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Antibiotic residues have been found to have potentially harmful effects on ecological and human health. Carbon nitride-based photocatalysts have widely focused on antibiotic photocatalytic degradation. Herein, we prepared Fe-modified g-C3N4 nanorod bunches (FCNBs) using chemical vapor co-deposition. Specifically, through the process of calcination, a blend of urea and chlorophyllin sodium iron salt underwent an intriguing transformation, resulting in the integration of Fe into the framework of the g-C3N4 nanorod cluster. The resulting photocatalyst exhibited remarkable stability and superior dispersibility. The prepared FCNBs had a unique structure, which was beneficial for increasing light absorption. Furthermore, the Fe species formed a chemical coordination with the g-C3N4 matrix, thereby altering the electronic structure of the matrix. This modification facilitated charge transfer, prolonged the carrier lifetime, and enhanced light absorption, all of which significantly increased the photocatalytic activity. The oxytetracycline degradation efficiency of FCNBs was 82.5%, and they demonstrated outstanding stability in cycle trials. This work introduces a promising photocatalyst for the degradation of antibiotics. [ABSTRACT FROM AUTHOR]

Wind erosion is recognized as one of the main environmental issues and seriously threatens ecosystem services in the Yarlung Zangbo River basin (YZRB), southern Tibetan Plateau. Exploring the spatiotemporal dynamics and drivers of wind erosion is crucial for improving regional ecosystem services and sustainable development. This study was conducted to examine the spatiotemporal patterns of soil wind erosion modulus (SWEM) in YZRB from 1990 to 2020 by using the revised wind erosion equation (RWEQ) and to identify the influence of climate change and anthropogenic activities on wind erosion dynamics. The results showed that temporally, the overall SWEM presented a significant downward trend (−0.912 t·hm−2·a−1) and a continuous downward trend in the key implementation areas of ecological engineering. Spatially, the severe area of wind erosion is mainly concentrated in the flat and broad river valley, where sand sources are widely distributed. Significant SWEM differences were found among various land use/cover (LULC) types. Exceeding 90% reduction rates in SWEM occurred in forests, grasslands, and cultivated land. Additionally, the influence analysis showed that climate change was the dominant factor driving the variations in wind erosion due to the reduction of wind speed. By contrast, the contribution of anthropogenic activities is relatively less, accounting for 43.50% of wind erosion change, which closely matches the transfer of LULC to grassland and forest land with the implementation area of ecological engineering projects. This study provides useful information on the driving mechanism of wind erosion, prevention service changes, and determining priority zones for desertification prevention in YZRB. We suggest that eco-restoration activities should be endorsed in the future, as well as the adaptive management that is required to control wind erosion and improve ecosystem services and human well-being for people in the YZRB region. [ABSTRACT FROM AUTHOR]

Simple Summary: The study found that Bacillus velezensis HN-Q-8 has an antagonistic effect on Alternaria solani. After being pretreated with strain HN-Q-8, which can induce potato plant resistance to early blight by regulating defensive enzyme activities and trig-gering the JA/ET pathway, as well as promote growth by regulating the contents of indole acetic acid, gibberellic acid 3 and abscisic acid, enhancing the chlorophyll content, and stimulating root activity. In addition, live bacteria and secondary metabolites should be used together for the best results. Thus, B. velezensis HN-Q-8 strain is an effective bacterial biocontrol agent, and our study can provide vital information for the research and development of biocontrol bacteria. Bacillus velezensis HN-Q-8, isolated in our previous study, has an antagonistic effect on Alternaria solani. After being pretreated with a fermentation liquid with HN-Q-8 bacterial cell suspensions, the potato leaves inoculated with A. solani displayed smaller lesion areas and less yellowing than the controls. Interestingly, the activity levels of superoxide dismutase, peroxidase, and catalase in potato seedlings were enhanced by the addition of the fermentation liquid with bacterial cells. Additionally, the overexpression of key genes related to induced resistance in the Jasmonate/Ethylene pathway was activated by the addition of the fermentation liquid, suggesting that the HN-Q-8 strain induced resistance to potato early blight. In addition, our laboratory and field experiments showed that the HN-Q-8 strain can promote potato seedling growth and significantly increase tuber yield. The root activity and chlorophyll content of potato seedlings were significantly increased along with the levels of indole acetic acid, gibberellic acid 3, and abscisic acid upon addition of the HN-Q-8 strain. The fermentation liquid with bacterial cells was more efficient in inducing disease resistance and promoting growth than bacterial cell suspensions alone or the fermentation liquid without bacterial cells. Thus, the B. velezensis HN-Q-8 strain is an effective bacterial biocontrol agent, augmenting the options available for potato cultivation. [ABSTRACT FROM AUTHOR]

