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Introduction: Growth hormone (GH) secreting pituitary adenoma is considered one of the most harmful types of Pituitary Neuroendocrine Tumors (PitNETs). Our previous research has found that high expression of Lysine methyltransferase 5A (KMT5A) is closely related to the proliferation of PitNETs. The aim of this study was to investigate the role and molecular mechanism of KMT5A in the progression of GH PitNETs. Methods: Immunohistochemistry, qRT-PCR, and Western blot (WB) were used to assess the expression levels of KMT5A in human normal pituitary and GH PitNETs, as well as in rat normal pituitary and GH3 cells. Additionally, we utilized RNA interference technology and treatment with a selective KMT5A inhibitor to decrease the expression of KMT5A in GH3 cells. CCK-8, EdU, flow cytometry (FCM), clone formation, and WB assay were further employed to evaluate the impact of KMT5A on the proliferation of GH3 cells in vitro. A xenograft model was established to evaluate the role of KMT5A in GH PitNETs progression in vivo. Results: KMT5A was highly expressed in GH PitNETs and GH3 cells. Moreover, the reduction of KMT5A expression led to inhibited growth of GH PitNETs and increased apoptosis of tumor cells, as indicated by the findings from CCK-8, EdU, clone formation, and FCM assays. Additionally, WB analysis identified the Wnt/β-catenin signaling pathway as a potential mechanism through which KMT5A promotes GH PitNETs progression. Conclusion: Our research suggests that KMT5A may facilitate the progression of GH PitNETs via the Wnt/β-catenin signaling pathway. Therefore, KMT5A may serve as a potential therapeutic target and molecular biomarker for GH PitNETs. [ABSTRACT FROM AUTHOR]

As an essential moisture transport channel over the Tibetan Plateau (TP), accurate simulation of precipitation over the southeastern TP (SETP) is crucial for downstream moisture transport and water resource assessment. To improve SETP's precipitation simulation accuracy, a Turbulent Orographic Form Drag (TOFD) scheme, which represents the TOFD effect of subgrid orography on model grids, is employed. The impact of TOFD on cloud and precipitation during the summer monsoon over the SETP is investigated from dynamical and cloud microphysical perspectives. Through comparison with ground observations and satellite precipitation data, TOFD reduces the simulated precipitation bias. Despite reducing moisture transport, TOFD enhances low-level convergence and high-level divergence by influencing the low-level wind, thereby strengthening updraft and cloud and precipitation processes before the slope of SETP. TOFD also increases total precipitation before the slope by promoting heavy precipitation and reducing weak precipitation. However, TOFD diminishes the updraft and cloud and precipitation processes over the slope of SETP by influencing low-level wind. The reduced moisture transport by TOFD leads to decreased precipitation over the slope. Additionally, TOFD reduces total precipitation over the slope by promoting weak precipitation and reducing heavy precipitation. Furthermore, the impact mechanism of TOFD on precipitation depends on the wind speed, which is weakened during weak precipitation period with reduced wind speed and enhanced during heavy precipitation period with increased wind speed. These findings enhance the understanding of the complex terrain's influence on cloud and precipitation and provide a basis for improving cloud and precipitation simulation over the SETP. [ABSTRACT FROM AUTHOR]

Background: Hospital chief financial officer (CFO) contributes to improving health system performance. However, how to become an excellent hospital CFO has rarely been considered from a holistic perspective. This paper aims to identify competencies required by hospital CFO to fulfil the position's responsibilities and explore effective implementation pathways to generate high performance and improve healthcare service. Methods: We conducted 61 semi-structured interviews with individuals in key leadership positions in China's hospitals and researchers focusing on healthcare system management to identify core competencies necessary for hospital CFO. Interviews were analysed through a multi-stage review process and modified via expert vetting using a national panel of 23 professors. Subsequently, interviews were conducted with 32 hospital CFOs from 14 provinces throughout September 2021 to May 2022. We scored the performance of 32 hospital CFOs in various aspects of competency and used the fuzzy-set qualitative comparative analysis to explore the competency configurations of excellent CFOs. Results: We identify seven core competencies necessary for a hospital CFO to fulfil management practices, including personal morality, resource management, strategy management, learning ability, negotiating skill, leadership skill, and financial management. The findings indicate that a single competency factor is not a necessary condition to become an excellent hospital CFO. The results of qualitative comparative analysis then make it possible to propose four configurational paths, namely, supportive, interpersonal, all-around development, and technical, to become an excellent hospital CFO and achieve effective managerial performance. Conclusions: The responsibilities of hospital CFOs are complex and varied, hence, a better understanding of competencies required by CFO is essential to implement their responsibilities effectively. The identification in this study of the four effective implementation pathways to becoming an excellent hospital CFO enriches the literature on hospital management and provides implications for China's hospitals and their CFOs. [ABSTRACT FROM AUTHOR]

Obesity is a serious health problem in modern life and increases the risk of many comorbidities including iron dyshomeostasis. In contrast to malnourished anemia, obesity-related iron dyshomeostasis is mainly caused by excessive fat accumulation, inflammation, and disordered gut microbiota. In obesity, iron dyshomeostasis also induces disorders associated with gut microbiota, neurodegenerative injury, oxidative damage, and fat accumulation in the liver. Selenium deficiency is often accompanied by obesity or iron deficiency, and selenium supplementation has been shown to alleviate obesity and overcome iron deficiency. Selenium inhibits fat accumulation and exhibits anti-inflammatory activity. It regulates gut microbiota, prevents neurodegenerative injury, alleviates oxidative damage to the body, and ameliorates hepatic fat accumulation. These effects theoretically meet the requirements for the inhibition of factors underlying obesity-related iron dyshomeostasis. Selenium supplementation may have a potential role in the alleviation of obesity-related iron dyshomeostasis. This review verifies this hypothesis in theory. All the currently reported causes and results of obesity-related iron dyshomeostasis are reviewed comprehensively, together with the effects of selenium. The challenges and strategies of selenium supplementation are also discussed. The findings demonstrate the possibility of selenium-containing drugs or functional foods in alleviating obesity-related iron dyshomeostasis. [ABSTRACT FROM AUTHOR]

Fatigue has many negative effects on human health. As such, it is desirable to develop anti-fatigue foods and understand the mechanisms of their action. Based on a comprehensive review of the literature, this article discusses the important roles of gut microbiota in fatigue and anti-fatigue. Studies have shown that an increase in pathogenic bacteria and a decrease in beneficial bacteria co-exist when fatigue is present in both rodents and humans, whereas changes in gut microbiota were reported after intervention with anti-fatigue foods. The roles of gut microbiota in the activities of anti-fatigue foods can also be explained in the causes and the effects of fatigue. Among the causes of fatigue, the accumulation of lactic acid, decrease of energy, and reduction of central nervous system function were related to gut microbiota metabolism. Among the harmful effects of fatigue, oxidative stress, inflammation, and intestinal barrier dysfunction were related to gut microbiota dysbiosis. Furthermore, gut microbiota, together with anti-fatigue foods, can inhibit pathogen growth, convert foods into highly anti-oxidative or anti-inflammatory products, produce short-chain fatty acids, maintain intestinal barrier integrity, inhibit intestinal inflammation, and stimulate the production of neurotransmitters that regulate the central nervous system. Therefore, it is believed that gut microbiota play important roles in the activities of anti-fatigue foods and may provide new insights on the development of anti-fatigue foods. [ABSTRACT FROM AUTHOR]

