCa patients with BCR.

Introduction: Metastatic castration-resistant prostate cancer (mCRPC) patients face challenges due to limited treatment options. About 50% of patients with mCRPC have a functional loss of phosphatase and tensin homology deleted on chromosome 10 (PTEN), leading to tumor progression, metastasis, and immune suppression. Moreover, elevated IL-23 produced by myeloid-derived suppressor cells (MDSCs) is found in CRPC patients, driving tumor progression. Therefore, a combination strategy based on PTEN restoration and IL-23 inhibition may block CRPC progression and metastasis.Methods: The antitumor effect of restoring PTEN expression combined with the IL-23 inhibitor Apilimod was studied in a mouse model of bone metastasis CRPC and mouse prostate cancer RM-1 cells. To verify the targeting ability of PTEN DNA coated with lipid nanoparticles (LNP@PTEN) in vitro and in vivo. In addition, RT-qPCR and flow cytometry were used to investigate the related mechanisms of the antitumor effect of LNP@PTEN combined with Apilimod.Results: LNPs exhibited significant tumor-targeting and tumor accumulation capabilities both in vitro and in vivo, enhancing PTEN expression and therapeutic efficacy. Additionally, the combination of LNP@PTEN with the IL-23 inhibitor Apilimod demonstrated enhanced inhibition of tumor growth, invasion, and metastasis (particularly secondary organ metastasis) compared to other groups, and extended the survival of mice to 41 days, providing a degree of bone protection. These effects may be attributed to the PTEN function restoration combined with IL-23 inhibition, which help reverse immune suppression in the tumor microenvironment by reducing MDSCs recruitment and increasing the CD8+/CD4+ T cell ratio.Discussion: In summary, these findings highlight the potential of LNPs for delivering gene therapeutic agents. And the combination of LNP@PTEN with Apilimod could achieve anti-tumor effects and improve tumor microenvironment. This combinational strategy opens new avenues for the treatment of mCRPC.

Background Retinal ischemic perivascular lesions (RIPLs) are an indicator of ischemia in the middle retina. We aimed to determine the relationship between RIPLs and single subcortical infarction (SSI). We also investigated the differences in cerebral small vessel disease imaging burden between groups with and without RIPLs in SSI. Methods and Results In this case–control study, we enrolled 82 patients with SSI and 72 nonstroke controls. All participants underwent magnetic resonance imaging and swept‐source optical coherence tomography/optical coherence tomography angiography. Small vessel disease markers such as lacunes, cerebral microbleeds, white matter hyperintensity, and perivascular spaces were rated on brain imaging. RIPLs were assessed via swept‐source optical coherence tomography. Optical coherence tomography angiography was used to measure the superficial vascular complex and deep vascular complex of the retina. After adjusting for risk factors, the presence of RIPLs was significantly associated with SSI (odds ratio [OR], 1.506 [95% CI, 1.365–1.662], P

In order to realize the real-time processing and analysis of astronomical ultra-wide bandwidth signals, this study proposes a sub-band division algorithm based on RFSoC. The algorithm uses Kaiser window to design FIR prototype low-pass filter, adopts critical sampling polyphase filter bank to decompose ultra-wide bandwidth signal into several sub-bands, and encapsulates each sub-band into VDIF data frame and sends it to GPU server. The algorithm is implemented on RFSoC platform, and its effectiveness is verified by simulation and actual observation. The experimental results show that the algorithm can divide the astronomical ultra-wide bandwidth signal into multiple sub-bands in real time, packetize and transmit them to GPU. This research provides reproducible design and project for ultra-wide bandwidth signal sub-band division with low spectrum leakage and aliasing, high data accuracy, and fast processing speed.

