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The scarcity of freshwater poses a significant threat to sustainable development and human well-being. Exploring and developing state-of-the-art semipermeable materials for seawater desalination could be a potential solution to address this issue. In this study, we unveil the desalination potential of a newly synthesized multilayer covalent organic framework (COF), named ABBPM, showcasing remarkable water permeance reaching 52 L cm−2 day−1 MPa−1 alongside a NaCl rejection rate of 97%. This outstanding performance can be attributed to the advantageous combination of its large pore size (∼3 nm), wide organic skeleton (∼0.94 nm), and the ordered ABC stacking pattern, which creates tortuous yet express water pathways, significantly enhancing filtration efficiency. Free energy analysis reveals that compared to the energy barriers (∼4 kJ mol−1) faced by water molecules, ions encounter higher energy barriers (∼9 kJ mol−1 to ∼11 kJ mol−1) when traversing the 3L ABBPM membrane, which can be primarily attributed to the broad organic skeleton. Moreover, the translocation velocity of water across the multilayer ABBPM membranes surpasses that observed in nanopores on a single-layer graphene or MoS2. Therefore, this study not only presents the multilayer ABBPM COF as a promising candidate for efficient desalination but also proposes a strategic design approach for layered porous structures, with pore sizes exceeding the diameters of hydrated ions, for desalination technology advancement. [ABSTRACT FROM AUTHOR]

Two-dimensional van der Waals materials, with atomic-level thickness and unique electronic structures, have tremendous potential in electronic device applications, making them highly desirable for research in high-performance non-volatile memory. Here, we report a method for the van der Waals epitaxial growth of air-stable and uniformly distributed thin films of a 1T-CrS2 single crystal, based on a simple chemical vapor deposition technique using a binary metal precursor co-reaction growth mechanism controlled by the evaporation rate of the precursor. The corresponding 1T-CrS2 electronic devices can maintain their electrical performance without degradation for up to one month in air. Based on this, we have constructed a floating-gate memory device with a full van der Waals heterostructure, exhibiting a large storage window ratio (approximately 79%), a high on/off ratio (107), and stability for over 1000 cycles. The device demonstrates excellent multi-level data storage stability and can be optically programmed with stable operation using 532 nm laser pulses, showcasing outstanding optoelectronic storage performance. The excellent electrical stability of these two-dimensional materials, the non-volatile nature of the devices, and the stable multi-level storage characteristics present enormous potential for the integration of high-performance non-volatile memory. [ABSTRACT FROM AUTHOR]

Continuous rotating detonation engines have been extensively studied due to their high thermal efficiency. The utilization of solid particles as fuel can effectively reduce costs and enhance detonation performance. We have constructed a compressible gas–solid multimedium flow combustion numerical method, employing the double flux model coupled with fifth-order weighted essentially non-oscillatory and third-order total variation diminishing Runge–Kutta schemes to solve the unsteady multi-component chemical reaction Eulerian–Eulerian equations. Finite-rate methods and surface reaction models are used to simulate the combustion of gaseous mixtures and carbon particles. The effects of the inlet total pressure spatial fluctuations and particle diameter on the flow field characteristics of the continuous rotating detonation engine are investigated. The results indicate that changing the fluctuation period significantly affects the number, propagation direction, and intensity of gas–solid two-phase continuous rotating detonation waves (CRDW). The variation of fluctuation amplitude noticeably alters the combustion characteristics of the two-phase continuous rotating detonation wave, and excessively high amplitudes cannot form continuous rotating detonation waves. Introducing solid particles into fuel significantly mitigates the impact of inlet total pressure spatial fluctuation and promotes propagation stability on the detonation waves. Moreover, when solid particle diameters reach or exceed the micrometer scale, they contribute more favorably to generating a stable detonation flow field. However, excessive particle sizes result in a low surface reaction rate and inadequate contribution of heat released from particle combustion to the propagation of detonation waves. [ABSTRACT FROM AUTHOR]

In this study, we successfully synthesized high-quality 2D layered BiOI crystals using a novel space-confined molten salt method. These crystals exhibit a bandgap of 1.9 eV, closely aligning with theoretical expectations. The photodetectors fabricated from these BiOI nanosheets demonstrate exceptional ultraviolet (UV) detection capabilities. Key performance metrics include an ultrahigh photoresponsivity of 1048 mA W−1, an impressive external quantum efficiency of 420%, and a significant detectivity of 4.7 × 1012 Jones, coupled with a fast response time of 420/690 μs at 310 nm. This study not only highlights the potential of BiOI in UV photodetectors but also marks a substantial advancement in the development of high-performance bismuth-based semiconductor optoelectronic devices. [ABSTRACT FROM AUTHOR]

Memristors have recently become powerful competitors toward artificial synapses and neuromorphic computation, arising from their structural and electrical similarity to biological synapses and neurons. From the diversity of materials, numerous organic and inorganic materials have proven to exhibit great potential in the application of memristors. Herein, this work focuses on a class of memristors based on organic frameworks (OFs) materials, and pay attention to the most advanced experimental demonstrations. First, the typical device structures and memristive switching mechanisms are introduced. Second, the latest progress of OFs‐based memristors is comprehensively summarized, including metal‐organic frameworks (MOFs), covalent organic frameworks (COFs), and hydrogen‐bonded organic frameworks (HOFs), as well as their applications in data storage, artificial synapses, and neuromorphic devices. Finally, the future challenges and prospects of OFs‐based memristors are deeply discussed. [ABSTRACT FROM AUTHOR]

