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Deep learning models can accurately predict molecular properties and help making the search for potential drug candidates faster and more efficient. Many existing methods are purely data driven, focusing on exploiting the intrinsic topology and construction rules of molecules without any chemical prior information. The high data dependency makes them difficult to generalize to a wider chemical space and leads to a lack of interpretability of predictions. Here, to address this issue, we introduce a chemical element-oriented knowledge graph to summarize the basic knowledge of elements and their closely related functional groups. We further propose a method for knowledge graph-enhanced molecular contrastive learning with functional prompt (KANO), exploiting external fundamental domain knowledge in both pre-training and fine-tuning. Specifically, with element-oriented knowledge graph as a prior, we first design an element-guided graph augmentation in contrastive-based pre-training to explore microscopic atomic associations without violating molecular semantics. Then, we learn functional prompts in fine-tuning to evoke the downstream task-related knowledge acquired by the pre-trained model. Extensive experiments show that KANO outperforms state-of-the-art baselines on 14 molecular property prediction datasets and provides chemically sound explanations for its predictions. This work contributes to more efficient drug design by offering a high-quality knowledge prior, interpretable molecular representation and superior prediction performance.

The objective of this study was to investigate the effect of environmental factors (soil nutrition and meteorological factors) on fruit quality traits of ‘Fuji’ apples. ‘Fuji’ apple fruits, soil samples, and meteorological data were investigated from 66 commercial orchards covering 22 counties of the Loess Plateau region in China. Partial least squares regression (PLSR) and linear programming were combined to analyze the quantitative relationship between fruit quality and environmental factors. The effect of meteorological factors (55.99%) on fruit quality was greater than that of soil nutrition factors (44.01%) in the Loess Plateau apple-producing region of China. Optimum environmental factors for high-quality ‘Fuji’ apples in the Loess Plateau region were: soil organic matter (13.94–17.93 g ∙ kg−1), total N (0.77–1.03 g ∙ kg−1), available N (68.39–115.87 mg ∙ kg−1), P (62.39–124.67 mg ∙ kg−1), K (324.41–468.62 mg ∙ kg−1), Ca (6.54 mg ∙ kg−1), Fe (14.97 mg ∙ kg−1), Zn (1.55–2.72 mg ∙ kg−1), B (0.37 mg ∙ kg−1), and soil pH (7.98–8.20); mean annual temperature (18 ℃), total annual precipitation (431.2–713.8 mm), monthly mean temperature (19.9 ℃), lowest temperature (8.03 ℃), highest temperature (19.63 to 27.25 ℃), temperature difference between day and night (12.41 ℃), total precipitation (338.3–589.8 mm), relative humidity (56.57–82.41%), and sunshine percentage (36.96–55.87%) during the growing period (April–October).

Hydrocephalus is a severe complication that can result from intracerebral hemorrhage, especially if this hemorrhage extends into the ventricles. Our previous study indicated that the NLRP3 inflammasome mediates cerebrospinal fluid hypersecretion in the choroid plexus epithelium. However, the pathogenesis of posthemorrhagic hydrocephalus remains unclear, and therapeutic strategies for prevention and treatment are lacking. In this study, an Nlrp3−/− rat model of intracerebral hemorrhage with ventricular extension and primary choroid plexus epithelial cell culture were used to investigate the potential effects of NLRP3-dependent lipid droplet formation and its role in the pathogenesis of posthemorrhagic hydrocephalus. The data indicated that NLRP3-mediated dysfunction of the blood–cerebrospinal fluid barrier (B-CSFB) accelerated neurological deficits and hydrocephalus, at least in part, through the formation of lipid droplets in the choroid plexus; these lipid droplets interacted with mitochondria and increased the release of mitochondrial reactive oxygen species that destroyed tight junctions in the choroid plexus after intracerebral hemorrhage with ventricular extension. This study broadens the current understanding of the relationship among NLRP3, lipid droplets and the B-CSFB and provides a new therapeutic target for the treatment of posthemorrhagic hydrocephalus. Strategies to protect the B-CSFB may be effective therapeutic approaches for posthemorrhagic hydrocephalus.