Pointing tracking control of marching turret-barrel system is one of the important topics in exploration of intelligent ground combat platform. This paper focuses on an adaptive robust control scheme for pointing tracking of marching turret-barrel system driven by a motor and an electric cylinder. Three types of possibly fast time-varying but bounded uncertainty are considered: system modeling error, external disturbance and road excitation. The uncertainty bounds are not necessary to be known. First, the pointing tracking system is constructed as a coupled, nonlinear and uncertain dynamical system with two interconnected (horizontal and vertical) subsystems. Second, a tracking error e is defined as a gauge of control objective, and then the dynamical equation of the pointing tracking system is built in state-space form. Third, for uncertainty control, a comprehensive uncertainty bound α is derived to measure the most conservative influence of the uncertainty, and then an adaptive law is proposed to evaluate it in real time. Finally, for pointing tracking control, an adaptive robust control is proposed to render the pointing tracking system to be practically stable; thereout, the objective of pointing tracking is achieved. This work should be among the first ever endeavours to cast all the coupling, nonlinearity and bound-unknown uncertainty into the pointing tracking framework of marching turret-barrel system.

This paper proposes an optimal parameter design of control scheme for mechanical systems by adopting the Stackelberg game theory. The goal of the control is to drive the mechanical system to follow the prescribed constraints. The system uncertainty is (possibly fast) time-varying and bounded. A β-measure is defined to gauge the performance. A robust control is proposed to render the β-measure uniformly ultimately bounded. This control scheme is based on feasible design parameters (i.e., parameters within prescribed range), and the choices of these parameters may not be unique. For optimal (unique) parameter selection, a Stackelberg game is formulated. By taking the control design parameters as the players, for each player, a cost function is built with the consideration of the performance cost, the time cost and the control cost. To follow, the Stackelberg strategy is then carried out via backward induction, which results in the choice of the optimal parameters.

2-花生四烯酸单甘酯（2-AG）是一种内源性大麻素，在神经、心血管和免疫等系统中具有一系列的生理活性。为实现2-AG的绿色高效制备，探究了脂肪酶催化醇解富含花生四烯酸的微生物油制备2-AG的方法。以2-单甘酯（2-MAG）含量为指标，通过单因素实验对酶法催化醇解反应条件进行了优化，并采用溶剂萃取法对产物进行纯化。结果表明：最佳反应条件为以Lipozyme 435脂肪酶为醇解脂肪酶、酶添加量4%（以油质量计）、油与无水乙醇物质的量比1∶ 40、叔丁醇为溶剂、油溶比2∶ 3、反应温度35 ℃、反应时间8 h，在最佳条件下粗产物中2-MAG含量为3363%；经溶剂萃取纯化后2-MAG的纯度达到了94.79%，其中2-AG含量为40.70%。 综上，酶法醇解富含花生四烯酸的微生物油可以获得高2-AG含量的2-MAG。2-Arachidonoylglycerol (2-AG) is an endogenous cannabinoid and exhibits a variety of biological activities in the central nervous, cardiovascular, and immune systems. To prepare 2-AG in a greener and efficient way, a lipase-catalyzed alcoholysis of microbial oil rich in arachidonic acid was used to synthesize 2-AG. With the 2-monoacylglycerol (2-MAG) content as an index, the reaction conditions of lipase-catalyzed alcoholysis were optimized by single factor experiment, and a solvent extraction method was employed to purify the product. The results showed that the optimal reaction conditions of lipase-catalyzed alcoholysis were as follows: Lipozyme 435 as alcoholysis enzyme, lipase dosage 4% (relative to oil mass), molar ratio of oil to anhydrous ethanol 1∶ 40, tert-butanol as solvent, ratio of oil to solvent 2∶ 3, reaction temperature 35 ℃ and reaction time 8 h. Under the optimal conditions, 2-MAG content in the crude product was up to 33.63%. The purity of 2-MAG after purification was up to 9479%, and the content of 2-AG was 40.70%. In conclusion, enzymatic alcoholysis of microbial oil rich in arachidonic acid can obtain 2-MAG with high 2-AG content.

In order to reveal the differences in the biosynthesis and metabolism of the major bioactive composition in sea buckthorn berry pulp during ripening, non-targeted metabolomics based on ultra-high performance liquid chromatography coupled to mass spectrometry (UPLC-MS) was used to analyze the metabolites of sea buckthorn berry pulp from two strains at different developmental stages (green and orange pulp). The results showed that the four sample groups had significant metabolic differences. A total of 124 significantly differential metabolites were detected among the four groups based on variable importance in the projection (VIP) > 1 and t-test P < 0.05, including organic acids, carbohydrates, lipids, flavonoids and secondary metabolites. According to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, 15, 7 and 4 significantly differential metabolites associated with lipid, flavonoid and serotonin metabolism were identified, respectively, and eight significantly differential metabolites involved in anticancer function were selected. The significant up-regulation of phosphatidylcholine (PC) (16:0/16:0) and glycerophosphocholine could be the reason for the high accumulation of lipids in sea buckthorn berry pulp. The significant upregulation of isorhamnetin was key for the high flavonoid content in sea buckthorn berry pulp. Relatively high contents of N-acetylserotonin, capecitabine, γ-aminobutyric acid (GABA) and other bioactive composition involved in anticancer function were shown in sea buckthorn berry pulp during its development. These results provide a scientific basis for revealing the metabolic mechanism of bioactive composition of sea buckthorn berries and developing related functional products.

