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Background: CTLA4, an immune checkpoint, plays an important role in tumor immunotherapy. The purpose of this study was to develop a pathomics signature to evaluate CTLA4 expression and predict clinical outcomes in clear cell renal cell carcinoma (ccRCC) patients. Methods: A total of 354 patients from the TCGA-KIRC dataset were enrolled in this study. The patients were stratified into two groups based on the level of CTLA4 expression, and overall survival rates were analyzed between groups. Pathological features were identified using machine learning algorithms, and a gradient boosting machine (GBM) was employed to construct the pathomics signatures for predicting prognosis and CTLA4 expression. The predictive performance of the model was subsequently assessed. Enrichment analysis was performed on diferentially expressed genes related to the pathomics score (PS). Additionally, correlations between PS and TMB, as well as immune infiltration profiles associated with different PS values, were explored. In vitro experiments, CTLA4 knockdown was performed to investigate its impact on cell proliferation, migration, invasion, TGF-β signaling pathway, and macrophage polarization. Results: High expression of CTLA4 was associated with an unfavorable prognosis in ccRCC patients. The pathomics signature displayed good performance in the validation set (AUC = 0.737; P

Rearranged renal cell carcinomas (RCC) are rare types of kidney cancer. The clinicopathological features of rearranged RCC require further validation. The pathological diagnosis usually depends on immunohistochemistry and molecular analysis. This study aimed to explore the expression features of anti-TFE3, TFEB, and ALK in different renal entities. In addition, we collected thirty-six TFE3-rearranged RCC, two TFEB-altered RCC, and one ALK-rearranged RCC to explore their clinicopathological features. We observed that TFE3 can sometimes be weakly expressed in non-TFE3-rearranged RCC. TFE3-rearranged RCC usually exhibited strong TFE3 expression. However, clear cell RCC and FH-deficient RCC also displayed strong TFE3 expression. TFEB also can be weakly expressed in clear cell RCC. However, ALK IHC showed a relatively high specificity and was negative for all non-ALK-rearranged RCC. The ALK-rearranged RCC was analyzed using next generation sequencing to explore gene alterations, and we identified a novel gene partner, SLIT1. ALK-rearranged RCC appears to have eosinophilic cytoplasm. Tumor cells with clear cytoplasm may exclude this diagnosis. Psammomatous bodies (22/38) and pattern multiplicity (35/38) were observed in more than half of the patients. In conclusion, weak TFE3 expression did not indicate TFE3 rearrangement. Strong TFE3 expression had a higher value for indicating TFE3-rearranged RCC, although other entities can also exhibit a strong pattern. Young age combined with morphological features (psammomatous calcification and pattern multiplicity) may indicate the diagnosis of rearranged RCC.

Summary: Cardiotoxicity induced by anticancer drugs interferes with the continuation of optimal treatment, inducing life-threatening risks or leading to long-term morbidity. The heart is a complex pluricellular organ comprised of cardiomyocytes and non-cardiomyocytes. Although the study of these cell populations has been often focusing on cardiomyocytes, the contributions of non-cardiomyocytes to development and disease are increasingly being appreciated as both dynamic and essential. This review summarized the role of non-cardiomyocytes in anticancer drug-induced cardiotoxicity, including the mechanism of direct damage to resident non-cardiomyocytes, cardiomyocytes injury caused by paracrine modality, myocardial inflammation induced by transient cell populations and the protective agents that focused on non-cardiomyocytes.

With the intensification of global climate change, the precipitation patterns are altered and grassland ecosystem is facing biodiversity loss and ecosystem services decline. It is of ecological significance to explore the underlying mechanisms of change in multiple ecosystem functions and services (multifunctionality) under altered precipitation. Plant community diversity (species, functional and phylogenetic diversity) has been proposed inducing links between ecosystem multifunctionality and environmental changes. However, which facet of plant community diversity can predict ecosystem function better remains controversial. Here, species, functional and phylogenetic diversity were investigated along precipitation gradients (−60%, −40%, −20%, CK, +20%, +40% and +60%) in the desert steppe of Inner Mongolia. In addition, ecosystem multifunctionality indices (averaging multifunctionality and threshold multifunctionality) were determined by eleven functions to assess the relationship between plant community diversity and multifunctionality under altered precipitation. We found that +40% and +60% precipitation significantly increased species richness by 52% and 33% and increased averaging multifunctionality by 20% and 46%. Functional and phylogenetic diversity at +60% precipitation were significantly higher than that at −60% treatment. Multifunctionality indices were positively correlated with precipitation gradients and plant community diversity. Importantly, species diversity possessed stronger predictive power of averaging multifunctionality than functional and phylogenetic diversity, which explained averaging multifunctionality of more than 38%. These results indicate that altered precipitation can change species composition of plant community and functions of ecosystem, further resulting in the closed relationship between species diversity and ecosystem multifunctionality. Our results highlight the critical role of species diversity in predicting multifunctionality of the altered precipitation conditions in desert steppes.