Endometrial cancer (EC) ranks fourth among the most common gynecologic malignancies. Despite advances in medical technology, the pathogenesis is still unclear. Numerous reports have identified the involvement of lncRNA in the malignant progression of endometrial cancer. The aim of the study was to investigate the expression level of lncRNA ENST00000585827 (lncRNA E27) in endometrial cancer and the molecular mechanism that regulates the development of endometrial cancer. Combined with the results of the previous study, PCR analysis confirmed that lncRNA E27 was significantly upregulated in endometrial cancer cell lines. The results of CCK-8, wound healing assay, and transwell experiments showed that lncRNA E27 could significantly inhibit cell proliferation, migration, and invasion. Flow cytometry results confirmed that lncRNA E27 could promote apoptosis. Furthermore, based on bioinformatics predictions, dual-luciferase assay and RT-qPCR analysis confirmed that miR-424, as its downstream molecule, competitively regulates the expression of E2F6/E2F7. Rescue experiments further supported that lncRNA E27 inhibited proliferation, migration, invasion, and promoted apoptosis of endometrial cancer through miR-424/E2F6/E2F7 signaling axis. Conclusively, our findings revealed the role of lncRNA E27 in regulating the miR-424/E2F6/E2F7 signaling axis during EC progression, opening up new strategies for the treatment of endometrial cancer.

Renal interstitial fibrosis is the common pathological process of various chronic kidney diseases to end-stage renal disease. Inhibition of fibroblast activation attenuates renal interstitial fibrosis. Our previous studies show that poricoic acid A (PAA) isolated from Poria cocos is a potent anti-fibrotic agent. In the present study we investigated the effects of PAA on renal fibroblast activation and interstitial fibrosis and the underlying mechanisms. Renal interstitial fibrosis was induced in rats or mice by unilateral ureteral obstruction (UUO). UUO rats were administered PAA (10 mg·kg−1·d−1, i.g.) for 1 or 2 weeks. An in vitro model of renal fibrosis was established in normal renal kidney fibroblasts (NRK-49F cells) treated with TGF-β1. We showed that PAA treatment rescued Sirt3 expression, and significantly attenuated renal fibroblast activation and interstitial fibrosis in both the in vivo and in vitro models. In TGF-β1-treated NRK-49F cells, we demonstrated that Sirt3 deacetylated β-catenin (a key transcription factor of fibroblast activation) and then accelerated its ubiquitin-dependent degradation, thus suppressing the protein expression and promoter activity of pro-fibrotic downstream target genes (twist, snail1, MMP-7 and PAI-1) to alleviate fibroblast activation; the lysine-49 (K49) of β-catenin was responsible for Sirt3-mediated β-catenin deacetylation. In molecular docking analysis, we found the potential interaction of Sirt3 and PAA. In both in vivo and in vitro models, pharmacological activation of Sirt3 by PAA significantly suppressed renal fibroblast activation via facilitating β-catenin K49 deacetylation. In UUO mice and NRK-49F cells, Sirt3 overexpression enhanced the anti-fibrotic effect of PAA, whereas Sirt3 knockdown weakened the effect. Taken together, PAA attenuates renal fibroblast activation and interstitial fibrosis by upregulating Sirt3 and inducing β-catenin K49 deacetylation, highlighting Sirt3 functions as a promising therapeutic target of renal fibroblast activation and interstitial fibrosis.

Cannibalism is commonly found among phytoseiids at almost all mobile life stages. The avoidance of kin cannibalism in the presence of non-kin has been observed in a limited number of phytoseiid species. However, studies examining kin recognition by individuals at different life stages are limited. Early experience with conspecifics can alter individuals' social behaviour at later stages. In this study, we examined the influence of ontogenetic isolation on cannibalism and kin recognition by the predatory mite Amblyseius herbicolus (Chant) (Acari: Phytoseiidae) at different life stages. In a choice test, A. herbicolus protonymphs, deutonymphs, pre-ovipositional adults, and ovipositional adults were used as predators, and larvae (siblings vs. non-siblings) were given as prey. Two rearing treatments were applied to the predators to generate different social experience during ontogeny: reared in isolation or in pairs with ad libitum mixed stages of Carpoglyphus lactis (Acari: Carpoglyphidae). Social experience with siblings during ontogeny significantly reduced the cannibalism rate. Despite the social experience during ontogeny, protonymphs, deutonymphs, and pre-ovipositional adults did not discriminate siblings from non-siblings during cannibalism. The discrimination behaviour between siblings and non-siblings of A. herbicolus occurred after adults became ovipositional. We hypothesize that A. herbicolus adults could learn the characteristics of their larvae through the contact with and assessment of their eggs during oviposition. The result of this study shows that kin discrimination could be phase-specific. Future studies can investigate if contact with non-kin (or non-sibling) eggs and subsequently hatching larvae can influence the discrimination ability of ovipositional adults.