Network security situation awareness (NSSA) is an integral part of cybersecurity defense, and it is essential for cybersecurity managers to respond to increasingly sophisticated cyber threats. Different from traditional security measures, NSSA can identify the behavior of various activities in the network and conduct intent understanding and impact assessment from a macro perspective so as to provide reasonable decision support, predicting the development trend of network security. It is a means to analyze the network security quantitatively. Although NSSA has received extensive attention and exploration, there is a lack of comprehensive reviews of the related technologies. This paper presents a state-of-the-art study on NSSA that can help bridge the current research status and future large-scale application. First, the paper provides a concise introduction to NSSA, highlighting its development process. Then, the paper focuses on the research progress of key technologies in recent years. We further discuss the classic use cases of NSSA. Finally, the survey details various challenges and potential research directions related to NSSA. [ABSTRACT FROM AUTHOR]

In this study, new multicomponent Fe54M5Cr15Mo6Si2B4P10C4 (M = Fe, Co, and Ni, denoted as Fe59, Fe54Co5, and Fe54Ni5, respectively) bulk metallic glasses (BMGs) with excellent corrosion and wear resistances were synthesized using the J-quenching technique and fluxing treatment. The synthesized Fe-based BMGs possessed a large glass-forming ability, and the maximum diameters of the Fe59, Fe54Co5, and Fe54Ni5 glassy alloy rods reached 5.5, 4.5, and 4.0 mm, respectively. The Fe59 BMG had a wide supercooled liquid region of 65 K. Potentiodynamic tests in 3.5 wt.% NaCl solution showed that the corrosion resistances of the synthesized Fe-based BMGs were relatively better than that of the 316L stainless steel. The Fe59 BMG had the highest corrosion resistance, with the lowest self-corrosion current density in the order of 10−8 A·cm−2. Wear tests showed that the synthesized Fe-based BMGs exhibited excellent wear resistances, and the wear rate of the Fe59 BMG was as low as approximately 1.73 × 10−15 m3·N−1·m−1. The rare-earth-element-free Fe-based BMGs, especially the Fe59 BMG, have a low cost, large glass-forming ability, and excellent wear and corrosion resistance, which make them good candidates for wear-and corrosion-resistant coating materials. [ABSTRACT FROM AUTHOR]

Due to the potential of thermal storage being similar to that of the conventional battery, air conditioning (AC) has gained great popularity for its potential to provide ancillary services and emergency reserves. In order to integrate numerous inverter ACs into secondary frequency control, a hierarchical distributed control framework which incorporates a virtual battery model of inverter AC is developed. A comprehensive derivation of a second-order virtual battery model has been strictly posed to formulate the frequency response characteristics of inverter AC. In the hierarchical control scheme, a modified control performance index is utilized to evaluate the available capacity of traditional regulation generators. A coordinated frequency control strategy is derived to exploit the complementary and advantageous characteristics of regulation generators and aggregated AC. A distributed consensus control strategy is developed to guarantee the fair participation of heterogeneous AC in frequency regulation. The finite-time consensus protocol is introduced to ensure the fast convergence of power tracking and the state-of-charge (SOC) consistency of numerous ACs. The effectiveness of the proposed control strategy is validated by a variety of illustrative examples. [ABSTRACT FROM AUTHOR]

With the increasing penetration of wind power and demand response integrated into the grid, the combined uncertainties from wind power and demand response have been a challenging concern for system operators. It is necessary to develop an approach to accommodate the combined uncertainties in the source side and load side. In this paper, the fuzzy stochastic conditional value-at-risk criterions are proposed as the risk measure of the combination of both wind power uncertainty and demand response uncertainty. To improve the computational tractability without sacrificing the accuracy, the fuzzy stochastic chance-constrained goal programming is proposed to transfer the fuzzy stochastic conditional value-at-risk to a deterministic equivalent. The operational risk of forecast error under fuzzy stochastic conditional value-at-risk assessment is represented by the shortage of reserve resource, which can be further divided into the load-shedding risk and the wind curtailment risk. To identify different priority levels for the different objective functions, the three-stage day-ahead unit commitment model is proposed through preemptive goal programming, in which the reliability requirement has the priority over the economic operation. Finally, a case simulation is performed on the IEEE 39-bus system to verify the effectiveness and efficiency of the proposed model. [ABSTRACT FROM AUTHOR]

A series of novel 2,4-diaminoquinazoline derivatives were designed, synthesized, and evaluated as p21-activated kinase 4 (PAK4) inhibitors. All compounds showed significant inhibitory activity against PAK4 (half-maximal inhibitory concentration IC50 < 1 μM). Among them, compounds 8d and 9c demonstrated the most potent inhibitory activity against PAK4 (IC50 = 0.060 μM and 0.068 μM, respectively). Furthermore, we observed that compounds 8d and 9c displayed potent antiproliferative activity against the A549 cell line and inhibited cell cycle distribution, migration, and invasion of this cell line. In addition, molecular docking analysis was performed to predict the possible binding mode of compound 8d. This series of compounds has the potential for further development as PAK4 inhibitors for anticancer activity. [ABSTRACT FROM AUTHOR]

