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Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by a progressive decline in liver function, leading to disruptions in liver integrity and metabolic function, resulting in lipid deposition and excessive accumulation of extracellular matrix (ECM). The pathogenesis of NAFLD is complex and not yet fully understood, contributing to the absence of specific therapeutic strategies. Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor pivotal in regulating lipid and glucose metabolism. However, the impacts of PPARγ on NAFLD remains insufficiently explored. Thus, this study aimed to investigate the role of PPARγ in NAFLD and its underlying molecular mechanisms. Chemical detection kits were utilized to quantify collagen content, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) level variations. Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to assess alterations in extracellular matrix-related genes and inflammatory response genes in liver tissue and HepG2 cells, while western blotting was conducted to analyze the levels of both PPARγ and the TGF-β/Smad signaling pathway. Our findings unveiled significantly reduced PPARγ expression in a rat model of NAFLD, leading to subsequent activation of the TGF-β/Smad signaling pathway. Furthermore, PPARγ activation effectively mitigated NAFLD progression by inhibiting inflammation and fibrosis-related gene expression and collagen production. On a cellular level, PPARγ activation was found to inhibit the expression of extracellular matrix-related genes such as matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9), along with inflammatory response genes interleukin (IL)-1β and IL-6. Additionally, PPARγ activation led to a significant decrease in the levels of ALT and AST. At the molecular level, PPARγ notably down-regulated the TGF-β/Smad signaling pathway, which is known to promote liver fibrosis. These groundbreaking findings underscore PPARγ activation as a promising therapeutic approach to delay NAFLD progression by targeting the TGF-β/Smad signaling pathway in hepatic cells. This highlights the potential of PPARγ as a promising therapeutic target for NAFLD management in clinical settings. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is a prevalent type of thoracic cancer with a poor prognosis and high mortality rate. However, the exact pathogenesis of this cancer is still not fully understood. One potential factor that can contribute to the development of lung adenocarcinoma is DNA methylation, which can cause changes in chromosome structure and potentially lead to the formation of tumors. The baculoviral IAP repeat containing the 5 (BIRC5) gene encodes the Survivin protein, which is a multifunctional gene involved in cell proliferation, migration, and invasion of tumor cells. This gene is elevated in various solid tumors, but its specific role and mechanism in lung adenocarcinoma are not well-known. To identify the potential biomarkers associated with lung adenocarcinoma, we screened the methylation-regulated differentially expressed genes (MeDEGs) of LUAD via bioinformatics analysis. Gene ontology (GO) process and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied to investigate the biological function and pathway of MeDEGs. A protein–protein interaction (PPI) network was employed to explore the key module and screen hub genes. We screened out eight hub genes whose products are aberrantly expressed, and whose DNA methylation modification level is significantly changed in lung adenocarcinoma. BIRC5 is a bona fide marker which was remarkably up-regulated in tumor tissues. Flow cytometry analysis, lactate dehydrogenase release (LDH) assay and Micro-PET imaging were performed in A549 cells and a mouse xenograft tumor to explore the function of BIRC5 in cell death of lung adenocarcinoma. We found that BIRC5 was up-regulated and related to a high mortality rate in lung adenocarcinoma patients. Mechanically, the knockdown of BIRC5 inhibited the proliferation of A549 cells and induced pyroptosis via caspase3/GSDME signaling. Our findings have unraveled that BIRC5 holds promise as a novel biomarker and therapeutic target for lung adenocarcinoma. Additionally, we have discovered a novel pathway in which BIRC5 inhibition can induce pyroptosis through the caspase3-GSDME pathway in lung adenocarcinoma cells. [ABSTRACT FROM AUTHOR]

Under the different temperature environment, the precast pile-soil interface characteristics has an important impact on the safety and long-term stability for pile foundation. A large precast pile-soil shear experimental device is used to carry out the direct shear test of concrete-loess interface with different moisture contents under different freezing temperatures. The variation laws of shear strength parameters are revealed with influencing factors, and the shear mechanism of interface is discussed. The stress-strain constitutive equation of interface is proposed, and the shear strength criterion is established with considering the effects of temperature and moisture content on cohesion and internal friction angle. The results show the curve of shear stress and shear displacement can be divided into three stages: elastic deformation stage, plastic deformation stage and sliding failure stage, which macroscopically reflects the shear failure mechanism of the frozen soil-concrete interface. The shear strength of the interface is affected by the test temperature, sample moisture content and normal stress. The lower the test temperature, the greater the shear strength of the interface; With the increase of normal stress, the shear strength of interface increases; With the increase of moisture content, the shear strength of the interface increases and then decreases. The relationship of shear stress and shear displacement of frozen soil-concrete interface can be well described by the piecewise combination of hyperbolic function and linear function. [ABSTRACT FROM AUTHOR]

Objectives: Carotid artery stenting (CAS) is an established treatment for local stenosis. The most common complication is new ipsilateral ischemic lesions (NIILs). This study aimed to develop models considering lesion morphological and compositional features, and radiomics to predict NIILs. Materials and methods: One hundred and forty-six patients who underwent brain MRI and high-resolution vessel wall MR imaging (hrVWI) before and after CAS were retrospectively recruited. Lumen and outer wall boundaries were segmented on hrVWI as well as atherosclerotic components. A traditional model was constructed with patient clinical information, and lesion morphological and compositional features. Least absolute shrinkage and selection operator algorithm was performed to determine key radiomics features for reconstructing a radiomics model. The model in predicting NIILs was trained and its performance was tested. Results: Sixty-one patients were NIIL-positive and eighty-five negative. Volume percentage of intraplaque hemorrhage (IPH) and patients' clinical presentation (symptomatic/asymptomatic) were risk factors of NIILs. The traditional model considering these two features achieved an area under the curve (AUC) of 0.778 and 0.777 in the training and test cohorts, respectively. Twenty-two key radiomics features were identified and the model based on these features achieved an AUC of 0.885 and 0.801 in the two cohorts. The AUCs of the combined model considering IPH volume percentage, clinical presentation, and radiomics features were 0.893 and 0.842 in the training and test cohort respectively. Conclusions: Compared with traditional features (clinical and compositional features), the combination of traditional and radiomics features improved the power in predicting NIILs after CAS. Key Points: • Volume percentage of IPH and symptomatic events were independent risk factors of new ipsilateral ischemic lesions (NIILs). • Radiomics features derived from carotid artery high-resolution vessel wall imaging had great potential in predicting NIILs after CAS. • The combination model with radiomics and traditional features further improved the diagnostic performance than traditional features alone. [ABSTRACT FROM AUTHOR]

A tillage microrelief unit is the smallest spatially discontinuous area unit of tillage microrelief. Understanding the impact of tillage microrelief units on splash erosion is essential for selecting suitable tillage measures and employing soil and water conservation practices. The objective of this study was to investigate the characteristics and mechanisms of splash erosion under different tillage microrelief units in various directions and distances using the rainfall simulation experiment in the soil landscape of the Loess Plateau region in China, characterized primarily by sloping farmland as the main land use type. Three typical microrelief units, namely, artificial digging (AD), contour tillage (CT), and straight slope conditions (SSC) were designed at 0°, 3°, 5°, 10°, 15°, and 20° slopes. Tillage microrelief units with high surface roughness produced more splash erosion than flat lands. Further, the highest surface roughness increased the total splash amount by 102% relative to flat lands. The tillage microrelief unit itself was elevated with a certain slope, which increased the downslope splash of CT, SSC, and AD by 121%, 173%, and 11%, respectively. Different surface roughness values and slopes under different microrelief units were used to determine the amount of splash erosion. The results showed that the total splash amount responded significantly (P < 0.01) to the interaction between surface roughness and slope, and the sensitivity to roughness was higher than that to slope. According to the single-factor analysis, the surface roughness of all slopes significantly influenced the amount of splash erosion. Furthermore, the sensitivity of the tillage microrelief unit to the slope decreased because of the high slope under high surface roughness. Overall, the results of this study showed that in different tillage microrelief units of slopes in the Loess Plateau, SSC and CT significantly increased the outward splash erosion in this area, while AD significantly decreased the outward splash erosion. Moreover, slope did not have a considerable influence. • Splash erosion under three different tillage microrelief units was examined. • Total splash amount responded significantly to surface roughness and slope. • Response of splash amount to surface roughness was greater than that to slope. • Surface roughness of all slopes influenced the amount of splash erosion. [ABSTRACT FROM AUTHOR]