To study the clinical value of three-dimensional ultrasonography (3D-US) in the morphological evaluation of rotator cuff tears (RCTs).Based on previously published literature, RCT patterns in our study were divided into crescent, L-shaped with the remnant tendon retracted to the anterior rotator cuff (aL-shaped), L-shaped with the remnant tendon retracted to the posterior rotator cuff (pL-shaped), T-shaped (a tear pattern that is a combination of aL-shaped and pL-shaped), U-shaped, and massive type. Two radiologists prospectively assessed the tear patterns using 3D-US as well as magnetic resonance imaging (MRI) and compared these results using arthroscopy to calculate diagnostic accuracy.Fifty-two patients (52 shoulders) were enrolled. The overall diagnostic accuracy of 3D-US in evaluating RCT patterns (82.7%, 43/52; 95% CI: 72.1-93.3%) was significantly higher (p = 0.008) than that of the MRI (57.7%, 31/52; 95% CI: 45.8-73.4%). The accuracy of 3D-US was higher than that of MRI for most types of tears (crescent: 95.0% vs. 55.0%, aL-shaped: 83.3% vs. 77.8%, pL-shaped: 50.0% vs. 25.0%, T-shaped: 75.0% vs. 0.0%, and massive type: 80.0% vs. 100.0%). The accuracies of 3D-US with respect to evaluation by the two radiologists were 84.6% (44/52) and 76.9% (40/52), and there was substantial agreement evident (κ = 0.709). The time taken by the two radiologists to reconstruct the 3D-US images and evaluate the tear pattern was5 min.The 3D-US can be used for the preoperative evaluation of RCT patterns, and thus be useful for the correct selection of the surgical repair technique for RCTs.• Few studies have been found exploring the value of 3D-US for the morphological evaluation of RCTs and correlated with the arthroscopic findings. • Based on previous studies on the morphological classification, anterior L shape (aL-shaped), and posterior L shape (pL-shaped) were used for the first time to describe the torn patterns of RCT.

Extensive protein synthesis is necessary for uncontrolled cancer cell proliferation, requiring hyperactive ribosome biogenesis. Our previous Pan-cancer study has identified EXOSC8 as a potential copy number variation (CNV)-driven rRNA metabolism-related oncogene in colorectal cancer (CRC). Herein, we further investigated proliferation-prompting functions and mechanisms of EXOSC8 in CRC by performing in silico analyses and wet-lab experiments. We uncovered that increased EXOSC8 expression and CNV levels are strongly associated with ribosome biogenesis-related factor levels in CRC, including ribosome proteins (RPs), eukaryotic translation initiation factors and RNA polymerase I/III. EXOSC8 silence decreases nucleolar protein and proliferation marker levels, as well as rRNA/DNA and global protein syntheses. Clinically, EXOSC8 is upregulated across human cancers, particularly CNV-driven upregulation in CRC was markedly associated with poor clinical outcomes. Mechanistically, EXOSC8 knockdown increased p53 levels in CRC, and the oncogenic proliferation phenotypes of EXOSC8 depended on p53 in vitro and in vivo. We discovered that EXOSC8 knockdown in CRC cells triggers ribosomal stress, nucleolar RPL5/11 being released into the nucleoplasm and "hijacking" Mdm2 to block its E3 ubiquitin ligase function, thus releasing and activating p53. Furthermore, our therapeutic experiments provided initial evidence that EXOSC8 might serve as a potential therapeutic target in CRC. Our findings revealed, for the first time, that the RNA exosome gene (EXOSC8) promotes CRC tumorigenesis by regulating cancer-related ribosome biogenesis in CRC. This study further extends our previous Pan-cancer study of the rRNA metabolism-related genes. The inhibition of EXOSC8 is a novel therapeutic strategy for the RPs-Mdm2-p53 ribosome biogenesis surveillance pathway in CRC.

