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A modified Hayward black hole is a nonsingular black hole. It is proposed that it would form when the pressure generated by quantum gravity can stop matter’s collapse as the matter reaches the Planck density. Strong deflection gravitational lensing occurring nearby its event horizon might provide some clues of these quantum effects in its central core. We investigate observables of the strong deflection lensing, including angular separations, brightness differences and time delays between its relativistic images, and we estimate their values for the supermassive black hole in the Galactic center. We find that it is possible to distinguish the modified Hayward black hole from a Schwarzschild one, but it demands a very high resolution, beyond current stage.

Wazwaz Kaur Boussinesq (WKB) equation can effectively simulate the behavior of water waves in shallow water, including the nonlinear effect and dispersion phenomenon of waves, which is of great significance for understanding the dynamic process of ocean, river and other water bodies. To enrich the wave equation theory, the (3+1)-dimensional integer order derivative of WKB equation is changed to the fractional one with beta derivative. The current work deals with the fractional (3+1)-dimensional WKB equation for discussing its chaotic behavior and establishing some new analytic solutions. The chaotic properties of the equation are verified by the trend of evolution along with time, Lyapunov exponents and initial sensitivity analysis. And then complete discrimination system for polynomial method is applied to derive some trigonometric, hyperbolic, Jacobi elliptic and other solutions. The graphical demonstrations are provided for part of these solutions. From these visualized graphs, the solitary, periodic and quasi-periodic wave are shown and the effect of fractional derivatives on the equation can be seen intuitively.

Ample evidence suggests that hepatic macrophages play key roles in the injury and repair mechanisms during liver disease progression. There are two major populations of hepatic macrophages: the liver resident Kupffer cells and the monocyte-derived macrophages, which rapidly infiltrate the liver during injury. Under different disease conditions, the tissue microenvironmental cues of the liver critically influence the phenotypes and functions of hepatic macrophages. Furthermore, hepatic macrophages interact with multiple cells types in the liver, such as hepatocytes, neutrophils, endothelial cells, and platelets. These crosstalk interactions are of paramount importance in regulating the extents of liver injury, repair, and ultimately liver disease progression. In this review, we summarize the novel findings highlighting the impact of injury-induced microenvironmental signals that determine the phenotype and function of hepatic macrophages. Moreover, we discuss the role of hepatic macrophages in homeostasis and pathological conditions through crosstalk interactions with other cells of the liver.

The daily temperatures from observational data, NCEP-2 and CFSR reanalysis data all exhibit long-range correlation (LRC) characteristics, which provides a test bed for assessing the reliability of reanalysis data. In this study, the quality of the NCEP-2 and CFSR data in China are evaluated on the basis of the LRC characteristics of daily temperatures, including daily average temperature (DAT), daily maximum temperature (DMAT), daily minimum temperature (DMIT), and diurnal temperature range (DTR). Compared with the observations, the quality of NCEP-2 daily temperature is relatively good in central and eastern Northwest China, and most of central and eastern China, especially for NCEP-2 DMAT. However, the NCEP-2 reanalysis data as well as CFSR has a significant difference with the LRC of the observations in most of Sichuan, Qinghai-Tibet Plateau and some areas of southwestern Xinjiang at a significance level of Alpha = 0.05. In general, the LRC characteristics of NCEP-2 daily temperature perform better than that of CFSR data. As far as DAT is concerned, CFSR perform worse in central and eastern Northwest China, and better than NCEP-2 only in South China and eastern Jiangnan. The quality of the CFSR DMAT is worse than that of NCEP-2 in central and eastern Northwest China, western Inner Mongolia, and eastern China. The quality of NCEP-2 DMIT is better than CFSR in central and eastern Northwest China, most of Inner Mongolia, and is worse than it in most of South China and eastern Jiangnan. The reliability of the CFSR DTR is very low in most of China.

Direct-current triboelectric nanogenerators arising from electrostatic breakdown can eliminate the bottleneck problem of air breakdown in conventional triboelectric nanogenerators, offering critical benefits of constant-current output, resistance to electromagnetic interference, and high output power density. Previous understanding is that its output characteristics are described by a capacitor-breakdown model or dictated by one or two discharge domains in direct-current triboelectric nanogenerators. Here, we demonstrate that the former holds only for ideal conditions and the latter cannot fully explain the dynamic process and output performance. We systematically image, define, and regulate three discharge domains in direct-current triboelectric nanogenerators, then a “cask model” is developed to bridge the cascaded-capacitor-breakdown dynamic model in ideal conditions and real outputs. Under its guidance, the output power is increased by an order of magnitude within a wide range of resistive loads. These unexplored discharge domains and optimization methods revolutionize the output performance and potential applications of direct-current triboelectric nanogenerators. Arising from contact electrification and electrostatic breakdown, DC triboelectric nanogenerators are a promising solution to the air breakdown bottleneck in conventional TENGs. Here, authors reveal and regulate three discharge domains enhancing the device output power by an order of magnitude.