The canonical transient receptor potential channel (TRPC) proteins form Ca2+-permeable cation channels that are involved in various heart diseases. However, the roles of specific TRPC proteins in myocardial ischemia/reperfusion (I/R) injury remain poorly understood. We observed that TRPC1 and TRPC6 were highly expressed in the area at risk (AAR) in a coronary artery ligation induced I/R model. Trpc1−/− mice exhibited improved cardiac function, lower serum Troponin T and serum creatine kinase level, smaller infarct volume, less fibrotic scars, and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6−/− mice. Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury. Furthermore, Trpc1 deficiency protected adult mouse ventricular myocytes (AMVMs) and HL-1 cells from death during hypoxia/reoxygenation (H/R) injury. RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species (ROS) generation in Trpc1−/− cardiomyocytes. Among these genes, oxoglutarate dehydrogenase-like (Ogdhl) was markedly downregulated. Moreover, Trpc1 deficiency impaired the calcineurin (CaN)/nuclear factor-kappa B (NF-κB) signaling pathway in AMVMs. Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions. Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter. The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes. In conclusion, our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R, leading to increased Ca2+ influx into associated cardiomyocytes. Subsequently, this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway, ultimately exacerbating ROS production and aggravating myocardial I/R injury.

为寻找与中国人乳脂脂质组成高相似的天然人乳替代脂，分析比较了3种鱼油(金鲳鱼油、银鲳鱼油和巴沙鱼油)的总脂肪酸、sn-2位脂肪酸、甘油三酯组成和含量。结果表明：金鲳鱼油中棕榈酸、油酸和亚油酸含量分别为24.93%、25.61%和26.52%，其中sn-2位棕榈酸的含量为39.71%，占总棕榈酸比例为53.10%；在3种鱼油中，金鲳鱼油总脂肪酸组成最接近中国人乳脂；甘油三酯组成分析结果证实，金鲳鱼油中富含1-油酸-2-棕榈酸-3-亚油酸甘油三酯（OPL,24.36%），其含量显著高于其他两种鱼油，且其1,3-二油酸-2-棕榈酸甘油三酯（OPO）的含量（16.79%）接近报道的中国人乳脂的平均含量（15.84%）。因此，金鲳鱼油是理想的中国婴儿配方奶粉专用油脂基料油，在人乳替代脂中具有良好的发展前景。To find natural human milk fat substitute with high similarity to the lipid composition of Chinese human milk fat, the composition and content of total fatty acid, sn-2 fatty acid, and triglyceride of three types of fish oil (gold pomfret oil, silver pomfret oil, and barramundi oil) were analyzed and compared. The results showed that in gold pomfret oil, the contents of palmitic acid, oleic acid and linoleic acid were 24.93%, 25.61% and 26.52%, respectively. The content of sn-2 palmitic acid was 39.71%, accounting for 53.10% of the total palmitic acid. Among the three fish oils, gold pomfret oil exhibited the closest total fatty acid composition to Chinese human milk fat. The results of triglyceride composition analysis confirmed that golden pomfret fish oil was rich in 1-oleoyl-2-palmitoyl-3-linoleoylglycerol (OPL,24.36%), which was significantly higher than the other two fish oils, and its 1,3-dioleoy1-2-palmitoylglyecrol (OPO) content (16.79%) was close to the average content of reported Chinese human milk fat (15.84%). Therefore, golden pomfret fish oil is an ideal lipid base oil for Chinese infant formula, which has a good development prospect in human milk fat substitute.

