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Directly linked porphyrin dimers have attracted considerable attention because of their intriguing electronic features. Most emphasis has been placed on either dimers with large dihedral angles between the constituent planar monomeric subunits or those with overall planarity, referred to as “Planar-Twisted-Planar” and “Planar-Planar-Planar”, respectively. Herein, we report a “Twisted-Planar-Twisted” framework, the hexaphyrin dimer D that exists in a trans configuration. Treatment of D with MeOH affords two isomeric dimers, MD1 and MD2 , both of which incorporate a methoxy moiety and exist in cis orientations with respect to the tethering linkage. The methanol-promoted conversion is accompanied by a readily discernible color change from green to brown and is not induced to an appreciable level by other alcohols. Dimer D thus acts as a rudimentary, albeit highly selective, reaction-based methanol indicator. This work provides a promising approach for constructing reaction-based chemosensors using porphyrinoid dimers of nonplanar subunits with biased reactivity. Directly linked porphyrin dimers show intriguing electronic features but emphasis has been placed on planar monomeric units. Here, the authors report a Twisted-Planar-Twisted framework which can undergo a cis-trans transformation accompanied by a colour change in presence of methanol, making this framework applicable as a methanol sensor.

Chronic stress has been shown to facilitate progression of epithelial ovarian cancer (EOC), however, the neuro-endocranial mechanism participating in this process still remains unclear. Here, we reported that chronic restraint stress (CRS) promoted the abdominal implantation metastasis of EOC cells and the expression of epithelial–mesenchymal transition-related markers in tumor-bearing mouse model, including TWIST, SLUG, SNAIL, and β-catenin. We observed that β-catenin co-expressed with SLUG and norepinephrine (NE) in tumor tissues obtained from nude mice. Further ex vivo experiments revealed that NE promoted migration and invasion of ovarian cancer cells and SLUG expression through upregulating expression and improving transcriptional function of β-catenin in vitro. A human phosphor-kinase array suggested that NE activated various kinases in ovarian cancer cells, and we further confirmed that AKT inhibitor reduced NE-mediated pro-metastatic impacts and activation of the β-catenin/SLUG axis. Furthermore, the expression levels of NE and β-catenin were examined in ovarian tumor tissues by using tumor tissue arrays. Results showed that the expression levels of both NE and β-catenin were associated with poor clinical stage of serous EOC. Moreover, we found that melatonin (MLT) effectively reduced the abdominal tumor burden of ovarian cancer induced by CRS, which was partially related to the inhibition of the NE/AKT/β-catenin/SLUG axis. Collectively, these findings suggest a novel mechanism for CRS-mediated ovarian cancer metastasis and MLT has a potential therapeutic efficacy against ovarian cancer.

Softening process greatly affects fruit texture and shelf life. Expansins (EXPs) are a group of structural proteins participating in cell wall loosening, which break the hydrogen bonding between cellulose microfibrils and hemicelluloses. However, our knowledge on how EXP genes are regulated in fruit ripening, especially in non-climacteric fleshy fruits, is limited. Here, we have identified the EXP genes in both the octoploid cultivated strawberry (Fragaria × ananassa) and one of its diploid progenitor species, woodland strawberry (Fragaria vesca). We found that EXP proteins in F. × ananassa were structurally more divergent than the ones in F. vesca. Transcriptome data suggested that FaEXP88, FaEXP114, FveEXP11 and FveEXP33 were the four candidate EXP genes more likely involved in fruit softening, whose transcript levels dramatically increased when firmness decreased during fruit maturation. Phylogenetic analyses showed that those candidate genes were closely clustered, indicating the presence of homoeolog expression dominance in the EXP gene family in strawberry. Moreover, we have performed chromatin immunoprecipitation (ChIP) experiments to investigate the distribution of histone modifications along the promoters and genic regions of the EXP genes in F. vesca. ChIP data revealed that the transcript levels of EXP genes were highly correlated with the enrichment of H3K9/K14 acetylation and H3K27 tri-methylation. Collectively, this study identifies the key EXP genes involved in strawberry fruit softening and reveals a regulatory role of histone modifications in their transcriptional regulation, which would facilitate functional studies of the EXP genes in the ripening of non-climacteric fruits.