Salmonella typhimurium (S. typhimurium), a prevalent cause of foodborne infection, induces significant changes in the host transcriptome and metabolome. The lack of therapeutics with minimal or no side effects prompts the scientific community to explore alternative therapies. This study investigates the therapeutic potential of a probiotic mixture comprising Lactobacillus acidophilus (L. acidophilus 1.3251) and Lactobacillus plantarum (L. plantarum 9513) against S. typhimurium, utilizing transcriptome and metabolomic analyses, a novel approach that has not been previously documented. Twenty-four SPF-BALB/c mice were divided into four groups: control negative group (CNG); positive control group (CPG); probiotic-supplemented non-challenged group (LAPG); and probiotic-supplemented Salmonella-challenged group (LAPST). An RNA-sequencing analysis of small intestinal (ileum) tissue revealed 2907 upregulated and 394 downregulated DEGs in the LAPST vs. CPG group. A functional analysis of DEGs highlighted their significantly altered gene ontology (GO) terms related to metabolism, gut integrity, cellular development, and immunity (p ≤ 0.05). The KEGG analysis showed that differentially expressed genes (DEGs) in the LAPST group were primarily involved in pathways related to gut integrity, immunity, and metabolism, such as MAPK, PI3K-Akt, AMPK, the tryptophan metabolism, the glycine, serine, and threonine metabolism, ECM–receptor interaction, and others. Additionally, the fecal metabolic analysis identified 1215 upregulated and 305 downregulated metabolites in the LAPST vs. CPG group, implying their involvement in KEGG pathways including bile secretion, propanoate metabolism, arginine and proline metabolism, amino acid biosynthesis, and protein digestion and absorption, which are vital for maintaining barrier integrity, immunity, and metabolism. In conclusion, these findings suggest that the administration of a probiotic mixture improves immunity, maintains gut homeostasis and barrier integrity, and enhances metabolism in Salmonella infection. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Typhimurium (S. Typhimurium), a foodborne pathogen that poses significant public health risks to humans and animals, presents a formidable challenge due to its antibiotic resistance. This study explores the potential of Lactobacillus acidophilus (L. acidophilus 1.3251) probiotics as an alternative strategy to combat antibiotic resistance associated with S. Typhimurium infection. In this investigation, twenty-four BALB/c mice were assigned to four groups: a non-infected, non-treated group (CNG); an infected, non-treated group (CPG); a group fed with L. acidophilus but not infected (LAG); and a group fed with L. acidophilus and challenged with Salmonella (LAST). The results revealed a reduction in Salmonella levels in the feces of mice, along with restored weight and improved overall health in the LAST compared to the CPG. The feeding of L. acidophilus was found to downregulate pro-inflammatory cytokine mRNA induced by Salmonella while upregulating anti-inflammatory cytokines. Additionally, it influenced the expression of mRNA transcript, encoding tight junction protein, oxidative stress-induced enzymes, and apoptosis-related mRNA expression. Furthermore, the LEfSe analysis demonstrated a significant shift in the abundance of critical commensal genera in the LAST, essential for maintaining gut homeostasis, metabolic reactions, anti-inflammatory responses, and butyrate production. Transcriptomic analysis revealed 2173 upregulated and 506 downregulated differentially expressed genes (DEGs) in the LAST vs. the CPG. Functional analysis of these DEGs highlighted their involvement in immunity, metabolism, and cellular development. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis indicated their role in tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), chemokine, Forkhead box O (FOXO), and transforming growth factor (TGF-β) signaling pathway. Moreover, the fecal metabolomic analysis identified 929 differential metabolites, with enrichment observed in valine, leucine, isoleucine, taurine, glycine, and other metabolites. These findings suggest that supplementation with L. acidophilus promotes the growth of beneficial commensal genera while mitigating Salmonella-induced intestinal disruption by modulating immunity, gut homeostasis, gut barrier integrity, and metabolism. [ABSTRACT FROM AUTHOR]

In order to ensure the safety of the Beijing–Shanghai high-speed railway during the construction and operation of the shield tunnel on Line R1 of the Jinan Metro, a numerical simulation of geological disturbance during the underpass of the small-radius stacked tunnel was carried out. We analyzed the mechanism of geological deformation and the construction factors affecting settlement and found that bridge settlement far exceeded safety standards without taking safety control measures. In this regard, safety control technologies such as setting isolation pile sleeve valve pipes, controlling shield tunneling parameters, grouting control technology, and trolley support technology have been proposed. Monitoring was conducted on the uneven settlement of the bridge surface, the internal and external stresses of the pipe segments, and the soil pressure they were subjected to. The results showed that the surface settlement of the bridge after safety control measures was controlled within the safety standard range, and the stress and soil pressure changes of the pipe reinforcement were within the allowable range, further verifying the effectiveness of the safety control measures. [ABSTRACT FROM AUTHOR]

BACKGROUND: In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high‐throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. RESULTS: Compared with the control group, the ulcer area in the WJSS low‐, medium‐ and high‐concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low‐, medium‐ and high‐concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different‐concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. CONCLUSION: Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid–ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti‐ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Cotton (Gossypium hirsutum L.) is one of the main crops in Uzbekistan, which makes a major contribution to the country's economy. The cotton industry has played a pivotal role in the economic landscape of Uzbekistan for decades, generating employment opportunities and supporting the livelihoods of countless individuals across the country. Therefore, having precise and up-to-date data on cotton cultivation areas is crucial for overseeing and effectively managing cotton fields. Nonetheless, there is currently no extensive, high-resolution approach that is appropriate for mapping cotton fields on a large scale, and it is necessary to address the issues related to the absence of ground-truth data, inadequate resolution, and timeliness. In this study, we introduced an effective approach for automatically mapping cotton fields on a large scale. A crop-type mapping method based on phenology was conducted to map cotton fields across the country. This research affirms the significance of phenological metrics in enhancing the mapping of cotton fields during the growing season in Uzbekistan. We used an adaptive feature-fusion network for crop classification using single-temporal Sentinel-2 images and automatically generated samples. The map achieved an overall accuracy (OA) of 0.947 and a kappa coefficient (KC) of 0.795. This model can be integrated with additional datasets to predict yield based on the identified crop type, thereby enhancing decision-making processes related to supply chain logistics and seasonal production forecasts. The early boll opening stage, occurring approximately a little more than a month before harvest, yielded the most precise identification of cotton fields. [ABSTRACT FROM AUTHOR]

To reduce traffic congestion and meet the demand for rail transportation, the diameters of shield tunnels are constantly expanded. The super-large diameter, deep depth and long distance of super-large-diameter shield tunnels, coupled with the limitation of existing structures on underground construction space, cause many problems in the construction of these tunnels, such as affecting existing structures. This study takes a shield project in Wuhan as the research object, uses the finite element method to simulate the influence of super-large-diameter shield tunnelling on the displacement of the existing Line 5 tunnel segments, and analyzes the influence of the isolation pile arrangement and length on the isolation effect. The analysis indicates that (1) the displacement of Line 5 decreases with an increasing horizontal center distance between the tunnels and increases with an increasing vertical center distance between the tunnels, with a maximum displacement of 17.9 mm; (2) the displacement direction and position of the maximum displacement of Line 5 vary with changes in the vertical center distance between the tunnels, but remain essentially constant with changes in the horizontal center distance; and (3) the isolation piles closer to the shield tunnel improve support, with its isolation effect on the Line 5 segment becoming limited. [ABSTRACT FROM AUTHOR]

