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Venetoclax and obinutuzumab are becoming frontline therapies for chronic lymphocytic leukemia (CLL) patients. Unfortunately, drug resistance still occurs, and the combination could be immunosuppressive. Lysosomes have previously been identified as a target for obinutuzumab cytotoxicity in CLL cells, but the mechanism remains unclear. In addition, studies have shown that lysosomotropic agents can cause synergistic cell death in vitro when combined with the BTK inhibitor, ibrutinib, in primary CLL cells. This indicates that targeting lysosomes could be a treatment strategy for CLL. In this study, we have shown that obinutuzumab induces lysosome membrane permeabilization (LMP) and cathepsin D release in CLL cells. Inhibition of cathepsins reduced obinutuzumab-induced cell death in CLL cells. We further determined that the lysosomotropic agent siramesine in combination with venetoclax increased cell death in primary CLL cells through an increase in reactive oxygen species (ROS) and cathepsin release. Siramesine treatment also induced synergistic cytotoxicity when combined with venetoclax. Microenvironmental factors IL4 and CD40L or incubation with HS-5 stromal cells failed to significantly protect CLL cells from siramesine- and venetoclax-induced apoptosis. We also found that siramesine treatment inhibited autophagy through reduced autolysosomes. Finally, the autophagy inhibitor chloroquine failed to further increase siramesine-induced cell death. Taken together, lysosome-targeting drugs could be an effective strategy in combination with venetoclax to overcome drug resistance in CLL. [ABSTRACT FROM AUTHOR]

The interaction between fig wasps and their host fig trees (Ficus spp.) is a striking example of an obligate pollination mutualism. Male and female fig wasps are confined within their natal patch instead of panmictic; under this circumstance, mating only occurs between individuals of the same patch. This is known as a local mate competition (LMC). It pays foundresses to invest mainly in daughters and to only produce enough sons to ensure that all female offspring can be fertilized, but in nature, pollinating fig wasps may face many problems with host quality, such as limitation of oviposition sites and the nutrition deficiency of the host fig. The sex ratio of wasps can determine the stability of fig–fig wasp mutualistic system and, thus, the stability of other species associated with it. In this study, we controlled the quality of host figs in three ways. The results showed that the host fig age can influence the sex ratio of pollinator offspring, while the foundress numbers and the presence of pollen have no significant effect on it. A compelling explanation for this result is that the sex-dependent mortality occurs. This is a novel finding of how host quality influences the interaction of fig and fig wasps, which can also help us understand the evolution and stability mechanism of this symbiotic system. [ABSTRACT FROM AUTHOR]

Objective: To assess lung deformation in patients with idiopathic pulmonary fibrosis (IPF) using with elastic registration algorithm applied to three-dimensional ultrashort echo time (3D-UTE) MRI and analyze relationship of lung deformation with the severity of IPF. Methods: Seventy-six patients with IPF (mean age: 62 ± 6 years) and 62 age- and gender-matched healthy controls (mean age: 58 ± 4 years) were prospectively enrolled. End-inspiration and end-expiration images acquired with a single breath-hold 3D-UTE sequence were registered using elastic registration algorithm. Jacobian determinants were calculated from deformation fields and represented on color maps. Jac-mean (absolute value of the log means of Jacobian determinants) and the Dice similarity coefficient (Dice) were compared between different groups. Results: Compared with healthy controls, the Jac-mean of IPF patients significantly decreased (0.21 ± 0.08 vs. 0.27 ± 0. 07, p < 0.001). Furthermore, the Jac-mean and Dice correlated with the metrics of pulmonary function tests and the composite physiological index. The lung deformation in IPF patients with dyspnea Medical Research Council (MRC) ≥ 3 (Jac-mean: 0.16 ± 0.03; Dice: 0.06 ± 0.02) was significantly lower than MRC1 (Jac-mean: 0. 25 ± 0.03, p < 0.001; Dice: 0.10 ± 0.01, p < 0.001) and MRC 2 (Jac-mean: 0.22 ± 0.11, p = 0.001; Dice: 0.08 ± 0.03, p = 0.006). Meanwhile, Jac-mean and Dice correlated with health-related quality of life, 6 min-walk distance, and the extent of pulmonary fibrosis. Jac-mean correlated with pulmonary vascular-related indexes on high-resolution CT. Conclusion: The decreased lung deformation in IPF patients correlated with the clinical severity of IPF patients. Elastic registration of inspiratory-to-expiratory 3D UTE MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. Critical relevance statement: This prospective study demonstrated that lung deformation decreased in idiopathic pulmonary fibrosis (IPF) patients and correlated with the severity of IPF. Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. Key points: • Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI could evaluate lung deformation. • Lung deformation significantly decreased in idiopathic pulmonary fibrosis (IPF) patients, compared with the healthy controls. • Reduced lung deformation of IPF patients correlated with worsened pulmonary function and the composite physiological index (CPI). [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphologic features, and PCOS is associated with infertility. PH domain Leucine-rich repeat Protein Phosphatase 1 (PHLPP1) has been shown to regulate AKT. The aim of present study is to investigate the role of PHLPP1 in PCOS. Methods: The expression levels of PHLPP1 in dihydrotestosterone (DHT)-treated human ovarian granular KGN cells were determined by qRT-PCR and Western blot. PHLPP1 was silenced or overexpressed using lentivirus. Cell proliferation was detected by CCK-8. Apoptosis and ROS generation were analyzed by flow cytometry. Glycolysis was analyzed by measuring extracellular acidification rate (ECAR). Results: DHT treatment suppressed proliferation, promoted apoptosis, enhanced ROS, and inhibited glycolysis in KGN cells. PHLPP1 silencing alleviated the DHT-induced suppression of proliferation and glycolysis, and promotion of apoptosis and ROS in KGN cells. PHLPP1 regulated cell proliferation and glycolysis in human KGN cells via the AKT signaling pathway. Conclusions: Our results showed that PHLPP1 mediates the proliferation and aerobic glycolysis activity of human ovarian granular cells through regulating AKT signaling. [ABSTRACT FROM AUTHOR]

Carotenoids, as natural tetraterpenes, play a pivotal role in the yellow coloration of peaches and contribute to human dietary health. Despite a relatively clear understanding of the carotenoid biosynthesis pathway, the regulatory mechanism of miRNAs involved in carotenoid synthesis in yellow peaches remain poorly elucidated. This study investigated a total of 14 carotenoids and 40 xanthophyll lipids, including six differentially accumulated carotenoids: violaxanthin, neoxanthin, lutein, zeaxanthin, cryptoxanthin, and (E/Z)-phytoene. An integrated analysis of RNA-seq, miRNA-seq and degradome sequencing revealed that miRNAs could modulate structural genes such as PSY2, CRTISO, ZDS1, CHYB, VDE, ZEP, NCED1, NCED3 and the transcription factors NAC, ARF, WRKY, MYB, and bZIP, thereby participating in carotenoid biosynthesis and metabolism. The authenticity of miRNAs and target gene was corroborated through quantitative real-time PCR. Moreover, through weighted gene coexpression network analysis and a phylogenetic evolutionary study, coexpressed genes and MYB transcription factors potentially implicated in carotenoid synthesis were identified. The results of transient expression experiments indicated that mdm-miR858 inhibited the expression of PpMYB9 through targeted cleavage. Building upon these findings, a regulatory network governing miRNA-mediated carotenoid synthesis was proposed. In summary, this study comprehensively identified miRNAs engaged in carotenoid biosynthesis and their putative target genes, thus enhancing the understanding of carotenoid accumulation and regulatory mechanism in yellow peach peel and expanding the gene regulatory network of carotenoid synthesis. [ABSTRACT FROM AUTHOR]