Tumor‐associated macrophage (TAM) infiltration facilitates glioma malignancy, but the underlying mechanisms remain unclear. Herein, it is reported that TAMs secrete exosomal LINC01232 to induce tumor immune escape. Mechanistically, LINC01232 is found to directly bind E2F2 and promote E2F2 entry into the nucleus; the two synergistically promots the transcription of NBR1. The increase in binding between NBR1 binding and the ubiquitinating MHC‐I protein through the ubiquitin domain causes an increase in the degradation of MHC‐I in autophagolysosomes and a decrease in the expression of MHC‐I on the surface of tumor cells, which in turn led to tumor cell escape from CD8+ CTL immune attack. Disruption of E2F2/NBR1/MHC‐I signaling with shRNAs or blockade with the corresponding antibodies largely abolishes the tumor‐supportive effects of LINC01232 and inhibits tumor growth driven by M2‐type macrophages. Importantly, knockdown of LINC01232 enhances the expression of MHC‐I on the surface of tumor cells and improves the response to reinfusion with CD8+ T cells. This study reveals the existence of critical molecular crosstalk between TAMs and glioma mediates through the LINC01232/E2F2/NBR1/MHC‐I axis to support malignant tumor growth, indicating that targeting this axis may have therapeutic potential. [ABSTRACT FROM AUTHOR]

Developmental dyslexia (DD) is the most common learning disorder. The alternations of intrinsic functional connectivity (FC) have been frequently reported to be associated with DD. However, previous research has predominately focused on static FC features. Using functional magnetic resonance imaging and a sliding time window approach, this study examined dynamic FC during rest in 22 children with DD and 38 age-matched controls. Results showed that compared to controls, dyslexic children exhibited increased temporal variability of FC in the left inferior frontal gyrus (IFG). Moreover, the higher dynamics of FC was correlated with poorer reading performance, confirming the role of atypical dynamic FC in DD. We found that the altered dynamic FC in dyslexics was associated with problematic regional activity and functional-structural coupling. This study for the first time reveals the aberrant dynamic FC in a pivotal language region, providing novel insights into the neural signature of DD. [ABSTRACT FROM AUTHOR]

Transplanting human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) tissue sheets effectively treat ischemic cardiomyopathy. Cardiac functional recovery relies on graft survival in which angiogenesis played an important part. ONO-1301 is a synthetic prostacyclin analog with proangiogenic effects. We hypothesized that transplantation of hiPSC-CM tissue sheets with slow-release ONO-1301 scaffold could promote hostgraft angiogenesis, enhance tissue survival and therapeutic effect. We developed hiPSC-CM tissue sheets with ONO-1301 slow-release scaffold and evaluated their morphology, gene expression, and effects on angiogenesis. Three tissue sheet layers were transplanted into a rat myocardial infarction (MI) model. Left ventricular ejection fraction, gene expression in the MI border zone, and angiogenesis effects were investigated 4 weeks after transplantation. In vitro assessment confirmed the slow-release of ONO-1301, and its pro-angiogenesis effects. In addition, in vivo data demonstrated that ONO-1301 administration positively correlated with graft survival. Cardiac tissue as thick as ∼900 μm was retained in the ONO (+) treated group. Additionally, left ventricular ejection fraction of the ONO (+) group was significantly enhanced, compared to ONO (−) group. The ONO (+) group also showed significantly improved interstitial fibrosis, higher capillary density, increased number of mature blood vessels, along with an enhanced supply of oxygen, and nutrients. Slow-release ONO-1301 scaffold provided an efficient delivery method for thick hiPSC-CM tissue. ONO-1301 promotes angiogenesis between the host and graft and improves nutritional and oxygen supply, thereby enhancing the survival of transplanted cells, effectively improving ejection fraction, and therapeutic effects. [ABSTRACT FROM AUTHOR]

Building robust letter‐to‐sound correspondences is a prerequisite for developing reading capacity. However, the neural mechanisms underlying the development of audiovisual integration for reading are largely unknown. This study used functional magnetic resonance imaging in a lexical decision task to investigate functional brain networks that support audiovisual integration during reading in developing child readers (10–12 years old) and skilled adult readers (20–28 years old). The results revealed enhanced connectivity in a prefrontal–superior temporal network (including the right medial frontal gyrus, right superior frontal gyrus, and left superior temporal gyrus) in adults relative to children, reflecting the development of attentional modulation of audiovisual integration involved in reading processing. Furthermore, the connectivity strength of this brain network was correlated with reading accuracy. Collectively, this study, for the first time, elucidates the differences in brain networks of audiovisual integration for reading between children and adults, promoting the understanding of the neurodevelopment of multisensory integration in high‐level human cognition. [ABSTRACT FROM AUTHOR]

The neural mechanisms that support handwriting, an important mode of human communication, are thought to be controlled by a central process (responsible for spelling) and a peripheral process (responsible for motor output). However, the relationship between central and peripheral processes has been debated. Using functional magnetic resonance imaging, this study examined the neural mechanisms underlying this relationship in Chinese handwriting in 36 children (mean age = 10.40 years) and 56 adults (mean age = 22.36 years) by manipulating character frequency (a central variable). Brain network analysis showed that character frequency reconfigured functional brain networks known to underlie motor processes, including the somatomotor and cerebellar network, in both children and adults, indicating that central processing cascades into peripheral processing. Furthermore, the network analysis characterized the interaction profiles between motor networks and linguistic‐cognitive networks, fully mapping the neural architecture that supports the interaction of central and peripheral processes involved in handwriting. Taken together, these results reveal the neural interface underlying the interaction between central and peripheral processes involved in handwriting in a logographic writing system, advancing our understanding of the neural basis of handwriting. [ABSTRACT FROM AUTHOR]

Among B-cell lymphoma, multiple myeloma (MM) is an incurable malignancy. miR-140-3p was known to be an inhibitor in malignant tumors. However, the function of miR-140-3p in MM remains unclear. qRT-PCR was performed to determine the expressions of miR-140-3p and BZW2 mRNA. The protein level of BZW2 was determined by the western blot. Cell viability or cell apoptosis was detected by the MTT assay or flow cytometry, respectively. Binding between miR-140-3p and BZW2 was validated using the dual luciferase assay. Xenograft model was applied to verify the results of in vitro study. The level of miR-140-3p was significantly downregulated in MM. Overpexression of miR-140-3p impaired the proliferation of MM cell lines and induced apoptosis in MM cells. miR-140-3p was validated to target BZW2 and inhibit the expression of BZW2. BZW2 was involved in the regulation of miR-140-3p on MM cell vitality and apoptosis. In vivo study revealed that miR-140-3p impeded tumorigenesis of MM cell line in nude mice. Our present study revealed that miR-140-3p served as a suppressor in MM by negatively regulating BZW2. Thus, miR-140-3p could act as a new target for treating MM. [ABSTRACT FROM AUTHOR]

Heart failure (HF) is the leading cause of death worldwide. The most effective HF treatment is heart transplantation, the use of which is restricted by the limited supply of donor hearts. The human pluripotent stem cell (hPSC), including human embryonic stem cell (hESC) and the induced pluripotent stem cells (hiPSC), could be produced in an infinite manner and differentiated into cardiomyocytes (CMs) with high efficiency. The hPSC-CMs have, thus, offered a promising alternative for heart transplant. In this review, we introduce the tissue-engineering technologies for hPSC-CM, including the materials for cell culture and tissue formation, and the delivery means into the heart. The most recent progress in clinical application of hPSC-CMs is also introduced. In addition, the bottleneck limitations and future perspectives for clinical translation are further discussed. [ABSTRACT FROM AUTHOR]