Accurate crop mapping can represent the fundamental data for digital agriculture and ecological security. However, current crop classification methods perform poorly in mountainous areas with small cropland field parcel areas and multiple crops under cultivation. This study proposed a new object-oriented classification method to address this issue, using multi-source data and object features to achieve multi-crop classification in mountainous areas. Firstly, a deep learning method was employed to extract cropland field parcels in mountainous areas. Subsequently, the fusion of multi-source data was carried out based on cropland field parcels, while object features tailored for mountainous crops were designed for crop classification. Comparative analysis indicates that the proposed classification method demonstrates exceptional performance, enabling accurate mapping of various crops in mountainous regions. The F1 score and overall accuracy (OA) of the proposed method are 0.8449 and 0.8502, representing a 10% improvement over the pixel-based random forest classification results. Furthermore, qualitative analysis reveals that the proposed method exhibits higher classification accuracy for smaller plots and more precise delineation of crop boundaries. Finally, meticulous crop mapping of corn, sorghum, rice, and other crops in Xishui County, Guizhou Province, demonstrates the significant potential of the proposed method in crop classification within mountainous scenarios. [ABSTRACT FROM AUTHOR]

Neuromorphic intelligent hardware technologies have undergone rapid advancement during the past decade, with the goal of building intelligent devices and systems capable of overcoming challenges associated with conventional hardware. Realization of neuromorphic intelligent hardware depends on major advances in materials science, condensed matter physics, device physics and engineering. As a revolutionary discovery, two-dimensional (2D) materials with atomically-thin thickness and exceptionally high tunability introduce a new physical paradigm and show great promise in the development of intelligent devices. Here, we give prominence to three categories of tunable properties (i.e., charge carrier, band structure, lattice structure) that are inherent for 2D materials and review their superiorities in constructing intelligent devices particularly in electronics and optoelectronics. Furthermore, we provide insight into how the unique physical mechanisms emerging in 2D materials offer a fertile ground for the design of diverse intelligence devices. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is a high-risk cancer, and its treatment is an important focus of biomedical research. Immuno-sonodynamic therapy (iSDT), a treatment strategy based on a combination of sonodynamic therapy (SDT) and an immune checkpoint blockade, has been proposed to achieve improved antitumor effects. In this study, chlorin e6 (Ce6) and the PD-1 inhibitor BMS202 were encapsulated into a cell membrane-camouflaged nanoliposome (Bio-Lipo-CB). SDS-PAGE assay and TEM proved the successful wrapping of cell membrane in liposomes, and Bio-Lipo-CB could selectively accumulate in 4T1 cells. Compared with Bio-Lipo-CB alone, Bio-Lipo-CB-SDT showed significant cytotoxicity with abundant ROS production and increased cell apoptosis rate. Moreover, after Bio-Lipo-CB-SDT treatment, calreticulin (CRT) extraversion to the cell membrane, HMGB1 and ATP release to extracellular, indicated immunogenic cell death (ICD). Furthermore, in vivo fluorescence imaging test showed that Bio-Lipo-CB can accumulate in the tumor site after 2 h injection. The in vivo antitumor experiment further confirmed the antitumor efficiency of Bio-Lipo-CB-SDT analysis and demonstrated that Bio-Lipo-CB-SDT induced ICD. The body weight and HE staining of normal organs primarily indicated the safety of this combined strategy. Our study is a proof of concept of synergistic tumor therapeutics based on SDT and checkpoint blockade immunotherapy using a bionic nanoplatform in TNBC. [ABSTRACT FROM AUTHOR]

This paper explores the impact of capital market openness on corporate green technology innovation using the Difference in Differences model (DID) and a quasi-natural experiment with the Shanghai-Hong Kong Stock Exchange using A-share listed corporations data from 2011 to 2020. The findings indicate that capital market openness has a significant promotion effect on corporate green technology innovation. This effect is consistent using Propensity Score Matching-Difference in Differences model (PSM-DID), counterfactual and placebo tests. Moreover, capital market openness can indirectly stimulate corporate green technology innovation by increasing corporate R&D investment and improving corporate management. Notably, the promotion effect of capital market openness on green technology innovation of SOEs and small-scale corporations is stronger. [ABSTRACT FROM AUTHOR]

As China's digital transformation accelerates, there is growing interest in whether the digital economy can effectively boost green innovation in industrial enterprises and enable China's development to break through the constraints of resources and environment. Therefore, this study analyzes the data of A-share industrial listed enterprises (2011–2020). Results indicate that the digital economy promotes green innovation. The impact of the digital economy on green innovation varies significantly among different types of enterprises, with stronger effects on state-owned enterprises. Digital economy enhances green innovation via boosting public attention and optimizing energy structure. Therefore, playing the role of monitoring public attention, and optimizing energy use are key strategies to promote corporate green innovation. [ABSTRACT FROM AUTHOR]

Salt stress, as a principal abiotic stress, harms the growth and metabolism of rice, thus affecting its yield and quality. The tillering stage is the key growth period that controls rice yield. Prohexadione-calcium (Pro-Ca) can increase the lodging resistance of plants by reducing plant height, but its effects on rice leaves and roots at the tillering stage under salt stress are still unclear. This study aimed to evaluate the ability of foliar spraying of Pro-Ca to regulate growth quality at the rice tillering stage under salt stress. The results showed that salt stress reduced the tillering ability of the rice and the antioxidant enzyme activity in the roots. Salt stress also reduced the net photosynthetic rate (Pn), stomatal conductance (Gs) and intercellular CO2 concentration (Ci) of the rice leaves and increased the contents of osmotic regulatory substances in the leaves and roots. The application of exogenous Pro-Ca onto the leaves increased the tiller number of the rice under salt stress and significantly increased the photosynthetic capacity of the leaves. Additionally, it increased the activities of antioxidant enzymes and the AsA content. The contents of an osmotic regulation substance, malondialdehyde (MDA), and H2O2 in the leaves and roots also decreased. These results suggested that Pro-Ca can increase the tillering ability, photosynthetic capacity, osmotic adjustment substance content levels and antioxidant enzyme activity levels in rice and reduce membrane lipid peroxidation, thus improving the salt tolerance of rice at the tillering stage. [ABSTRACT FROM AUTHOR]

A novel short‐chain alcohol dehydrogenase from Tarenaya hassleriana labeled as putative tropinone reductase was heterologously expressed in Escherichia coli. Purified recombinant protein had molecular weight of approximately 30 kDa on 12% sodium dodecyl sulfate‐polyacrylamide gel electrophoresis. T. hassleriana tropinone reductase‐like enzyme (ThTRL) had not detected oxidative activity. The optimum pH for enzyme activity of ThTRL was weakly acidic (pH 5.0). 50°C was the optimum temperature for ThTRL. The highest catalytic efficiency and substrate affinity for recombinant ThTRL were observed with (+)‐camphorquinone (kcat/Km = 814.3 s–1 mM–1, Km = 44.25 μM). ThTRL exhibited a broad substrate specificity and reduced various carbonyl compounds, including small lipophilic aldehydes and ketones, terpene ketones, and their structural analogs. [ABSTRACT FROM AUTHOR]