Multi-View Stereo (MVS) is a crucial technique for reconstructing the geometric structure of a scene, given the known camera parameters. Previous deep learning-based MVS methods have mainly focused on improving the reconstruction quality but overlooked the running efficiency during the actual algorithm deployment. For example, deformable convolutions have been introduced to improve the accuracy of the reconstruction results further, however, its inability for parallel optimization caused low inference speed. In this paper, we propose AdaptMVSNet which is device-friendly and reconstruction-efficient, while preserving the original results. To this end, adaptive convolution is introduced to significantly improve the efficiency in speed and metrics compared to current methods. In addition, an attention fusion module is proposed to blend features from adaptive convolution and the feature pyramid network. Our experiments demonstrate that our proposed approach achieves state-of-the-art performance and is almost 2 × faster than the recent fastest MVS method. We will release our source code. [Display omitted] [ABSTRACT FROM AUTHOR]

Cells with various structures and proteins naturally come together to cooperate in vivo. This study used cell spheroids cultured in agarose micro-wells as a 3D model to study the movement of cells or spheroids toward other spheroids. The formation dynamics of tumor spheroids and the interactions of two batches of cells in the agarose micro-wells were studied. The results showed that a concave bottom micro-well (diameter: 2 mm, depth: 2 mm) prepared from 3% agarose could be used to study the interaction of two batches of cells. The initial tumor cell numbers from 5 × 103 cells/well to 6 × 104 cells/well all could form 3D spheroids after 3 days of incubation. Adding the second batch of DU 145 cells to the existing DU 145 spheroid resulted in the formation of satellite cell spheroids around the existing parental tumor spheroid. Complete fusion of two generation cell spheroids was observed when the parental spheroids were formed from 1 × 104 and 2 × 104 cells, and the second batch of cells was 5 × 103 per well. A higher amount of the second batch of cells (1 × 104 cell/well) led to the formation of independent satellite spheroids after 48 h of co-culture, suggesting the behavior of the second batch of cells towards existing parental spheroids depended on various factors, such as the volume of the parental spheroids and the number of the second batch cells. The interactions between the tumor spheroids and Human Umbilical Vein Endothelial Cells (HUVECs) were modeled on concave agarose micro-wells. The HUVECs (3 × 103 cell/well) were observed to gather around the parental tumor spheroids formed from 1 × 104, 2 × 104, and 3 × 104 cells per well rather than aggregate on their own to form HUVEC spheroids. This study highlights the importance of analyzing the biological properties of cells before designing experimental procedures for the sequential fusion of cell spheroids. The study further emphasizes the significant roles that cell density and the volume of the spheroids play in determining the location and movement of cells. [ABSTRACT FROM AUTHOR]

Objective: We aimed to quantitatively study the characteristic of diaphragm and chest wall motion using free-breathing dynamic magnetic resonance imaging (D-MRI) in Chinese people with normal lung function. Methods: 74 male subjects (mean age, 37 ± 11 years old) were prospectively enrolled, and they underwent high-resolution CT(HRCT), pulmonary functional tests (PFTs), and D-MRI in the same day. D-MRI was acquired with a gradient-echo sequence during the quiet and deep breathing. The motion of the diaphragm and chest wall were respectively assessed by measuring thoracic anteroposterior diameter (AP), left–right diameter (LR), cranial–caudal diameter (CC), and thoracic area ratios between end-inspiration and end-expiration. The effect of age, body mass index (BMI), and smoking on respiratory muscle function was also analyzed. Results: The mean ratio of right and left AP was greater than that of LR on three transversal planes during both quiet and deep breathing. The mean ratio at the anterior diaphragm (AND, Quiet: 1.04 ± 0.03; Deep: 1.15 ± 0.09) was weaker than that of the apex (vs. APD, Quiet: 1.08 ± 0.05, p < 0.001; Deep: 1.29 ± 0.12, p < 0.001) and posterior diaphragm (vs. POD, Quiet: 1.09 ± 0.04, p < 0.001; Deep: 1.30 ± 0.12, p < 0.001) both in quiet and deep breathing. Compared with non-smokers, the left AP and thoracic area ratios in smokers were significantly decreased (p < 0.05). However, the ratios of AP, LR, CC, and thoracic area on each plane were similar among groups in different age and BMI. Conclusions: During both quiet and deep breathing, the chest wall motion is prominent in the anteroposterior direction. The motions of diaphragm apex and posterior diaphragm were more prominent than that of the anterior diaphragm. Smoking may affect the respiratory muscle mobility. Dynamic MRI can quantitatively evaluate the motion of respiratory muscles. [ABSTRACT FROM AUTHOR]

The secondary metabolites of the phytopathogenic fungus Corynespora cassiicola CC01 from Hevea brasiliensis were investigated. As a result, two new compounds, 5-acetyl-7-hydroxy-6- methoxybenzofuran-2(3H)-one (1) and (S)-2-(2,3-dihydrofuro [3,2-c]pyridin-2-yl)propan-2-ol (2), together with seven known compounds, 4,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one (3), 3,6,8-trihydroxy-3,4-dihydronaphthalen-1(2H)-one (4), curvulin acid (5), 2-methyl-5-carboxymethyl- 7-hydroxychromone (6), tyrosol (7), p-hydroxybenzoic acid (8) and cerevisterol (9), were isolated from the fermentation extract by comprehensive silica gel, reverse phase silica gel, Sephadex-LH20 column chromatography and high-performance liquid chromatography (HPLC). The structures of these compounds were identified by using high-resolution electrospray mass spectrometry (HRESIMS), nuclear magnetic resonance spectroscopy (NMR), optical rotation, ultraviolet and infrared spectroscopy techniques and a comparison of NMR data with those reported in the literature. Compounds 1 and 2 were new compounds, and compounds 3–9 were discovered from this phytopathogenic fungus for the first time. Compounds 1–9 were tested for phytotoxicity against the fresh tender leaf of Hevea brasiliensis, and the results show that none of them were phytotoxic. Additionally, these compounds were subjected to an antimicrobial assay against three bacteria (E. coli, methicillin-resistant Staphylococcus aureus and Micrococcus luteus), but they showed no activity. [ABSTRACT FROM AUTHOR]

Tea polysaccharide (TPS) is the second most abundant ingredient in tea following tea polyphenols. As a complex polysaccharide, TPS has a complex chemical structure and a variety of bioactivities, such as anti-oxidation, hypoglycemia, hypolipidemic, immune regulation, and anti-tumor. Additionally, it shows excellent development and application prospects in food, cosmetics, and medical and health care products. However, numerous studies have shown that the bioactivity of TPS is closely related to its sources, processing methods, and extraction methods. Therefore, the authors of this paper reviewed the relevant recent research and conducted a comprehensive and systematic review of the extraction methods, physicochemical properties, and bioactivities of TPS to strengthen the understanding and exploration of the bioactivities of TPS. This review provides a reference for preparing and developing functional TPS products. [ABSTRACT FROM AUTHOR]

