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In gravitational collapses, the horizon and singularity’s realisation in the finite future of the proper time used co-moving observer happens in the future of infinitely far away future of the normal time used outside probe. To the latter the horizon and singularity defined in the singularity theorem are physical realities only in the sense of uncertainty principle and ensemble interpretation. We provide two exact time dependent solution families to the Einstein equation and show that they form a pair of complementary description for the microscopic state of black holes by showing that the Bekenstein–Hawking entropy formula follows properly from their canonical wave function’s degeneracy. We also develop an eXact One Body method for general relativity two-body dynamics whose conservative part calls no post newtonian approximation as input and applies to the full three stages of black hole binary merger events. By this method, we analytically calculate the gravitational wave forms following from such merger processes. In the case black holes carry exact and apriori horizon and singularity our wave forms agree with those following from conventional effective one body method but exhibit more consistent late time behaviour. In the case black holes carry only asymptotic horizon and extended inner structure thus experiencing banana shape deformation as the merger occurs, our wave forms exhibit all features especially the late time quasi-normal mode type oscillation seen in real observations.

Recently, researchers have been studying methods to introduce deep learning into automated optical inspection (AOI) systems to reduce labor costs. However, the integration of deep learning in the industry may encounter major challenges such as sample imbalance (defective products that only account for a small proportion). Therefore, in this study, an anomaly detection neural network, dual auto-encoder generative adversarial network (DAGAN), was developed to solve the problem of sample imbalance. With skip-connection and dual auto-encoder architecture, the proposed method exhibited excellent image reconstruction ability and training stability. Three datasets, namely public industrial detection training set, MVTec AD, with mobile phone screen glass and wood defect detection datasets, were used to verify the inspection ability of DAGAN. In addition, training with a limited amount of data was proposed to verify its detection ability. The results demonstrated that the areas under the curve (AUCs) of DAGAN were better than previous generative adversarial network-based anomaly detection models in 13 out of 17 categories in these datasets, especially in categories with high variability or noise. The maximum AUC improvement was 0.250 (toothbrush). Moreover, the proposed method exhibited better detection ability than the U-Net auto-encoder, which indicates the function of discriminator in this application. Furthermore, the proposed method had a high level of AUCs when using only a small amount of training data. DAGAN can significantly reduce the time and cost of collecting and labeling data when it is applied to industrial detection.

In this paper, we examine two types of interacting holographic dark energy model using Pantheon supernova data, BAO BOSS DR12, CMB Planck 2015, fgas (gas mass fraction) and SZ/Xray (Sunyaev–Zeldovich effect and X-ray emission) data from galaxy clusters (GC). In particular, we considered the Holographic Ricci dark energy and Extended holographic Ricci dark energy models. During this analysis, we considered seven types of phenomenological interaction terms (three linear and four non-linear) Q 1 = 3 H b ρ D + ρ m , Q 2 = 3 H b ρ D , Q 3 = 3 H b ρ m , Q 4 = 3 H b ρ D + ρ D 2 ρ D + ρ m , Q 5 = 3 H b ρ m + ρ m 2 ρ D + ρ m , Q 6 = 3 H b ρ D + ρ m + ρ D 2 ρ D + ρ m , Q 7 = 3 H b ( ρ D + ρ m + ρ m 2 ρ D + ρ m ) respectively. To find the best model we apply Bayesian Inference (BI) and use the Λ CDM as the referring model for comparison. Using the Bayesian Evidence model selection method we note that the Q 3 and Q 5 interaction terms are favored by observational data among the other ones. The obtained results also demonstrated that the evidence from the Bayesian inference method against the considered types of holographic Ricci dark energy model is strong since the Λ CDM is considered as the reference model and also the Λ CDM is preferred over the models. We also observed that the values of the deceleration parameter and the transition redshift for all models are compatible with the latest observational data and Planck 2015. In addition, we studied the jerk parameter for all models. Using our modified CAMB code, we observed that the interacting models suppress the CMB spectrum at low multipoles and enhances the acoustic peaks.