Handwriting is a vital skill for everyday human activities. It has a wealth of information about writers' characteristics and can hint toward underlying neurological conditions, such as Parkinson's disease, autism, dyslexia, and attention‐deficit/hyperactivity disorder (ADHD). Many previous studies have reported a link between personality and individual differences in handwriting, but the evidence for the relationship tends to be anecdotal in nature. Using functional magnetic resonance imaging (fMRI), we examined whether the association between personality traits and handwriting was instantiated at the neural level. Results showed that the personality trait of conscientiousness modulated brain activation in the left premotor cortex and right inferior/middle frontal gyrus, which may reflect the impact of personality on orthography‐to‐grapheme transformation and executive control involved in handwriting. Such correlations were not observed in symbol‐drawing or word‐reading tasks, suggesting the specificity of the link between conscientiousness and handwriting in these regions. Moreover, using a connectome‐based predictive modeling approach, we found that individuals' conscientiousness scores could be predicted based on handwriting‐related functional brain networks, suggesting that the influence of personality on handwriting may occur within a broader network. Our findings provide neural evidence for the link between personality and handwriting processing, extending our understanding of the nature of individual differences in handwriting. [ABSTRACT FROM AUTHOR]

Differential morphological profile (DMP) and differential attribute profile (DAP) are effective tools for automated building extraction from very high-resolution (VHR) images. Compared to the DMP, DAP provides a more flexible way to model image features not only related to the scale of regions, but also any measure (structural, spatial, and spectral) that can be evaluated in the region. The DAP series can be regarded as a structural spectrum that depicts the responses of the image components related to different attributes and scales. However, the conventional DAP-based building feature extraction approach ignores discriminative information for features that are across the scales in the attribute profiles. In this study, an improvement in the discriminatory power of DAP for building feature extraction is proposed. To obtain the entire differential profiles, a scale-span difference attribute profile called generalized DAP (GDAP) is presented, based on which, a new generalized morphological attribute-building index is proposed for the automatic extraction of buildings from VHR imagery. The GDAP can describe the complete attribute spectrum and measure the difference between arbitrary scales, which is more appropriate for representing the multiscale characteristics of buildings. The performance of the proposed method was validated using VHR datasets from an aerial platform. In terms of statistical precision and visual inspection, the results of the proposed framework are superior to those of the relevant supervised and unsupervised building extraction approaches. [ABSTRACT FROM AUTHOR]

The development of high‐performance dopant‐free silicon solar cells is severely bottlenecked by opaque electron selective contact. In this paper, high transmittance (80.5% on glass) and low work function (2.92 eV) lithium fluoride (LiFx)/MgFxOy electron contact stack by tailoring the composition of MgFxOy hybrid film is reported. This hybrid structure exhibits a high conductivity (2978.4 S cm−1) and a low contact resistivity (2.0 mΩ cm2). The element profile of LiFx/MgFxOy contact is measured and the reaction kinetics is analyzed. As a proof‐of‐concept, this electron selective contact is applied for dopant‐free silicon solar cells. An impressive efficiency of 21.3% is achieved on dopant‐free monofacial solar cell with molybdenum oxide (MoOx)/zinc‐doped indium oxide (IZO) hole contact. An efficiency bifaciality of 71% is obtained for dopant‐free bifacial solar cell with full‐area LiFx/MgFxOy/ITO (tin‐doped indium oxide) transparent electron contact. It is the highest efficiency bifaciality so far for dopant‐free bifacial solar cells to the best knowledge. Both cell configurations with LiFx/MgFxOy contacts show excellent environment stability. The cell efficiency maintains more than 95% of its initial value after keeping in air for 1500 h. This work provides a new idea to achieve transparent electron contact, showing a great potential for high‐efficiency and low‐cost optoelectronic devices. [ABSTRACT FROM AUTHOR]

The entrainment rate (λ) is difficult to estimate, and its uncertainties cause a significant error in convection parameterization and precipitation simulation, especially over the Tibetan Plateau, where observations are scarce. The λ over the Tibetan Plateau, and its adjacent regions, is estimated for the first time using five-year satellite data and a reanalysis dataset. The λ and cloud base environmental relative humidity (RH) decrease with an increase in terrain height. Quantitatively, the correlation between λ and RH changes from positive at low terrain heights to negative at high terrain heights, and the underlying mechanisms are here interpreted. When the terrain height is below 1 km, large RH decreases the difference in moist static energy (MSE) between the clouds and the environment and increases λ. When the terrain height is above 1 km, the correlation between λ and RH is related to the difference between MSE turning point and cloud base, because of decreases in specific humidity near the surface with increasing terrain height. These results enhance the theoretical understanding of the factors affecting λ and pave the way for improving the parameterization of λ. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a type of breast tumor that currently lacks options for targeted therapy. Tremendous effort has been made to identify treatment targets for TNBC. Here, we report that the expression level of anaphase promoting complex (APC) coactivator Cdh1 in TNBC is elevated compared to that in the adjacent healthy tissues, and high levels of Cdh1 expression are correlated with poor prognoses, suggesting that Cdh1 contributes to the progression of TNBC. Interfering with the function of Cdh1 can potentiate the cytotoxic effects of PARP inhibitors against BRCA-deficient and BRCA-proficient TNBC cells through inducing DNA damage, checkpoint activation, cell cycle arrest, and apoptosis. Further investigation reveals that Cdh1 promotes BRCA1 foci formation and prevents untangled DNA entering mitosis in response to PARP inhibition (PARPi) in TNBC cells. Collectively, these results suggest that APC/Cdh1 is a potential molecular target for PARPi-based therapies against TNBCs. [ABSTRACT FROM AUTHOR]

Containership delays affect arrival times of subsequent ports and various shipping routes, putting marine logistics at risk of disruption. Analyzing containership delay propagation risks and understanding the underlying propagation mechanism are critical for optimizing port operations and minimizing disruptions in container shipping networks. To address this challenge, this study applies causality analysis to the container shipping network to investigate the propagation risks of containership delays. A novel dimensionality reduction algorithm, in which the concept of effective transfer entropy is introduced, is employed to reduce errors and quantify the containership delay propagation risk causality. By estimating the effective multivariate transfer entropy, containership delay propagation risk networks are established for three regions: global region, East Asia, and Southeast Asia, where container ports serve as nodes and the connections represent the delay propagation risk relationships among ports. The quantitative analysis results show that each port affects 3 other ports on average and is affected by the delay propagation risks in 3 ports on average. The network density in Southeast Asian region is 0.36, compared with 0.14 and 0.13 in the global and East Asian regions, respectively. This implies that the propagation risks of containership delays will be more intensive in Southeast Asian region. Non-key ports are mainly affected unidirectionally by the delay propagation risks from key ports. To further comprehend containership delay propagation risks, numerical simulations are conducted using the network Susceptible Infected Recovered model. The results indicate that ports with high outdegrees exhibit higher risks of causing delay propagation and a wider range of influence. To improve the stability of ports operations, "infection rate" and "recovery rate" should be reduced and increased, respectively. This study proposes a novel method to construct shipping network and fills the gap in research on delay propagation risks in the field of shipping and provides valuable insights into the underlying mechanisms in containership delay propagation, assisting maritime managers in making informed decisions and implementing effective governance measures to reduce containership delay propagation risks. •This study offers a new method based on causality analysis for shipping network construction. •There is no clear correlation between a port's throughput and its risk level in delay propagation. •Non-key ports tend to receive delay propagation risks from key ports unidirectionally. •The degree in the containership delay propagation risk network measures delay propagation risks. [ABSTRACT FROM AUTHOR]