In recent years, doped graphene has been often used as a gas-sensitive material, and its gas adsorption energy has received extensive attention. However, the numerous types of doped graphene make the simulation calculation study of their adsorption energy highly costly and time consuming. In this study, in order to accurately and quickly examine the CO adsorption capacity of different boron-doped graphene structures, 1864 different sets of CO adsorption energy on boron-doped graphene were obtained by simulation based on density functional theory (DFT), and an overall framework based on machine learning was then proposed. After that, three different machine learning methods were evaluated, and the random forest method was found to perform best, with the average root mean square error achieving around 0.051. This study demonstrates the power of machine learning models in uncovering complex and hidden structure–property relations in boron-doped graphene and provides the possibility of using a data-driven method for the rational design of gas-sensitive materials. [ABSTRACT FROM AUTHOR]

Lithium (Li)–air batteries with super‐high energy density have attracted wide attention, but they usually exhibit poor performance due to dendrite/passivation on anode and insoluble discharge products on cathode. Many recent works have just designed highly efficient catalysts or only prepared stable anodes to solve one aspect of the above issues. Herein, an iodine (I)‐containing polymer/alloy layer‐based Li (IPA‐Li) via the replacement reaction of zinc iodide (ZnI2) and Li and subsequent polymerization of ethyl α‐cyanoacrylate (ECA) is designed to tackle both the anode and cathode problems. The homogeneous polymer layer and LiZn alloy in IPA‐Li not only suppress the passivation caused by attack of O2/H2O, but also guide uniform Li plating/stripping behavior to inhibit dendrite formation. Moreover, soluble I‐containing species in IPA‐Li obviously promote decomposition of discharge products at low voltages. Compared with bare Li, IPA‐Li shows a longer lifespan (1200 h at 1 mA cm−2) in the symmetric cell. Hence, the electrochemical performance of IPA‐Li‐based Li–O2 batteries is also much better than Li‐based cells. Moreover, IPA‐Li‐based Li–air battery operates stably >120 cycles with low‐overpotential of <1.6 V in ambient air, while the Li–air battery fast decays only after 25 cycles. This strategy provides a new way to construct high‐performance Li–air batteries. [ABSTRACT FROM AUTHOR]

Objectives: We sought to build a high-risk plaque MRI-based model (HRPMM) using radiomics features and machine learning for differentiating symptomatic from asymptomatic carotid plaques. Materials and methods: One hundred sixty-two patients with carotid stenosis were randomly divided into training and test cohorts. Multi-contrast MRI including time of flight (TOF), T1- and T2-weighted imaging, and contrast-enhanced imaging was done. Radiological characteristics of the carotid plaques were recorded and calculated to build a traditional model. After extracting the radiomics features on these images, we constructed HRPMM with least absolute shrinkage and selection operator algorithm in the training cohort and evaluated its performance in the test cohort. A combined model was also built using both the traditional and radiomics features. The performance of all the models in the identification of high-risk carotid plaque was compared. Results: Intraplaque hemorrhage and lipid-rich necrotic core were independently associated with clinical symptoms and were used to build the traditional model, which achieved an area under the curve (AUC) of 0.825 versus 0.804 in the training and test cohorts. The HRPMM and the combined model achieved an AUC of 0.988 versus 0.984 and of 0.989 versus 0.986 respectively in the two cohorts. Both the radiomics model and combined model outperformed the traditional model, whereas the combined model showed no significant difference with the HRPMM. Conclusions: Our MRI-based radiomics model can accurately distinguish symptomatic from asymptomatic carotid plaques. It is superior to the traditional model in the identification of high-risk plaques. Key Points: • Carotid plaque multi-contrast MRI stores other valuable information to be further exploited by radiomics analysis. • Radiomics analysis can accurately distinguish symptomatic from asymptomatic carotid plaques. • The radiomics model is superior to the traditional model in the identification of high-risk plaques. [ABSTRACT FROM AUTHOR]

The physicochemical parameters of hot-boned bovine semimembranosus muscles after s ous vide cooking were investigated. Hot-boned or wet-aged steaks were collected, and cooked by different cooking methods, including sous vide (57 °C, 11 h, SV), grilling (at 200 °C to the central temperature of 72 °C, GR) or boiling (100 °C, 2 h, BO). The meat color, tenderness, water-holding capacity, degree of oxidation, myoglobin denaturation and sensory quality traits were determined, as well as the changes in the microstructure. Compared to other cooking methods, SV reduced the degree of oxidation and muscle shortening, and significantly improved the water holding capacity (WHC), tenderness, connective tissue content and overall acceptability for both hot-boned and wet-aged steaks. The oxidation and muscle shortening were reduced in hot-boned SV steaks (P < 0.05), and the water-holding capacity and sensory scores for juiciness, connective tissue content and overall acceptability were increased (P < 0.05) compared to the wet-aged steaks. The combination of hot-boning and SV cooking resulted in an acceptable tenderness, better overall sensory acceptability and higher WHC than other combinations of muscle states and cooking methods. Therefore, it is a good choice to cook hot-boned semimembranosus muscles using SV to improve the eating quality, which can eliminate the need for aging, benefiting the beef industry. [ABSTRACT FROM AUTHOR]

• Surface microrelief highly changed the partitioning of surface and sub-surface flow. • DOM concentration in sub-surface flow was 7∼18 times that in surface flow. • Higher O/C but lower H/C DOM were detected in sub-surface flow than surface flow. • Microrelief with higher surface storage capacity caused larger DOM export flux. Rainfall-runoff process mobilizes considerable dissolved organic matter (DOM) from soils to aquatic systems via surface and sub-surface flow pathways. Microrelief induced by tillage management can alter this flow partitioning and thus likely affect the associated pathway and composition of DOM exports during rainfall. This study conducted rainfall simulation experiments, combined with three-dimensional fluorescence spectra analysis and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) technology, to explore the effects of different surface microreliefs treatments on the quantity and composition of DOM exports at a plot scale. Four typical microrelief treatments (i.e., contour tillage (CP), longitudinal tillage (LP), artificial digging tillage (AP), and flat tillage (CK, as control)) were selected. Results showed that ratios of surface to sub-surface flow volume under four treatments were in order of LP (193:1)>CK (73:1)>AP (4.5:1)>CP (0.5:1). DOM concentrations in sub-surface flow (13.37∼33.50 mg L-1) were 7∼18 times of that in surface flow (0.03∼4.56 mg L-1). The total export fluxes of DOM were 134, 139, 563, and 1214 mg m-2 at LP, CK, AP, and CP treatments, respectively, with proportions of 8%, 17%, 82%, and 98% via sub-surface flow. Compared to surface flow, DOM molecular composition in sub-surface flow showed a significant feature of higher oxygen to carbon ratio, higher molecular weight, and lower hydrogen to carbon ratio. The findings indicated that microrelief with higher surface storage capacity tends to favor a large flux of DOM export, primarily via sub-surface flow, which might significantly affect the DOM cycling in the receiving aquatic ecosystems. [Display omitted] [ABSTRACT FROM AUTHOR]

Dexmedetomidine, which is a highly selective α2 adrenoreceptor agonist, enhances the analgesic efficacy and prolongs the analgesic duration when administered in combination with local anesthetics. The current study aimed to evaluate the effects of dexmedetomidine combined with ropivacaine in ultrasound-guided transversus abdominis plane (TAP) block on post-operative analgesia following cesarean section (CS). A total of 70 patients scheduled for CS were divided randomly into 2 groups: The ropivacaine (R) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml 0.9% normal saline, and the dexmedetomidine (RD) group, in which patients were administered bilateral 20 ml 0.3% ropivacaine and 2 ml dexmedetomidine (0.5 µg/kg). The primary outcome was pain-free duration, and secondary outcomes included heart rate (HR) and mean blood pressure (MBP) measurements, visual analogue scale (VAS) pain scores, number of patients who required rescue analgesic, time to first request for analgesia and patient satisfaction. There was no significant difference in HR and MBP between the two groups at 1 h post-surgery (P>0.05). However, VAS pain scores decreased at 6 and 8 h post-surgery [2 (1-2) vs. 0 (0-0.25) and 2 (2-3) vs. 0 (0-1), respectively; P<0.05], pain-free duration was prolonged (5.91±1.08 vs. 9.62±1.46 h; P<0.05), the number of patients who required rescue analgesic was reduced (19 vs. 9; P<0.05), the time to first request for analgesia was prolonged (7.10±1.21 vs. 11.60±2.11 h; P<0.05) and patient satisfaction was improved [3.5 (3-4) vs. 4 (4-5); P<0.05] in the RD group compared with the R group. Furthermore, no bradycardia or hypotension was observed. In conclusion, the results of the present study demonstrated that adding 0.5 µg/kg dexmedetomidine to 0.3% ropivacaine used in TAP block in patients undergoing CS prolonged pain-free duration, decreased VAS pain scores, reduced the number of patients who required rescue analgesic, prolonged the time to first request for analgesia and improved the patient satisfaction without serious side effects. [ABSTRACT FROM AUTHOR]