A tapered pile (TP) is a new type of pile with a good bearing capacity, and scholars have conducted in-depth research on its static bearing characteristics. However, there is relatively little research on its dynamic bearing characteristics. In this paper, the horizontal vibration behavior of a tapered pile in arbitrarily layered soil is studied. Utilizing the Winkler foundation model and Timoshenko beam model to simulate pile-surrounding soil (PSS) and a tapered pile, respectively, the horizontal vibration model of a tapered pile embedded in layered soil was built. The analytical solutions for the horizontal displacement (HD), bending moment (BM), and shear force (SF) of a tapered pile were derived, and then the solutions for the horizontal dynamic impedance (HDI), rocking dynamic impedance (RDI), and horizontal-rocking coupling dynamic impedance (HRDI) of pile head were obtained. Using the present solutions, the effects of soil and pile properties on the horizontal vibration characteristics of a tapered pile were systemically studied. The ability of a tapered pile–soil system to resist horizontal vibration can be improved by strengthening the upper soil, but this ability cannot be further improved by increasing the thickness of the strengthened upper soil if its thickness is greater than the critical influence thickness. [ABSTRACT FROM AUTHOR]

The vertical vibration of a viscoelastic pile immersed in arbitrarily layered soil is investigated by taking the interaction among pile, pile surrounding soil (PSS) and pile end soil (PES) into account. Firstly, considering both the stratification and stress wave effect of soil, a mathematical model of the pile–soil system is established based on the fictitious soil pile (FSP) model. Then, utilizing the impedance function transfer method and Laplace transform technique, the analytical solutions of the vertical dynamic impedance of pile are derived in the frequency domain. The analytical solutions are validated by comparing them with other existing solutions. Finally, a parametric study is put forward to investigate the properties of PES on the vertical dynamic impedance of pile. The results reveal that the properties of PES have a significant effect on the vertical dynamic impedance of pile, but there is a critical influence thickness for this effect. For the cases of the PES thickness exceeding the critical influence thickness, further increase of PES thickness will not affect the dynamic behavior of the pile–soil system. [ABSTRACT FROM AUTHOR]

A novel multidimensional fitness function genetic algorithm is proposed to optimize test vectors of R-2R Digital-to-Analog Converters (DAC). The proposed method employs distribution of characteristic vectors and the number of test vectors to formulate a multidimensional fitness function to search a non-dominate (ND) solution set. The searching process is directed by a ND sort method. Each individual in the ND set does not contain redundant test vectors. The test vectors are taken as the input excitation of the circuit under test (CUT) and the fault diagnosis is performed. As the number of test vectors increases, the accuracy of fault diagnosis also increases. The validity of the proposed method is verified by fault diagnosis. The average fault diagnosis rate is more than 85% for the R-2R network under the influence of tolerance. In addition, the parametric faults of ± 50 % deviation from the nominal value in each resistor of the R-2R network can be detected in the proposed method. Finally, the comparative experiments and results are briefly described in this paper. [ABSTRACT FROM AUTHOR]

Objective: To investigate the associations between pre-pregnancy body mass index (BMI) and neonatal outcomes in women undergoing autologous frozen-thawed embryo transfer (FET).Design: Retrospective cohort study.Setting(s): University-affiliated reproductive medical center.Patient(s): A total of 16,240 women with singleton deliveries achieved by autologous FET.Intervention(s): None.Main Outcome Measure(s): Neonatal outcomes included preterm birth (PTB), low birth weight (LBW), small-for-gestational age (SGA), large-for-gestational age (LGA), fetal macrosomia, and birth defects.Result(s): After adjusting for confounding factors, our study showed that in autologous FET cycles, the overweight women (23 kg/m2≤ BMI <27.5 kg/m2) were associated with increased rates of PTB (adjusted odds ratio [aOR], 1.226; 95% confidence interval [CI], 1.060-1.418), macrosomia (aOR, 1.692; 95% CI, 1.491-1.921), and LGA (aOR, 1.980; 95% CI, 1.715-2.286); and the obese women (BMI ≥27.5 kg/m2) were significantly associated with increased PTB (aOR, 1.503; 95% CI, 1.167-1.936), early PTB (aOR, 2.829; 95% CI, 1.679-4.765), very LBW (aOR, 3.087; 95% CI, 1.720-5.542), macrosomia (aOR, 2.325; 95% CI, 1.862-2.904), and LGA (aOR, 3.235; 95% CI, 2.561-4.085). The rate of SGA infants was higher in the underweight women (BMI <18.5 kg/m2) (aOR, 1.687; 95% CI, 1.375-2.071) than that in the normal-weight women (18.5 kg/m2≤ BMI ≤23 kg/m2). No significant difference was observed in the risk of birth defects between normal-weight cases and other BMI categories.Conclusion(s): Among women undergoing FET, pre-pregnancy BMI affected neonatal outcomes of singletons. BMI in Asian categories for overweight and obese showed significant increases in PTB, macrosomia, and LGA; early PTB and very LBW only increased in obese cases. In addition, underweight status was associated with increased risk of SGA. In contrast, there was no association between pre-pregnancy BMI and birth defects in FET cycles. [ABSTRACT FROM AUTHOR]

The experience in virtual reality (VR) is unique, in that observers are in a real-world location while browsing through a virtual scene. Previous studies have investigated the effect of the virtual environment on distance estimation. However, it is unclear how the real-world environment influences distance estimation in VR. Here, we measured the distance estimation using a bisection (Experiment 1) and a blind-walking (Experiments 2 and 3) method. Participants performed distance judgments in VR, which rendered either virtual indoor or outdoor scenes. Experiments were also carried out in either real-world indoor or outdoor locations. In the bisection experiment, judged distance in virtual outdoor was greater than that in virtual indoor. However, the real-world environment had no impact on distance judgment estimated by bisection. In the blind-walking experiment, judged distance in real-world outdoor was greater than that in real-world indoor. On the other hand, the virtual environment had no impact on distance judgment estimated by blind-walking. Generally, our results suggest that both the virtual and real-world environments have an impact on distance judgment in VR. Especially, the real-world environment where a person is physically located during a VR experience influences the person's distance estimation in VR. [ABSTRACT FROM AUTHOR]

The experience in virtual reality (VR) is unique, in that observers are in a real-world location while browsing through a virtual scene. Previous studies have investigated the effect of the virtual environment on distance estimation. However, it is unclear how the real-world environment influences distance estimation in VR. Here, we measured the distance estimation using a bisection (Experiment 1) and a blind-walking (Experiments 2 and 3) method. Participants performed distance judgments in VR, which rendered either virtual indoor or outdoor scenes. Experiments were also carried out in either real-world indoor or outdoor locations. In the bisection experiment, judged distance in virtual outdoor was greater than that in virtual indoor. However, the real-world environment had no impact on distance judgment estimated by bisection. In the blind-walking experiment, judged distance in real-world outdoor was greater than that in real-world indoor. On the other hand, the virtual environment had no impact on distance judgment estimated by blind-walking. Generally, our results suggest that both the virtual and real-world environments have an impact on distance judgment in VR. Especially, the real-world environment where a person is physically located during a VR experience influences the person's distance estimation in VR. [ABSTRACT FROM AUTHOR]

Most existing three-dimensional (3D) impact angle guidance laws against maneuvering target focus on terminal-angle-constrained guidance without considering the field-of-view (FOV) limit. In this study, a 3D nonsingular FOV-constrained guidance strategy with the desired impact angles is proposed. The analytical expression between the desired impact angles and terminal light-of-sight angles is derived by integrating the transition matrix in the interception time with the collision triangle theory. A novel fixed-time sliding mode surface is presented and, based on it, guidance commands are generated. The radial basis function neural networks are combined with composite intelligent learning to improve the approximation precision of target maneuvering. Furthermore, a barrier Lyapunov function is used in the pitch plane to satisfy the FOV constraint. For the capturability analysis, the analytical achievable impact sets are calculated. Simulations are demonstrated to verify the effectiveness and robustness of the proposed guidance strategy. [ABSTRACT FROM AUTHOR]