Highlights: This review summarizes current developments in interface engineering for electrocatalytic CO2 reduction reaction (CO2RR). The interface engineering for electrocatalytic CO2RR involves the metal–metal interface, metal–metal oxide interface, metal–nonmetal interface, metal oxide–metal oxide interface, organic molecules–inorganic materials interface, electrode–electrolyte interface, and molecular catalysts–electrode interface. The opportunities and challenges of interface engineering for CO2RR are proposed.Electrocatalytic CO2 reduction reaction (CO2RR) can store and transform the intermittent renewable energy in the form of chemical energy for industrial production of chemicals and fuels, which can dramatically reduce CO2 emission and contribute to carbon-neutral cycle. Efficient electrocatalytic reduction of chemically inert CO2 is challenging from thermodynamic and kinetic points of view. Therefore, low-cost, highly efficient, and readily available electrocatalysts have been the focus for promoting the conversion of CO2. Very recently, interface engineering has been considered as a highly effective strategy to modulate the electrocatalytic performance through electronic and/or structural modulation, regulations of electron/proton/mass/intermediates, and the control of local reactant concentration, thereby achieving desirable reaction pathway, inhibiting competing hydrogen generation, breaking binding-energy scaling relations of intermediates, and promoting CO2 mass transfer. In this review, we aim to provide a comprehensive overview of current developments in interface engineering for CO2RR from both a theoretical and experimental standpoint, involving interfaces between metal and metal, metal and metal oxide, metal and nonmetal, metal oxide and metal oxide, organic molecules and inorganic materials, electrode and electrolyte, molecular catalysts and electrode, etc. Finally, the opportunities and challenges of interface engineering for CO2RR are proposed. [ABSTRACT FROM AUTHOR]

Tumor‐specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1‐matrix metalloproteinase (MT1‐MMP)‐cleavable spacer is used to assemble low‐density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR‐T‐PD. The liposome‐linked cRGDfK prodrug on MR‐T‐PD surface is first activated by MT1‐MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4‐fold higher accumulation and a wider distribution of MR‐T‐PD in tumors. Furthermore, MR‐T‐PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor‐specific manner, MR‐T‐PD exerts superior efficacy (a 5.9‐fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug‐based smart liposome system represents a promising paradigm for pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

Metacognition is the ability to introspect and control ongoing cognitive processes. Despite the extensive investigation of the brain architectures supporting metacognition for perception and memory, little is known about the neural basis of metacognitive capacity for motor function, a vital aspect of human behavior. Here, using functional and structural magnetic resonance imaging (MRI), we examined the brain substrates underlying self-awareness of handwriting, a highly practiced visuomotor skill. Results showed that experienced adult writers generally overestimated their handwriting quality, and such overestimation was more pronounced in men relative to women. Individual variations in self-awareness of handwriting quality were positively correlated with gray matter volume in the left fusiform gyrus, right middle frontal gyrus and right precuneus. The left fusiform gyrus and right middle frontal gyrus are thought to represent domain-specific brain mechanisms for handwriting self-awareness, while the right precuneus that has been reported in other domains likely represents a domain-general brain mechanism for metacognition. Furthermore, the activity of these structurally related regions in a handwriting task was not correlated with self-awareness of handwriting, suggesting the correlation with metacognition was independent of task performance. Together, this study reveals that metacognition for practiced motor skills relies on both domain-general and domain-specific brain systems, extending our understanding about the neural basis of human metacognition. [ABSTRACT FROM AUTHOR]

Dramatic shortages of filtering facepiece respirator supplies generally occur following the outbreak of a pandemic such as COVID-19. Here, the decontamination and reuse of respirators are considered. Among decontamination methods, microwave irradiation has great potential because of easy access of microwave ovens. However, can a respirator be heated in a microwave oven for a certain time and then be reused? Herein, we demonstrate that dry microwave irradiation cannot heat infectious aerosols or droplets up to their deactivation temperature. The microwave absorption performance of a single aerosol or droplet was analyzed theoretically. The multiphysics simulation results indicate that a single aerosol or droplet can be barely heated under dry microwave irradiation. Experiments were carried out using a traveling wave system to verify the simulation. Following this, we simulated multiple aerosols and droplets on a respirator material, with the results indicating that the aerosols and droplets were at the same temperature as that of the respirator. Experimental measurements using a microwave oven demonstrated that the temperature increase of an N95 respirator under dry heating is less than 10 °C, which is far less than the temperature required to deactivate the COVID-19 virus. Although dry microwave heating cannot be used to heat the aerosols or droplets, microwave-generated steam has proved effective in deactivating infectious biological organisms. Therefore, to successfully decontaminate a used respirator in a microwave oven, a reservoir with a small amount of water beneath the respirator (or a steam bag to accommodate it) is essential to the decontamination process. [ABSTRACT FROM AUTHOR]

Artemisia sphaerocephala Krasch polysaccharide (ASKP) consists of two main fractions, 60P (molecular weight at 551 kDa) and 60S (molecular weight at 39 kDa). The anti-obesity effects of ASKP and its two fractions were investigated in high-fat-diet-fed mice and showed similar capability in efficiently preventing the development of obesity. The final body weight and body weight gain of obesity mice model were reduced by 12.44% and 35.33% by ASKP, 10.63% and 34.35% by 60P, and 7.82% and 20.04% by 60S. They also showed similar efficiency to ameliorate dyslipidemia, systematic inflammation, and gut dysbiosis. The colonic genes of barrier integrity were significantly upregulated and the genes of hepatic lipid metabolism and that of colonic inflammatory response were suppressed. They attenuated the gut dysbiosis in obese mice, such as the significant enrichment of beneficial genera (Bifidobacterium and Olsenella) and suppression of harmful ones (Mucispirillum and Helicobacter). Significant enrichment of carbohydrate metabolism associated with the promotion of short-chain fatty acid production and decrease of the metabolisms related to obesity and gut dysbiosis (valine, leucine, and isoleucine biosynthesis, and nitrogen metabolism) were also observed by the administration of ASKP, 60P, and 60S. Overall, these polysaccharides showed potential in acting as prebiotics in preventing high-fat-diet-induced obesity. • Artemisia sphaerocephala Krasch polysaccharide fractions prevent obesity. • Hepatic lipid metabolism and colonic barrier dysfunction were suppressed. • All fractions ameliorate gut dysbiosis and promote SCFA production. • Valine, leucine, and isoleucine biosynthesis, and nitrogen metabolism decreased. • ASKP, 60P, and 60S showed similar capability in preventing obesity. [ABSTRACT FROM AUTHOR]

Poly(ethylene glycol) (PEG) is widely utilized as a hydrophilic coating to extend the circulation time and improve the tumor accumulation of polymeric micelles. Nonetheless, PEGylated micelles often activate complement proteins, leading to accelerated blood clearance and negatively impacting drug efficacy and safety. Here, we have crafted amphiphilic block copolymers that merge hydrophilic sulfoxide-containing polymers (psulfoxides) with the hydrophobic drug 7-ethyl-10-hydroxylcamptothecin (SN38) into drug-conjugate micelles. Our findings show that the specific variant, PMSEA-PSN38 micelles, remarkably reduce protein fouling, prolong blood circulation, and improve intratumoral accumulation, culminating in significantly increased anti-cancer efficacy compared with PEG-PSN38 counterpart. Additionally, PMSEA-PSN38 micelles effectively inhibit complement activation, mitigate leukocyte uptake, and attenuate hyperactivation of inflammatory cells, diminishing their ability to stimulate tumor metastasis and cause inflammation. As a result, PMSEA-PSN38 micelles show exceptional promise in the realm of anti-metastasis and significantly abate SN38-induced intestinal toxicity. This study underscores the promising role of psulfoxides as viable PEG substitutes in the design of polymeric micelles for efficacious anti-cancer drug delivery. This study emphasizes PMSEA's potential as a sulfoxide-containing polymer for anti-cancer drug delivery, offering an alternative to PEG in constructing polymeric prodrug micelles efficiently. [Display omitted] • Sulfoxide-containing polymer PMeSEA presents a promising alternative to PEG. • Micelles grafted with PMeSEA successfully diminish complement system activation. • Reducing complement activation enhances the antitumor activity of PMeSEA-micelles. [ABSTRACT FROM AUTHOR]