To optimize the extraction process of total saponins and polysaccharides of the jujube kernel and study its antioxidant effect, Box-behnken method was used to optimize the extraction process of total saponins and polysaccharides from semen ziziphi spinosae, and three antioxidant detection methods were used to study the antioxidant effects of different processed products of semen ziziphi spinosae. The results show that optimal extraction conditions of total saponins are as follows ultrasonic power 228.5 W, liquid-solid ratio 70:1,ethanol volume fraction 10%, and extraction time 21.1 min. The best extraction process of polysaccharides: ultrasonic power 200 W, liquid-solid ratio 70:1,ethanol volume fraction 21.2%, and extraction time 27.7 min. The total saponin content of stir-fried semen ziziphi spinosae is higher, and the polysaccharide content of raw-stir-fried semen ziziphi spinosae is higher. The total saponins and polysaccharides of semen ziziphi spinosae have certain antioxidant capacity. The optimized process can provide a basis for the development and application of jujube kernel. [ABSTRACT FROM AUTHOR]

Background: Coronary microvascular dysfunction (CMD) is a leading cause of ischemic heart disease. Over the past few decades, considerable progress has been made with respect to research on CMD. The present study summarized the current research hotspots and trends on CMD by applying a bibliometric approach. Methods: Relevant publications between 2002 and 2022 were extracted from the Web of Science Core Collection. Visualization network maps of countries, institutions, authors, and co-cited authors were built using VOSviewer. CiteSpace was used for keyword analysis and the construction of a dual-map overlay of journals and a timeline view of co-cited references. Results: 1539 CMD-related publications were extracted for bibliometric analysis. The annual publications generally showed an upward trend. The United States of America was the most prolific country, with 515 publications (33.5%). Camici P. G. was the most influential author, whereas the European Heart Journal, Circulation, and Journal of the American College of Cardiology were the most authoritative journals. Research hotspot analysis revealed that endothelial dysfunction as well as reduced nitric oxide production or bioavailability played critical roles in CMD development. Positron emission tomography was the most widely used imaging method for diagnosis. In addition, microvascular angina, hypertrophic cardiomyopathy, and heart failure have attracted much attention as the main clinical implications. Furthermore, international standards for CMD diagnosis and management may be the future research directions. Conclusions: This study offers a comprehensive view about the hotspots and development trends of CMD, which can assist subsequent researchers and guide future directions. [ABSTRACT FROM AUTHOR]

Background: Coronary microvascular dysfunction (CMD) is a leading cause of ischemic heart disease. Over the past few decades, considerable progress has been made with respect to research on CMD. The present study summarized the current research hotspots and trends on CMD by applying a bibliometric approach. Methods: Relevant publications between 2002 and 2022 were extracted from the Web of Science Core Collection. Visualization network maps of countries, institutions, authors, and co-cited authors were built using VOSviewer. CiteSpace was used for keyword analysis and the construction of a dual-map overlay of journals and a timeline view of co-cited references. Results: 1539 CMD-related publications were extracted for bibliometric analysis. The annual publications generally showed an upward trend. The United States of America was the most prolific country, with 515 publications (33.5%). Camici P. G. was the most influential author, whereas the European Heart Journal, Circulation, and Journal of the American College of Cardiology were the most authoritative journals. Research hotspot analysis revealed that endothelial dysfunction as well as reduced nitric oxide production or bioavailability played critical roles in CMD development. Positron emission tomography was the most widely used imaging method for diagnosis. In addition, microvascular angina, hypertrophic cardiomyopathy, and heart failure have attracted much attention as the main clinical implications. Furthermore, international standards for CMD diagnosis and management may be the future research directions. Conclusions: This study offers a comprehensive view about the hotspots and development trends of CMD, which can assist subsequent researchers and guide future directions. [ABSTRACT FROM AUTHOR]

Background: Coronary microvascular dysfunction (CMD) is a leading cause of ischemic heart disease. Over the past few decades, considerable progress has been made with respect to research on CMD. The present study summarized the current research hotspots and trends on CMD by applying a bibliometric approach. Methods: Relevant publications between 2002 and 2022 were extracted from the Web of Science Core Collection. Visualization network maps of countries, institutions, authors, and co-cited authors were built using VOSviewer. CiteSpace was used for keyword analysis and the construction of a dual-map overlay of journals and a timeline view of co-cited references. Results: 1539 CMD-related publications were extracted for bibliometric analysis. The annual publications generally showed an upward trend. The United States of America was the most prolific country, with 515 publications (33.5%). Camici P. G. was the most influential author, whereas the European Heart Journal, Circulation, and Journal of the American College of Cardiology were the most authoritative journals. Research hotspot analysis revealed that endothelial dysfunction as well as reduced nitric oxide production or bioavailability played critical roles in CMD development. Positron emission tomography was the most widely used imaging method for diagnosis. In addition, microvascular angina, hypertrophic cardiomyopathy, and heart failure have attracted much attention as the main clinical implications. Furthermore, international standards for CMD diagnosis and management may be the future research directions. Conclusions: This study offers a comprehensive view about the hotspots and development trends of CMD, which can assist subsequent researchers and guide future directions. [ABSTRACT FROM AUTHOR]

Ultrasonic‐assisted extraction is a rapid and effective extraction method that uses ultrasound energy and solvents to extract target compounds from various plant matrices. In this study, the ultrasonic‐assisted extraction conditions of sour jujube were optimized. A five‐level central composite design (CCD) with four variables was used to evaluate ultrasonic treatment variables influencing the total saponin content (TSC), total flavonoid content (TFC), and total phenolic content (TPC) extracted from sour jujube. The solvent concentration, extraction time, ultrasonic power, and solid‐to‐liquid (S/L) ratio were optimized using aqueous ethanol and methanol solutions as extraction solvents. A central composite design (CCD) was used for an in‐depth study, and then the optimal value that could produce the maximum TPC, TFC, TSC, and four in vitro antioxidant activities (scavenging activity of hydroxyl free radicals, ferric‐reducing antioxidant power (FRAP), phosphomolybdic acid reduction method, and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) radical‐scavenging activity) was determined. Hydrogen peroxide‐induced oxidative stress experiment confirmed that the Jujube extract could have an antioxidant role in vivo. The relationship between the contents of three compounds and the antioxidant activity in vitro and in vivo was further studied. The results showed that optimizing methanol and ethanol extraction process parameters could improve target components' extraction efficiency. Under the optimum conditions, the TFC and TPC yields of sour jujube by ethanol are better than methanol, while the yield of TSC by methanol is better than ethanol. In vivo data showed that Jujube extract protects against the adverse effects of oxidative stress and improves the life span of female and male Drosophila. This study provides a valuable reference for the full use of Ziziphus jujube, as well as a new direction in food development. [ABSTRACT FROM AUTHOR]