• Temporal changes in splash detachment rate and interrill wash rate were studied. • Erosion-limiting degree was defined and presented. • Erosion-limiting degree increased linearly with increasing slope gradient. Better understanding of raindrop detachment, interrill wash and erosion-limiting degree in interrill processes is critical for accurately modelling interrill erosion and implementing proper anti-erosion strategies. Simulated rainfall experiments were conducted on a clayey loessal soil at three rainfall intensities (42, 60 and 90 mm h−1), five slope gradients (7°, 10°, 15°, 20° and 25°) and rainfall duration of 40 min. Results showed that raindrop detachment rate initially decreased rapidly within a few minutes and then reached a relative steady state during rainfall. The initial and steady raindrop detachment rate increased with increased rainfall intensity. Interrill wash rate peaked early and then decreased to a relative constant rate during the rainfall. The initial, maximum and steady interrill wash rate increased with increased rainfall intensity and slope gradient. Erosion-limiting degree (ELD), defined as the ratio of interrill wash rate to raindrop detachment rate, ranged from 10.99% to 35.70% under experimental conditions, indicating that interrill erosion system was transport-limited. The ELD decreased with rainfall intensity and increased linearly (R 2 = 0.90) with slope gradient. The higher the rainfall intensity, the stronger the transport-limiting in interrill erosion processes; the steeper the slope gradient, the weaker the transport-limiting in interrill erosion processes. Raindrop detachment is the dominant process in detaching soil particles, whereas interrill flow contributes to washing out detached sediments. The findings of this study, especially ELD , largely improved the understanding of interrill erosion processes. [ABSTRACT FROM AUTHOR]

Ring Finger Protein 113 (RNF113A), an ubiquitin E3 ligase, is genetically associated with many biological processes, including proliferation, differentiation, cell death, and neurogenesis. Recently, RNF113A has been found to be an abnormal expression in many diseases, such as X-linked trichothiodystrophy syndrome and esophageal cancer. Here, we explore the potential mechanism of RNF113A in the progression of cervical cancer (CC). In this study, we evaluated the expression level and biological function of RNF113A in CC both in vitro and in vivo by bioinformatic prediction, DIA proteomic analysis, compensation experiment, Co-IP, dual-luciferase reporter assay and nude mouse xenograft to identify the RNF113A-associated autophagy pathways involved with tumorigenesis. Consistent with the prediction from biological information analysis, we found that RNF113A was highly expressed in human CC tissues and cells. In addition, this study illustrated that the high expression of RNF113A dramatically promoted proliferation and suppressed autophagy both in vitro and in vivo. In contrast, low expression of RNF113A enhanced autophagy activities and inhibited tumor growth in CC. We also found that miRNA-197, the level of which (negative correlation with RNF113A) declined in human CC, directly restrained the expression of RNF113A. Mechanistically, proteomic and mechanistic assays uncovered that RNF113A confirmed as the direct downstream target of miR-197, promoted proliferation and restrained autophagy in CC not through direct ubiquitination degradation of autophagy marker Beclin1 but via CXCR4/CXCL12/AKT/ERK/Beclin1 signal transduction axis. In summary, we found a new miR-197/RNF113 A/CXCR4/CXCL12/AKT/ERK/Beclin1 regulation pathway that plays an important part in the survival and progression of CC. [ABSTRACT FROM AUTHOR]

The present study aimed to examine the expression of interleukin-6 receptor (IL-6R) mRNA and protein in pulp tissues, blood and saliva from patients with pulpitis. It also investigated the association between IL-6R and microRNA (miR)-30b, as well as their effects on pulpitis. A total of 28 patients with pulpitis were recruited into the experimental group and 16 subjects with no pulpitis who also underwent tooth extraction were recruited into the control group. Pulp tissues, plasma and saliva were collected from all participants. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of IL-6R mRNA and miR-30b in all sample types. Western blot analysis was performed to examine the protein expression of IL-6R in pulp tissues, while ELISA was used to determine the contents of IL-6R protein in the plasma and saliva samples. A dual luciferase reporter assay was performed to verify the interactions between IL-6R and miR-30b. The expression of IL-6R mRNA in the pulp tissues, plasma and saliva was significantly increased in patients with pulpitis compared with the control group. Similarly, the IL-6R protein expression in the samples from patients with pulpitis were also significantly increased compared with the control group. Conversely, the expression of miR-30b was significantly reduced in the samples from patients with pulpitis compared with the control group. The dual luciferase reporter assay revealed that miR-30b may bind with the 3′-untranslated seed region of IL-6R mRNA to regulate its expression. The present study demonstrated that the upregulated expression of IL-6R in pulp tissues, plasma and saliva from patients with pulpitis was associated with the downregulation of miR-30b expression. In addition, miR-30b may affect the progression of pulpitis via IL-6R and may be a potential genetic marker for the diagnosis of pulpitis. [ABSTRACT FROM AUTHOR]

Highlights • Another method was provided to determine T c of raindrop-impacted interrill flow. • T c can be calculated using power function equation of slope gradient and rainfall intensity. • Stream power together with rainfall kinetic energy can best describe T c. Abstract Interrill erosion processes typically involve such scientific issues as detachment-limited and transport-limited erosion behaviour. An accurate estimation of the sediment transport capacity ( T c ) by raindrop-impacted overland flow is critical for interrill erosion modelling and for evaluating sediment budgets under erosion-limiting conditions. Simulated rainfall experiments with rainfall intensities from 0.8 to 2.5 mm min−1 over a three-area soil pan with slope gradients from 12.7% to 46.6% were conducted to identify the transport-limited cases and determine T c by raindrop-impacted overland flow within the transport-limited systems of interrill erosion processes. Results indicated that T c increased as a power function of rainfall intensity and slope gradient ( R2 = 0.84, NSE = 0.75), and T c was more sensitive to rainfall intensity than to slope gradient. In terms of R2 and NSE , stream power was the key hydraulic parameter that influenced T c among flow velocity ( R2 = 0.64, NSE = 0.39), shear stress ( R2 = 0.53, NSE = 0.23), stream power ( R2 = 0.76, NSE = 0.52) and unit stream power ( R2 = 0.49, NSE = 0.16). The addition of rainfall physical parameters in response equations of T c in addition to hydraulic parameter, could improve an accuracy of T c modelling. Stream power combined with rainfall kinetic energy can best describe the T c of raindrop-impacted overland flow within the transport-limited system of interrill erosion processes by a power-exponent function ( R2 = 0.90, NSE = 0.72). Rainfall kinetic energy can reduce the Darcy-Weisbach resistance coefficient of raindrop-impacted overland flow and thus benefit sediment transporting. This study provides another method for directly identifying the T c of raindrop-impacted overland flow in interrill erosion processes on steep loess slopes, and points out that rainfall impacts should be particularly considered when studying T c by raindrop-impacted overland flow. [ABSTRACT FROM AUTHOR]