For the low efficiency and large loss of cascade pumping stations, aiming to maximize system efficiency, an optimized scheduling model of cascade pumping stations is established with consideration of multiple constraints, and the optimal scheduling method based on the improved sparrow search algorithm (BSSA) is proposed. The BSSA is initialized by the Bernoulli chaotic map to solve the insufficient initial diversity of the sparrow search algorithm (SSA). The random boundary strategy is introduced to avoid local optimum when dealing with the scheduling problem of pumping stations. The performance and improvement strategy of BSSA are verified by eight benchmark functions. Results show that BSSA has better convergence accuracy and faster speed. BSSA is applied to a three-stage pumping station considering three flow conditions, and compared with the current scheme, particle swarm optimization and genetic algorithm optimization schemes, the operation efficiency of SSA can be increased by 0.72–0.96%, and operation cost can be reduced by ¥263,000/a–¥363,300/a. On this basis, the improvement of 0.04–0.30% and ¥14,800/a–¥109,900/a can be further achieved by the BSSA, which confirms the feasibility and effectiveness of BSSA to solve the pumping station optimal scheduling problem. The findings present useful reference for the optimized scheduling of pumping station system. HIGHLIGHTS An optimal scheduling model of cascade pumping stations is established.; The sparrow search algorithm is improved as BSSA by using the Bernoulli chaotic map and random boundary treatment.; An optimization method for cascade pumping stations based on BSSA is provided.; The feasibility and effectiveness of the proposed method are confirmed.;

Objective: To analyze the clinical features and genetic changes of 3 children in short stature with ACAN gene mutation. Methods: The clinical data, laboratory examinations, and genetic testing results of 3 children with ACAN gene mutations diagnosed with short stature at our pediatric endocrine disease clinic from 2018 to 2020 were collected, and the literature was reviewed for analysis and summary. Results: All the three children had a short family history, and their clinical manifestations were short stature. One patient had a slight limitation of the flexion activity of the thoracolumbar spine, and no other system abnormalities were found. Among them, the oldest of the 3 children was 5 years and 1 month, and the bone age was roughly consistent with or slightly advanced than the actual age, and the peak growth hormone challenge in 2 cases was less than 10 μg/L. The variations in the ACAN gene are c.G1877A and c.7360, respectively_ 7361del and c.7038_ 7039insCGGTGT, case 1 and case 2 are novel mutations that have not been reported in major databases. After the application of recombinant human growth hormone, the height of all three children improved. Reviewing the literature at home and abroad, we found that there were 120 children and 216 relatives reported at present. Among them, there were 80 ACAN gene variants related to short stature registered in HGMD, of which short stature was the most important clinical manifestation, followed by skeletal dysplasia. Conclusions: Mutations of ACAN gene mainly lead to short stature and skeletal dysplasia in children, and their clinical bone phenotypes are diverse, which can also only be manifested as short stature. For children with short stature, especially those with short stature family history, no matter whether they have skeletal abnormalities, they should be alert to this gene mutation.

Abstract Credit risk assessment involves conducting a fair review and evaluation of an assessed subject’s solvency and creditworthiness. In the context of real estate enterprises, credit risk assessment provides a basis for banks and other financial institutions to choose suitable investment objects. Additionally, it encourages real estate enterprises to abide by market norms and provide reliable information for the standardized management of the real estate industry. However, Chinese real estate companies are hesitant to disclose their actual operating data due to privacy concerns, making subjective evaluation approaches inevitable, occupying important roles in accomplishing Chinese real estate enterprise credit risk assessment tasks. To improve the normative and reliability of credit risk assessment for Chinese real estate enterprises, this study proposes an integrated multi-criteria group decision-making approach. First, a credit risk assessment index for Chinese real estate enterprises is established. Then, the proposed framework combines proportional hesitant fuzzy linguistic term sets and preference ranking organization method for enrichment evaluation II methods. This approach is suitable for processing large amounts of data with high uncertainty, which is often the case in credit risk assessment tasks of Chinese real estate enterprises involving massive subjective evaluation information. Finally, the proposed model is validated through a case study accompanied by sensitivity and comparative analyses to verify its rationality and feasibility. This study contributes to the research on credit assessment for Chinese real estate enterprises and provides a revised paradigm for real estate enterprise credit risk assessment.