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To meet the requirements of safety control during the fuel loading and refueling of nuclear reactors, a reactor first loading monitoring system was developed, and the related mechanical structure and electrical structure design and manufacturing of the system were completed including 3He proportional probe and pulse counter device, etc. The probe assembly adopts a new structure. The mechanical structure is a combination of a bridle structure waterproof connector, a waterproof tube and a load-bearing multi-core shielded cable. A fast charge sensitive preamplifier and a high-voltage module were integrated in the probe. The pulse counting device consist of several NIM modular plug-in units is mounted on a NIM rack mounting unit and a cabinet. The system contains four measurement channels and an acousto-optic alarm channel, which can realize functions such as counting rate display and over-threshold acousto-optic alarm. The tests show the system meets the requirements for neutron flux rate monitoring during nuclear reactor fuel loading and has been applied to unit 5 and unit 6 of Hongyanhe Nuclear Power Plant.

There is a close connection between epigenetic regulation, cancer metabolism, and immunology. The combination of epigenetic therapy and immunotherapy provides a promising avenue for cancer management. As an epigenetic regulator of histone acetylation, panobinostat can induce histone acetylation and inhibit tumor cell proliferation, as well as regulate aerobic glycolysis and reprogram intratumoral immune cells. JQ1 is a BRD4 inhibitor that can suppress PD-L1 expression. Herein, we proposed a chemo-free, epigenetic-based combination therapy of panobinostat/JQ1 for metastatic colorectal cancer. A novel targeted binary-drug liposome was developed based on lactoferrin-mediated binding with the LRP-1 receptor. It was found that the tumor-targeted delivery was further enhanced by in situ formation of albumin corona. The lactoferrin modification and endogenous albumin adsorption contribute a dual-targeting effect on the receptors of both LRP-1 and SPARC that were overexpressed in tumor cells and immune cells (e.g., tumor-associated macrophages). The targeted liposomal therapy was effective to suppress the crosstalk between tumor metabolism and immune evasion via glycolysis inhibition and immune normalization. Consequently, lactic acid production was reduced and angiogenesis inhibited; TAM switched to an anti-tumor phenotype, and the anti-tumor function of the effector CD8+ T cells was reinforced. The strategy provides a potential method for remodeling the tumor immune microenvironment (TIME).

Abstract Objective The purpose of this research was to explore the application value of a three-dimensional (3D)-printed heart in surgery for left ventricular outflow tract (LVOT) obstruction. Methods From August 2019 to October 2021, 46 patients with LVOT obstruction underwent surgical treatment at our institution. According to the treatment method, 22 and 24 patients were allocated to the experimental and control groups, respectively. In the experimental group, each patient’s 3D-printed heart model was used for simulated preoperative surgery, and then the Morrow operation was performed. In the control group, only the Morrow operation was performed, without simulated preoperative surgery using a 3D-printed heart model. The intraoperative and postoperative data of patients in the two groups were recorded, and the clinical data of patients were compared between the two groups. Results The operation time, cardiopulmonary bypass time, intraoperative blood loss, hospitalization time, LVOT pressure difference (LVP), postoperative interventricular septal thickness (IST), aortic regurgitation (AR), systolic anterior motion (SAM), and postoperative left ventricular flow velocity (LVFV) were significantly lower in the experimental group than in the control group (P 0.05). Conclusion A 3D-printed heart model for simulated surgery in vitro is conducive to formulating a more reasonable surgical plan and reducing the trauma and duration of surgery, thereby promoting the recovery and maintenance of the heart.

Abstract. Background:. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by complex and various clinical manifestations. The study aimed to analyze clinical features and cerebral magnetic resonance imaging (MRI) changes of hyperintense white matter (WM) lesions in SLE patients. Methods:. This was a retrospective study based on a consecutive cohort of 1191 SLE patients; 273 patients for whom cerebral MRI data were available were enrolled to assess hyperintense WM lesions associated with SLE. Patients were assigned to two groups, i.e., with or without hyperintense WM lesions. The MRI assessment showed that the hyperintense WM lesions could be classified into three categories: type A, periventricular hyperintense WM lesions; type B, subcortical hyperintense WM lesions; and type C, multiple discrete hyperintense WM lesions. The clinical and MRI characteristics were analyzed. Factors related to hyperintense WM lesions were identified by multivariate logistic regression analysis. Results:. Among the 273 SLE patients with available cerebral MRI scans, 35.9% (98/273) had hyperintense WM lesions associated with SLE. The proportions of types A, B, and C were 54.1% (53/98), 11.2% (11/98), and 92.9% (91/98), respectively. Fifty-one percents of the patients showed an overlap of two or three types. Type C was the most common subgroup to be combined with other types. Compared with those without hyperintense WM lesions, the patients with hyperintense WM lesions were associated with neuropsychiatric SLE (NPSLE), lupus nephritis (LN), hypertension, and hyperuricemia (P = 0.002, P = 0.018, P = 0.045, and P = 0.036, respectively). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with hyperintense WM lesions (P = 0.029 and P = 0.027, respectively), and these patients were more likely to present with disease damage (P