Two major factors contribute to the failure of axonal regrowth in the central nervous system (CNS), namely, the neuronal intrinsic regenerative capacity and the extrinsic local inhibitory microenvironments. However, a preconditioning peripheral nerve lesion could substantially enhance the regeneration of central axons following a subsequent spinal cord injury. In the present review, we summarize the molecular mechanisms of the preconditioning injury effect on promoting axonal regeneration. The injury signal transduction resulting from preconditioning peripheral nerve injury regulates the RAG expression to enhance axonal regeneration. Importantly, preconditioning peripheral nerve injury triggers interactions between neurons and nonneuronal cells to amplify and maintain their effects. Additionally, the preconditioning injury impacts mitochondria, protein, and lipid synthesis. All these coordinated changes endow axonal regeneration. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) constitute a group of >200-nucleotide ncRNA molecules. lncRNAs regulate several cell functions, such as proliferation, apoptosis, invasion and metastasis. Meanwhile, lncRNAs are abnormally expressed in human malignancies, where they suppress or promote tumor growth. The present study focused on growth arrest-specific transcript 5 (GAS5), a well-known lncRNA that acts as a tumor suppressor but is suppressed in multiple types of cancer, including mammary carcinoma, prostate cancer, colorectal cancer, gastric cancer, melanoma, esophageal squamous cell carcinoma, lung cancer, ovarian cancer, cervical cancer, gliomas, osteosarcoma, pancreatic cancer, bladder cancer, kidney cancer, papillary thyroid carcinoma, neuroblastoma, endometrial cancer and liver cancer. Notably, GAS5 is overexpressed in liver cancer, potentially functioning as an oncogene. In the present study, the diagnostic and therapeutic roles of GAS5 in different tumors were reviewed, with a summary of the potential clinical application of the lncRNA, which may help identify novel study directions for GAS5. [ABSTRACT FROM AUTHOR]

Study Question: Is there any association between the number of oocytes retrieved and neonatal outcomes following IVF/ICSI treatment for patients using a freeze-all strategy?Summary Answer: There was no increased risk of adverse neonatal outcomes in cycles with high number of oocytes retrieved (≥ 16) compared to those with 10-15 oocytes retrieved in freeze-all cycles.What Is Known Already: Recent studies have found that there is an increased risk of preterm birth (PTB, <37 weeks gestation) and low birth weight (LBW, <2500 g) following IVF in women with a high number (>20) of oocytes retrieved in fresh embryo transfer (ET) cycles. Other studies have found that there is an association between the number of oocytes retrieved and placenta praevia. However, the association between the number of oocytes retrieved and neonatal outcomes when using a freeze-all strategy is unknown.Study Design, Size, Duration: This retrospective cohort study included 14 170 women with singleton deliveries achieved by a freeze-all strategy performed between November 2006 and December 2017 in China. Only the first delivery from one episode of ovarian stimulation was included.Participants/materials, Setting, Methods: Only cycles using a freeze-all strategy performed during the study period and resulting in singleton live births were included. Patients were categorized into five groups according to the number of oocytes retrieved: 1-3, 4-9, 10-15, 16-20 or >20 oocytes. In univariate and multivariate logistic regression analysis of the association between ovarian response and the outcomes of PTB, early PTB, LBW and other neonatal outcomes, the 10 to 15 oocyte category was used as a reference and other four groups were analysed as dummy variables. Multiple linear regression analysis was used to evaluate possible associations of birth weight z-scores and the number of oocytes retrieved (analysed as a continuous variable) with other confounding factors.Main Results and the Role Of Chance: After adjusted for confounding factors, no significant differences were observed in the risk of PTB (P = 0.837), LBW (P = 0.974), early PTB (P = 0.341), very LBW (P = 0.848), congenital malformation (P = 0.916) and other adverse neonatal outcome among patients with different number of oocytes retrieved. There was a higher risk of early PTB among women with a poor ovarian response (1-3 oocytes) compared with women with a normal response (10-15 oocytes) (1.5% vs 0.8%), crude odds ratio (OR): 2.001, 95% CI: 1.159-3.465, P = 0.013. However, the difference was not significant after adjusting for confounders, adjusted OR: 1.753, 95% CI: 0.997-3.081, P = 0.051.Limitations, Reasons For Caution: Data on some known confounders such as smoking and medical history of gestational diabetes mellitus and preeclampsia were lacking. As with any retrospective study, unknown confounders may affect outcomes.Wider Implications Of the Findings: In the freeze-all cycles, there was no association between number of oocytes retrieved and adverse neonatal outcomes. This is a reassuring finding for both clinicians and patients who are planning to use freeze-all cycles for a variety of indications.Study Funding/competing Interest(s): Grants from the National Natural Science Foundation of China (NSFC) (31770989 to Y.W.) and the Shanghai Ninth People's Hospital Foundation of China (JYLJ030 to Y.W.). None of the authors have any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

A novel structural wall with hinge support and buckling restrained braces (BRBs) set in the base (HWBB) is studied. HWBB can be applied to precast manufacturing due to its considerable ductility and the separate loading mechanism in HWBB–frame structure. In elastic stage, BRBs play a brace role to make the hinged wall resist horizontal forces like a shear wall. BRBs dissipate seismic energy through plastic and hysteresis effects after yielding and the damage is only concentrated in BRBs. The performance of an HWBB is equivalent to a shear wall structure with excellent ductility and stable energy dissipation capacity. Numerical analysis indicates that the hinged wall body in the HWBB well controls the deformation mode of the structure, avoiding the concentration of story drifts, thereby protecting the remaining parts of the structure. It is revealed that the moments of the wall body will generate significant increments after BRBs yielding, and the Seismic Intensity Superposition Method is proposed to calculate the moments. In this method, nonlinear response of an HWBB can be regarded as the sum of the responses of two elastic corresponding structures excited with two parts of the seismic intensity, respectively. Modes and moments equations of the hinged wall with uniform distribution of stiffness and mass are derived, and calculation results coincide with that of the nonlinear time history analysis (NHA). For a more general case, the white noise scan method is proposed to solve the structure's natural characteristics and to further calculate the response. Finally, the post-yielding moment calculation method and the process based on design response spectrum are proposed. It is proved that the moments from proposed Seismic Intensity Superposition Method can envelop most of the moments from NHA, and it is a good estimate of the response of HWBB in nonlinear stage. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Morphology-controllable fabrication of MoS 2 nanostructure has been achieved. • Morphology-evolution mechanism under template-free conditions was proposed. • MoS 2 nanoflower exhibits the enhanced photoreduction activity of Cr(VI). • Nice photostability of MoS 2 nanoflower has been obtained. Abstract Morphology-controllable fabrication of MoS 2 nanostructure assembled from nanosheets has been achieved by a template-free method via mild hydrothermal process. The morphologies of the MoS 2 nanostructure can be modulated by changing the dosage of sodium molybdate, and a possible formation mechanism is proposed. The photocatalytic activity of as-prepared samples is evaluated by photoreduction of Cr(VI) under visible light irradiation. The results reveal that MoS 2 nanoflower structure composed of intersected nanosheets exhibits an enhanced photocatalytic performance, and lots of characterizations are applied to study enhanced photoreduction activities. Good photocatalytic stability can also be observed in 5 cycling tests for the MoS 2 nanoflower. Finally, a possible photocatalytic reduction mechanism is proposed. [ABSTRACT FROM AUTHOR]