Inhibition of photosynthesis is a central, primary response that is observed in both desiccation-tolerant and desiccation-sensitive plants affected by drought stress. Decreased photosynthesis during drought stress can either be due to the limitation of carbon dioxide entry through the stomata and the mesophyll cells, due to increased oxidative stress or due to decreased activity of photosynthetic enzymes. Although the photosynthetic rates decrease in both desiccation-tolerant and sensitive plants during drought, the remarkable difference lies in the complete recovery of photosynthesis after rehydration in desiccation-tolerant plants. Desiccation of sensitive plants leads to irreparable damages of the photosynthetic membranes, in contrast the photosynthetic apparatus is deactivated during desiccation in desiccation-tolerant plants. Desiccation-tolerant plants employ different strategies to protect and/or maintain the structural integrity of the photosynthetic apparatus to reactivate photosynthesis upon water availability. Two major mechanisms are distinguished. Homoiochlorophyllous desiccation-tolerant plants preserve chlorophyll and thylakoid membranes and require active protection mechanisms, while poikilochlorophyllous plants degrade chlorophyll in a regulated manner but then require de novo synthesis during rehydration. Desiccation-tolerant plants, particularly homoiochlorophyllous plants, employ conserved and novel antioxidant enzymes/metabolites to minimize the oxidative damage and to protect the photosynthetic machinery. De novo synthesized, stress-induced proteins in combination with antioxidants are localized in chloroplasts and are important components of the protective network. Genome sequence informations provide some clues on selection of genes involved in protecting photosynthetic structures; e.g. ELIP genes (early light inducible proteins) are enriched in the genomes and more abundantly expressed in homoiochlorophyllous desiccation-tolerant plants. This review focuses on the mechanisms that operate in the desiccation-tolerant plants to protect the photosynthetic apparatus during desiccation. [ABSTRACT FROM AUTHOR]

In this paper, graphene field effect transistors with amorphous silicon gate dielectric have been fabricated. A reverse hysteresis effect in these transistors is observed at room temperature. This property is different from that of the graphene field effect transistors with SiO 2 gate dielectric. After the transfer characteristics of the graphene transistors, the time evolution of drain current of the graphene devices, and the Raman and infrared spectrum of the α-Si are investigated, the reverse hysteresis is attributed to the defects and hydrogen atoms in surface of the amorphous silicon. This result is helpful to understand the hysteresis effect of graphene devices and enhance the reliability of graphene circuits. [ABSTRACT FROM AUTHOR]

Oropetium thomaeum is a desiccation tolerant grass and acquisition of desiccation tolerance is correlated with changes in carbohydrate metabolism. Here we address the question whether the changes in carbohydrate metabolism are specific to the dehydration process or whether other environmental factors such as high temperature, low temperature, hypoxia, salinity or exogenous ABA application trigger the same or different changes in the sugar metabolism. Fifteen different sugar metabolites were identified by GC/MS, including erythritol, arabinose, fructose, galactose, glucose, myo -inositol, sedoheptulose, sucrose, trehalose, galactinol, maltose, raffinose, manninotriose and stachyose. Together with starch, these sugars were placed into the pathways of sucrose metabolism and raffinose family oligosaccharides (RFOs) metabolism, as well as into the group of rare sugars. By comparing the changes of sugars under various stresses, we concluded that the changes in the sugar metabolism are both convergent and divergent in response to different stresses. Except for the general response to stress, such as starch degradation, the changes of specific sugar metabolites reflect a stress-specific response of O. thomaeum . Erythritol seems to be specific for dehydration, myo -inositol for salt stress and trehalose for hypoxia stress. Similar as dehydration, low temperature, salt stress and ABA application resulted in the accumulation of sucrose and RFOs in O. thomaeum , which indicates that these stresses share high similarity with dehydration. Thus it is proposed that sucrose and RFOs have a general protective role under these stresses. In contrast sucrose and RFOs did not accumulate in response to high temperature or hypoxia whose effects tend to be consumptive and destructive. The accumulation of galactose, melibiose and manninotriose demonstrate that RFOs are degraded under stress. The accumulation of these sugar metabolites might result from the reaction of RFOs and stress-produced hydroxyl radicals, which supports a possible role of RFOs in stress defense. In addition, ABA application led to substantial synthesis of stachyose which occurs only in response to dehydration, indicating that stachyose synthesis is possibly closely related to ABA in O. thomaeum . [ABSTRACT FROM AUTHOR]

A series of hydroxamic acid-based HDACIs with 4-aminoquinazolinyl moieties as capping groups was profiled. Most compounds showed more potent HDACs inhibition activity than clinically used drug SAHA. Among them, compounds 5f and 5h selectively inhibited HDAC 1,2 over HDAC8, and showed strong activity in several cellular assays, not possessing significant toxicity to primary human cells and hERG inhibition. Strikingly, 5f possessed acceptable pharmacokinetic characteristics and exhibited significant antitumor activity in an A549 xenograft model study at well tolerated doses. [ABSTRACT FROM AUTHOR]

The synthesis and biological evaluation of a variety of 4-piperazinyl-containing Chidamide derivatives is described. Some of these compounds were shown to inhibit HDAC1 with IC 50 values below micromolar range, and inhibited proliferation of several human cancer cells, not possessing toxicity to human normal cells and hERG K + ion channels. Compound 9g , proved to be the most potent and efficacious derivative in this series, was orally active in an HCT116 xenograft model in vivo . [ABSTRACT FROM AUTHOR]

• Soil detachment capacity and rill erodibility decreased during growing season. • Rill erodibility (K r) decreased as an exponential function of root density. • Soil detachment capacity was simulated by shear stress, soil cohesion, bulk density, and root length density. Near soil-surface characteristics change significantly with crop growth in sloping farmlands and thereby induce the temporal variations in soil detachment by rill flow. In this study, variations in soil detachment capacity by rill flow (Dc) and soil erosion resistance to rill flow as reflected by rill erodibility (K r) and critical shear stress (τ c) during crop growth stages were quantified in sloping farmlands of the Loess Plateau, China. The soil samples were collected from four different plots (one control and three crop plots—soybean, corn, and millet) and subjected to flume experiments under different shear stress (τ) levels (5.16–15.61 Pa). The near soil-surface characteristics including soil moisture content (SMC), soil bulk density (BD), soil cohesion (Coh), mean weight diameter (MWD), soil organic matter content (SOM), root length density (RLD), root surface area density (RSAD), and root mass density (RMD), were measured to explain the variations in soil detachment during crop growth stages. The results showed that SMC fluctuated greatly, whereas BD, Coh, MWD, SOM, RLD, RSAD, and RMD increased gradually with crop growth. Measured Dc and fitted K r significantly decreased with crop growth during one growing season. The mean values of Dc for soybean, corn, and millet decreased by 61.19–67.23%, K r decreased by 55.53–61.36%, and τ c increased by 16.0–18.31% compared to those for the bare soil control. The decrease in Dc and K r were significantly affected by BD, Coh, SOM, MWD and RLD, RSAD, and RMD (p < 0.01). Seasonal variations in Dc were well simulated by τ , BD, Coh, and RLD (R 2 = 0.96, NSE = 0.96). The findings demonstrate that it is essential to consider the seasonal variations in soil detachment for optimizing soil and water conservation measures in sloping farmlands. [ABSTRACT FROM AUTHOR]

Two wide band gap functional compounds of phenylbis(4-(spiro [fluorene-9,9'-xanthen]-2-yl)phenyl)phosphine oxide ( 2SFOPO ) and (4-(9-ethyl-9H- carbazol-3-yl)phenyl)(phenyl)(4-(spiro[fluorene-9,9′-xanthen]-2-yl)phenyl)phosphine oxide ( SFOPO-CZ ) were designed, synthesized and characterized. Their thermal, photophysical, electrochemical properties and device applications were further investigated to correlate the chemical structure of bipolar host materials with the electroluminescent performance for phosphorescent organic light-emitting diodes (PhOLEDs). Both of them show high thermal stability with glass transition temperatures in a range of 105–122 °C and thermal decomposition temperatures at 5% weight loss in a range of 406–494 °C. The optical band gaps of compound 2SFOPO and SFOPO-CZ in CH 2 Cl 2 solution are 3.46 and 3.35 eV, and their triplet energy levels are 2.51 eV and 2.52 eV, respectively. The high photoluminescent quantum efficiency of emissive layer of doped green device up to 50% is obtained. Employing the developed materials, efficient green and red PhOLED in simple device configurations have been demonstrated. As a result, the green PhOLEDs of compound SFOPO-CZ doped with tris(2-phenylpyridine) iridium shows electroluminescent performance with a maximum current efficiency ( CE max ) of 52.83 cd A −1 , maximum luminance of 34,604 cd/m 2 , maximum power efficiency ( PE max ) of 39.50 lm W −1 and maximum external quantum efficiency ( EQE max ) of 14.1%. The red PhOLED hosted by compound 2SFOPO with bis(2-phenylpyridine)(acetylacetonato) iridium(III) as the guest exhibits a CE max of 20.99 cd A −1 , maximum luminance of 33,032 cd/m 2 , PE max of 20.72 lm W −1 and EQE max of 14.0%. Compound SFOPO-CZ exhibits better green device performance, while compound 2SFOPO shows better red device performance in PhOLEDs. [ABSTRACT FROM AUTHOR]