Abstract Background Melanin is an important antioxidant in food and has been used in medicine and cosmetology. Chicken meat with high melanin content from black-boned chickens have been considered a high nutritious food with potential medicinal properties. The molecular mechanism of melanogenesis of skeletal muscle in black-boned chickens remain poorly understood. This study investigated the biological gene-metabolite associations regulating the muscle melanogenesis pathways in Wuliangshan black-boned chickens with two normal boned chicken breeds as control. Results We identified 25 differentially expressed genes and 11 transcription factors in the melanogenesis pathways. High levels of the meat flavor compounds inosine monophosphate, hypoxanthine, lysophospholipid, hydroxyoctadecadienoic acid, and nicotinamide mononucleotide were found in Wuliangshan black-boned chickens. Conclusion Integrative analysis of transcriptomics and metabolomics revealed the dual physiological functions of the PDZK1 gene, involved in pigmentation and/or melanogenesis and regulating the phospholipid signaling processes in muscle of black boned chickens.

Abstract Background To identify the critical genes in the onset and progression of Immunoglobulin A nephropathy (IgAN) and to explore its immune cell infiltration feature. Methods Differentially expressed genes (DEGs) were firstly screened from 1 blood-derived dataset GSE73953 and a glomerulus derived dataset GSE93798 through limma analysis, overlap genes omitting and weighted gene correlation network analysis (WGCNA) and further reduced according to expression pattern and correlation with the clinical features: eGFR and proteinuria, followed by external validation using the GSE37460 dataset and an IgAN cohort. In addition, the CIBERSORT tool for immune cell infiltration analysis, ceRNA network construction and Connectivity Map (CMAP) were also performed. Results A total of 195 DEGs were found, and among them, 3 upregulated (ORMDL2, NRP1, and COL4A1) and 3 downregulated genes (ST13, HSPA8 and PKP4) are verified to correlate clinically, and finally ORMDL2, NRP1 and COL4A1 were validated in patient cohort and with the ability of IgAN discrimination (highest AUC was COL4A1: 97.14%). The immune cell infiltration results revealed that significant differences could be found on resting memory CD4 T cells, activated NK cells, and M2 macrophages between control and IgAN. Conclusions Our results demonstrated here that significantly upregulated DEGs: ORMDL2, NRP1 and COL4A1, could be served as the diagnostic marker for IgAN, and dysregulated immune cell infiltration hinted possible the immune system intervention point in the setting of IgAN.

Shape memory polymers, with intrinsic enhanced strength and high thermal stability, are highly demanded in aerospace, engineering manufacturing, and spatial structures. In this paper, we develop a series of thermoplastic shape memory poly(ether ether ketone)s (PEEKs) for the first time, achieving an excellent shape memory ability, high strength, and great thermal stability via a condensation polymerization. Through tuning the proportion of different bisphenol monomers, the flexibility of molecular main chains is adjusted, resulting in the regulation of transition temperature and mechanical performances. Synthesized PEEKs possess the tunable Tg from 143.3°C to 178.6°C, the enhanced tensile strength from 48.4 to 65.1 MPa, and Young’s modulus from 0.45 to 1.8 GPa, in addition to the excellent heat-triggered shape memory effect, as indicated by high recovery ratio (94%–98.9%) and fixity ratio (over 99.5%). Furthermore, after incorporating the magnetocaloric Fe3O4 particles, the composites exhibit remotely noncontact magnetic-triggered shape memory behaviors (Fe3O4 content over 10 wt%). These synthesized Tg tunable shape memory PEEKs and the composites have wide utilization potential in fields of engineering and aerospace structures, owing to the excellent mechanical properties, thermal stability, unique programmable deformation ability, and remote actuation.