The dynamic damage constitutive model has limitations and needs to reflect the quantitative relationship between the elastic modulus and joint inclination angle of the slate. This paper constructs a dynamic damage constitutive model considering the influence of joint inclination on the elastic modulus of slate. First, the slate impact test reveals the changing law of the elastic modulus of slate under different joint inclination angles. The elastic modulus of slate with joint inclination angle shows a “U” type changing law, and the elastic modulus is the smallest when the joint inclination angle is 52.5°, and the elastic modulus is relatively larger when 0° and 90°. The mathematical model of slate joint inclination and elastic modulus was obtained by fitting the test data, and the fitting accuracy reached 94.86%. Then, the dynamic damage constitutive model of slate was established based on the statistical distribution theory, and the quantitative relationship between joint inclination and elastic modulus was introduced into the damage eigen structure equation to correct the elastic modulus. Finally, comparing the theoretical calculations with the experimental results, the stress–strain curves of the slate before damage are in good agreement, proving the model’s rationality in this paper.

Premature ovarian failure (POF) is one of the most common complications among female patients with tumors treated with chemotherapy and requires advanced treatment strategies. Human amniotic epithelial cell (hAEC)-based therapy mediates tissue regeneration in a variety of diseases, and increasing evidence suggests that the therapeutic efficacy of hAECs mainly depends on paracrine action. This study aimed to identify exosomes derived from hAECs and explored the therapeutic potential in ovaries damaged by chemotherapy and the underlying molecular mechanism. hAEC-derived exosomes exhibited a cup- or sphere-shaped morphology with a mean diameter of 100 nm and were positive for Alix, CD63, and CD9. hAEC exosomes increased the number of follicles and improved ovarian function in POF mice. During the early stage of transplantation, hAEC exosomes significantly inhibited granulosa cell apoptosis, protected the ovarian vasculature from damage, and were involved in maintaining the number of primordial follicles in the injured ovaries. Enriched microRNAs (miRNAs) existed in hAEC exosomes, and target genes were enriched in phosphatidylinositol signaling and apoptosis pathways. Studies in vitro demonstrated that hAEC exosomes inhibited chemotherapy-induced granulosa cell apoptosis via transferring functional miRNAs, such as miR-1246. Our findings demonstrate that hAEC-derived exosomes have the potential to restore ovarian function in chemotherapy-induced POF mice by transferring miRNAs. [Display omitted]

Postmenopausal women have a higher incidence of stroke compared to the age-matched males, and the estrogen was thought to be the main cause of such difference. However, estrogen replacement therapy for the prevention of postmenopausal stroke shows controversial results and is widely disputed due to its serious side effects after chronic administration. Genistein (Gen), a natural phytoestrogen with fewer side effects, has a protective effect against cerebral ischemia damage. However, whether Gen could effectively prevent postmenopausal stroke has not been elucidated. In the current study, reproductively senescent mice were treated with Gen (10 mg/kg) for two weeks before having transient cerebral ischemia insults. Neurological scores, infarct volumes, and cell apoptosis were evaluated 24 h after reperfusion. The levels of inflammatory factors and nod-like receptor protein 3 (NLRP3) inflammsome-related proteins were also examined. The results showed that Gen treatment reduced infarct volumes, improved neurological scores, attenuated apoptosis, and decreased inflammatory factor release. The expression of NLRP3 inflammasome-related proteins in microglia was downregulated by Gen. However, the overexpression of NLRP3 in microglia abrogated the Gen-induced inhibition of inflammatory factor release and reversed the neuroprotective effect of Gen. Taken together, the results suggest that Gen treatment could attenuate the acute injury induced by cerebral ischemia in reproductively senescent mice via the inhibition of the NLRP3 inflammasome in microglia, indicating that Gen could be a candidate drug for the treatment of stroke in postmenopausal women.