The toroidal field (TF) coil is a crucial system in the tokamak, which provides the main magnetic field to confine the plasma. One TF coil of the China Fusion Engineering Test Reactor (CFETR) will be constructed with the support of the Chinese government in the next five years. In order to study the quench behavior of the CFETR TF coil, the assumed quench initiation at the maximum and minimum temperature margin position of the TF coil is analyzed, and the effect of the quench detection threshold on the hot spot temperature is studied. It is found that 0.5 V quench detection voltage leads to hot spot temperature above 250 K in the low-field region. In order to meet the design criteria of the hot spot temperature, the quench detection voltage should be less than 0.2 V. [ABSTRACT FROM AUTHOR]

Powdered sorbents in aqueous solutions suffer from the deficiency in the solid/liquid separation even the sorption capacities were higher than their bulk or less-dispersed forms. The combination of powdered sorbents with membranes would be highly desired to balance the contradiction between high separation efficiency and sorption capability. In this study, cellulose/ball-milled bone char (CL/MB) membranes with sub-micrometer diameter (276.0–281.7 nm) and developed porosity (21.5–98.6 m2/g) were fabricated by electrospinning technique. Bone chars originated from the pyrolysis of bone residuals at 350 °C, 500 °C and 650 °C could well dispersed in the electrospinning solvent. CL/MB membranes could adsorb U(VI) with fast kinetics (180.0 min), efficient capacity (309.8 mg/g at pH 5.00 and T 298 K) and excellent selectivity against the interference of coexisting ions in simulated waters. With spectroscopic analysis, the formation of (Ca(UO 2) 2 (PO 4) 2 (H 2 O) 3 precipitation was dominant for the selectivity. The surface complexation of O-/reductive N-groups with U(VI), the electrostatic attraction of deprotonated O- with positively charged U(VI) species, the cation exchange of U(VI) with Ca2+ components, and the cation-π coordination of U(VI) should also be considered. This study pave the way for the feasible utilization of electrospun CL/MB membranes as a promising sorbent to capture aquatic U(VI). [Display omitted] [ABSTRACT FROM AUTHOR]

In this work, a novel quantum ant colony optimization algorithm for automated guided vehicles (AGVs) path planning based on Bloch coordinates of pheromones is proposed. In consideration of the difficulty in solving the AGVs path planning problem because of NP-hard computational complexity, this approach combines the advantages of quantum theory and ant colony algorithm to obtain feasible, conflict-free, and optimal paths. To expand the search space, the pheromones on paths are coded according to Bloch coordinates. To make full use of the pheromones of three-dimensional Bloch coordinates, they are chosen with certain probabilities in accordance with the paths they obtained. Repulsions among AGVs are supposed to exist to avoid conflicts. A repulsion factor is employed in the state transition rule to increase the space–time distance among AGVs as much as possible. We compare the performance of the proposed algorithm with those of the other three methods in simulation of AGVs path planning at an automated container terminal. Simulation results illustrate the superiority of the proposed algorithm. [ABSTRACT FROM AUTHOR]

Artemisia sphaerocephala Krasch polysaccharide (ASKP) and its two fractions—60P (branched xylan) and 60S (branched glucomannan), were subjected to simulated gastrointestinal digestion and in vitro fermentation by human fecal microbiota. The results showed that all polysaccharide fractions could transit through gastrointestinal tract without dramatic degradation and be utilized by gut microbiota. ASKP exhibited the highest depletion rate and highest capability to decrease the pH than its fractions. Meanwhile, 60S showed the stronger capability to increase the production of propionic acid and reduce the ratio of acetic acid to propionic acid. At the phylum level, all polysaccharides efficiently reduced the Firmicutes/Bacteroidetes ratio and relative abundance of Proteobacteria, with ASKP being the most capable to suppress the proliferation of Proteobacteria. At the genus level, ASKP and 60P markedly promoted the growth of Bacteroidetes , and 60S promoted the growth of Parabacteroides and Collinsella. Prediction on metabolic function revealed that polysaccharide administration could dramatically change the metabolic profile of bacteria compared with fructooligosaccharides. Besides, all the polysaccharides dramatically promoted the bile acid metabolism. Compared with 60S, ASKP and 60P showed stronger ability to suppress the metabolisms on carbohydrate and amino acid. In summary, both ASKP and its two fractions showed the prebiotic potentials. Unlabelled Image • Artemisia sphaerocephala Krasch polysaccharide fractions show prebiotic potential. • All fractions transit through the gastrointestinal tract without degradation. • All fractions exhibit capability to reduce pH value and promote SCFAs production. • All fractions modulate the composition of gut microbiota. • All fraction dramatically changed the profile of metabolic pathways of bacteria. [ABSTRACT FROM AUTHOR]

Morphological building indexes (MBI) have proven to be effective tools for automated building spatial-feature-extraction tasks in images from urban areas. However, owing to the intrinsic shortcomings of MBI, commission and omission errors occur in regions with spectral properties similar to those of buildings and dark heterogeneous roofs, respectively. Some targets (such as bright bare land or roads) can cause substantial interference, which poses an even greater challenge in performing accurate building detection from images of complex environments. In this study, a new automated building detection approach based on a morphological attribute profile is presented with the goal of reducing commission and omission errors. As the first step, corners are detected in very high-resolution (VHR) remote sensing images through an automatic optimization procedure, and weighted spatial voting is performed to predict the presence of built-up areas. Then, by investigating the properties between the attribute filters and buildings, a novel morphological attribute building index is constructed by considering the extracted built-up area as an input image. To validate the detection performance, the approach was tested using VHR images with 1-m spatial resolution. The quantitative assessment indicates that the proposed approach improves the building detection accuracy in images of complex environments. [ABSTRACT FROM AUTHOR]

Solitary pulmonary nodules are the main manifestation of pulmonary lesions. Doctors often make diagnosis by observing the lung CT images. In order to further study the brain response structure and construct a brain-computer interface, we propose an isolated pulmonary nodule detection model based on a brain-computer interface. First, a single channel time-frequency feature extraction model is constructed based on the analysis of EEG data. Second, a multilayer fusion model is proposed to establish the brain-computer interface by connecting the brain electrical signal with a computer. Finally, according to image presentation, a three-frame image presentation method with different window widths and window positions is proposed to effectively detect the solitary pulmonary nodules. [ABSTRACT FROM AUTHOR]