Abstract Core-shell structural composites are promising to quench the desire for low-cost, lightweight and multifunctional magnetic materials, but the fabrication of highly pure shell nanoparticles with a desired morphology on a heterogeneous nuclear is still a big challenge. This study gives a successful illustration by in-situ synthesizing BaFe 12 O 19 nanoparticles as a shell on Al 2 O 3 core powders using BaCl 2 and FeCl 3 as precursors, instead of commonly used Ba(NO 3) 2 and Fe(NO 3) 3 , by a modified heterogeneous precipitation process followed by calcination for crystallization. After calcination of the precipitants from the raw precursor mixture of BaCl 2 :FeCl 3 for 1:10 at 800 °C, and for 1:8.5 at 900 °C, respectively, pure BaFe 12 O 19 formed on pristine Al 2 O 3 , mostly with a hexagonal plane, about 100–200 nm in basal diameter and 20–100 nm in thickness. The highest saturation magnetization and coercivity of the coated Al 2 O 3 @ BaFe 12 O 19 powders was 23.3 emu/g and 5149 Oe, quite higher than that of the direct-mixed Al 2 O 3 -BaFe 12 O 19 composite powder, and BaFe 12 O 19 -containing composites reported in literature, which could be attributed to the hexagonal shape of BaFe 12 O 19 and uniform shell dispersion on Al 2 O 3 core. The formation mechanism for the Al 2 O 3 @BaFe 12 O 19 powders was discussed in detail. [ABSTRACT FROM AUTHOR]

Abstract Herein, sucrose-derived hydrothermal carbon spheres have been chosen as the hard template to successfully synthesize the ZnO hollow spheres with trace C remained (denoted as C/ZnO) via the facile adsorption and calcination. By subsequent sulfuration reaction, partial of ZnO in the C/ZnO can convert to ZnS, thus yielding the ternary composites C/ZnS/ZnO. It is found that the resultant ZnS content in the C/ZnS/ZnO hollow nanospheres catalysts could be tuned by the sulfuration time, which greatly affects the photocatalytic activity. Particularly, the C/ZnS/ZnO sample with 30 min sulfuration treatment exhibits the best photocatalytic activity toward the photodegradation of tetracycline (TC) under visible light irradiation. Compared with the commercial ZnO and C/ZnO, both the trace C and ZnS are proved to improve the surface electron-transfer efficiency of the C/ZnS/ZnO hollow nanospheres. Meanwhile, its intrinsic hollow structure also successfully increases the light-harvesting efficiency. As a result, the C/ZnS/ZnO hollow nanospheres are verified to have the multi-enhanced photocatalytic performance. Graphical abstract Image 1 Highlights • Novel hollow C/ZnS/ZnO nanospheres have been successfully constructed. • The hollow structure increases the light-harvesting efficiency. • Sulfuration time tunes ZnS content and affects photocatalytic properties. • The hole (h+) is the main reactive species in the photodegradation process. [ABSTRACT FROM AUTHOR]

The process of rice domestication has been studied for decades based on changing morphological characteristics in assemblages of both macroremains, such as charred seeds and spikelet bases, and microremains, such as phytoliths, esp. bulliform and double-peaked phytoliths. The applicability of these indicators in determining if a specific assemblage is wild or domesticated, however, is rarely discussed. To understand the significance of these indicators in the determination of domestication, we collected 38 archaeological samples from eight Neolithic sites, dating from 10-2ka BP, in the lower Yangtze River region to analyze and compare the changes of these different indicators over eight thousand years. The data demonstrate that the comprehensive analysis of multiple indicators may be the best method to study the process of rice domestication developed thus far. An assemblage of rice remains can be identified as domesticated forms if they meet the following criteria simultaneously: 1) the proportion of domesticated-type bulliform phytoliths is more than 73%; and 2) the proportion of domesticated-type rice spikelet bases is higher than 75%. Furthermore, we found that each indicator tends to change steadily and gradually over time, and each stabilized at a different time, suggesting that the characteristics of domesticated rice developed slowly and successively. Changes of multiple indicators during the period between 10,000–2,000 yr BP indicate that the process of rice domestication in the lower Yangtze River region lasted as long as ca. 6,000 years during the Neolithic, and can be divided into three stages with the turning points in the middle Hemudu-late Majiabang culture (6,500–5,800yr BP) and the late Liangzhu culture (4,600–4,300yr BP). [ABSTRACT FROM AUTHOR]

Optical cavity with backside optical coupling is one of the prevalent optical structures for superconducting nanowire single photon detector. A single layer anti-reflection coating (ARC) on the backside of the substrate is often adopted to enhance the transmittance to the substrate. We here apply a multilayer ARC to further increase the transmittance from 94.5% to 99.5%. An NbTiN SNSPD made on such a substrate with cavity structure presents a system detection efficiency of 90.1% at a dark count rate (DCR) of 100 Hz, which is the best value reported for backside optical coupled SNSPD at 1550 nm. It shows a timing jitter of ∼40.7 ps and the recovery time constant of ∼22.9 ns. [ABSTRACT FROM AUTHOR]

By constructing two scaling matrices, i.e., a function matrix $\Lambda (t)$ and a constant matrix W which is not equal to the identity matrix, a kind of $W-\Lambda(t)$ synchronization between fractional-order and integer-order chaotic (hyper-chaotic) systems with different dimensions is investigated in this paper. Based on the fractional-order Lyapunov direct method, a controller is designed to drive the synchronization error convergence to zero asymptotically. Finally, four numerical examples are presented to illustrate the effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]

Due to the excessive cost and scarcity of Pt metal, it is very vital to enhance the utilization efficiency and recovery yield of Pt-based catalysts. Herein, we employ a facile and simple approach to synthesize the hierarchical γ-Fe 2 O 3 microflowers supported Pt, which is assembled from γ-Fe 2 O 3 nanosheets as building blocks. Further analysis demonstrated that well-dispersed Pt nanoparticles with average size of 1.5 nm are uniformly supported on the γ-Fe 2 O 3 nanosheets and the hierarchical structure provides a large surface area and abundant macropores and mesopores. The resultant Pt/Fe 2 O 3 microflowers show superior catalytic performance for the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP), including high conversion and excellent recycling durability. Furthermore, the unique magnetically separable property of the Pt/Fe 2 O 3 microflowers makes their recovery easy after reaction using an external magnet, which not only saves the cost and time but also tremendously increases the recovery yield of catalyst. Consequently, the magnetically recoverable Pt/Fe 2 O 3 catalyst with the facile synthesized strategy, good catalytic performance and high utilization efficiency would be well expected as a potential candidate for practical utilization. [ABSTRACT FROM AUTHOR]

Excessive price and scarcity of Pt species make it very necessary to enhance the atom utilization and catalytic efficiency of Pt catalysts for implementing their industrial practicality. Here, natural cotton is adopted as the precursor to in-situ support well-dispersed and uniform-sized Ni nanoparticles, which then work as nanoislands to effectively deposit single-atom Pt via the galvanic replacement reaction. On the resulting fibrous carbon matrix, the monocrystalline Ni particles are verified to tightly anchor isolated Pt atoms to form the alloyed PtNi nanoparticles. In the 4-nitrophenol (4-NP) reduction to 4-aminophenol (4-AP), the catalytic activity of the bimetallic PtNi/C catalyst with the low Pt loading (0.81%) maximally reaches 25 times as high as the primary Ni/C product. Simulated calculations demonstrate that the single-atom Pt centers on PtNi nanoparticles rapidly capture and split H 2 molecules, while Ni atoms strongly adsorb 4-NP molecule to activate the -NO 2 group. Therefore, the trapped H atom could easily attack the -NO 2 and reduce 4-NP. Cotton is utilized to in-situ prepare well-dispersed and uniform-sized PtNi/C bimetallic catalysts with the superior activity in the 4-nitrophenol reduction. [Display omitted] • Natural cotton has been utilized for fabricating the Ni/C catalyst. • Ni nanoparticles work as nanoislands to deposit single-Atom Pt, forming PtNi nanoparticles. • The PtNi/C catalyst exhibits a great catalytic performance for reduction of 4-NP. • Catalytic mechanism of the PtNi/C bimetallic catalyst has been explored. [ABSTRACT FROM AUTHOR]