Purpose -- The purpose of this paper is establishing a general mathematical model and theoretical design rules for 3D printing of biomaterials. Additive manufacturing of biomaterials provides many opportunities for fabrication of complex tissue structures, which are difficult to fabricate by traditional manufacturing methods. Related problems and research tasks are raised by the study on biomaterials' 3D printing. Most researchers are interested in the materials studies; however, the corresponded additive manufacturing machine is facing some technical problems in printing user-prepared biomaterials. New biomaterials have uncertainty in physical properties, such as viscosity and surface tension coefficient. Therefore, the 3D printing process requires lots of trials to achieve proper printing parameters, such as printing layer thickness, maximum printing line distance and printing nozzle's feeding speed; otherwise, the desired computer-aided design (CAD) file will not be printed successfully in 3D printing. Design/methodology/approach -- Most additive manufacturing machine for user-prepared bio-material use pneumatic valve dispensers or extruder as printing nozzle, because the air pressure activated valve can print many different materials, which have a wide range of viscosity. We studied the structure inside the pneumatic valve dispenser in our 3D heterogeneous printing machine, and established mathematical models for 3D printing CAD structure and fluid behaviors inside the dispenser during printing process. Findings -- Based on theoretical modeling, we found that the bio-material's viscosity, surface tension coefficient and pneumatic valve dispenser's dispensing step time will affect the final structure directly. We verified our mathematical model by printing of two kinds of self-prepared biomaterials, and the results supported our modeling and theoretical calculation. Research limitations/implications -- For a certain kinds of biomaterials, the mathematical model and design rules will have unique solutions to the functions and equations. Therefore, each biomaterial's physical data should be collected and input to the model for specified solutions. However, for each user-made 3D printing machine, the core programming code can be modified to adjust the parameters, which follows our mathematical model and the related CAD design rules. Originality -- This study will provide a universal mathematical method to set up design rules for new user-prepared biomaterials in 3D printing of a CAD structure. [ABSTRACT FROM AUTHOR]

1. Entinostat, also known as SNDX-275 or MS-275, is a novel, potent, orally bioavailable, class I selective histone deacetylase inhibitor. Pre-clinical data has show that MS-275 can enhance the activity of lapatinib in HER2+ metastatic inflammatory and non-inflammatory breast cancer. This study examined whether oral administration of MS-275 to the rats with lapatinib led to any pharmacokinetic interactions. 2. To evaluate pharmacokinetic interaction of MS-275 and lapatinib in rat, a sensitive and simple LC-MS method was developed to simultaneously determine MS-275 and lapatinib in rat plasma with carbamazepine as internal standard (IS). Eighteen rats were divided randomly into three groups, lapatinib group (lapatinib 15 mg/kg, n = 8), MS-275 group (MS-275 15 mg/kg, n = 8) and co-administration group (MS-275 15 mg/kg and lapatinib 15 mg/kg, n = 8). 3. There was no statistical pharmacokinetics difference for MS-275 in MS-275 group and co-administration group; the lapatinib could not influence the pharmacokinetic profile of MS-275 in rats. However, there is a statistical pharmacokinetics difference between lapatinib in the lapatinib group and co-administration group, when co-oral administration MS-275 with lapatinib, AUC increased from 2375.5 to 9900.3 ng/mL h ( p < 0.05), Cmax increased from 538.0 to 2578.2 ng/mL ( p < 0.01), CL decreased from 6.2 to 1.7 L/h/kg ( p < 0.01). 4. These data indicate MS-275 could obviously influence the pharmacokinetic profile of lapatinib in rats, which might cause drug-drug interactions in humans when using lapatinib with MS-275. Further investigations should be carried out to elucidate the synergistic mechanisms between the two drugs. [ABSTRACT FROM AUTHOR]

1. Mocetinostat (MGCD0103) is a benzamide histone deacetylase inhibitor undergoing clinical trials for treatment of various cancers including Hodgkin's lymphoma, follicular lymphoma and acute myelogenous leukemia. A sensitive and selective liquid chromatography mass spectrometry method for determination of MGCD0103 in rat plasma was developed. 2. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile was used as sample preparation. Chromatographic separation was achieved on a C18 (2.1 mm × 50 mm, 3.5 µm) column with acetonitrile−0.1% formic acid in water as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; selective ion monitoring (SIM) mode was used for quantification using target fragment ions m/z 397 for MGCD0103 and m/z 326 for the IS. 3. Calibration plots were linear over the range of 5-5000 ng/mL for MGCD0103 in rat plasma. Mean recoveries of MGCD0103 in rat plasma were in the range of 89.7-96.1%. RSD of intra-day and inter-day precision were both <11%. The accuracy of the method ranged from 96.5% to 109.7%. The matrix effects for MGCD0103 were between 94.5% and 97.4%. 4. The method was successfully applied to pharmacokinetic study of MGCD0103 after oral (15 mg/kg) and intravenous (3 mg/kg) administration in rats. The bioavailability of MGCD0103 was 29.3% in rats. [ABSTRACT FROM AUTHOR]

• We discuss the domain shift and domain adaptation problems in polyp detection datasets from different hospitals or endoscope models. To the best of our knowledge, this is the first paper to discuss the domain distribution differences between polyp detection datasets. • We propose a novel end-to-end network, which has two pipelines, to simultaneously learn the feature distribution of the source and target domains and reduce the distribution difference in the feature space of the two domains. • The proposed method requires only a small amount of unlabeled data from the target domain to improve the performance of the polyp detection model on the target domain. • The DRRN is very simple, easy to implement, and can be easily transferred to other tasks. It does not require additional adversarial networks, so the network is easy to train, converges quickly, and has fewer parameters. Background and objective: Currently, the best performing methods in colonoscopy polyp detection are primarily based on deep neural networks (DNNs), which are usually trained on large amounts of labeled data. However, different hospitals use different endoscope models and set different imaging parameters, which causes the collected endoscopic images and videos to vary greatly in style. There may be variations in the color space, brightness, contrast, and resolution, and there are also differences between white light endoscopy (WLE) and narrow band image endoscopy (NBIE). We call these variations the domain shift. The DNN performance may decrease when the training data and the testing data come from different hospitals or different endoscope models. Additionally, it is quite difficult to collect enough new labeled data and retrain a new DNN model before deploying that DNN to a new hospital or endoscope model. Methods: To solve this problem, we propose a domain adaptation model called Deep Reconstruction-Recoding Network (DRRN), which jointly learns a shared encoding representation for two tasks: i) a supervised object detection network for labeled source data, and ii) an unsupervised reconstruction-recoding network for unlabeled target data. Through the DRRN, the object detection network's encoder not only learns the features from the labeled source domain, but also encodes useful information from the unlabeled target domain. Therefore, the distribution difference of the two domains' feature spaces can be reduced. Results: We evaluate the performance of the DRRN on a series of cross-domain datasets. Compared with training the polyp detection network using only source data, the performance of the DRRN on the target domain is improved. Through feature statistics and visualization, it is demonstrated that the DRRN can learn the common distribution and feature invariance of the two domains. The distribution difference between the feature spaces of the two domains can be reduced. Conclusion: The DRRN can improve cross-domain polyp detection. With the DRRN, the generalization performance of the DNN-based polyp detection model can be improved without additional labeled data. This improvement allows the polyp detection model to be easily transferred to datasets from different hospitals or different endoscope models. [ABSTRACT FROM AUTHOR]

