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In On Certainty, Wittgenstein introduces the metaphor of “hinge propositions” to refer to those propositions that must remain certain if a language is to be used meaningfully within a community, such as “the earth has existed long before my birth” or “here is one hand”. This paper argues that religious belief can be understood as a distinctive form of hinge proposition for two reasons. First, if two individuals disagree on hinge propositions, they can be seen as belonging to different forms of life or language. It is impossible for them to understand each other. This is also true with disputes over religious beliefs. Second, for Wittgenstein, religious belief is not a theoretical assertion but a way of living, and therefore disputes over religious beliefs are deeper than any other dispute in ordinary life.

The Arctic climate system exhibits dramatic changes in autumn, yet its connection to the tropics remains unclear. This study leverages inter-basin/region teleconnectivity (IB(R)T) analysis to unveil the key teleconnected regions responsible for the connection between autumn Arctic temperature and tropical sea surface temperature (SST). A robust positive correlation is identified between North American Arctic (NAA) temperatures and North Tropical Atlantic (NTA) SST, with the NTA SST leading by one season. Observational evidence reveals that western Pacific (WP) subtropical high (WPSH) and SST play an intermediary role in this cross-seasonal tropical-Arctic connection. Summertime NTA warming triggers an intensification of the WPSH, subsequently inducing autumnal warming of WP SST via inter-basin interactions. This intensified WP convection generates a Rossby wave train propagating from the Northern WP eastward towards the NAA, ultimately leading to an anomalous high over the NAA. The increased atmospheric thickness and air temperature enhances downward longwave radiation, further contributing to surface warming over the NAA. The linear baroclinic model experiments, forced with thermal anomalies corresponding to WP SST warming, successfully reproduce the observed atmospheric circulation response and the associated air temperature changes over the NAA. Our findings provide insights into the role of inter-basin connections in Tropical-Arctic linkages.

Rosmarinic acid (RosA), a natural poly-phenolic compound isolated from a variety of Labiatae herbs, has been reported to have a range of biological effects. To investigate the cardioprotective effects of RosA against myocardial ischaemia/reperfusion (I/R) injury. Male C57BL/6J mice were given RosA (100 mg/kg) via intragastric administration. After 1 week of administration, the mice were subjected to 30 min/24 h myocardial I/R injury. The mice were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + I/R, and RosA + I/R. Infarct size (IS), cardiac function (including EF, FS), histopathology, serum enzyme activities, ROS changes, cis aconitase (ACO) activity, and specific mRNA and protein levels were assessed in vivo. HL-1 cells were pre-treated with or without RosA (50 μM), followed by stimulation with 9 h/6 h of oxygen and glucose deprivation/re-oxygenation (OGD/R). The cells were randomly subdivided into 4 groups: Vehicle, RosA, Vehicle + OGD/R, and RosA + OGD/R. Lactate dehydrogenase (LDH) levels, ACO activity, ROS changes and protein levels were measured in vitro. Treatment with RosA reduced the following indicators in vivo (p < 0.05): (1) IS (14.5%); (2) EF (-23.4%) and FS (-18.4%); (3) the myocardial injury enzymes CK-MB (20.8 ng/mL) and cTnI (7.7 ng/mL); (4) DHE-ROS: (94.1%); (5) ACO activity (-2.1 mU/mg protein); (6) ogdh mRNA level (122.9%); and (7) OGDH protein level (69.9%). Moreover, treatment with RosA attenuated the following indicators in vitro (p < 0.05): (1) LDH level (191 U/L); (2) DHE-ROS: (165.2%); (3) ACO activity (-3.2 mU/mg protein); (4) ogdh mRNA level (70.0%); and (5) OGDH (110.1%), p-IκB-a (56.8%), and p-NF-κB (57.7%) protein levels. RosA has the potential to treat myocardial I/R injury with potential application in the clinic.