We have demonstrated that the T1-state energy of a fluorescence dopant (FD) is close to that of the thermally activated delayed fluorescence (TADF)-type exciplex co-host, and the energy loss caused by the T1 states of the FD could be suppressed in TADF-sensitized fluorescence (TSF) OLEDs. To further improve device efficiency following this strategy, two compounds, TPA-FQ and dTPA-FQ, were constructed using 2-phenylfuro[2,3-b]quinoxaline (FQ) and triphenylamine (TPA) as the acceptor and donor, respectively. dTPA-FQ, with two ortho-installed TPA units, has a higher photoluminescence quantum yield (PLQY; 100%), a more rapid radiation transition of the S1 state (Kr = 1.79 × 108 s−1), and a smaller ΔES1T1 value (0.24 eV) in comparison to TPA-FQ with only one TPA unit (PLQY: 79%; Kr = 5.03 × 107 s−1; ΔES1T1 = 0.47 eV). Transient photoluminescence and absorption spectroscopy experiments revealed that both compounds are green fluorescence emitters. The dTPA-FQ shows a T1–T1 difference of only 0.05 eV from the co-host, 4,4′,4′′-tri(N-carbazolyl)triphenylamine and (1,3,5-triazine-2,4,6-triyl)-tris(benzene-3,1-diyl)-tris(diphenylphosphine oxide) (TCTA:PO-T2T), and, thus, T1 energy loss could be inhibited in the dTPA-FQ doped co-host device. As a result, an external quantum efficiency (EQE) of 10.9% has been achieved, while the device with the TPA-FQ doped co-host presents degraded device efficiency (EQE = 4.8%) due to its relatively large T1–T1 difference of 0.1 eV and lower PLQY. In the non-doped devices, the TPA-FQ device shows better device performance than the dTPA-FQ one; its luminance reaches 47 880 cd m−2 at a low voltage of 8.5 V, its EQE is up to 3.9% at 100 cd m−2, and it exhibits only 6.2% efficiency roll-off as the luminance is changed from 10 000 cd m−2 to 30 000 cd m−2. Our experiments demonstrated that the key considerations for designing a FD for a TSF system should be a high PLQY and small T1 energy difference between the FD and co-host. [ABSTRACT FROM AUTHOR]

Some small cell lung cancers (SCLCs) are highly sensitive to inhibitors of the histone demethylase LSD1. LSD1 inhibitors are thought to induce their anti-proliferative effects by blocking neuroendocrine differentiation, but the mechanisms by which LSD1 controls the SCLC neuroendocrine phenotype are not well understood. To identify genes required for LSD1 inhibitor sensitivity in SCLC, we performed a positive selection genome-wide CRISPR/Cas9 loss of function screen and found that ZFP36L1, an mRNA-binding protein that destabilizes mRNAs, is required for LSD1 inhibitor sensitivity. LSD1 binds and represses ZFP36L1 and upon LSD1 inhibition, ZFP36L1 expression is restored, which is sufficient to block the SCLC neuroendocrine differentiation phenotype and induce a non-neuroendocrine "inflammatory" phenotype. Mechanistically, ZFP36L1 binds and destabilizes SOX2 and INSM1 mRNAs, two transcription factors that are required for SCLC neuroendocrine differentiation. This work identifies ZFP36L1 as an LSD1 target gene that controls the SCLC neuroendocrine phenotype and demonstrates that modulating mRNA stability of lineage transcription factors controls neuroendocrine to non-neuroendocrine plasticity. LSD1 inhibition blocks the neuroendocrine phenotype of some small cell lung cancers (SCLCs). Here, a genome-wide CRISPR/Cas9 LSD1 inhibitor resistance screen identifies the mRNA-binding protein ZFP36L1 as a gene repressed by LSD1 that when restored inhibits SCLC neuroendocrine differentiation. [ABSTRACT FROM AUTHOR]

Seawater desalination is believed to be the most promising solution to solve the current crisis of global freshwater deficiency. The applications of nanoporous graphene filters and biological water channels have greatly improved the desalination efficiency. Here, we report the auspicious performance of a tunable nanoporous desalination filter using monolayer r-N-GDY through combination of molecular dynamics simulations and first-principles calculations. In striking contrast to graphene, the r-N-GDY filter can be switched between a high-flux "open" state and a "closed" state by applying tensile strain, yielding a highly tunable nanopore interface. The critical transition between "open" and "closed" states occurs at a moderate strain of 4%. For the "open" state, the water permeability reaches 47 L per cm2 per day per MPa with strong ion rejection which is superior to that of almost all previously reported membrane structures. Given these advantages, the r-N-GDY presents great prospects as a controllable nanoporous membrane for efficient desalination and other applications. [ABSTRACT FROM AUTHOR]

To learn more about the impact of college sports services on student sports activity intentions, as well as the function of pleasure and involvement as a mediating factor in this process. According to the nature of the service, this study separates college sports services into basic and advanced sports two types, selects 482 students from five institutions in Hunan Province for a questionnaire survey based on spatial dimensions, and analyzes the data using a structural equation model. The findings show that (1) there is a positive correlation between college students' perception levels of basic and advanced sports services (p = 0.01); (2) perception of basic sports services is closely related to cognize involvement (r = 0.717), and perception of advanced sports services is closely related to affective involvement (r = 0.830); and (3) perception of basic sports services is closely related to cognize involvement (r = 0.717). (3) Satisfaction and involvement show a substantial mediation effect between sports service and sports behavioral intention, with involvement having a bigger influence on sports behavioral intention (effect percent = 52.63%) than satisfaction. (4) Advanced sports services are easier to improve students' behavioral intentions than basic sports services in a comparison of the two categories of college sports services. To summarize the findings of the four studies, it can be seen that ensuring the balanced development of basic and advanced sports services, adjusting service content to increase student involvement, and improving resource allocation to advanced sports service content are all effective ways to strengthen students' sports behavioral intention in the service strategy. [ABSTRACT FROM AUTHOR]