Abstract. Background:. Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia. Methods:. This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high- risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years. Results:. A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group. Conclusions:. In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) continue to wreak havoc across the globe. Higher transmissibility and immunologic resistance of VOCs bring unprecedented challenges to epidemic extinguishment. Here we describe a monoclonal antibody, 2G1, that neutralizes all current VOCs and has surprising tolerance to mutations adjacent to or within its interaction epitope. Cryo-electron microscopy structure showed that 2G1 bound to the tip of receptor binding domain (RBD) of spike protein with small contact interface but strong hydrophobic effect, which resulted in nanomolar to sub-nanomolar affinities to spike proteins. The epitope of 2G1 on RBD partially overlaps with angiotensin converting enzyme 2 (ACE2) interface, which enables 2G1 to block interaction between RBD and ACE2. The narrow binding epitope but high affinity bestow outstanding therapeutic efficacy upon 2G1 that neutralized VOCs with sub-nanomolar half maximal inhibitory concentration in vitro. In SARS-CoV-2, Beta or Delta variant-challenged transgenic mice and rhesus macaque models, 2G1 protected animals from clinical illness and eliminated viral burden, without serious impact to animal safety. Mutagenesis experiments suggest that 2G1 is potentially capable of dealing with emerging SARS-CoV-2 variants in the future. This report characterized the therapeutic antibodies specific to the tip of spike against SARS-CoV-2 variants and highlights the potential clinical applications as well as for developing vaccine and cocktail therapy.

Accumulation of acylcarnitines is a characteristic feature of various metabolic disorders affecting fatty acid metabolism. Despite extensive research, no specific molecules have been identified to induce ferroptosis through the regulation of acylcarnitine metabolism. In this study, acylcarnitine accumulation was identified based on cell metabolomics study after the treatment with Stemona alkaloid derivative (SA-11), which was proved to induce ferroptosis in our previous research. Furthermore, the CPT-1 level was proved to significantly increase, while the CPT-2 level indicated no significant difference, which resulted in the accumulation of acylcarnitine. Besides, the ferroptosis-inducing ability of SA-11 was significantly enhanced by the addition of exogenous acylcarnitine, presumably due to the production of additional ROS. This hypothesis was corroborated by the observation of increased ROS levels in HCT-116 cells treated with SA-11 compared to the control group. These findings suggest that targeting acylcarnitine metabolism, particularly through CPT-1, may offer a novel therapeutic strategy for cancer treatment by enhancing ferroptosis induction. [ABSTRACT FROM AUTHOR]

Background: The best antiviral treatment for chronic hepatitis B (CHB) poses a complex challenge. The treatment effect of the combination of nucleoside analogues (NAs) and pegylated interferon alpha (PegIFN) was still in debate. Methods: We studied patients treated with NAs and PegIFN-2b at our institution from November 2019 to January 2022. Logistic regression identified independent factors influencing clinical cure. The predictive accuracy of the formula was assessed using the Receiver operating characteristic (ROC) curve at different time points (before therapy, 12 weeks, and 24 weeks into treatment). Results: A total of 120 patients were enrolled in the final analysis. Among the cohort of patients under study, 71 (59.1%) patients had clinical cure while 49 (40.9%) patients did not. Hepatitis B surface antigen (HBsAg) at baseline and age were the powerful variables predicting the clearance of HBsAg. The area under the ROC (AUC) was 0.907 for pre-treatment predictive model, 0.958 for 12-week predictive model and 0.747 for 24-week predictive model. Conclusion: This study provided predictive formulas for clinical cure, offering valuable insights for CHB treatment. PegIFN and NAs exhibited efficacy. Future research that explores additional factors, such as HBV genotype, in a larger cohort study is needed. [ABSTRACT FROM AUTHOR]

We research extremal S-asymptotically ω-periodic mild solutions to elastic systems by using upper and lower solutions. In our first result, it is assumed that the semigroup is compact. In addition, in our second result, the semigroup does not need to be compact and not assuming lower and upper solutions. Our conclusion is drawn using measures of noncompactness. Finally, the existence of mild solutions for damped equations is discussed as an application. [ABSTRACT FROM AUTHOR]