In the context of global warming, vegetation activity in northeastern East Asia (40–45°N, 105–130°E) (NEA) shows a significant growth trend on a multidecadal scale, but how vegetation changes on a decadal scale is unclear. In this study, we find a significant trend of vegetation greening in northeastern East Asia during 1982–1998 and a slowdown in the greening trend during 1998–2014. Trend analysis of the extreme climate indices reveals that the trends of precipitation-related extreme climate indices are similar to those of vegetation change, and further correlation analysis reveals that precipitation-related extreme climate indices have a strong positive correlation with the NDVI. The results indicate that the vegetation in northeastern East Asia is more sensitive to precipitation changes, especially extreme precipitation, compared with the temperature and related extreme indices. Furthermore, the analysis of large-scale atmospheric circulation changes suggests a role of Northwest Pacific subtropical high (NPSH) in the trend changes of precipitation-related extreme indices. The strengthening of NPSH before 1998 enhances the moisture transport to the NEA, providing abundant water vapor favorable for extreme precipitation events, while after 1998, the NPSH trend is much weakened, corresponding to a decrease in the moisture transport trend.

Protein homeostasis (proteostasis) is a potential mechanism that contributes to cancer cell survival and drug resistance. Constitutively active androgen receptor (AR) variants confer anti-androgen resistance in advanced prostate cancer. However, the role of proteostasis involved in next generation anti-androgen resistance and the mechanisms of AR variant regulation are poorly defined. Here we show that the ubiquitin-proteasome-system (UPS) is suppressed in enzalutamide/abiraterone resistant prostate cancer. AR/AR-V7 proteostasis requires the interaction of E3 ubiquitin ligase STUB1 and HSP70 complex. STUB1 disassociates AR/AR-V7 from HSP70, leading to AR/AR-V7 ubiquitination and degradation. Inhibition of HSP70 significantly inhibits prostate tumor growth and improves enzalutamide/abiraterone treatments through AR/AR-V7 suppression. Clinically, HSP70 expression is upregulated and correlated with AR/AR-V7 levels in high Gleason score prostate tumors. Our results reveal a novel mechanism of anti-androgen resistance via UPS alteration which could be targeted through inhibition of HSP70 to reduce AR-V7 expression and overcome resistance to AR-targeted therapies. The AR-V7 isoform is associated with anti-androgen drug resistance in prostate cancer. Here, the authors show that AR-V7 protein stability is regulated by HSP70/STUB1 complex-mediated proteostasis which confers drug resistance in late stage prostate cancer. Inhibition of HSP70 re-sensitizes resistant cells to enzalutamide therapy.

Introduction. Acute lung injury (ALI) induced by sepsis is a process related to inflammatory reactions, which involves lung cell apoptosis and production of inflammatory cytokine. Here, lipopolysaccharide (LPS) was applied to stimulate the mouse or human normal lung epithelial cell line (BEAS-2B) to construct a sepsis model in vivo and in vitro, and we also investigated the effect of miR-497-5p on sepsis-induced ALI. Material and Methods. Before LPS treatment, miR-497-5p antagomir was injected intravenously into mice to inhibit miR-497-5p expression in vivo. Similarly, miR-497-5p was knocked down in BEAS-2B cells. Luciferase reporter assay was applied to predict and confirm the miR-497-5p target gene. Cell viability, apoptosis, the levels of miR-497-5p, IL2RB, SP1, inflammatory cytokine, and lung injury were assessed. Results. In BEAS-2B cells, a significant increase of apoptosis and inflammatory cytokine was shown after LPS stimulation. In septic mice, increased inflammatory cytokine production and apoptosis in lung cells and pulmonary morphological abnormalities were shown. The miR-497-5p inhibitor transfection showed antiapoptotic and anti-inflammatory effects on BEAS-2B cells upon LPS stimulation. In septic mice, the miR-497-5p antagomir injection also alleviated ALI, apoptosis, and inflammation caused by sepsis. The downregulation of IL2RB in BEAS-2B cells reversed the protective effects of the miR-497-5p inhibitor against ALI. Conclusion. In conclusion, downregulation of miR-497-5p reduced ALI caused by sepsis through targeting IL2RB, indicating the potential effect of miR-497-5p for improving ALI caused by sepsis.