The root of Royle ex Wight, known as Baishouwu, has been widely used for a tonic supplement since ancient times. The current study was performed to explore the effect of Baishouwu extract on the development of experimental hepatocellular carcinoma (HCC) and the potential mechanism involved. Rats were injected diethylnitrosamine (DEN) to initiate the multistep hepatocarcinogenesis. Animals were treated concurrently with Baishouwu extract given daily by oral gavage for 20 weeks to evaluate its protective effects. Time series sera and organ samples from each group were collected to evaluate the effect of Baishouwu extract on hepatic carcinogenesis. It was found that Baishouwu extract pretreatment successfully attenuated liver injury induced by DEN, as shown by decreased levels of serum biochemical indicators (AST, ALT, ALP, TP, and T-BIL). Administration of Baishouwu extract inhibited the fibrosis-related index in serum and live tissue, respectively from inflammation stage to HCC stage after DEN treatment. It significantly reduced the incidence and multiplicity of DEN-induced HCC development in a dose-dependent manner. Macroscopic and microscopic features suggested that pretreatment with Baishouwu extract for 20 weeks was effective in inhibiting DEN-induced inflammation, liver fibrosis, and HCC. Furthermore, TLR4 overexpression induced by DEN was decreased by Baishouwu extract, leading to the markedly down-regulated levels of MyD88, TRAF6, NF-κB p65, TGF-β1 and α-SMA in hepatitis, cirrhosis, and hepatocarcinoma. In conclusion, Baishouwu extract exhibited potent effect on the development of HCC by altering TLR4/MyD88/ NF-κB signaling pathway in the sequence of hepatic inflammation-fibrosis-cancer, which provided novel insights into the mechanism of Baishouwu extract as a candidate for the pretreatment of HCC in the future.

Background Sensory organ diseases (SOD) pose a considerable challenge to global health. This study analyzed the burden of SOD from 1990 to 2021 using data from the Global Burden of Disease (GBD) 2021. Methods We analyzed prevalence, disability-adjusted life years (DALYs), and age-standardized rates using Joinpoint regression and age-period-cohort (APC) models to separate the effects of age, period, and birth cohort. Health inequalities were evaluated through the slope index of inequality (SII) and concentration index (CI). Additionally, we identified risk factors influencing DALYs and projected future disease burden trends for 2022 to 2051 using Bayesian age-period-cohort (BAPC) models. Results In 2021, the global prevalent cases of SOD reached 2,386,160,888 (95% uncertainty interval [UI]: 2,207,871,226 to 2,591,000,614), with 77,327,293 DALYs cases (95% UI: 53,419,192 to 107,972,583). Age-related hearing loss was the most common condition, accounting for 1,545,690,283 prevalent cases (95% UI: 1,480,358,023 to 1,618,714,974) and 44,449,944 DALYs cases (95% UI: 30,689,648 to 62,029,878). The highest age-standardized prevalence rates (ASPR) for blindness and vision loss were observed in Southern Sub-Saharan Africa and South Asia. DALYs attributable to high fasting plasma glucose and high body mass index (BMI) increased significantly from 903,991 to 97,878 in 1990 to 1,555,976 and 229,558 in 2021, respectively. Health inequality analysis revealed a reduction in both SII and CI for SOD from 1990 to 2021, indicating an improvement in health inequality. Future projections indicate that from 2022 to 2051, ASPR for SOD will continue to increase, with the ASPR of blindness and vision loss increasing by about 17.78%. While age-standardized DALYs rates (ASDR) are expected to stabilize, with the ASDR of age-related and other hearing losses is expected to rise by approximately 0.67%. Conclusion The burden of SOD is high and unevenly distributed. Increasing prevalence and DALYs highlight the need for targeted interventions. Future efforts should focus on risk mitigation and reducing health inequalities.