• The long-term natural aging characteristics of the VO X films were studied in details. • Aging was found to cause a dramatic change in surface composition rather than optical properties. • An aging mechanism involving interface aging and diffusion aging was proposed. • The results provided valuable information for improving the atmospheric durability of VO X films. We experimentally investigate the long-term atmospheric durability of thermochromic vanadium oxide (VO X) films. The VO X films were deposited on glass substrates by reactive direct current magnetron sputtering and were then in-situ annealed at the preparation temperature ≤350 °C. The X-ray photoelectron spectroscopy (XPS) was applied to investigate the surface compositions of the natural aged films, while the optical properties of the films were characterized by the spectrophotometer and spectroscopic ellipsometry. The XPS results reveal that the oxygen-deficient VO X (X < 2.5) components possessing remarkable chemical changes is preferred to react with the O 2 and H 2 O in the air and become high oxidation state compounds. However, it is worth to note that the optical properties of the films shows extra-low variation performance (e.g. linear increasing rate of transmittance ~0.00448% per day @ λ = 600 nm). The aging mechanism of the VO X films in air was interpreted in terms of the interface aging and the diffusion-reaction aging on basis of the above experimental results. This study would provide valuable experience of the natural aging of VO X films. [ABSTRACT FROM AUTHOR]

Highlights: [•] First report of a fully validated LC–MS assay for CUDC-101 in rat plasma. [•] First report of CUDC-101 plasma pharmacokinetics in rat. [•] Simple one-step protein precipitation by acetonitrile/methanol (9/1) was used. [•] A cheap IS (carbamazepine) was used in the method. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of novel quinazolinyl-containing benzamides derivatives were designed. • Compounds 11a selectively inhibited HDAC1 over the other HDACs isoforms. • 11a inhibited proliferation of several human cancer cells. • 11a had acceptable safety and oral pharmacokinetic properties. • 11a showed significant antitumour activity in vivo. A series of quinazolinyl-containing benzamide derivatives were designed, synthesized and evaluated for their in vitro histone deacetylase 1 (HDAC1) inhibitory activities. Compounds 11a surpassed the known class I selective HDAC inhibitor MS-275 in both HDAC1 enzymatic inhibitory activity and cellular anti-proliferative activity against a selected set of cancer cell types (Hut78, K562, Hep3B and HCT116 cells) with no observed effects on human normal cells. In particular, compound 11a inhibited HDAC1 over the other tested HDACs isoforms (HDAC2, HDAC6 and HDAC8) with acceptable safety profiles. Moreover, compound 11a displayed favorable oral pharmacokinetic properties and showed significant antitumor activity in the A549 tumor xenograft model in vivo. [ABSTRACT FROM AUTHOR]

Abstract: A high throughput screening (HTS) hit, 1 (Plk1 K i =2.2μM) was optimized and evaluated for the enzymatic inhibition of Plk-1 kinase. Molecular modeling suggested the importance of adding a hydrophobic aromatic amine side chain in order to improve the potency by a classic kinase H-donor–acceptor binding mode. Extensive SAR studies led to the discovery of 49 (Plk1 K i =5 nM; EC50 =1.05μM), which demonstrated moderate efficacy at 100mpk in a MiaPaCa tumor model, with no overt toxicity. [Copyright &y& Elsevier]

Abstract: Multifunctional bone scaffold materials have been produced from a biodegradable polymer, poly(l-lactic acid) (PLLA), and 1–10% wt of octadecylamine-functionalized nanodiamond (ND-ODA) via solution casting followed by compression molding. By comparison to pure PLLA, the addition of 10% wt of ND-ODA resulted in a significant improvement of the mechanical properties of the composite matrix, including a 280% increase in the strain at failure and a 310% increase in fracture energy in tensile tests. The biomimetic process of bonelike apatite growth on the ND-ODA/PLLA scaffolds was studied using microscopic and spectroscopic techniques. The enhanced mechanical properties and the increased mineralization capability with higher ND-ODA concentration suggest that these biodegradable composites may potentially be useful for a variety of biomedical applications, including scaffolds for orthopedic regenerative engineering. [Copyright &y& Elsevier]

The effects of smoking on survival in BM patients have yet to be reviewed and meta-analysed. However, previous studies have shown that smokers had a greater risk of dying from lung cancer compared to non-smokers. This meta-analysis, therefore, aimed to analyse the effects of cigarette smoking on overall survival (OS) and progression-free survival (PFS) in lung cancer BM patients. PubMed, Embase, Web of Science, Cochrane and Google Scholar were searched for comparative studies regarding the effects of smoking on incidence and survival in brain metastases patients up to December 2020. Three independent reviewers extracted overall survival (OS) and progression-free survival data (PFS). Random-effects models were used to pool multivariate-adjusted hazard ratios (HR). Out of 1890 studies, fifteen studies with a total of 2915 patients met our inclusion criteria. Amongst lung carcinoma BM patients, those who were smokers (ever or yes) had a worse overall survival (HR: 1.34, 95% CI 1.13, 1.60, I2: 72.1%, p-heterogeneity < 0.001) than those who were non-smokers (never or no). A subgroup analysis showed the association to remain significant in the ever/never subgroup (HR: 1.34, 95% CI 1.11, 1.63) but not in the yes/no smoking subgroup (HR: 1.30, 95% CI 0.44, 3.88). This difference between the two subgroups was not statistically significant (p = 0.91). Amongst lung carcinoma BM patients, smoking was associated with a worse OS and PFS. Future studies examining BMs should report survival data stratified by uniform smoking status definitions. [ABSTRACT FROM AUTHOR]

Abstract: Superior mechanical properties, rich surface chemistry, and good biocompatibility of diamond nanoparticles make them attractive in biomaterial applications. A multifunctional fluorescent composite bone scaffold material has been produced utilizing a biodegradable polymer, poly(l-lactic acid) (PLLA), and octadecylamine-functionalized nanodiamond (ND-ODA). The uniform dispersion of nanoparticles in the polymer led to significant increase in hardness and Young’s modulus of the composites. Addition of 10%wt of ND-ODA resulted in more than 200% increase in Young’s modulus and 800% increase in hardness, bringing the nanocomposite properties close to that of the human cortical bone. Testing of ND-ODA/PLLA as a matrix supporting murine osteoblast (7F2) cell growth for up to 1 week showed that the addition of ND-ODA had no negative effects on cell proliferation. ND-ODA serves as a multifunctional additive providing improved mechanical properties, bright fluorescence, and options for drug loading and delivery via surface modification. Thus ND-ODA/PLLA composites open up numerous avenues for their use as components of bone scaffolds and smart surgical tools such as fixation devices in musculoskeletal tissue engineering and regenerative medicine. Intense fluorescence of ND-ODA/PLLA scaffolds can be used to monitor bone re-growth replacing the implant in vivo. [ABSTRACT FROM AUTHOR]

• Low-cost copper mesh by a maskless nanosecond laser direct ablation process. • The square shaped mesh without outward radial mass on the edge of metallic meshes. • The copper mesh presents an excellent a filtration in Vis and NIR regions. • The copper mesh was demonstrated enhanced thermal shielding efficiency. Laser direct fabrication of metallic mesh is a very promising structure for the next-generation transparent electrodes due to its outstanding optical and electrical properties. However, photoelectric properties and morphologies of the metallic mesh electrodes are not excellent after Gaussian pulse laser writing technology, which largely restricts the development of laser direct ablation process for the fabrication of high-quality transparent electrodes. In this study, we present newly developed copper mesh transparent electrode by spatially modulated one-step top-flat square nanosecond laser direct writing ablation of Cu film under ambient conditions. The copper square shaped electrode without outward radial mass transfer of molten metal, and no structural deformation and damage on the edge of metallic meshes. The clean square shaped of copper meshes structure not only shows high optical transparency in visual region and excellent a filtration in NIR regions, but also presents electrothermogenic of conductive copper mesh. In addition, the clean square shaped of copper mesh electrode on glass was demonstrated enhanced thermal shielding efficiency and defrost test as the smart windows. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we report the X-ray crystal structure of an N-terminally truncated variant of the bacterial serpin, tengpin (tengpinΔ42). Our data reveal that tengpinΔ42 adopts a variation of the latent conformation in which the reactive center loop is hyperinserted into the A β-sheet and removed from the vicinity of the C-sheet. This conformational change leaves the C β-sheet completely exposed and permits antiparallel edge–strand interactions between the exposed portion of the reactive center loop of one molecule and strand s2C of the C β-sheet of the neighboring molecule in the crystal lattice. Our structural data thus reveal that tengpinΔ42 forms a loop C-sheet polymer in the crystal lattice. In vivo serpins have a propensity to misfold and form long-chain polymers, a process that underlies serpinopathies such as emphysema, thrombosis and dementia. Native serpins are thought to polymerize via a loop A-sheet mechanism. However, studies on plasminogen activator inhibitor 1 and the S49P variant of human neuroserpin reveal that the latent form of these molecules can also polymerize. Polymerization of latent neuroserpin may be important for the development of familial encephalopathy with neuroserpin inclusion bodies. Our structural data provide a possible mechanism for polymerization by latent serpins. [Copyright &y& Elsevier]