Background Insects exhibit remarkable resilience and maintain high levels of reproduction despite frequently encountering nutritional restriction. However, the mechanisms governing their adaptive reproductive strategies under nutrition-restricted conditions remain poorly understood. The German cockroach Blattella germanica , a widespread urban pest, exhibits remarkable reproductive capabilities even in domestic environments where food resources are frequently limited. Results In this study, we demonstrate that the ovary plays a crucial role in promoting vitellogenin biosynthesis and oocyte development under nutrition-restricted conditions through hemiovariectomy. Employing transcriptome analysis, RNAi screening, and fluorescence in situ hybridization, we identified an ovarian-enriched insulin-like peptide gene ( BgILP2 ) that is dramatically upregulated during low nutrition conditions. Repression of BgILP2 impairs vitellogenesis in the fat body through downregulation of p-AKT and p-ERK levels while simultaneously disrupting juvenile hormone synthesis, ultimately leading to delayed oocyte development under nutrient restriction. Furthermore, under low-nutrient conditions, repression of BgILP2 led to elevated circulating sugar levels, reduced lipid and glycogen storage, and a modest increase in the lifespan of female cockroaches. Conclusions The ovarian-enriched BgILP2 responds to nutritional stress and activates the insulin signaling pathway to sustain oocyte development under nutrient-restricted conditions. Furthermore, BgILP2 mediates energy allocation and prioritizes reproductive investment potentially at the expense of longevity, which reflects a tradeoff between reproduction and somatic maintenance under nutrient restriction. These findings provide novel insights into the molecular mechanisms and adaptive strategies that enable cockroaches to maintain reproductive success in food-limited environments. Graphical Abstract

Esophageal squamous dysplasia is believed to be the precursor lesion of esophageal squamous cell carcinoma (ESCC); however, the genetic evolution from dysplasia to ESCC remains poorly understood. Here, we applied multi-region whole-exome sequencing to samples from two cohorts, 45 ESCC patients with matched dysplasia and carcinoma samples, and 13 tumor-free patients with only dysplasia samples. Our analysis reveals that dysplasia is heavily mutated and harbors most of the driver events reported in ESCC. Moreover, dysplasia is polyclonal, and remarkable heterogeneity is often observed between tumors and their neighboring dysplasia samples. Notably, copy number alterations are prevalent in dysplasia and persist during the ESCC progression, which is distinct from the development of esophageal adenocarcinoma. The sharp contrast in the prevalence of the ‘two-hit’ event on TP53 between the two cohorts suggests that the complete inactivation of TP53 is essential in promoting the development of ESCC. The pathogenesis of oesophageal squamous cell carcinoma is a multi-step process but the genetic determinants behind this progression are unknown. Here the authors use multi-region exome sequencing to comprehensively investigate the genetic evolution of precursor dysplastic lesions and untransformed oesophagus.

The cost-effectiveness of nivolumab plus bevacizumab and chemotherapy for patients with advanced non-squamous non-small-cell lung-cancer (NSCLC) was uncleared yet. The current analysis aimed to evaluate the cost-effectiveness of nivolumab plus bevacizumab and chemotherapy compared with bevacizumab plus chemotherapy for patients with untreated non-squamous NSCLC in Chinese context. A partitioned survival model that simulated 3-week patients transition in 20-year time horizon was conducted to evaluate the economic value. The clinical data were obtained from TASUKI-52 trial, cost and utility values were gathered from the local charges and previously published studies. Sensitivity analyses were conducted to examine the robustness of the model results when parameters changed, subgroup analyses were also conducted to enhance the comprehensiveness of the analysis. Nivolumab plus bevacizumab and chemotherapy yielded an additional 0.90 QALYs with the marginal cost of $231,948.33, resulting in the incremental cost-effectiveness ratio (ICER) of $256,791.53 per additional quality-adjusted life-years (QALYs) gained, which higher than the Chinese willingness-to-pay (WTP) threshold of $39,057/QALY. Sensitivity analyses confirmed the robustness of the model outcomes. Subgroup analyses revealed that nivolumab plus bevacizumab and chemotherapy was unlikely to be the cost-effective option for all subgroups due to the unfavorable ICERs. Nivolumab plus bevacizumab and chemotherapy was unlikely to be the cost-effective first-line therapy for untreated advanced non-squamous NSCLC patients compared with bevacizumab plus chemotherapy from the perspective of Chinese health-care system.

Background More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. Methods Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. Results Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo , while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. Conclusions Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.

The current analysis aimed to evaluate the cost-effectiveness of benmelstobart plus anlotinib and chemotherapy for patients with ES-SCLC from the Chinese health-care system perspective. A mathematical decision model that simulated patients’ 3-week transition in 20-year time horizon was conducted to evaluate the economic value. Survival and safety data were gathered from ETER701 trial, cost and utility values were obtained from the local charges and previously published studies. Sensitivity and subgroup analyses were performed to examine the robustness of the model results and to support the health-decision making. For intention-to-treat (ITT) patients, benmelstobart plus anlotinib and carboplatin/etoposide could bring additional 0.60 and 0.71 QALYs with marginal cost of $91,424.86 and $98,504.86 compared with anlotinib plus carboplatin/etoposide and carboplatin plus etoposide, respectively, resulting in an incremental cost-effectiveness ratios (ICERs) were $153,444.29/QALY and $138,272.39/QALY, respectively, which were higher than the Chinese willingness-to-pay (WTP) threshold. Sensitivity analyses and subgroup analyses confirmed the robustness of the model results when parameters changed. Benmelstobart plus anlotinib and carboplatin/etoposide was unlikely to be the cost-effective first-line strategy compared with anlotinib plus carboplatin/etoposide and carboplatin plus etoposide for ES-SCLC patients in China. Reducing the price of benmelstobart could increase its cost-effectiveness.