Whether bone marrow regulates bone metabolism through endocrine and paracrine mechanism remains largely unknown. Here, we found that (i) myeloid cell‐specific myeloid‐derived growth factor (MYDGF) deficiency decreased bone mass and bone strength in young and aged mice; (ii) myeloid cell‐specific MYDGF restoration prevented decreases in bone mass and bone strength in MYDGF knockout mice; moreover, myeloid cell‐derived MYDGF improved the progress of bone defects healing, prevented ovariectomy (OVX)‐induced bone loss and age‐related osteoporosis; (iii) MYDGF inhibited osteoclastogenesis and promoted osteoblast differentiation in vivo and in vitro; and (iv) PKCβ‐NF‐κB and MAPK1/3‐STAT3 pathways were involved in the regulation of MYDGF on bone metabolism. Thus, we concluded that myeloid cell‐derived MYDGF is a positive regulator of bone homeostasis by inhibiting bone resorption and promoting bone formation. MYDGF may become a potential novel therapeutic drug for osteoporosis, and bone marrow may become a potential therapeutic target for bone metabolic disorders. SYNOPSIS: Myeloid‐derived growth factor (MYDGF) positively regulates bone homeostasis by inhibiting bone resorption and promoting bone formation. Myeloid cell specific MYDGF deficiency decreases bone mass and bone strength in mice.MYDGF restoration prevents decreases in bone mass and bone strength in mice.MYDGF inhibits osteoclastogenesis and promoted osteoblast differentiation in vivo and in vitro.PKCβ‐NF‐κB and MAPK1/3‐STAT3 pathways are involved in the regulation of MYDGF on bone metabolism. [ABSTRACT FROM AUTHOR]

A novel molecular scaffold, dibenzo[f,h]furo[2,3-b]quinoxaline (diBFQ), and its derivatives, 3,6-bis(4-isopropylphenyl)-11-phenyldibenzo[f,h]furo[2,3-b]quinoxaline (dP-diBFQ) and furo[2′,3′:5,6]pyrazino[2,3-f][1,10]phenanthroline (FPPhen), were designed and synthesized, showing highly efficient pure and deep blue emission. The unsubstituted molecular scaffolds diBFQ and FPPhen exhibit emission from 424–445 nm with PLQYs of ∼70%, and the disubstituted derivative of diBFQ, dP-diBFQ, shows a PLQY of 79.1%. Our experimental and theoretical investigations revealed that the additional N atoms in FPPhen facilitate the electron distribution of the HOMO orbital localizing on a smaller π-conjugate fragment compared with diBFQ, which resulted in the emission peak blue-shifting from 445 nm for diBFQ to 424 nm for FPPhen. Furthermore, introducing the steric substituent isopropylphenyl into the diBFQ scaffold would help to suppress aggregates of dP-diBFQ molecules and improve the fluorescence efficiency. OLEDs using dP-diBFQ as dopants show pure blue emission with CIE coordinates of (0.154, 0.102) and an EQE of 2.28%. Upon increasing the dopant concentration, the EQE and current efficiency could be improved to 2.63% and 4.7 cd A−1, but aggregate emission with a peak from 472–476 nm was clearly observed due to molecular aggregation. Our studies clearly suggested that diBFQ and FPPhen scaffolds are promising fluorescence cores for deep and pure-blue emission. [ABSTRACT FROM AUTHOR]

Background: Nanoscale drug delivery systems have emerged as broadly applicable approach for chemo-photothermal therapy. However, these nanoscale drug delivery systems suffer from carrier-induced toxicity, uncontrolled drug release and low drug carrying capacity issues. Thus, to develop carrier-free nanoparticles self-assembled from amphiphilic drug molecules, containing photothermal agent and anticancer drug, are very attractive. Results: In this study, we conjugated camptothecin (CPT) with a photothermal agent new indocyanine green (IR820) via a redox-responsive disulfide linker. The resulting amphiphilic drug–drug conjugate (IR820-SS-CPT) can self-assemble into nanoparticles (IR820-SS-CPT NPs) in aqueous solution, thus remarkably improving the membrane permeability of IR820 and the aqueous solubility of CPT. The disulfide bond in the IR820-SS-CPT NPs could be cleaved in GSH rich tumor microenvironment, leading to the on demand release of the conjugated drug. Importantly, the IR820-SS-CPT NPs displayed an extremely high therapeutic agent loading efficiency (approaching 100%). Besides, in vitro experimental results indicated that IR820-SS-CPT NPs displayed remarkable tumor cell killing efficiency. Especially, the IR820-SS-CPT NPs exhibited excellent anti-tumor effects in vivo. Both in vitro and in vivo experiments were conducted, which have indicated that the design of IR820-SS-CPT NPs can provide an efficient nanotherapeutics for chemo-photothermal therapy. Conclusion: A novel activatable amphiphilic small molecular prodrug IR820-SS-CPT has been developed in this study, which integrated multiple advantages of GSH-triggered drug release, high therapeutic agent content, and combined chemo-photothermal therapy into one drug delivery system. [ABSTRACT FROM AUTHOR]

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-β induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling. The therapies for bone metastatic prostate cancer are limited and the underlying mechanisms are unclear. Here, the authors show that bone derived TGF-β induces acetylation of KLF5 (Ac-KLF5), and Ac-KLF5 promotes prostate cancer bone metastasis and resistance to docetaxel by upregulating CXCR4. [ABSTRACT FROM AUTHOR]

We have investigated the focusing of the spoof surface acoustic waves (SSAWs) on a rigid surface engraved with array of cylindrical holes. To focus the SSAWs launched along x direction, the holes array, with a shape of rectangle as a whole, is fabricated to possess gradient index of refraction along both the +y and -y directions, which is achieved by varying linearly the radii of the holes along the corresponding directions. Good focusing performance has been demonstrated experimentally, which is in good agreement with the numerical simulations. This acoustic system is believed to have potential applications in acoustic field such as high resolution detecting. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Myeloid-derived growth factor (MYDGF), mainly secreted by bone marrow-derived cells, has been known to promote glucagon-like peptide-1 production and improve glucose/lipid metabolism in mouse models of diabetes, but little is known about the functions of MYDGF in diabetic kidney disease (DKD). Here, we investigated whether MYDGF can prevent the progression of DKD. Methods: In vivo experiments, both loss- and gain-of-function strategies were used to evaluate the effect of MYDGF on albuminuria and pathological glomerular lesions. We used streptozotocin-treated Mydgf knockout and wild-type mice on high fat diets to induce a model of DKD. Then, albuminuria, glomerular lesions and podocyte injury were evaluated in Mydgf knockout and wild-type DKD mice treated with adeno-associated virus-mediated Mydgf gene transfer. In vitro and ex vivo experiments, the expression of slit diaphragm protein nephrin and podocyte apoptosis were evaluated in conditionally immortalised mouse podocytes and isolated glomeruli from non-diabetic wild-type mice treated with recombinant MYDGF. Results: MYDGF deficiency caused more severe podocyte injury in DKD mice, including the disruption of slit diaphragm proteins (nephrin and podocin) and an increase in desmin expression and podocyte apoptosis, and subsequently caused more severe glomerular injury and increased albuminuria by 39.6% compared with those of wild-type DKD mice (p < 0.01). Inversely, MYDGF replenishment attenuated podocyte and glomerular injury in both wild-type and Mydgf knockout DKD mice and then decreased albuminuria by 36.7% in wild-type DKD mice (p < 0.01) and 34.9% in Mydgf knockout DKD mice (p < 0.01). Moreover, recombinant MYDGF preserved nephrin expression and inhibited podocyte apoptosis in vitro and ex vivo. Mechanistically, the renoprotection of MYDGF was attributed to the activation of the Akt/Bcl-2-associated death promoter (BAD) pathway. Conclusions/interpretation: The study demonstrates that MYDGF protects podocytes from injury and prevents the progression of DKD, providing a novel strategy for the treatment of DKD. [ABSTRACT FROM AUTHOR]