The aim of this study was to investigate the underlying protective mechanisms of asiaticoside (AS) against liver fibrosis (LF) both in vivo and in vitro. A rat model with carbon tetrachloride (CCl

In order to explore the adsorption characteristics of phosphorus from molecules with different molecular structures and varying number of phosphate groups on metal-modified biochar, walnut shell biochar was modified with LaCl

Granular waste rocks filled in goaf can replace coal seams to support roofs, thus reducing the extent of overlying strata movement, and thus reducing the environment damage caused by coal mining. To better to control the compression-induced deformation (CID) of waste rocks for backfill (WRBs), a loose material, it is feasible to apply lateral cyclic loads on granular waste rocks in advance. In order to study the effect of lateral cyclic loading on granular waste rocks, by utilising pre-lateral cyclic loading and axial loading, the deformation of granular waste rocks under load was tested on a compression simulation experimental platform for solid backfill materials. Furthermore, the changes in displacement, stress and mass of granular waste rocks during lateral cyclic loading were attained. The test results showed that (1) the loading stress progressively increased with the growth of the loading displacement, in which the rising process was divided into three stages according to the rate of loading. (2) With the increase in number of loading cycles, the rate of increase of stress in stage I increased and the stress reached increasingly higher levels; at the same time, stage II was gradually shortened. Eventually, only a single stage prevailed as the stress rapidly reached its preset maximum value, and the final displacement of the samples gradually declined. (3) The axial stress-strain curves of the samples exhibited a quasi-exponential relationship. Through lateral cyclic loading, the relative density of WRBs was significantly improved, and their deformation resistance was strengthened. (4) During backfill mining, lateral cyclic loads were applied to granular waste rocks, which improved the bearing capacity thereof and reduced strata movement and surface subsidence. This is beneficial to the protection of the surface environment and surrounding buildings.

In this paper, we study the dynamics of rogue waves on the doubleperiodic background for a nonlinear Schrodinger equation with higher-order effects. First, we consider two types of double-periodic solutions in terms of the Jacobi elliptic functions. When the elliptic modulus approaches 1, such both double-periodic wave solutions can reduce to the Akhmediev breather solution. Second, with both double-periodic waves as seed solutions, we derive rogue wave solutions from the Darboux transformation method. Further, we demonstrate localized structures of rogue waves formed on double-periodic waves for two sets of different eigenvalues. In addition, we discuss how the higher-order effect affects double-periodic background waves and rogue waves. We expect that our obtained results may help understand rogue waves manifestations on the double-periodic background occurring in hydrodynamics and nonlinear optics with higher-order effects.PACS numbers: 05.45.Yv, 02.30.Ik

This paper proposes a new stochastic eco-epidemiological model with nonlinear incidence rate and feedback controls. First, we prove that the stochastic system has a unique global positive solution. Second, by constructing a series of appropriate stochastic Lyapunov functions, the asymptotic behaviors around the equilibria of deterministic model are obtained, and we demonstrate that the stochastic system exists a stationary Markov process. Third, the conditions for persistence in the mean and extinction of the stochastic system are established. Finally, we carry out some numerical simulations with respect to different stochastic parameters to verify our analytical results. The obtained results indicate that the stochastic perturbations and feedback controls have crucial effects on the survivability of system.

Background Previous meta-analysis had concluded that desferrioxamine mesylate (DFO) could effectively treat intracerebral hematoma (ICH) in animal models. We hope to confirm that DFO could treat ICH patients effectively through the systemic review and meta-analysis of clinical researches. Method Data extraction included hematoma volume (HV), reduction of National Institute of Health Stroke Scale (NIHSS) scores, and relative perihematomal edema (RPHE). The standard mean difference (SMD) and 95% confidence interval (95%CI) were calculated by fixed effects model. I-square (I2) statistic was used to test the heterogeneity. All p values were two-side with a significant level at 0.05. Results Five randomized controlled trials were included in the meta-analysis, which included 239 patients. At 7 days after onset, there was significant difference of RPHE development (− 1.87 (− 2.22, − 1.51) (I2 = 0, p = 0.639)) and significant difference of HV absorption (− 0.71 (− 1.06, 0.36) (I2 = 17.5%, p = 0.271)) between DFO and control groups. There was significant difference of reduction of NHISS scores (0.25 (0.05, 0.46) (I2 = 0, p = 0.992)) between DFO and control groups at 30 days after onset. Conclusion DFO reduced HV and perihematomal edema in ICH patients at 7 days after onset and improve neurological function at 30 days after onset efficiently and safely. DFO might be a new route of improving treatment of ICH.