Abstract: The reaction of the metal complexes MO2Cl2(mebipy) (M=Mo, W) with two equivalents thiophenol by the exact same procedure leads to two different products for molybdenum [Mo2O4(SPh)2(mebipy)2] and tungsten [WO2(SPh)2(mebipy)]. To understand why this is the case the redox potentials of the starting materials were measured showing that the redox potential for thiophenol is lower than the redox potentials (MV ↔MVI) for both of the metal precursors. A reduction of the metal and oxidation of the sulfur should be possible for both reactions but occurs only for the molybdenum compound. Theoretical calculations show that different metal–sulfur bond strengths are as well and equally responsible for the differing reaction behaviour as are the redox potentials. [Copyright &y& Elsevier]

Abstract: Although biopsy has been considered mandatory in diagnosing liver fibrosis, there is a high demand for alternative effective and noninvasive methods. In this study we aimed to develop a noninvasive and effective method using the plasma amino acid profiles for the diagnosis of liver fibrosis. Materials and methods: Fifty-three patients with chronic hepatitis C infection were included in the study. Plasma amino acid concentration was analyzed and severity of fibrosis was staged based on biopsy. We employed a previously published amino acid-based approach to develop a discriminator (designated as an “amino-index”) for the diagnosis of patients with advanced liver fibrosis. The area under the receiver operating characteristic curve (AUC) was used for evaluation of the diagnosis. Results: (Phe)/(Val)+(Thr+Met+Orn)/(Pro+Gly) was derived as the optimal amino index. The AUCs were 0.92±0.04 (SE) and 0.99±0.01 for discriminating advanced fibrosis (fibrosis stages F3 and F4) and for discriminating cirrhosis, respectively. By use of the optimal cut-off values, both the sensitivity and specificity achieved a score over 0.88. Conclusion: Fibrosis index based on amino acid concentration could be applied to diagnose liver fibrosis as a convenient noninvasive approach. [Copyright &y& Elsevier]

[Display omitted] Serotonin reuptake inhibition combined with the action targeting 5-hydroxytryptamine receptor subtypes can serve as a potential target for the development of antidepressant drugs. Herein a series of new aralkyl piperazines and piperidines were designed and synthesized by the structural modifications of the previously discovered aralkyl piperidine compound 1 , targeting SSRI/5-HT 1A /5-HT 7. The results exhibited that compound 5a showed strong binding to 5-HT 1A and 5-HT 7 (K i of 0.46 nM, 2.7 nM, respectively) and a high level of serotonin reuptake inhibition (IC 50 of 1.9 nM), all of which were significantly elevated compared to 1. In particular, compound 5a showed weaker inhibitory activity against hERG than 1 , and demonstrated good stability in liver microsomes in vitro. The preliminary screening using FST indicated that orally administered 5a , at a high dose, could reduce immobility time in mice markedly, indicating potential antidepressant activity. [ABSTRACT FROM AUTHOR]

Histone deacetylase 6 (HDAC6), as the key regulatory enzyme, plays an important role in the development of the nervous system. More and more studies indicate that HDAC6 has become a promising therapeutic target for CNS diseases. Herein we designed and synthesized a series of novel HDAC6 inhibitors with benzothiadiazinyl systems as cap groups and evaluated their activity in vitro and in vivo. Among them, compound 3 exhibited superior selective inhibitory activity against HDAC6 (IC50 = 5.1 nM, about 30‐fold selectivity over HDAC1). The results of docking showed that compound 3 can interact well with the key amino acid residues of HDAC6. Compound 3 showed lower cytotoxicity (20 μM to SH‐SY5Y cells, inhibition rate = 25.75%) and better neuroprotective activity against L‐glutamate‐induced SH‐SY5Y cell injury model in vitro. Meanwhile, compound 3 exhibited weak cardiotoxicity (10 μM hERG inhibition rate = 17.35%) and possess good druggability properties. Especially, compound 3 could significantly reduce cerebral infarction from 49.87% to 32.18%, and similar with butylphthalide in MCAO model, indicating potential clinical application prospects for alleviating ischemic stroke‐induced brain infarction. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and analyze radiomics models based on non-contrast-enhanced computed tomography (CT) and different phases of contrast-enhanced CT in predicting Ki-67 proliferation index (PI) among patients with pathologically confirmed gastrointestinal stromal tumors (GISTs). Methods: A total of 383 patients with pathologically proven GIST were divided into a training set (n = 218, vendor 1) and 2 validation sets (n = 96, vendor 2; n = 69, vendors 3–5). Radiomics features extracted from the most recent non-contrast-enhanced and three contrast-enhanced CT scan prior to pathological examination. Random forest models were trained for each phase to predict tumors with high Ki-67 proliferation index (Ki-67>10%) and were evaluated using the area under the receiver operating characteristic curve (AUC) and other metrics on the validation sets. Results: Out of 107 radiomics features extracted from each phase of CT images, four were selected for analysis. The model trained using the non-contrast-enhanced phase achieved an AUC of 0.792 in the training set and 0.822 and 0.711 in the two validation sets, similar to models trained on different contrast-enhanced phases (p > 0.05). Several relevant features, including NGTDM Busyness and tumor size, remained predictive in non-contrast-enhanced and different contrast-enhanced images. Conclusion: The results of this study indicate that a radiomics model based on non-contrast-enhanced CT matches that of models based on different phases of contrast-enhanced CT in predicting the Ki-67 PI of GIST. GIST may exhibit similar radiological patterns irrespective of the use of contrast agent, and such radiomics features may help quantify these patterns to predict Ki-67 PI of GISTs. Clinical relevance statement: GIST may exhibit similar radiomics patterns irrespective of contrast agent; thus, radiomics models based on non-contrast-enhanced CT could be an alternative for risk stratification in GIST patients with contraindication to contrast agent. Key Points: • Performance of radiomics models in predicting Ki-67 proliferation based on different CT phases is evaluated. • Non-contrast-enhanced CT–based radiomics models performed similarly to contrast-enhanced CT in risk stratification in GIST patients. • NGTDM Busyness remains stable to contrast agents in GISTs in radiomics models. [ABSTRACT FROM AUTHOR]

Examines the manganese(III)-based oxidative free-radical cyclization of phenylmenthyl esters. Characterization of the products of the cyclization; Extent and direction of the reaction; Use of beta-keto sulfoxide as a substrate for the oxidative free-radical cyclization; Description of the synthetic pathway; Diastereoselectivity of the cyclization.

• Mean weight diameter of splash-detached sediments first increased and then decreased with increasing rainfall intensity. • Mean weight diameter increased logarithmically with increasing slope gradient. • Equation of mean weight diameter with rainfall kinetic energy, depth and velocity of runoff was established for clay loam. Knowledge of the size-selective characteristics of splash-detached sediments can progress the understanding of splash and subsequent interrill wash erosion processes, as well as improve their modelling. Rainfall intensity (I) and slope gradient (S), as well as rainfall kinetic energy (KE), runoff depth (h) and runoff velocity (v) have important effects on splash-detached sediment size. The objectives of this study were to explore the responses of the size-selective characteristics (expressed by mean weight diameter, MWD) of splash-detached sediments to I and S , and to identify the relationships of MWD of splash-detached sediments with KE , h and v. Simulated rainfall experiments were conducted on clay loam under different rainfall intensities (0.7, 1.0, 1.5, 2.0, and 2.5 mm min−1) and slope gradients (7, 10, 15, 20, and 25°) at the simulated rainfall hall in Yangling, China in 2017. Results showed that the MWD was 72.74–164.17 μm for the splash-detached sediments, which was lower than that of the soil matrix (183.23 μm). MWD increased logarithmically with increasing S , and MWD first increased and then decreased with increasing I or KE parabolically. The relationship of MWD with I and S can be described by an exponential-power combination equation (MWD = 216 e -1.25I I 1.81 S 0.28, R2 = 0.88). MWD was negatively related to h and positively related to v. Comprehensive response of MWD to KE , h and v can be described by an exponential-power combination equation (MWD = 0.33 e -0.002KE KE 1.18 h -0.20 v 0.27, R2 = 0.85). These findings showed that splash-detached sediment size was significantly affected by I and S , as well as KE , h and v. The study could be helpful in soil conservation management for similar conditions of soil, rainfall and land use. [ABSTRACT FROM AUTHOR]