Limited penetration of chemotherapeutic drugs through the blood brain barrier (BBB), and the increased chemo-resistance of glioma cells due to macroautophagy/autophagy, result in high tumor recurrence and extremely limited survival of glioma patients. Ultrasound-targeted microbubble destruction (UTMD) is a technique of transient and reversible BBB disruption, which greatly facilitates intracerebral drug delivery. In addition, sonodynamic therapy (SDT) based on ultrasound stimulation and a sonosensitizer, can be a safe and noninvasive strategy for treating glioma. We innovatively designed a smart "all-in-one" nanosensitizer platform by incorporating the sonoactive chlorin e6 (Ce6) and an autophagy inhibitor-hydroxychloroquine (HCQ) into angiopep-2 peptide-modified liposomes (designated as ACHL), which integrates multiple diagnostic and therapeutic functions. ACHL selectively accumulated in the brain tumors during the optimal time-window of transient UTMD-mediated BBB opening. The nanosensitizer then responded to a second ultrasonic stimulation, and simultaneously unloaded HCQ and generated ROS in the glioma cells. The sonotherapy triggered apoptosis as well as MAPK/p38-PINK1-PRKN-dependent mitophagy, in which the antioxidant relieved the sonotoxicity and MAPK/p38 activation, while the inhibition of MAPK/p38 attenuated the progression toward mitophagy by compromising redistribution of PRKN. Moreover, HCQ blocking autophagosome degradation, augmented intracellular ROS production and resulted in an oxidative-damage regenerative loop. ACHL-SDT treatment using this construct significantly inhibited the xenograft-tumor growth and prolonged the survival time of tumor-bearing mice, exhibiting an improved therapeutic efficiency. All together, we demonstrated a precision sonotherapy with simultaneous apoptosis induction and mitophagy inhibition, which served as an intelligently strategic sense of working alongside, providing new insights into the theranostics of brain tumors. ACHL: Angiopep-2-modified liposomes loaded with Ce6 and hydroxychloroquine; ACL: Angiopep-2-modified liposomes loaded with Ce6; BBB: blood brain barrier; Ce6: chlorin e6; CHL: liposomes loaded with Ce6 and hydroxychloroquine; CL: liposomes loaded with Ce6; CNS: central nervous system; DDS: drug delivery system; EB: Evans blue; FUS: focused ultrasound; HCQ: hydroxychloroquine; LRP1: low density lipoprotein receptor-related protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MBs: microbubbles; MTG: MitoTracker Green; MTR: MitoTracker Red; MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS: phosphate-buffered saline; PDI: polydispersity index; PINK1: PTEN induced kinase 1; PRKN/parkin: parkin RBR E3 ubiquitin protein ligase; ROS: reactive oxygen species; SDT: sonodynamic therapy; SQSTM1: sequestome 1; TA: terephthalic acid; TEM: transmission electron microscopy; TUNEL: terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling; US: ultrasound; UTMD: ultrasound-targeted microbubble destruction. [ABSTRACT FROM AUTHOR]

Prostate development depends on balanced cell proliferation and differentiation, and acetylated KLF5 is known to alter epithelial proliferation. It remains elusive whether post-translational modifications of transcription factors can differentially determine adult stem/progenitor cell fate. Here we report that, in human and mouse prostates, Klf5 is expressed in both basal and luminal cells, with basal cells preferentially expressing acetylated Klf5. Functionally, Klf5 is indispensable for maintaining basal progenitors, their luminal differentiation, and the proliferation of their basal and luminal progenies. Acetylated Klf5 is also essential for basal progenitors' maintenance and proper luminal differentiation, as deacetylation of Klf5 causes excess basal-to-luminal differentiation; attenuates androgen-mediated organoid organization; and retards postnatal prostate development. In basal progenitor-derived luminal cells, Klf5 deacetylation increases their proliferation and attenuates their survival and regeneration following castration and subsequent androgen restoration. Mechanistically, Klf5 deacetylation activates Notch signaling. Klf5 and its acetylation thus contribute to postnatal prostate development and regeneration by controlling basal progenitor cell fate. The role of the Klf5 in early and postnatal prostate development and in regeneration is unclear. Here, the authors show that Klf5 acetylation regulates and maintains luminal differentiation of prostate basal progenitors and is essential following androgen-induced regeneration. [ABSTRACT FROM AUTHOR]

Organic semiconductors combining high mobility and efficient solid fluorescence are in high demand for developing organic light-emitting transistors and electrically driven organic lasers. But, achieving such dual functional molecules is extremely challenging. In this manuscript, we report 2-phenylbenzo[g]furo[2,3-b]quinoxaline derivatives (3a–3c) and develop a new synthesis method for the furo[2,3-b]quinoxaline core. It was found that 3a exhibited favorable aggregation induced emissive enhancement behavior and reasonable hole mobility. The absolute photoluminescence quantum yield of 3a is determined to be 22.1% in solid powders and can reach a maximum of 19.7% in 50% water in THF, twice that in CH2Cl2 solution (9.2%) and dispersed in PS film (9.3%). The single crystal and thin film organic field-effect transistor of 3a show a hole mobility of 2.58 × 10−2 cm2 V−1 s−1 and 5.7 × 10−3 cm2 V−1 s−1, respectively. Our results demonstrated that the 2-phenyl-benzo[g]furo[2,3-b]quinoxaline skeleton is a promising candidate for building multifunctional organic optoelectronics. [ABSTRACT FROM AUTHOR]