• Artemisia sphaerocephala Krasch polysaccharide alleviated obesity in mice. • Relative expression of genes related to lipid metabolism was downregulated. • Gut dysbiosis induced by the high-fat diet was reversed at various level. • Selected bacterial genera were strongly associated with the obesity. Artemisia sphaerocephala Krasch polysaccharide (ASKP) has been proved to have many bioactivities. To determine the underlying mechanisms on anti-obesogenic effect of ASKP in mice, parameters related to obesity, gut microbiota composition, and the correlation between the parameters and specific bacterial taxa were investigated. The results showed that ASKP significantly alleviated high-fat-diet-induced obesity in mice with the amelioration of dyslipidemia, and metabolic endotoxaemia. Relative expression analyses of genes indicated that ASKP administration modulated hepatic lipid metabolism with the downregulation of related genes, including ACC-1, FAS, SREBP-1c, and PPARγ. 16S rRNA analysis showed that ASKP mediated the gut dysbiosis induced by high-fat diet, such as the reduction of Proteobacteria, AF12 , and Helicobacter. Spearman's correlation showed that some specific genera, such as Odoribacter , AF12 , and Rikenella , were strongly associated with obesity-related parameters. Our results demonstrated that ASKP could serve as a potential prebiotic agent in the prevention of diet-induced obesity. [ABSTRACT FROM AUTHOR]

Directed differentiation methods allow acquisition of high-purity cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs); however, their immaturity characteristic limits their application for drug screening and regenerative therapy. The rapid electrical pacing of cardiomyocytes has been used for efficiently promoting the maturation of cardiomyocytes, here we describe a simple device in modified culture plate on which hiPSC-derived cardiomyocytes can form three-dimensional self-organized tissue rings (SOTRs). Using calcium imaging, we show that within the ring, reentrant waves (ReWs) of action potential spontaneously originated and ran robustly at a frequency up to 4 Hz. After 2 weeks, SOTRs with ReWs show higher maturation including structural organization, increased cardiac-specific gene expression, enhanced Ca2+-handling properties, an increased oxygen-consumption rate, and enhanced contractile force. We subsequently use a mathematical model to interpret the origination, propagation, and long-term behavior of the ReWs within the SOTRs. Li et al. describe a modified culture plate on which hiPSC-derived cardiomyocytes can form 3D self-organized tissue rings (SOTR). Within this ring, re-entrant waves of action potential spontaneously originate and promote cardiomyocytes maturation. They further use a mathematical model to interpret the origination, propagation, and behaviour of the reentrant waves within SOTRs. [ABSTRACT FROM AUTHOR]

The effect of Artemisia sphaerocephala Krasch polysaccharide (ASKP) on the gelatinization and retrogradation of wheat starch (WS) was studied. RVA results displayed that ASKP addition increased the setback values of WS, which indicated that ASKP might promote the short‐term retrogradation of WS. DSC and XRD results demonstrated that the retrogradation percentage of WS during long‐time storage significantly decreased with the addition of ASKP, suggesting the inhibition effect of ASKP on the long‐term retrogradation of WS. As shown in TPA test, ASKP addition increased the hardness of starch gel at the beginning but decreased it after 14 days' storage. Results of FT‐IR revealed that ASKP could promote the water retention and intermolecular hydrogen bonding formation. With the addition of ASKP, the spin–spin relaxation time measured by LF‐NMR decreased from 358.47 ms to 274.15 ms, illustrating that the WS paste containing ASKP had higher water retention ability. Leached amylose content results manifested the interaction between WS and ASKP. In summary, ASKP has potential to be a modifier on the retrogradation of starch in food processing. [ABSTRACT FROM AUTHOR]

Septin 2 (SEPT2) is a tumor-related gene belonging to the SEPT family that affects the cellular processes of hepatoma carcinoma cells, glioblastoma cells and mesangial cells and is highly expressed in breast cancer, biliary tract cancer and acute myeloid leukemia. Colorectal cancer (CRC) is the third most common type of malignancy in humans. In the present study, Oncomine database was used to compare the expression pattern of SEPT2 mRNA between CRC and normal tissues. Additionally, protein expression in 90 pairs of CRC and paracancerous tissues was analyzed by western blotting and immunohistochemistry (IHC). The results showed that SEPT2 was highly expressed in CRC tissues at the mRNA and protein levels. SEPT2 expression quantified by IHC was associated with lymph node metastasis, the degree of differentiation and TNM staging. Increased SEPT2 wass associated with reduced overall survival (OS) according to Kaplan-Meier analysis. COX proportional hazard analysis indicated that SEPT2 was an independent factor that influenced the OS of patients with CRC. Therefore, SEPT2 was associated with the occurrence, progression and prognosis of CRC and thus, may be a marker and prognostic indicator of CRC. [ABSTRACT FROM AUTHOR]

Sub/supercritical water liquefication (SCWL) is a water-based thermochemical technology as well as an environmentally friendly treatment by converting wet feedstock into bioenergy. In the present study, a systematic investigation of SCWL of lignite was carried out covering a temperature range between 320 and 440 °C when residence time increased from 5 min to 40 min. The highest bio-oil oil yield of 34.3% with solid residue of 52.7% was obtained at 440 °C for 5 min. Phenol derivatives, carboxylic acids, long chain hydrocarbons, ketones, and naphthalene were the main bio-oil composition through FTIR and GC-MS analysis. Gas yields and their exact compositions were also determined and CO 2 was the dominate gas product but the percentage of CH 4 became significant at severe SCWL conditions. A conclusion was drawn that fast liquefaction (e.g. 5 min) at relative higher temperature (e.g. 400 °C) which avoid excessive gasification and repolymerization reactions was an optimization strategy for high yield bio-oil production from SCWL of lignite. • A systematic investigation of lignite SCWL was carried out for bio-oil production. • The condition was given for highest bio-oil production. • The reason of low bio-oil yield was given at excessive SCWL condition. • The component of gas, bio-oil, and solid products was discussed. [ABSTRACT FROM AUTHOR]

The proton exchange membrane fuel cell gas control has been one key point in fuel cell management systems. The complexity and coupling of the air management system make it difficult to achieve precise air intake adjustment. In this paper, an accurate joint control method for the air flow and pressure regulation is proposed. The nonlinear mathematical model of the air management system is developed to describe the output characteristic and state change. Based on this, the feedback linearization method is proposed to obtain the direct correspondence between control variables and controlled variables. In addition, to solve the problem that the controlled variables cannot be measured directly, an extended state observer is applied to estimate the stack cathode pressure. The sliding mode predictive control method is proposed to control the oxygen excess ratio and cathode pressure simultaneously. The relative order of the system is used to design the sliding mode surface, and the corresponding predictive model is proposed. The results obtained by simulation experiments show that pressure and mass flow have little effect on each other through decoupling. The proposed algorithm has been verified to have high precision, fast response, and robustness through comparative experiments. [ABSTRACT FROM AUTHOR]