Increasing lines of evidence identified that dexmedetomidine (DEX) exerted protective effects against sepsis-stimulated acute lung injury via anti-inflammation, anti-oxidation and anti-apoptosis. However, the mechanisms remain unclear. Herein, we investigated whether DEX afforded lung protection by regulating the process of mitochondrial dynamics through the HIF-1a/HO-1 pathway in vivo and in vitro. Using C57BL/6J mice exposed to lipopolysaccharide, it was initially observed that preemptive administration of DEX (50μg/kg) alleviated lung pathologic injury, reduced oxidative stress indices (OSI), improved mitochondrial dysfunction, upregulated the expression of HIF-1α and HO-1, accompanied by shifting the dynamic course of mitochondria into fusion. Moreover, HO-1-knockout mice or HO-1 siRNA transfected NR8383 cells were pretreated with HIF-1α stabilizer DMOG and DEX to validate the effect of HIF-1a/HO-1 pathway on DEX-mediated mitochondrial dynamics in a model of endotoxin-induced lung injury. We found that pretreatment with DEX and DMOG distinctly relieved lung injury, decreased the levels of mitochondrial ROS and mtDNA, reduced OSI, increased nuclear accumulation of HIF-1a and HO-1 protein in wild type mice but not HO-1 KO mice. Similar observations were recapitulated in NC siRNA transfected NR8383 cells after LPS stimulation but not HO-1 siRNA transfected cells. Concertedly, DEX reversed the impaired mitochondrial morphology in LPS stimulated-wild type mice or NC siRNA transfected NR8383 cells, upregulated the expression of mitochondrial fusion protein, while downregulated the expression of fission protein in HIF-1a/HO-1 dependent pathway. Altogether, our data both in vivo and in vitro certified that DEX treatment ameliorated endotoxin-induced acute lung injury by preserving the dynamic equilibrium of mitochondrial fusion/fission through the regulation of HIF-1a/HO-1 signaling pathway.

Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) are prone to anoikis after single cell dissociation. The small molecule, Y-27632 is known to increase survival of hESCs and hiPSCs by inhibiting the Rho-associated protein kinase (ROCK). However, the underlying mechanisms are still unclear. Here, we thoroughly screened small molecules to investigate the adhesion and survival of hESCs in adherent culture. Y-27632 provided higher adhesion and survival of hESCs by increased cell migration and preventing cell blebbing in single dissociated cells. The combination of Matrigel with poly-d-lysine increased the attachment and survival of dissociated cells via actin filament and microtubule spreading in Y-27632-treated cells. Although Y-27632 prevented apoptosis by suppressing actin filament contraction, microtubule bundling, and blebbing, prolonged Y-27632 treatment presented a different morphology in the attached growing hESC colony. It induced apoptosis of cells by promoting cytoplasmic spread, E-cadherin structural change, and increased detachment. It also induced actin cytoskeleton disruption, combined with microtubule and intermediate filament elongation. For optimal hPSC culture, our research suggests that Y-27632 should be removed shortly after passaging. Keywords: Cytoskeletal changes, ROCK inhibitor, Apoptosis, Human embryonic stem cells, Adhesion, Extracellular matrices

Unmanned aerial vehicle (UAV) synthetic aperture radar (SAR) image characteristics, such as large geometric distortions, striped inhomogeneous radiation, severe speckle noise and ultra-high resolution, pose significant challenges to multi-view UAV SAR image registration. To address these issues, we propose a robust multi-view UAV SAR image registration algorithm based on the selective correlation of the log gradient descriptor. First, slant range UAV SAR images are geocoded using a publicly available digital elevation model to attenuate the topographic distortions. Second, we follow a template matching framework to obtain gridded correspondences. A log gradient that effectively handles noise in dark areas while resisting speckle noise is developed. A histogram of oriented log gradient (HOLG) is designed based on a simplified histogram of oriented gradient structure to weaken the effects of striped radiation noise. Moreover, a selective correlation strategy is designed, and a similarity metric named HOLGSC is proposed based on the selective correlation of the HOLG descriptors to overcome the effects of the unstable geometric structures of shadows and trees. Finally, after removing outliers from the matching results, we introduce the as-projective-as possible transformation model to establish geometric correspondences. We obtain several UAV SAR images and compose nine multi-view UAV SAR image pairs for experiments. The experimental results confirm that the proposed algorithm is effective and outperforms the existing state-of-the-art algorithms. In addition, a preliminary stitching result of these UAV SAR images is also presented.