Krüppel‐like factor 5 (KLF5) both suppresses and promotes tumor growth depending on cellular context. The mechanisms underlying tumor promotion could be targetable for therapy. Although a number of transcriptional targets of KLF5 have been identified and implicated in KLF5‐mediated tumor growth, how KLF5 regulates these genes remains to be addressed. Here we performed coimmunoprecipitation (co‐IP) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) in the TSU‐Pr1 bladder cancer cell line, in which KLF5 is shown to promote tumor growth, to identify KLF5‐interacting nuclear proteins that are necessary for KLF5's tumor promoting function. LC–MS/MS revealed 122 potential KLF5 binding proteins in the nuclear proteins precipitated by the KLF5 antibody, and the top nine candidates included AHNAK, TFAM, HSDL2, HNRNPC, CINP, IST1, FBL, PABPC1 and SNRNP40. SRB assays of these nine proteins indicated that silencing CINP had the most potent inhibitory effect on cell growth in KLF5‐expressing cells but did not affect parental TSU‐Pr1 cells. Further analyses not only confirmed the physical interaction between KLF5 and CINP, also demonstrated that knockdown of CINP attenuated the effects of KLF5 on cell cycle progression, apoptosis and tumorigenesis. Silencing CINP also attenuated the effect of KLF5 on the expression of a number of genes and signaling pathways, including cell cycle regulator Cyclin D1 and apoptosis‐related Caspase 7. These results suggest that CINP is a cofactor of KLF5 that is crucial for the promotion of tumor growth, and that the KLF5‐CINP interaction could be a novel therapeutic target for inhibiting KLF5‐promoted tumor growth. What's new? The role of Krüppel‐like factor 5 (KLF5) in promoting cell proliferation and tumorigenesis is well‐established, but although several KLF5 transcriptional targets have been identified, how KLF5 regulates these genes remains elusive. Here, using immunoprecipitation combined with mass spectrometry, the authors identified a number of KLF5‐interacting nuclear proteins. Functional screening revealed that the Cdk2‐interacting protein CINP is required for KLF5's tumor promoting function and a KLF5 cofactor. CINP knockdown attenuated the effects of KLF5 on cell and tumor growth by decelerating cell cycle progression and inducing apoptosis in KLF5‐expressing cells. The KLF5‐CINP interaction provides a therapeutic opportunity for targeting KLF5‐mediated tumorigenesis. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11) has been shown to promote stem cell activity and rejuvenate the function of multiple organs in old mice, but little is known about the functions of GDF11 in the diabetic rat model of hindlimb ischemia. In this study, we found that systematic replenishment of GDF11 rescues angiogenic function of endothelial progenitor cells (EPCs) and subsequently improves vascularization and increases blood flow in diabetic rats with hindlimb ischemia. Conversely, anti-GDF11 monoclonal antibody treatment caused impairment of vascularization and thus, decreased blood flow. In vitro treatment of EPCs with recombinant GDF11 attenuated EPC dysfunction and apoptosis. Mechanistically, the GDF11-mediated positive effects could be attributed to the activation of the transforming growth factor-β/Smad2/3 and protein kinase B/hypoxia-inducible factor 1α pathways. These findings suggest that GDF11 repletion may enhance EPC resistance to diabetes-induced damage, improve angiogenesis, and thus, increase blood flow. This benefit of GDF11 may lead to a new therapeutic approach for diabetic hindlimb ischemia. [ABSTRACT FROM AUTHOR]

Applying ultrasound (US) to drug delivery and disease therapy is important work. Sonodynamic therapy (SDT)-a comprehensive therapy using US and a sonosensitizer-exhibits antineoplastic activity in many tumors. In this study, we investigated the feasibility of using a new sonosensitizer (sinoporphyrin sodium, DVDMS) loaded into liposome-microbubble complexes (DLMBs) as a possible candidate to enhance SDT against breast cancer. DLMBs were synthesized via the biotin-avidin linkage and confirmed to have good US response. US-induced cavitation played a key role to trigger a boosted payload release from DLMBs and improve the cellular uptake and intratumoral diffusion of DVDMS to realize better SDT effect. The combination of DLMBs and US treatment resulted in significant changes to cell morphology, mitochondria damage, and cell apoptosis in vitro. In vivo, the combined treatment markedly inhibited tumor growth, which appeared to result from increased apoptosis and reduced proliferation activity. The significant increase in the antitumor effect of DLMBs plus US suggests their potential use as a new approach to promote the killing activity of SDT against breast cancer. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11) has been implicated in the regulation of islet development and a variety of aging conditions, but little is known about the physiological functions of GDF11 in adult pancreatic islets. Here, we showed that systematic replenishment of GDF11 not only preserved insulin secretion but also improved the survival and morphology of β-cells and improved glucose metabolism in both nongenetic and genetic mouse models of type 2 diabetes (T2D). Conversely, anti-GDF11 monoclonal antibody treatment caused β-cell failure and lethal T2D. In vitro treatment of isolated murine islets and MIN6 cells with recombinant GDF11 attenuated glucotoxicity-induced β-cell dysfunction and apoptosis. Mechanistically, the GDF11-mediated protective effects could be attributed to the activation of transforming growth factor-β/Smad2 and phosphatidylinositol-4,5-bisphosphate 3-kinase-AKT-FoxO1 signaling. These findings suggest that GDF11 repletion may improve β-cell function and mass and thus may lead to a new therapeutic approach for T2D. [ABSTRACT FROM AUTHOR]

Ginsenoside Rb1 (GS-Rb1) is a well-known antioxidant derived from traditionally used herbal medicine ginseng. It has been suggested that reactive oxygen species (ROS) is involved in chronic kidney disease (CKD) in which GS-Rb1 may play a protective role. The aim of this study was to evaluate prospectively the effects of GS-Rb1 in patients with early chronic kidney disease. 197 patients who have been diagnosed with early CKD (stage 2 or 3) were recruited and randomly assigned to receive GS-Rb1 (500 mg daily oral administration, n = 103) or placebo ( n = 94) for consecutive 6 months. Analytical procedures performed at baseline, the end of the treatments, and 6 months after the treatments included renal function evaluation (creatinine and urea clearance), oxidative stress measurement, inflammation assessment, and lipid profile. Of 177 patients completing the study, the GS-Rb1 group ( n = 91) showed a positive response in significantly alleviating renal function impairments compared to the placebo group ( n = 86). In addition, GS-Rb1 treatment was effective in reducing the extent of oxidative stress and inflammation in CKD patients, whereas continued deterioration was observed in the placebo group. Thus, extended treatment of patients using GS-Rb1 may present an antioxidant-based approach to slow the progression of CKD at the early stages. [ABSTRACT FROM AUTHOR]