SDA1 encodes a highly conserved protein that is widely distributed in eukaryotic organisms. SDA1 is essential for cell cycle progression and organization of the actin cytoskeleton in yeasts and humans. In this study, we identified a P hytophthora capsici orthologue of yeast SDA1, named PcSDA1. In P . capsici, PcSDA1 is strongly expressed in three asexual developmental states (mycelium, sporangia and germinating cysts), as well as late in infection. Silencing or overexpression of PcSDA1 in P . capsici transformants affected the growth of hyphae and sporangiophores, sporangial development, cyst germination and zoospore release. Phalloidin staining confirmed that PcSDA1 is required for organization of the actin cytoskeleton. Moreover, 4′,6-diamidino-2-phenylindole ( DAPI) staining and PcSDA1-green fluorescent protein ( GFP) fusions revealed that PcSDA1 is involved in the regulation of nuclear distribution in hyphae and sporangia. Both silenced and overexpression transformants showed severely diminished virulence. Thus, our results suggest that PcSDA1 plays a similar role in the regulation of the actin cytoskeleton and nuclear division in this filamentous organism as in non-filamentous yeasts and human cells. [ABSTRACT FROM AUTHOR]

Breast cancer and diabetes are significant health challenges, and effective treatments for both diseases are lacking. Proton pump inhibitors (PPIs) have demonstrated anticancer and hypoglycemic effects, but their mechanisms of action are not yet fully understood. We used the GeneCards and PharmMapper databases to identify therapeutic targets for diabetes, breast cancer and PPIs. We identified common targets and constructed a regulatory network of diseases and drugs using the STRING database and Cytoscape software. We also explored the binding between small molecule ligands and protein receptors using Discovery Studio software. We identified 33 shared targets for breast cancer, diabetes, and PPIs including lansoprazole, omeprazole, and pantoprazole, which play a critical role in fatty acid transport, insulin resistance, apoptosis, and cancer-related signaling pathways. Our findings demonstrated that PPIs had a strong affinity for AKT1 and MMP9. This study provides insights into the mechanisms of action of PPIs in breast cancer and diabetes and identifies AKT1 and MMP9 as critical targets for future drug development. Our findings highlight the potential of PPIs as a novel therapeutic approach for these challenging diseases. [ABSTRACT FROM AUTHOR]

Perfluorooctane sulfonate (PFOS) is a man-made environmental pollutant that is toxic to mammals. However, the neurotoxic effects of PFOS remain largely unexplored. In this study, we determined the role of an astrocyte specific gap junction protein, connexin 43 (Cx43), in PFOS-induced apoptosis. The rate of astrocyte apoptosis was higher in cortex astrocytes after PFOS treatment. These astrocytes also showed up-regulated expression of Cx43 and higher levels of cleaved caspase-3. Elevated ROS accumulation and decreased Δ Ψm also confirmed the presence of PFOS-induced apoptosis. However, the exposure of astrocytes to PFOS together with carbenoxolone (CBX) significantly reduced both Cx43 and cleaved caspase-3 levels. These results indicate that Cx43 plays a proapoptotic role in PFOS-induced apoptosis in cortex astrocyte cells. [ABSTRACT FROM AUTHOR]

Background and Purpose Recent reports have suggested that salidroside could protect cardiomyocytes from oxidative injury and stimulate glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase ( AMPK). The aim of this study was to evaluate the therapeutic effects of salidroside on diabetic mice and to explore the underlying mechanisms. Experimental Approach The therapeutic effects of salidroside on type 2 diabetes were investigated. Increasing doses of salidroside (25, 50 and 100 mg·kg−1·day−1) were administered p.o. to db/db mice for 8 weeks. Biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of salidroside. Primary cultured mouse hepatocytes were used to further explore the underlying mechanisms in vitro. Key Results Salidroside dramatically reduced blood glucose and serum insulin levels and alleviated insulin resistance. Hypolipidaemic effects and amelioration of liver steatosis were observed after salidroside administration. In vitro, salidroside dose-dependently induced an increase in the phosphorylations of AMPK and PI3K/ Akt, as well as glycogen synthase kinase 3β ( GSK3β) in hepatocytes. Furthermore, salidroside-stimulated AMPK activation was found to suppress the expression of PEPCK and glucose-6-phosphatase. Salidroside-induced AMPK activation also resulted in phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory chain complex I and disturbed oxidation/phosphorylation coupling and moderately depolarized the mitochondrial membrane potential, resulting in a transient increase in the AMP/ ATP ratio. Conclusions and Implications Salidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria-related AMPK/ PI3K/ Akt/ GSK3β pathway [ABSTRACT FROM AUTHOR]

Background and Purpose: Recent reports have suggested that salidroside could protect cardiomyocytes from oxidative injury and stimulate glucose uptake in skeletal muscle cells by activating AMP-activated protein kinase (AMPK). The aim of this study was to evaluate the therapeutic effects of salidroside on diabetic mice and to explore the underlying mechanisms. Experimental Approach: The therapeutic effects of salidroside on type 2 diabetes were investigated. Increasing doses of salidroside (25, 50 and 100 mg·kg(-1) ·day(-1)) were administered p.o. to db/db mice for 8 weeks. Biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of salidroside. Primary cultured mouse hepatocytes were used to further explore the underlying mechanisms in vitro. Key Results: Salidroside dramatically reduced blood glucose and serum insulin levels and alleviated insulin resistance. Hypolipidaemic effects and amelioration of liver steatosis were observed after salidroside administration. In vitro, salidroside dose-dependently induced an increase in the phosphorylations of AMPK and PI3K/Akt, as well as glycogen synthase kinase 3β (GSK3β) in hepatocytes. Furthermore, salidroside-stimulated AMPK activation was found to suppress the expression of PEPCK and glucose-6-phosphatase. Salidroside-induced AMPK activation also resulted in phosphorylation of acetyl CoA carboxylase, which can reduce lipid accumulation in peripheral tissues. In isolated mitochondria, salidroside inhibited respiratory chain complex I and disturbed oxidation/phosphorylation coupling and moderately depolarized the mitochondrial membrane potential, resulting in a transient increase in the AMP/ATP ratio. Conclusions and Implications: Salidroside exerts an antidiabetic effect by improving the cellular metabolic flux through the activation of a mitochondria-related AMPK/PI3K/Akt/GSK3β pathway. [ABSTRACT FROM AUTHOR]

In this paper complexes with N -nilpotent differentials are considered. We describe the loop functor Ω and the suspension functor Σ in the category C N ( A ) of N -complexes on an abelian category A to provide an effective construction of left and right triangles in the homotopy category K N ( A ) of N -complexes, and prove that K N ( A ) together with the functors Ω , Σ and the classes of left and right triangles mentioned above is a pretriangulated category. We also investigate different homologies and get another example of pretriangulated categories, i.e., the derived category D N ( A ) of N -complexes. Some basic properties are given. [ABSTRACT FROM AUTHOR]