Abstract Artemisia sphaerocephala Krasch polysaccharide (ASKP) has previously been reported to ameliorate the hyperglycemia and oxidative stress in type 2 diabetes mellitus and was separated into two fractions of 60P and 60S. To determine the major functional fraction in ASKP, the antidiabetic effects of ASKP and its two fractions were investigated in diabetic db/db mice. As a result, 60P showed the highest and 60S showed the lowest capability in many aspects: decreasing the fasting blood glucose, glycated serum protein, and the insulin resistance in db/db mice; reversing the dyslipidemia caused by diabetes as indicated by the decreased levels of total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and non-esterified fatty acid; as well as exerting antioxidant activities (increases in catalase, superoxide dismutase, and glutathione peroxidase, and a decrease in malondialdehyde) and hepatoprotective activities (increases in total protein and albumin, decreases in alanine aminotransferase and aspartate aminotransferase) in the liver of db/db mice. Liver histopathological observation, using both hematoxylin-eosin staining and periodic acid-Schiff reagent staining, indicated that all polysaccharide fractions could ameliorate the deterioration of hepatic lesions and increase the hepatic glycogen storage in db/db mice. Furthermore, analysis of relative mRNA expression levels suggested that all polysaccharide fractions promoted the glycogen synthesis by up-regulating the expressions of peroxisome proliferator-activated receptor-γ, glucose transporter-4, phosphoinositide 3-kinase, protein kinase B, and glucokinase and inhibited gluconeogenesis via down-regulating the expression of phosphoenopyruvate carboxykinase. Overall, 60P showed as the major antidiabetic fraction in ASKP. Graphical abstract Image 1 Highlights • The study shows antidiabetic effects of different Artemisia sphaerocephala Krasch polysaccharide fractions in db/db mice. • All the fractions could ameliorate hyperglycemia, insulin resistance, hyperlipidemia and oxidative stress in db/db mice. • The polysaccharides may increase the glycogen synthesis and inhibit gluconeogenesis to mediate hepatic glycogen storage. • Integrating all parameters, 60P achieved the highest, while 60S showed the lowest antidiabetic effects in db/db mice. [ABSTRACT FROM AUTHOR]

Partitioning defective protein 3 (Pard3) has been reported to inhibit the progression of numerous human cancer cell types. However, the role of Pard3 in glioma progression remains unclear. In this study, the expression of Pard3 was measured in human gliomas of different grades by both quantitative polymerase chain reaction and Western blotting. The effect of Pard3 on glioma progression was tested using cell counting kit‐8 assays, EdU assays, colony formation assays, cell migration, and invasion assays and tumor xenografts. The effect of Pard3 on Ras homolog family member A (RhoA) protein levels, subcellular localization, and transcriptional activity was measured by immunoblotting and immunofluorescence. Our results indicate that Pard3 functions as a tumor suppressor in gliomas and that the loss of Pard3 protein is strongly associated with a higher grade and poorer outcome. Pard3 overexpression inhibits glioma progression by upregulating RhoA protein levels. However, the level of GTP‐RhoA protein remained unchanged. Further evidence demonstrates that Pard3 regulates RhoA protein levels, subcellular localization and transcriptional activity by activating atypical protein kinase C/NF‐κB signaling. Mouse modeling experiments show that Pard3 overexpression inhibits glioma cell growth in vivo. Taken together, these findings identify RhoA as a novel target of Pard3 in gliomas and substantiate a novel regulatory role for Pard3 in glioma progression. This study reveals that Pard3 plays an inhibitory role in gliomas by regulating RhoA, which reveals a potential benefit for Pard3 activators in the prevention and therapy of gliomas.Overexpression of partitioning defective protein 3 inhibits glioma cell proliferation, migration, and invasion. [ABSTRACT FROM AUTHOR]

Abstract Free amino acids are important bioactive ingredients in herbs and herbal products. Coptis herbs contain a variety of free amino acids; however, studies have not yet analyzed the relationship between free amino acids and species of Coptis herbs. In the current study, the contents of 20 free amino acids in Coptis chinensis Franch., Coptis teeta Wall., and Coptis deltoidea C.Y. Cheng et Hsiao were determined using an automatic amino acid analyzer to evaluate the differences between the three species. We found that the major amino acids (Asn, Arg, and γ-aminobutyric acid (GABA)) were significantly more in C. chinensis than in the other two species. In addition, Asp content was significantly more in C. deltoidea. The study concluded that Asn can be used to identify C. deltoidea , C. chinensis , and C. teeta , and Gln and Arg can be used to distinguish C. teeta from C. chinensis and C. deltoidea. These findings suggested that free amino acids as active ingredients can be used to identify Coptis herb species. Highlights • The contents of 20 free amino acids in C. deltoidea , C. chinensis , and C. teeta were determined. • There were differences in the contents of major amino acids in three different Coptis herb species. • Free amino acids as active ingredients can be used to identify different species of Coptis herbs. [ABSTRACT FROM AUTHOR]

Abstract Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck squamous carcinoma that is notorious for its high metastatic potential. In this study, we reported that FOXA1 protein was decreased in NPC cells. Loss of FOXA1 is associated with lymph node metastasis and poor prognosis. Silencing FOXA1 in NP69 and C666-1 NPC cells accelerated cell proliferation and migration, while re-expression of FOXA1 has opposite effects. Microarray and RNA-seq analysis revealed that re-expression of FOXA1 in NPC cells reprogrammed the TGF-β-stimulated transcription program, which is characterized by promotion of TGF-β-inducible tumor-suppressive targets but repression of TGF-β-inducible oncogenes expression in NPC cells, leading to restoration of NPC cell sensitivity to TGF-β′s growth-inhibitory effect. BAMBI, a TGF-β responsive tumor suppressor, was induced by FOXA1 in NPC cells. FOXA1 binding on the BAMBI gene facilitated SMAD2/3 binding to the BAMBI promoter via increasing BAMBI associated H3K4me1 and H3K27ac modification. Enforced expression of BAMBI in NPC cells suppressed cell proliferation and invasiveness. Our data suggested that FOXA1 is a master factor in controlling the TGF-β-stimulated transcriptome and a regulator of TGF-β biological functions in NPC oncogenesis. Highlights • We reported the first time that loss of FOXA1 predicts unfavorable prognosis in NPC. • FOXA1 is a bona fide tumor suppressor gene in NPC development. • FOXA1 reprograms TGF-β-stimulated transcription from a metastasis promotive to a growth suppressive program. • FOXA1 cooperates with TGF-β activated SMAD complex to upregulate BAMBI expression in NPC cells. [ABSTRACT FROM AUTHOR]

14‐3‐3ζ has been reported to function as critical regulators of diverse cellular responses. However, the role of 14‐3‐3ζ in gliomas progression remains largely unknown. The expression level of 14‐3‐3ζ and Snail was detected by Western blot analysis and quantitative polymerase chain reaction in different grades of human gliomas. The effect of 14‐3‐3ζ on gliomas progression was measured using cell migration and invasion assay, the colony formation experiment, and CCK‐8 assay. The effect of 14‐3‐3ζ on PI3K/AKT/Snail signaling protein expression levels was tested by Western blotting. Firstly, 14‐3‐3ζ was often up‐regulated in high‐grade gliomas relative to low‐grade gliomas, and this overexpression was significantly related to tumor size, Karnofsky Performance Scale score and weaker disease‐free survival. Secondly, the overexpression of 14‐3‐3ζ promoted gliomas cells proliferation, migration, and invasion. Conversely, the knockdown of 14‐3‐3ζ suppressed gliomas cells proliferation, migration, and invasion. Furthermore, subsequent mechanistic studies showed that 14‐3‐3ζ could activate PI3K/AKT/Snail signaling pathway to facilitate gliomas cells proliferation, migration, and invasion. This study shows that the overexpression of 14‐3‐3ζ can promote remarkably gliomas cells proliferation, migration, and invasion by regulating the Snail protein expression through activating PI3K/AKT signaling, and it may serve as a potential prognostic marker and therapeutic target for gliomas. Although aberrant expression of 14‐3‐3ζ contributes to tumor progression and metastasis in a number of carcinomas, the status of 14‐3‐3ζ and its correlation with prognosis in glioma, which is a common, morbid, and frequently lethal malignancy, are still controversial. This study shows that the overexpression of 14‐3‐3ζ can promote remarkably gliomas cells proliferation, migration, and invasion by regulating the Snail protein expression through activating PI3K/AKT signaling, and it may serve as a potential prognostic marker and therapeutic target for gliomas. [ABSTRACT FROM AUTHOR]