The advantages of rapid amplification of nucleic acid without a template based on terminal deoxyribonucleotidyl transferase (TdT) have been widely used in the field of biosensors. However, the catalytic efficiency of TdT is affected by extension conditions. The sensitivity of TdT- mediated biosensors can be improved only under appropriate conditions. Therefore, in this review, we provide a comprehensive overview of TdT extension characteristics and its applications in biosensors. We focus on the relationship between TdT extension conditions and extension efficiency. Furthermore, the construction strategy of TdT-mediated biosensors according to five different recognition types and their applications in targets are discussed and, finally, several current challenges and prospects in the field are taken into consideration. Brief introduction to terminal deoxyribonucleotidyl transferase (TdT) characteristics. Provided a systematic and comprehensive summary of TdT extension conditions. Summarized the four effect factors of catalytic efficiency based on extension conditions and enzyme conformation. Sensing strategies of TdT-mediated biosensors for five different recognitions were summarized in detail. The applications of TdT-mediated biosensors in six targets were introduced in detail. [ABSTRACT FROM AUTHOR]

To study the influence of various factors on coal permeability in the process of coal seam water injection and the relationship between water injection parameters, an experimental system of highly pressurized water invasion and gas seepage is developed. The system consists of four parts: an overburden pressure loading unit, a micro water injection control unit, a gas injection, and vacuum pumping unit, data acquisition and real-time monitoring unit. It can not only be used for coal seam water injection radial seepage experiments. It can also be used as a set of experimental systems to simulate the geothermal exploitation of deep coal seams and explore the heat transfer law of geothermal exploitation. To verify its applicability, a coal seam water injection seepage experiment is carried out based on the experimental system. The results show that the coal permeability increases by 7–31% before and after water injection; at the same time, under different stress conditions, the internal and external pressure difference of the coal sample before and after water injection has a decrease of 0.01–0.05 MPa. The conclusion is consistent with previous studies, which shows that the experimental system is accurate and reliable. [ABSTRACT FROM AUTHOR]

The contraction behavior of monotonically expanded cavities is intriguing as it offers insights into certain geotechnical scenarios, especially for pressuremeter tests, where the unloading data is equally informative as the loading data. Despite many solutions for cavity expansion, attempts for the analyses of cavity contraction from an expanded state were rarely made. To extend previous solutions to include contraction, this paper presents a novel semianalytical solution for drained contraction of spherical and cylindrical cavities from an initially expanded state in soils characterized by a unified state parameter model for clay and sand (CASM). Given the nonself-similar nature of the contraction after expansion problems, the hybrid Eulerian-Lagrangian (HEL) approach is employed to derive distributions and evolutions of stresses and strains around the cavities during the unloading process. Combined with the previous expansion solution, the complete loading-unloading cavity pressure curves and stress paths at the cavity wall are presented and verified against numerical simulations. Following validation through comparisons with calibration chamber pressuremeter tests conducted in Stockton Beach sand, a new method for the interpretation of pressuremeter testing data is developed based on the proposed solution. This method demonstrates its capability in the back-calculation of the effective horizontal stresses and state parameters for four distinct types of sands. [ABSTRACT FROM AUTHOR]

Transcription factor ELONGATED HYPOCOTYL5 (HY5) is the central hub for seedling photomorphogenesis. E3 ubiquitin (Ub) ligase CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1) inhibits HY5 protein accumulation through ubiquitination. However, the process of HY5 deubiquitination, which antagonizes E3 ligase-mediated ubiquitination to maintain HY5 homeostasis has never been studied. Here, we identified that Arabidopsis thaliana deubiquitinating enzyme, Ub-SPECIFIC PROTEASE 14 (UBP14) physically interacts with HY5 and enhances its protein stability by deubiquitination. The da3-1 mutant lacking UBP14 function exhibited a long hypocotyl phenotype, and UBP14 deficiency led to the failure of rapid accumulation of HY5 during dark to light. In addition, UBP14 preferred to stabilize nonphosphorylated form of HY5 which is more readily bound to downstream target genes. HY5 promoted the expression and protein accumulation of UBP14 for positive feedback to facilitate photomorphogenesis. Our findings thus established a mechanism by which UBP14 stabilizes HY5 protein by deubiquitination to promote photomorphogenesis in A. thaliana. [ABSTRACT FROM AUTHOR]