The internal structure and dynamics of Earth have been shaped by the 660 km boundary between the mantle transition zone and lower mantle. However, due to the paucity of natural samples from this depth, the nature of this boundary—its composition and volatile fluxes across it—remain debated. Here we analyse the mineral inclusions in a rare type IaB gem diamond from the Karowe mine (Botswana). We discovered recovered lower-mantle minerals ringwoodite + ferropericlase + low-Ni enstatite (MgSiO 3 ) in a polyphase inclusion, together with other principal lower-mantle minerals and hydrous phases, place its origin at ~23.5 GPa and ~1,650 °C, corresponding to the depth at the 660 km discontinuity. The petrological character of the inclusions indicates that ringwoodite (∼Mg 1.84 Fe 0.15 SiO 4 ) breaks down into bridgmanite (∼Mg 0.93 Fe 0.07 SiO 3 ) and ferropericlase (∼Mg 0.84 Fe 0.16 O) in a water-saturated environment at the 660 km discontinuity and reveals that the peridotitic composition and hydrous conditions extend at least across the transition zone and into the lower mantle. Hydrous conditions extend across the 660 km discontinuity between Earth’s mantle transition zone and lower mantle, according to analysis of a polyphase mineral inclusion in a gem diamond from the Karowe mine, Botswana

Fe-S-P compounds have been observed in many meteorites and could be the important components in planetary cores. Here we investigated the phase stability of Fe3(S,P) solid solutions and synthesized high-quality Fe3(S1-xPx) high-pressure phases in the multi-anvil press. The physical properties of Fe3(S0.5P0.5) were further studied in the diamond-anvil cell by synchrotron X-ray diffraction and emission spectroscopy. The solubility of S in the Fe3(S,P) solid solution increases with increasing pressure. The minimum pressure to synthesize the pure Fe3S and Fe3(S0.13P0.87) is about 21 and 8 GPa, respectively. The observed discontinuity in unit-cell parameters at about 18 GPa is caused by the high-spin to low-spin transition of iron, supported by X-ray emission spectroscopy data. The sulfur solubility in Fe3(S,P) solid solutions could be an excellent pressure indicator if such solid solutions are found in nature.

[...]patients with ≥3 high-risk features (eg, T4, N+) had a median FFS of 8.2 months versus 45.2 months in lower-risk groups, suggesting intrinsic tumor biology may dominate over therapeutic benefit.4 A single-arm design cannot disentangle treatment effect from confounding by baseline risk. Survivorship bias in Quality of Life assessments Quality of Life analyses showed no significant decline (p=0.94), but only 39% of patients completed 12 nivolumab cycles, with 18% discontinuing due to progression. [...]the NEXT trial highlights the feasibility of adjuvant nivolumab in MIUC but underscores critical gaps in study design, biomarker validation, and clinical translation.

It is of great significance to study the thermal radiation anomalies of earthquake swarms in the same area in terms of selecting abnormal characteristic determination parameters, optimizing and determining the processing model, and understanding the abnormal machine. In this paper, we investigated short-term and long-term thermal radiation anomalies induced by earthquake swarms in Iran and Pakistan between 2007 and 2016. The anomalies were extracted from infrared remote sensing black body temperature data from the China Geostationary Meteorological Satellites (FY-2C/2E/2F/2G) using the multiscale time-frequency relative power spectrum (MS T-FRPS) method. By analyzing and summarizing the thermal radiation anomalies of series earthquake groups with consistency law through a stable and reliable MS T-FRPS method, we first obtained the relationship between anomalies and ShakeMaps from USGS and proposed the anomaly regional indicator (ARI) to determine seismic anomalies and the magnitude decision factor (MDF) to determine seismic magnitude. In addition, we explored the following discussions: earthquake impact on regional thermal radiation background and the relationship between thermal anomalies and earthquake magnitude and the like. Future research directions using the MS T-FRPS method to characterize regional thermal radiation anomalies induced by strong earthquakes could help improve the accuracy of earthquake magnitude determination.