• The relationship between morphology and pulse overlap rate has been established. • Local field enhancement effect was utilized to induce the directional splitting of surface periodic structures. • The large-area subwavelength periodic structures were fabricated by twice laser direct-writing scanning technology. We presented a theoretical and experimental study for the evolution of femtosecond laser direct-writing induced large area of periodic surface structures on As 2 S 3 glass. The laser direct-writing induced large area of low spatial frequency LIPSS (LSFL) structures can be fabricated with the overlap rate increases from 65% to 80%. The evolution process can be defined by the competition between the laser fluence and pulse overlap rate. What is more important is that, based on secondary femtosecond laser scanning process, the interaction between the initial LSFL structures induced by the first scanning and the laser pulse of the second scanning process can induce local field enhancement effect, which can directly split the surface periodic structures of LSFL. Such new subsequent high spatial frequency LIPSS (HSFL) fabrication process is quite different from the traditional multi-pulse induced HSFL and can be used to fabricate large-area HSFL structures. [ABSTRACT FROM AUTHOR]

Density functional theory (DFT) calculations have been made to investigate the adsorption and sensing properties of harmful nitrogen oxides (NO, NO2) on rhodium (Rh) doped hexagonal boron nitride (BN) to explore the feasibility of constructing Rh‐doped BN (Rh‐BN) based gas sensors. For each gas molecule, various adsorption positions and orientations were examined. The calculations illustrate that the most stable structure is that the Rh atom is located directly above the N atom, and a stable chemical bond with a length of 2.096 Å formed between the Rh atom and N atom, with significant binding energy (Eb) of −1.561 eV. Moreover, the adsorption performance of the Rh‐BN monolayer towards nitrogen oxide is in the order as NO2>NO, with Ea of −3.919 eV and −3.318 eV, respectively. This indicates that the Rh‐BN single layer possesses ideal adsorption and sensing properties. Furthermore, by doping the Rh atom, impurities are introduced into the intrinsic BN band structure, which improves the interaction between BN and adsorbed gas molecules. Following the adsorption of NO and NO2, the bandgap (Eg) of the doped BN is wider, which indicates that gas adsorption reduces the conductivity of the system, but enhances the sensitivity of the system. The above calculation and analysis are of great importance for the exploration of the Rh‐BN monolayer as an innovative gas detection material. [ABSTRACT FROM AUTHOR]

• Replace the self-attention layer in Transformer with graph convolution for improved local representation learning. • A novel fused framework is proposed which combine graph neural network and graph Transformer. • Inter-atomic distance features are extracted for learning interaction information of atom pairs more accurately. Graph Transformer architecture started to catch fire in molecular properties prediction due to its ability to represent complex interactions between all nodes. However, the self-attention mechanism in Transformer encoder part transforms the graph data into a fully-connected graph for graph representation learning, causing the loss of the original structural information of the graph. In this work, Local Transformer is proposed to keep the original graph structure and aggregate local information of nodes. In the model, a simple graph convolution is designed to replace the self-attention module, which reaches the state-of-the-art performance on ZINC dataset. Further, in order to rectify the problem that graph neural networks(GNNs) cannot capture long-range interactions of atoms, a novel end-to-end framework combined the GNN with Local and Global Transformer is proposed, which achieves good results on QM9 dataset. [ABSTRACT FROM AUTHOR]

Background: This study aimed to uncover the effect of miR-138-5p on the proliferation and metastasis of PCa cell lines, and further explore the potential regulatory mechanisms via regulating FOXC1. Methods: 60 pairs cancer tissues and corresponding paracancerous ones from PCa patients were collected to assess the expression level of miR-138-5p by qRT-PCR. Subsequently, over-expression of miR-138-5p were established to explore the proliferation and metastasis of miR-138-5p in PCa cell lines was analyzed by CCK-8, Transwell assay and Wounding healing assay, respectively. Bioinformatics analysis and luciferase reporter gene assay were performed to search for the target genes of miR-138-5p, and FOXC1 was selected. Finally, the biological role of miR-138-5p and FOXC1 in the progression of PCa was clarified by a series of rescue experiments. Results: The results of qRT-PCR revealed that miR-138-5p was lowly expressed in PCa tissues and cell lines. Besides, the PCa patients with low-miR-138-5p had a high Gleason score, lymph node metastasis and poor prognosis of PCa, compared with these patients with high-miR-138-5p. Over-expression of miR-138-5p inhibited the proliferative, migratory and invasive capacities of PC-3 and DU-145 cells. Bioinformatics analysis and luciferase reporter gene assay suggested that FOXC1 was predicted to be the target gene of miR-138-5p. Moreover, FOXC1 expression level was negatively correlated to that of miR-138-5p in PCa tissues. Importantly, over-expression of FOXC1 could reverse miR-138-5p mimic induced-inhibition of PCa malignant progression. Conclusions: Downregulated miR-138-5p was closely associated with high Gleason score, more lymph node metastasis and poor prognosis of PCa patients. In addition, miR-138-5p alleviated the malignant progression of PCa by targeting and downregulating FOXC1. [ABSTRACT FROM AUTHOR]

The marine stabilized platform is a critical apparatus to ensure the stability of offshore equipment and operations with respect to the inertial coordinate system. However, the hydraulic actuating system of the platform is challenging to control due to the severe offshore environment and hydraulic parameter perturbations. Therefore, to improve the stability and anti-disturbance performance of the hydraulic actuators on the marine stabilized platform, an extended state observer-based sliding mode control (ESO-SMC) method is proposed in the paper. We first analyze the kinematic model of the platform and the dynamic model of the hydraulic servo system. Then, ESO-SMC is designed, and its stability is verified. The novel Marine Predator Algorithm (MPA) is used to optimize the parameters in ESO-SMC design. Simulation is performed in MATLAB/Simulink using an engineering ship model and a stabilized platform model on the ship. Compared with the traditional Sliding Mode Control (SMC), Velocity Feedforward PID (VFPID), and PID methods, ESO-SMC performs best in resisting external wave load disturbances and flow gain parameter perturbations. In conclusion, ESO-SMC is a reliable control approach for enhancing the anti-interference performance of the hydraulic servo system on marine stabilized platforms in the simulation. • An ESO-SMC method for hydraulic actuators on the marine stabilized platform. • A novel MPA is used to optimize parameters in the ESO-SMC design. • The wave load and cylinder hydraulic parameter disturbances are investigated. • ESO-SMC outperforms SMC, VFPID, and PID in terms of handling disturbances. [ABSTRACT FROM AUTHOR]

Lithium‐ion batteries (LIBs) adopting layered oxide cathodes with high nickel content (Ni ≥ 0.9) always suffer from extremely poor cycle life, especially at elevated temperatures and higher charging cut‐off voltages. Adding small amounts of functional additives is considered to be one of the most economic and efficacious strategies to resolve this issue. Herein, cyano‐groups are introduced innovatively into a siloxane to delicately synthesize a novel cyano‐siloxane additive, namely 2,2,7,7‐tetramethyl‐3,6‐dioxa‐2,7‐disilaoctane‐4,4,5,5‐tetracarbonitrile (TDSTCN). Encouragingly, 0.5 wt.% TDSTCN additive enables ultrahigh nickel LiNi0.9Co0.05Mn0.05O2/graphite (NCM90/Gr) full cells with dramatically increased cycle life, especially at an elevated temperature of 50 °C and a high charging cut‐off voltage of 4.5 V. The characterizations reveal that the TDSTCN additive can scavenge HF and promote the formation of robust stable interface layers on NCM90 cathode and Gr anode due to the synergistic effects of cyano‐groups and Si−O bonds. These results reveal the great significance of designing one single additive with several functional groups in enhancing the comprehensive electrochemical performances of high Ni LIBs. [ABSTRACT FROM AUTHOR]