The abnormal deformation of urban surfaces threatens the human living environment, and extreme regional weather can affect the response law of surface deformation. To explore the changes in surface time series response after extreme weather and the causes of deformation in Zhengzhou, the MTInSAR was used to obtain the surface deformation from 2020 to 2022, and the time series changes of groundwater equivalent water height were retrieved by GRACE. The results show that: (a) There are three large subsidence bowls in Zhengzhou, and the maximum subsidence rate is −40.2 mm/yr. (b) The extreme rainstorm in Zhengzhou alleviated the surface deformation quickly, lasting approximately 6 months. However, surface subsidence still occurred after the extreme rainstorm. The water storage coefficient of the elastic skeleton in the Zhengzhou area showed an increasing trend. (c) Precipitation can lead to surface uplift by influencing the change of groundwater level. There is a delay time of 0.75–1 month between groundwater level change and surface uplift response in the characteristic region. These results provide scientific data support and causal analysis for disaster prevention and reduction of abnormal deformation in Zhengzhou. Key Points: Impact of extreme rainstorm on surface in Zhengzhou from 2020 to 2022There are three subsidence bowls in Zhengzhou area, and the uneven deformation is obviousExtreme rainstorm weather can alleviate the occurrence of surface subsidence in short term [ABSTRACT FROM AUTHOR]

The threshold pressure gradient becomes notably evident during water injection in soft, low-permeability coal seams. This phenomenon reduces the pressure hydrodynamic force and limits the effectiveness of dust reduction measures in coal mines through water injection. In this study, several mathematical models were developed to clarify the mechanism behind the threshold pressure gradient and identify the key parameters affecting permeability changes during this process. This model combines the stress sensitivity properties of the fluid boundary layer and coal body with fractal theory. The validity of the mathematical model was confirmed by comparing it with both visual experimental results from nuclear magnetic resonance water injection and other theoretical models. Particularly, the Bingham model effectively predicts the effective permeability of coal. Through the analysis of the influencing factors, it is found that the effective permeability increases with the pressure difference, pore compression coefficient, porosity, and maximum pore radius. Conversely, it decreases as the yield stress, fluid viscosity, tortuosity fractal dimension, and pore size distribution fractal dimension increase. Upon considering the impact of various factors, the pore compression coefficient was identified as having the most significant effect on coal permeability, whereas the yield stress has the greatest influence on the threshold pressure gradient. Collectively, our findings provide a theoretical foundation for enhancing the efficacy of water injection in soft, low-permeability coal seams. [ABSTRACT FROM AUTHOR]

(1) Background: Epidemiological studies on the relationship between serum copper and hypertension are contradictory. We assessed the relationship between serum copper and blood pressure among adults in the United States. (2) Methods: We divided hypertension into two categories: treated hypertension and untreated hypertension. Linear or logistic regression analysis was applied to investigate the association between serum copper concentrations and blood pressure levels. (3) Results: As compared to quartile 1, the odds ratios (ORs) for untreated hypertension in quartiles 2, 3, and 4 were 1.02 (0.74–1.42), 1.23 (0.88–1.72), and 1.08 (0.74–1.58), respectively, in multivariable analysis (all p > 0.05). In non-hypertension, as compared with quartile 1, the β (95% CI) of systolic blood pressure for quartiles 2, 3, and 4 was −0.92 (−2.07–0.23), −0.05 (−1.30–1.20), and −0.48 (−1.83–0.88), respectively, in multivariable analysis (all p > 0.05). As compared to quartile 1, the ORs for treated hypertension in quartiles 2, 3, and 4 were 1.36 (0.88–2.10), 1.35 (0.87–2.09), and 1.56 (0.98–2.47), respectively, upon multivariable analysis including antihypertensive medication use as a covariate (all p > 0.05). Furthermore, 1SD increase in serum copper was non-significantly associated with 1.16 (0.97–1.37)-fold increased risk of hypertension in multivariable analysis (p = 0.096). (4) Conclusion: In the present study, we discovered that the serum copper concentration was not related with hypertension or blood pressure levels. Antihypertensive drug use may distort the correlation between copper and blood pressure levels. Information on antihypertensive drug use may be taken into account when identifying new risk factors for hypertension.

In order to address the problems associated with low detection accuracy, weak detection ability of small targets, insufficiently obvious differentiation of colors, and inability to accurately locate the actual position of the target object in the Formula Student Autonomous China, the YOLOv5s algorithm is improved by adding coordinate attention, modifying the color space transformation module, and adding a normalized Gaussian Wasserstein distance module and a monocular camera distance measurement module. Finally, it is experimentally verified that by adding and modifying the above modules, the YOLOv5s algorithm’s precision is improved by 6.9%, recall by 4.4%, and mean average precision by 4.9%; although the detection frame rate decreases, it still meets the requirement. Monocular camera distance measurement has a maximum error of 5.64% within 20 m in the Z-direction and 5.33% in the X-direction.