Purpose: This randomized controlled trial aimed to study the effects of Yijinjing plus Elastic Band Resistance exercise on intrahepatic lipid (IHL), body fat distribution, glucolipid metabolism and biomarkers of inflammation in middle-aged and older people with pre-diabetes mellitus (PDM). Participants agesnd methods: 34 PDM participants (mean age, 62.62 ± 4.71 years; body mass index [BMI], 25.98 ± 2.44 kg/m2) were randomly assigned to the exercise group (n = 17) or control group (n = 17). The exercise group performed moderate-intensity Yijinjing and Elastic Band Resistance training 5 times per week for 6 months. The control group maintained their previous lifestyle. We measured body composition (body weight and body fat distribution), IHL, plasma glucose, lipid and the homeostatic model assessment of insulin resistance (HOMA-IR), inflammatory cytokines at baseline and 6 months. Results: Compared with baseline, exercise significantly reduced IHL (reduction of 1.91 % ± 2.61 % vs an increase of 0.38 % ± 1.85 % for controls; P = 0.007), BMI (reduction of 1.38 ± 0.88 kg/m2 vs an increase of 0.24 ± 1.02 kg/m2 for controls; P = 0.001), upper limb fat mass, thigh fat mass and whole body fat mass. Fasting glucose, HOMA-IR, plasma total cholesterol (TC), and triglyceride (TG) were decreased in the exercise group (P

In this study, we aimed to establish an innovative and efficient preparation method of potato resistant starch (PRS). To achieve this, we prepared type 3 resistant starch (RS3) from native potato starch (PS) using an ultrasonic method combined with autoclave gelatinization and optimized by the response surface method to study the structure and properties of potato RS3 (PRS3) and its effect on the quality of steamed bread. Under optimal treatment conditions, the PRS3 content increased from 7.5% to 15.9%. Compared with PS, the B-type crystal structure of PRS3 was destroyed, and the content of hydroxyl groups was increased, but no new chemical groups were introduced. PRS3 had a rougher surface and a lower crystallinity, gelatinization temperature, viscosity, setback value, and breakdown value. The low content (5%) of PRS3 had a stable viscosity and was easily degraded by bacteria, which can improve the quality of steamed bread to a certain extent. When the PRS3 content was over 10%, it competed with the gluten protein to absorb water, which reduced the contents of β-turn and α-helix in the dough, increased the contents of β-fold, and weakened the structure of the gluten network. It also decreased the specific volume and elasticity of the steamed bread and increased the spreading rate, hardness, and chewiness. Steamed bread prepared with a flour mixture containing 5% PRS3 was similar to the presidential acceptance of control flour. In this study, a new sustainable and efficient PRS3 preparation method was established, which has certain guiding significance for the processing of Functional steamed bread with high-resistant starch.

This paper presents a theoretical and numerical study of angle steel joints for conductors in transmission tower structures in the medium and heavy icing area. The results show that the deformation of the angle steel joint in suspension towers is controlled by the vertical load, and the deformation of the angle steel joint in strain towers is controlled by the tension load. The bolt of the angle steel joint for conductors is tension-controlled. A theoretical method considering the bending stiffness ratio of the angle steel plate and the bolt is derived. The proposed theoretical method quantifies the bending stiffness difference in the angle steel plate and bolt group, and the effects of bolt layout and load cases are considered. The numerical results are in good agreement with theoretical results by validating the internal forces and neutral axis depth. The accuracy of the proposed theoretical method is higher than that of theoretical methods based on steel structure principles. The proposed theoretical method is of great significance to the development of transmission tower structure design.

Although active constituents extracted from plants show robust in vitro pharmacological effects, low in vivo absorption greatly limits the widespread application of these compounds. A strategy of using phyto-phospholipid complexes represents a promising approach to increase the oral bioavailability of active constituents, which is consist of ‘‘label-friendly” phospholipids and active constituents. Hydrogen bond interactions between active constituents and phospholipids enable phospholipid complexes as an integral part. This review provides an update on four important issues related to phyto-phospholipid complexes: active constituents, phospholipids, solvents, and stoichiometric ratios. We also discuss recent progress in research on the preparation, characterization, structural verification, and increased bioavailability of phyto-phospholipid complexes. Keywords: Phyto-phospholipid complexes, Active constituents, Hydrogen bonds, Bioavailability

Purpose: This study aimed to evaluate the effect of delayed lactogenesis Ⅱ on early milk volume in mothers expressing milk for their preterm infants. Methods: 142 mothers with preterm infants participated in a longitudinal cohort study, the milk volumes over 14 days postpartum between mothers with delayed lactogenesis Ⅱ (≥ 72 hours) and mothers with non-delayed lactogenesis Ⅱ(< 72 hours) were compared using Wilcoxon's rank sum tests. Results: The prevalence of delayed lactogenesisⅡ among mothers of preterm infants was 36.0% (36/100). There existed negative correlations between the onset of lactogenesis Ⅱ and the daily milk volumes( rs = −0.525∼−0.354, p = .002 ∼ p < .001). The milk volumes in every 24-hour of the 14 days postpartum in delayed group were significantly less than that in non-delayed group (p = .002 ∼ p < .001). After controlling for the covariates, pregnancy-induced hypertension syndrome, delayed expression initiation, shorter daily sleeping time were found to be the risk factors for delayed lactogenesis Ⅱ. Conclusion: Delayed lactogenesis Ⅱ was associated with lower milk volume in early postpartum period. Women who were at risk for delayed lactogenesis Ⅱ need targeted interventions and additional support during pregnancy and postpartum. Keywords: lactation, milk, human, premature birth