Abstract A phytochemical investigation on the peeled stem of Syringa pinnatifolia Hemsl. led to the isolation and structural identification of one new sesquiterpenoid, alashanoid J (1), five triterpenoids (2 – 6), two lignans (7 and 8), and two other phenolic constituents (9 and 10). The structure of alashanoid J was elucidated by MS, 1D and 2D NMR spectroscopic data analysis, and the known compounds were determined on the basis of NMR and MS analysis and literature comparison with those in literature. The discovery of these constituents confirmed the current taxonomic division of this species under the level of genus Syringa. Graphical abstract Image 1 Highlights • Ten constituents were isolated from the stem of Syringa pinnatifolia. • Alashanoid J (1) was a new humulane-type sesquiterpenoid. • Seven constituents (2 – 5 , 9 , and 10) were isolated from the genus for the first time. • Compounds 1 – 8 provide evidence for division of Pinnatifoliae under the genus. [ABSTRACT FROM AUTHOR]

China is a country with a high incidence of gastric cancer (GC), where the GC incidence and the resultant mortality rates account for 50% of those worldwide. Surgical resection remains the primary treatment for GC. However, postoperative patients have a poor prognosis as the majority of patients present with metastases at the time of diagnosis. Therefore, the identification of novel treatment targets is required. The present study aimed to determine the effects of barrier-to-autointegration factor 1 (BANF1) on the clinical features and prognosis of GC, which may aid in discovering a novel tumor diagnostic biomarker and treatment target. The BANF1 gene expression profiles for normal and gastric tumor tissues were downloaded from the Gene Expression Omnibus GSE54129 data set to analyse the expression of BANF1 at the mRNA levels. Then, online survival analysis was performed using the GC database with the Kaplan-Meier Plotter (http://kmplot.com/analysis/) data. To examine the association between BANF1 and clinical features and prognosis, 132 postoperative GC pathological specimens were collected for immunohistochemical analyses. In the GSE54129 data sets, BANF1 expression at the mRNA level was significantly higher in the tumor tissue compared with that in the normal tissue. The same result was obtained in following the immunohistochemical analyses. In addition, BANF1 expression was associated with the patient age, tumor differentiation and infiltration depth. The survival time of BANF1 high-expression patients was shorter compared with that of the low-expression patients, and tumor differentiation status and tumor node metastasis stage were independent prognostic factors of the overall survival of patients with GC. The results of the present study suggest that BANF1 is associated with the clinical features and prognosis of GC. It may be a novel indicator of tumor prognosis and a potential therapeutic target for GC. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is a unique subtype of head and neck squamous carcinoma that is notorious for its high metastatic potential. In this study, we reported that FOXA1 protein was decreased in NPC cells. Loss of FOXA1 is associated with lymph node metastasis and poor prognosis. Silencing FOXA1 in NP69 and C666-1 NPC cells accelerated cell proliferation and migration, while re-expression of FOXA1 has opposite effects. Microarray and RNA-seq analysis revealed that re-expression of FOXA1 in NPC cells reprogrammed the TGF-β-stimulated transcription program, which is characterized by promotion of TGF-β-inducible tumor-suppressive targets but repression of TGF-β-inducible oncogenes expression in NPC cells, leading to restoration of NPC cell sensitivity to TGF-β's growth-inhibitory effect. BAMBI, a TGF-β responsive tumor suppressor, was induced by FOXA1 in NPC cells. FOXA1 binding on the BAMBI gene facilitated SMAD2/3 binding to the BAMBI promoter via increasing BAMBI associated H3K4me1 and H3K27ac modification. Enforced expression of BAMBI in NPC cells suppressed cell proliferation and invasiveness. Our data suggested that FOXA1 is a master factor in controlling the TGF-β-stimulated transcriptome and a regulator of TGF-β biological functions in NPC oncogenesis. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with leptomeningeal metastases (LM); however, a proportion of the patients with resistant tumors do not benefit from EGFR-TKI treatment. In the present study the case of a female patient with advanced lung adenocarcinoma harboring the EGFR L858R mutation (encoded in exon 21) who developed intracranial metastases following treatment with erlotinib after gefitinib failure is reported. The patient achieved a partial response (PR) after four cycles of chemotherapy with pemetrexed/cisplatin. However, after 4 months, LM were detected. The patient was treated with osimertinib, a third-generation EGFR-TKI, but the LM continued to progress and the patient eventually succumbed to the disease (overall survival, 6 months). Therefore, LM in patients without the EGFR T790M mutation (encoded in exon 20) appear to be resistant to treatment with the third-generation TKI osimertinib, which may be associated with human epidermal growth factor receptor 2 amplification. Further clinical trials are required to confirm our results. [ABSTRACT FROM AUTHOR]

To realize higher coverage rate, lower reading interference and cost efficiency of radio-frequency identification network in logistics under uncertainties, a novel robust radio-frequency identification network planning model is built and a robust particle swarm optimization is proposed. In radio-frequency identification network planning model, coverage is established by referring the probabilistic sensing model of sensor with uncertain sensing range; reading interference is calculated by concentric map-based Monte Carlo method; cost efficiency is described with the quantity of readers. In robust particle swarm optimization, a sampling method, the sampling size of which varies with iterations, is put forward to improve the robustness of robust particle swarm optimization within limited sampling size. In particular, the exploitation speed in the prophase of robust particle swarm optimization is quickened by smaller expected sampling size; the exploitation precision in the anaphase of robust particle swarm optimization is ensured by larger expected sampling size. Simulation results show that, compared with the other three methods, the planning solution obtained by this work is more conducive to enhance the coverage rate and reduce interference and cost. [ABSTRACT FROM AUTHOR]

Human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs) are a promising source for cell transplantation into the damaged heart, which has limited regenerative ability. Many methods have been developed to obtain large amounts of functional CMs from hPSCs for therapeutic applications. However, during the differentiation process, a mixed population of various cardiac cells, including ventricular, atrial, and pacemaker cells, is generated, which hampers the proper functional analysis and evaluation of cell properties. Here, we established NKX2-5 eGFP/w and MLC2v mCherry/w hPSC double knock-ins that allow for labeling, tracing, purification, and analysis of the development of ventricular cells from early to late stages. As with the endogenous transcriptional activities of these genes, MLC2v-mCherry expression following NKX2-5-eGFP expression was observed under previously established culture conditions, which mimic the in vivo cardiac developmental process. Patch-clamp and microelectrode array electrophysiological analyses showed that the NKX2-5 and MLC2v double-positive cells possess ventricular-like properties. The results demonstrate that the NKX2-5 eGFP/w and MLC2v mCherry/w hPSCs provide a powerful model system to capture region-specific cardiac differentiation from early to late stages. Our study would facilitate subtype-specific cardiac development and functional analysis using the hPSC-derived sources. [ABSTRACT FROM AUTHOR]

The chemoselective alkylation and olefination of alkylnitriles with alcohols have been developed by simply controlling the reaction atmosphere. A binuclear rhodium complex catalyzes the alkylation reaction under argon through a hydrogen-borrowing pathway and the olefination reaction under oxygen through aerobic dehydrogenation. Broad substrate scope is demonstrated, permitting the synthesis of some important organic building blocks. Mechanistic studies suggest that the alkylation product may be formed through conjugate reduction of an alkene intermediate by a rhodium hydride, whereas the formation of olefin product may be due to the oxidation of the rhodium hydride complex with molecular oxygen. [ABSTRACT FROM AUTHOR]