Background The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP 3 R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum (ER) mitochondria coupling, in the mechanism of podocyte apoptosis is unclear. This study aimed to understand the roles of this axis in podocyte apoptosis and explore potential targets for podocyte protection. Methods The expression of IP 3 R, Grp75, VDAC1, and MCU and mitochondrial Ca 2+ were analyzed during Adriamycin- or angiotensin II-induced apoptosis in cultured mouse podocytes. The interaction between IP 3 R, Grp75, and VDAC1 was investigated using co-immunoprecipitation experiments. The effects of IP 3 R, Grp75, and MCU agonists and antagonists on mitochondrial Ca 2+ and apoptosis were investigated in cultured podocytes. The podocyte-protective effects of an MCU inhibitor were further investigated in rats with Adriamycin-induced nephropathy. Results Increased expression of IP 3 R, Grp75, VDAC1 and MCU, enhanced interaction among the IP 3 R-Grp75-VDAC1 complex, mitochondrial Ca 2+ overload, and increased active caspase-3 levels were confirmed during Adriamycin- or angiotensin II-induced mouse podocyte apoptosis. Agonists of this axis facilitated mitochondrial Ca 2+ overload and podocyte apoptosis, whereas specific antagonists against IP 3 R, Grp75, or MCU prevented mitochondrial Ca 2+ overload and podocyte apoptosis. A specific MCU inhibitor prevented Adriamycin-induced proteinuria and podocyte foot process effacement in rats. Conclusions This study identified a novel pathway in which the IP 3 R-Grp75-VDAC1-MCU calcium regulation axis mediated podocyte apoptosis by facilitating mitochondrial Ca 2+ overload. Antagonists that inhibit Ca 2+ transfer from ER to mitochondria protected mouse podocytes from apoptosis. An MCU inhibitor protected podocytes and decreased proteinuria in rats with Adriamycin-induced nephropathy. Therefore, antagonists to this pathway have promise as novel podocyte-protective drugs.

Diabetic wounds, as one of the most challenging complications of diabetes, exhibit impaired healing due to hyperglycemia, infection, vascular damage, microvascular deficits, dysregulated immune responses, and neuropathy. Conventional treatments are often limited by low drug bioavailability, transient therapeutic effects, and insufficient synergy across multiple pathways. Natural bioactive compounds are potential alternatives due to their multifunctional properties, including antioxidant, antimicrobial, and proangiogenic activities; however, their application is constrained by poor water solubility and rapid metabolism. Their integration with natural or synthetic nanovehicles significantly enhances stability, targeting, and controlled-release capabilities, while enhancing synergistic antimicrobial, immunomodulatory, and pro-repair functions. This review systematically catalogs the application of nanomaterial-loaded biomolecules, focuses on innovative progress in plant-based and animal-derived nanosystems, and further elucidates the multimodal therapeutic potential of synthetic–natural hybrid nanosystems. By synthesizing cutting-edge research, we also summarize advantageous features, development prospects, and existing challenges from the three dimensions of mechanistic evidence, preclinical validation, and current nanodelivery platforms, and propose a framework for grading application potential to provide a theoretical basis and strategic guidance for the rational design and clinical translation of future nanomedicines.

The connectivity is an important feature of the reservoir geological heterogeneity that effects fluid flow responses. In geostatistical modeling, random realizations are generated to describe reservoir heterogeneities. But these realizations do not necessarily honor connectivity data. Especially in multiple-point geostatistical modeling, ensuring the connectivity data of these realizations consistent with the training image is a challenge. The connectivity data of the training image is an important factor in assessing the quality of simulation results in modeling a fluvial hydrocarbon reservoir with meandering channels. The calibration of geological/geostatistical model realizations by measured data is generally performed through history matching, which is an inversion process. This method requires a parameterization of the geostatistical model to allow the updating of an initial model realization. The gradual deformation method has been used to parameterize geostatistical realizations. This method uses a perturbation mechanism to smoothly modify model realizations generated by sequential (not necessarily Gaussian) simulations while preserving its spatial variability. In this paper, a workflow is presented to calibrate the model realizations to the connectivity data. This workflow ensures that the connectivity of model realizations generated by SNESIM is consistent with the training image, and it is applicable to both multiple-point and two-point geostatistical modeling methods based on sequential simulation. This workflow incorporates the computation of the model connectivity function and its calibration to connectivity data using the gradual deformation method. This involves defining and minimizing an objective function, which quantifies the mismatch between the model connectivity function and the connectivity data. In the case study, multiple initial realizations are utilized to construct a final realization of the reservoir model that honors the connectivity data.