Morchella esculenta (L.) Pers., referred to as Morel, is a medicinal and edible homologous fungus, which contains many bioactive substances. In Morel, polysaccharides are the most abundant and have various bioactivities. In the present work, two novel polysaccharides, Se-MPS and MPS, were prepared and purified from selenium-enriched (Se-enriched) and common Morel mycelia, respectively, and their structural and immunomodulatory properties were evaluated. The results show that Se-enriched treatment significantly changed the polysaccharides' chemical composition, molecular weight, and sugar chain configuration. In addition, the Se-enriched treatment also improved the polysaccharides' fragmentation and thermal stability. Importantly, Se-enriched Morel polysaccharide (Se-MPS) could significantly enhance phagocytosis of RAW 264.7 macrophage cells and, remarkably, activate their immune response via activating the TLR4-TRAF6-MAPKs-NF-κB cascade signaling pathway, finally exerting an immunomodulatory function. Based on these findings, selenium-enriched Morel polysaccharide appears to have more potential for development and utilization in functional foods or medicines than ordinary Morel polysaccharide. [ABSTRACT FROM AUTHOR]

Background: Studies on the incidence of venous thromboembolism (VTE) events in patients with interstitial lung disease (ILD) are limited and the results are inconsistent. The aim of this research was to investigate the incidence and risk factors of VTE in ILD during hospitalization. Materials and methods: In this retrospective, cross-sectional, observational study, a total of 5009 patients diagnosed with ILD from January 2016 to March 2022 in our hospital were retrospectively included. In ILD patients, VTE including pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT) were screened from the electronic medical record system. Diagnosis of PTE and DVT were performed by CT pulmonary angiography (CTPA), CTV or ultrasound. And then the incidence and risk factors of VTE in different types of ILD were assessed. Results: Among 5009 patients with ILD, VTE was detected in 129 (2.6%) patients, including 15(0.3%) patients with both PTE and DVT, 34 (0.7%) patients with PTE and 80 (1.6%) patients with DVT. 85.1% of patients with APE were in the intermediate-low risk group. The incidence of VTE in Anti-Neutrophil Cytoplasmic Antibodies -associated vasculitis related ILD (ANCA-AV-ILD), hypersensitivity pneumonitis and idiopathic pulmonary fibrosis (IPF) respectively was 7.9% and 3.6% and 3.5%. In patients with connective tissue disease-associated ILD (CTD-ILD), the incidence of VTE, DVT, PTE, combined PTE and DVT respectively was 3.0%, 2.3%, 0.4% and 0.3%. Among the various risk factors, different ILD categories, age ≥ 80 years (OR 4.178, 95% CI 2.097–8.321, P < 0.001), respiratory failure (OR 2.382, 95% CI 1.533–3.702, P < 0.001) and varicose veins (OR 3.718, 95% CI 1.066–12.964, P = 0.039) were independent risk factors of VTE. The incidence of VTE in patients with ILD increased with the length of time in hospital from 2.2% (< 7 days) to 6.4% (> 21 days). Conclusion: The incidence of VTE during hospitalization in ILD patients was 2.6%, with a 1.6% incidence of DVT, higher than the 0.7% incidence of PTE. Advanced age, ILD categories, respiratory failure and varicose veins as independent risk factors for the development of VTE should be closely monitored. [ABSTRACT FROM AUTHOR]

Background and Purpose The retention of plasma low-density lipoprotein ( LDL) particles in subendothelial space following transcytosis across the endothelium is the initial step of atherosclerosis. Whether or not C-reactive protein ( CRP) can directly affect the transcytosis of LDL is not clear. Here we have examined the effect of CRP on transcytosis of LDL across endothelial cells and have explored the underlying mechanisms. Experimental Approach Effects of CRP on transcytosis of FITC-labelled LDL were examined with human umbilical vein endothelial cells and venous rings in vitro and, in vivo, ApoE-/- mice. Laser scanning confocal microscopy, immunohistochemistry and Oil Red O staining were used to assay LDL. Key Results CRP increased transcytosis of LDL. An NADPH oxidase inhibitor, diphenylene iodonium, and the reducing agent, dithiothreitol partly or completely blocked CRP-stimulated increase of LDL transcytosis. The PKC inhibitor, bisindolylmaleimide I and the Src kinase inhibitor, PP2, blocked the trafficking of the molecules responsible for transcytosis. Confocal imaging analysis revealed that CRP stimulated LDL uptake by endothelial cells and vessel walls. In Apo E-/- mice, CRP significantly promoted early changes of atherosclerosis, which were blocked by inhibitors of transcytosis. Conclusions and Implications CRP promoted atherosclerosis by directly increasing the transcytosis of LDL across endothelial cells and increasing LDL retention in vascular walls. These actions of CRP were associated with generation of reactive oxygen species, activation of PKC and Src, and translocation of caveolar or soluble forms of the N-ethylmaleimide-sensitive factor attachment protein. [ABSTRACT FROM AUTHOR]

This study proposes two nonsingular distributed cooperative guidance strategies to solve the problem of the three-dimensional (3D) cooperative guidance of multiple interceptors attacking a stationary target. The cooperative 3D nonlinear engagement kinematics is first formulated. We then derive guidance commands based on two expressions of the time-to-go estimate by using a combination of the multi-agent consensus algorithm and the nonsingular guidance law, where they are presented without the assumption of a small lead angle. An additional component of the guidance command is investigated to prevent the Lyapunov function from becoming negative semi-definite, and the finite-time stability of the consensus error is guaranteed. Following the convergence of the consensus error, the stability of the lead angle is presented without confining the control parameter. By using the proposed strategies, multiple interceptors can attack the target simultaneously, and the impact time is determined during engagement. A number of simulation scenarios are considered to verify the effectiveness of the proposed control strategies. [ABSTRACT FROM AUTHOR]

Poor preservation of plant macroremains in the acid soils of southern subtropical China has hampered understanding of prehistoric diets in the region and of the spread of domesticated rice southwards from the Yangtze River region. According to records in ancient books and archaeological discoveries from historical sites, it is presumed that roots and tubers were the staple plant foods in this region before rice agriculture was widely practiced. But no direct evidences provided to test the hypothesis. Here we present evidence from starch and phytolith analyses of samples obtained during systematic excavations at the site of Xincun on the southern coast of China, demonstrating that during 3,350–2,470 aBC humans exploited sago palms, bananas, freshwater roots and tubers, fern roots, acorns, Job's-tears as well as wild rice. A dominance of starches and phytoliths from palms suggest that the sago-type palms were an important plant food prior to the rice in south subtropical China. We also believe that because of their reliance on a wide range of starch-rich plant foods, the transition towards labour intensive rice agriculture was a slow process. [ABSTRACT FROM AUTHOR]