During the manufacturing process of oil-immersed current transformers, metallic particles may become embedded in the insulation wrapping, and the resulting electric field distortion is one of the primary causes of failure. Historically, the shape of metallic particles has often been simplified to a standard sphere, whereas in practice, these particles are predominantly irregular. In this study, ellipsoidal and flaky particles were selected to represent smooth and angular surfaces, respectively. Using COMSOL Multiphysics® (version 6.2) software, a three-dimensional simulation model of an oil-immersed inverted current transformer was developed, and the influence of defect position and size on electric field characteristics was analyzed. The results indicate that both types of defects cause electric field distortion, with longer particles exerting a greater influence on the electric field distribution. Under the voltage of a 220 kV system, elliptical particles (9 mm half shaft) lead to the maximum electric field intensity of main insulation of up to 45.1 × 106 V/m, while the maximum field strength of flaky particles (length 30 mm) is 28.9 × 106 V/m. Additionally, the closer the particles are to the inner side of the main insulation, the more significant their influence on the electric field distribution becomes. The findings provide a foundation for fault analysis and propagation studies related to the main insulation of current transformers.

In this research, a new triterpenoid, tirucalla-8,24-diene-3β,11β-diol-7-one (1), and eupha-8,24-diene-3β,11β-diol-7-one (2), which was isolated from Euphorbia kansui for the first time, together with twelve other known compounds (3–14), were isolated from the ethyl acetate extract of Euphorbia kansui. Their structures were elucidated based on High resolution electrospray ionization mass spectrometry (HR-ESI-MS), Infrared Spectroscopy (IR), 1D and 2D Nuclear Magnetic Resonance (NMR) data. Both constituents 1 and 2 exhibited moderate cytotoxicity against colon cancer HCT-116, gastric cancer MKN-45 and breast cancer MCF-7.

Background Weight misperceptions are common in children and adolescents, which is related to the engagement of weight loss behaviors. The aim of this study was to investigate the association between body weight perception and weight loss behaviors of lower-calorie diets and increased levels of physical activity (PA). Methods The Ningbo Youth Risk Behavior Survey was conducted from 2007 to 2022. A multistage, stratified cluster sampling procedure was utilized to draw target adolescents aged 12 to 18 years participating in each survey wave (2007, 2012, 2017, 2022). Data of anthropometry, weight perception, and weight loss behaviors were collected through self-administered questionnaires. A binary generalized linear model was used to examine associations between body weight perception and weight loss behaviors of lower calorie diets and increased levels of PA. Results The sample sizes for each survey wave were 777, 885, 1588 and 2638. The prevalence of overweight (OW)/obesity (OB), self-perception of OW/OB and overestimated perception increased from 7.6%, 27.0% and 29.1% in 2007 to 16.3%, 39.9% and 41.4% in 2022, respectively. Adolescents that perceived themselves as OW/OB had higher odds of lower-calorie diets (OR: 4.2, 3.3–5.4) and increased level of PA (OR: 3.8, 2.9-5.0), whereas adolescents that perceived themselves as underweight had lower odds of lower-calorie diets (OR: 0.371, 0.253–0.542) and increased levels of PA (OR: 0.381, 0.295–0.559). Conclusion OW, self-perception of OW/OB and overestimated perception were prevalent in Chinese adolescents. Self-perception of OW/OB was positively associated with lower-calorie diets and increased levels of PA. The results can support public health specialists to promote health education of body perception and improve self-esteem in Chinese children and adolescents.

This paper proposes a denoising method of vibration signal based on improved multiresolution singular value decomposition (IMRSVD) and effective component selection. A new construction method of trajectory matrix is used, which can enhance the oscillating component of the original signal. Next, based on the improved trajectory matrix, singular value decomposition (SVD), which plays the role of pre-decomposition, is used to obtain multiple one-dimensional components, and the further decomposition of that is achieved by multiresolution singular value decomposition (MRSVD). Finally, the effective components selection of a series of decomposed signal components is achieved based on the proposed feature evaluation index (FEI). The denoising experiments are carried out using the simulation signal and the vibration signal of planetary gear, respectively. The experimental results show that the proposed method performs better than the traditional SVD denoising method, and the weak fault feature in the vibration signal can be extracted successfully. In addition, the comparison between periodic modulation intensity (PMI) and FEI displays that the proposed method has better robustness and accuracy than the interference components with similar frequency. Thus, the proposed method is an effective weak fault feature extraction and denoising tool of vibration signals for fault diagnosis.