Purpose Hepatocellular carcinoma (HCC) cases are closely associated with chronic inflammation and fibrosis which is known as hepatic inflammation-fibrosis-cancer (IFC) axis. The aim of this study is to elucidate the development characteristics of the rat HCC model based on IFC axis. Methods The diethylnitrosamine (DEN)-induced rat HCC, which presents a stepwise histopathological progression that is similar to human HCC, was used to analyze the features of the different stages (inflammation, fibrosis, cancer). Rats were injected DEN at a dose of 30 mg/kg body weight twice a week for 11 weeks and the animals were observed until week 20. Time series sera and organ samples from the DEN animal model were collected to evaluate the dynamic changes. Results It was found that serum biochemical indicators (AST, ALT, ALP, TP, T-BIL, IL-6, TNF-α) from DEN-treated group were higher than that from control group. Fibrosis-related index in serum and live tissue were increased, respectively, from week 4 after DEN treatment. The expression of TGF-β1 and α-SMA in DEN-treated group was higher than that in control group. JAK2/STAT3 signaling was significantly up-regulated in DEN-treated group compared to that in control group. The histological examination confirmed that the hepatocarcinogenesis model was successfully established, and 100% of the animals in the DEN-exposed group developed liver tumors at 20 weeks. According to the pathological changes, the model characterized resulted in three stages: the inflammation stage (week 2–6), the fibrosis stage (week 8–12), and the HCC stage (week 14–20). Conclusions The results suggested that the HCC development was associated with IFC axis. The serial progression of hepatocarcinogenesis was according to the sequence of hepatic inflammation, fibrosis and then hepatic tumor.

The swim bladder of the croceine croaker (Pseudosciaena crocea) was believed to have good curative effects in various diseases, including amnesia, insomnia, dizziness, anepithymia, and weakness after giving birth, in traditional Chinese medicine. However, there is no research focusing on the antioxidant and anti-fatigue peptides from croceine croaker swim bladders at present. Therefore, the purpose of this study was to investigate the bioactivities of peptide fractions from the protein hydrolysate of croceine croaker related to antioxidant and anti-fatigue effects. In the study, swim bladder peptide fraction (SBP-III-3) was isolated from the protein hydrolysate of the croceine croaker, and its antioxidant and anti-fatigue activities were measured using in vitro and in vivo methods. The results indicated that SBP-III-3 exhibited good scavenging activities on hydroxyl radicals (HO•) (EC50 (the concentration where a sample caused a 50% decrease of the initial concentration of HO•) = 0.867 mg/mL), 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH•) (EC50 = 0.895 mg/mL), superoxide anion radical ( O 2 − •) (EC50 = 0.871 mg/mL), and 2,2′-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical (ABTS+•) (EC50 = 0.346 mg/mL). SBP-III-3 also showed protective effects on DNA damage in a concentration-effect manner and prolonged the swimming time to exhaustion of Institute of Cancer Research (ICR) mice by 57.9%–107.5% greater than that of the control. SBP-III-3 could increase the levels of muscle glucose (9.4%–115.2% increase) and liver glycogen (35.7%–157.3%), and decrease the levels of blood urea nitrogen (BUN), lactic acid (LA), and malondialdehyde (MDA) by 16.4%–22.4%, 13.9%–20.1%, and 28.0%–53.6%, respectively. SBP-III-3 also enhanced the activity of lactic dehydrogenase to scavenge excessive LA for slowing the development of fatigue. In addition, SBP-III-3 increased the activities superoxide dismutase, catalase, and glutathione peroxidase to reduce the reactive oxygen species (ROS) damage in mice. In conclusion, SBP-III-3 possessed good anti-fatigue capacities on mice by inhibiting the oxidative reactions and provided an important basis for developing the swim bladder peptide functional food.