Aims Diabetes is a major risk factor for cardiovascular diseases. Circulating endothelial microparticles (EMP) are increased in diabetic patients, but their potential contribution in atherogenesis is unclear. We sought to determine the role of EMP derived under high glucose conditions in the development of atherosclerosis. Methods and results EMP were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMP were defined as ‘injured’ EMP (iEMP) and their effects were compared with EMP generated from ‘healthy’ untreated HCAEC. iEMP injection significantly impaired endothelial function in ApoE−/− mice compared with EMP and vehicle treatment. Immunofluorescent experiments showed increased macrophage infiltration and adhesion protein expression in atherosclerotic lesions of iEMP-treated ApoE−/− mice compared with controls. To further investigate the underlying mechanism of iEMP-induced vascular inflammation, additional in vitro experiments were performed. iEMP, but not EMP, induced activation of HCAEC in a time- and dose-dependent manner and increased monocyte adhesion. Further experiments demonstrated that iEMP induced activation of HCAEC by phosphorylation of p38 into its biologically active form phospho-p38. Inhibition of p38 activation abrogated iEMP-dependent induction of adhesion proteins and monocyte adhesion on HCAEC. Moreover, we could demonstrate that iEMP show increased NADPH oxidase activity and contain significantly higher level of reactive oxygen species (ROS) than EMP. iEMP triggered ROS production in HCAEC and thereby activate p38 in an ROS-dependent manner. Conclusion High glucose condition increases NADPH oxidase activity in endothelial microparticles that amplify endothelial inflammation and impair endothelial function by promoting activation of the endothelium. These findings provide new insights into the pathogenesis of diabetes-associated atherosclerosis. [ABSTRACT FROM PUBLISHER]

Human pose estimation (HPE) is a research hotspot in the field of computer vision. Most of the existing approaches first generate low-resolution representation from high-resolution representation through continuous serial downsampling, and then reconstruct high-resolution results from low-resolution features through continuous serial upsampling, which loses a lot of effective feature information and leads to slow model inference. In this paper, the Fast Accuracy Network (FANet), a framework that enables fast and high-accuracy HPE, is proposed. The innovation lies in that, first of all, a grid structure is proposed and adopted, which can be regarded as a set of deep paths and shallow paths. The structure uses multiple high-resolution and low-resolution branch pairs to perform skip-level connections at different scale-space levels so that the information can be exchanged between different resolution representations for many times. The feature information fusion of multi-scale space is realized to obtain more abundant feature information. Second, an improved bottleneck block is proposed to extract effective feature information with fewer parameters, ensuring that the computational burden is reduced without sacrificing accuracy performance. The experimental results show that, compared with other current models, FANet has faster inference speed on the premise of a slight improvement in accuracy performance. [ABSTRACT FROM AUTHOR]

Background: The evaluation of refraction is indispensable in ophthalmic clinics, generally requiring a refractor or retinoscopy under cycloplegia. Retinal fundus photographs (RFPs) supply a wealth of information related to the human eye and might provide a promising approach that is more convenient and objective. Here, we aimed to develop and validate a fusion model-based deep learning system (FMDLS) to identify ocular refraction via RFPs and compare with the cycloplegic refraction. In this population-based comparative study, we retrospectively collected 11,973 RFPs from May 1, 2020 to November 20, 2021. The performance of the regression models for sphere and cylinder was evaluated using mean absolute error (MAE). The accuracy, sensitivity, specificity, area under the receiver operating characteristic curve, and F1-score were used to evaluate the classification model of the cylinder axis. Results: Overall, 7873 RFPs were retained for analysis. For sphere and cylinder, the MAE values between the FMDLS and cycloplegic refraction were 0.50 D and 0.31 D, representing an increase of 29.41% and 26.67%, respectively, when compared with the single models. The correlation coefficients (r) were 0.949 and 0.807, respectively. For axis analysis, the accuracy, specificity, sensitivity, and area under the curve value of the classification model were 0.89, 0.941, 0.882, and 0.814, respectively, and the F1-score was 0.88. Conclusions: The FMDLS successfully identified the ocular refraction in sphere, cylinder, and axis, and showed good agreement with the cycloplegic refraction. The RFPs can provide not only comprehensive fundus information but also the refractive state of the eye, highlighting their potential clinical value. [ABSTRACT FROM AUTHOR]

Objective: Current studies focus on the prevalence rate of lung cancer in idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease (CTD-LID). Our aim was to investigate the prevalence of malignancies in patients with various subtypes of ILD. Methods: A total of 5350 patients diagnosed with ILD between January 2015 and December 2021 were retrospectively included. The prevalence of different malignancies and different ILDs was assessed using complete follow-up data. Results: A total of 248 patients (139 males; 65—IQR, 57 to 72—years) out of 5350 patients with ILD were confirmed with malignancies. A total of 69% of patients with ILD and malignances were older than 60 years old. The prevalence of malignancies in ILD patients was 4.6%, and lung cancer had the most common incidence of 1.9%, followed by malignancies in the digestive system of 0.9%. Among the different ILD subtypes, the prevalence of malignancies such as organizing pneumonia (OP), idiopathic pulmonary fibrosis (IPF), anti-neutrophil cytoplasmic antibodies-associated vasculitis-related ILD(AAV-ILD), nonspecific interstitial pneumonia (NSIP), CTD-ILD, hypersensitivity pneumonitis (HP), sarcoidosis, and other types of ILD was 6.8%, 5.0%, 4.7%, 4.3%, 2.5%, 2.2%, 1.2%, and 6.9%, respectively. The incidence of lung cancer as the most common tumor in IPF was 3.9%, with adenocarcinoma predominating (1.7%). The highest rate of malignancy occurring in RA of CTD-ILD was 2.4%. Conclusion: Older patients with ILD (≥60 years) including OP, IPF, AAV-ILD, NSIP, CTD-ILD, and HP, were associated with a higher incidence of malignancy, especially males aged from 60 to 69 years. These epidemiological results indicate that it is essential for physicians to pay more attention to the screening of and management strategies for different malignancies, according to the specific ILD subtypes. [ABSTRACT FROM AUTHOR]

Non-technical summary Women during their child-bearing years have longer QT intervals in their electrocardiograms than men and are more susceptible to lethal arrhythmias elicited by drugs that delay repolarization. Current theories posit that women have a reduced 'repolarization reserve' due to reduced potassium currents resulting in longer QT and greater repolarization delays. We proposed an alternative mechanism of higher calcium currents in women which would likewise prolong QT intervals, delay repolarization while increasing the force of contractions and intracellular calcium load. Here, we show that physiological concentrations of oestrogen increase the calcium current only in cells from the base of the heart, by increasing messenger RNA and proteins levels that encode for the calcium current. Moreover, oestrogen acts by interacting with oestrogen receptors (ER)α but not ERβ which may explain why hormone replacement therapy increases the risk of arrhythmia and offers a possible protective solution of using an oestrogen mimetic that selectively binds to ERβ. [ABSTRACT FROM AUTHOR]

Women of child bearing age are known to have longer QT intervals on their electrocardiogram recordings due to sex-differences in the heart that are mediated by the sex hormone oestrogen. This results in a higher risk of lethal arrhythmias in women when their QT interval is prolonged further through drugs or inherited congenital diseases (i.e. long QT syndrome). Using rabbit hearts, which exhibit the same sex-differences as in humans, it is here shown for the first time that oestrogen up-regulates the sodium-calcium exchanger (NCX), a critical protein that regulates calcium ions in the heart and thereby alters the force of contraction, but only at the base of the ventricles (where the heart has its widest cross section). This effect accounts for the greater risk of long QT-related arrhythmias in women. [ABSTRACT FROM AUTHOR]

The article focuses on the study on human Fyn-related kinase. It notes that Frk causes cancers via dysregulations in signal transduction and expression and purification of hFrk were held by bacterial expression system. It says the expression of kinase domain mixing with hexahistidine purification tag showed in Escherichia coli and the study uses Western blot analysis in analyzing purified hFrk. Results reveal that protein production might promote structure-based drug design initiatives.