Multidrug bacterial resistance endangers clinically effective antimicrobial therapy and continues to cause major public health problems, which have been upgraded to unprecedented levels in recent years, worldwide. β-Lactam antibiotics have become an important weapon to fight against pathogen infections due to their broad spectrum. Unfortunately, the emergence of antibiotic resistance genes (ARGs) has severely astricted the application of β-lactam antibiotics. Of these, New Delhi metallo-β-lactamase-1 (NDM-1) represents the most disturbing development due to its substrate promiscuity, the appearance of variants, and transferability. Given the clinical correlation of β-lactam antibiotics and NDM-1-mediated resistance, the discovery, and development of combination drugs, including NDM-1 inhibitors, for NDM-1 bacterial infections, seems particularly attractive and urgent. This review summarizes the research related to the development and optimization of effective NDM-1 inhibitors. The detailed generalization of crystal structure, enzyme activity center and catalytic mechanism, variants and global distribution, mechanism of action of existing inhibitors, and the development of scaffolds provides a reference for finding potential clinically effective NDM-1 inhibitors against drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Landform changes caused by human activities can directly affect the recharge of groundwater, and are reflected in the temporal and spatial changes in groundwater stable isotope composition. These changes are particularly evident in high-intensity farming areas. In this study, we tested and analyzed groundwater stable isotope samples at different elevations of rice terraces in a typical agricultural watershed of the Hani Terraces, a World Heritage Cultural Landscape in southwest China. Thus, we determined the characteristic variations and factors that influence the temporal and spatial effects on groundwater stable isotopes in the Hani Terraces, which are under the influence of high-intensity farming activities. The elevation gradients of δ18O and δ2H in groundwater are significantly increased due to farming activities. The values were 0.88‰ (100 m)−1 and −4.5‰ (100 m)−1, respectively, and they changed with time. The groundwater circulation cycle is approximately three months. We also used the special temporal and spatial variation characteristics of the groundwater isotopes as a way to evaluate the source and periodic changes of groundwater recharge. In addition, high-intensity rice farming activities, such as ploughing every year from October to January can increase the supply of terraced water to groundwater, thus ensuring the sustainability of rice cultivation in the terraces during the dry season. This demonstrates the role of human wisdom in the sustainable and benign transformation of surface cover and the regulation of groundwater circulation. [ABSTRACT FROM AUTHOR]

Current strategies are not especially successful in the treatment of acute myeloid leukemia (AML). The identification and characterization of oncogenes crucial to the survival and growth of leukemia cells will provide potential targets for the exploitation of novel therapies. Herein, we report that the elevated expression of SH3 domain-binding protein 5 (SH3BP5) significantly correlates with poor outcomes of AML patients. To test whether SH3BP5 contributes to the growth and survival of AML cells, we use the shRNA-encoding lentivirus system to achieve the knockdown of SH3BP5 expression in human AML cell lines U937, THP-1, Kasumi-1, and MV4-11. Functionally, the knockdown of SH3BP5 expression markedly inhibits the cell viability and induced apoptosis of these leukemia cells. Mechanistically, western blot analysis indicates that the knockdown of SH3BP5 expression decreases the phosphorylation of JNK and BAD. Moreover, the JNK agonist anisomycin rescues the growth inhibition phenotype of SH3BP5 deficiency in THP-1 cells. Moreover, the expression of SH3BP5 positively correlates with CD25 and CD123 levels. Finally, our study highlights the crucial role of SH3BP5 in promoting the survival of AML cells, and its suppression may be a potential therapeutic strategy for treating human AML. [ABSTRACT FROM AUTHOR]

With the increasing attention of the clean and efficient use of energy, the regional integrated energy system (RIES), as an efficient measure to improve energy efficiency, is tending to play an important role in the field of energy supply. The configuration of multiple energy storage equipment in the RIES can greatly improve the economy of the system, which is an important research direction of RIES planning. However, at present the research on the configuration optimization of electric-gas-thermal multi-energy storage devices in RIES is insufficient. Under this background, a method for configuring the rated capacity and power of various energy storage devices in the RIES under both off-grid and grid-connected operating modes was proposed in this paper, and the configuration optimization model was also established. Firstly, the RIES was divided into four parts: Energy supply, energy conversion, energy storage and the load. Based on the energy hub concept, the four parts were modeled respectively. Secondly, considering the influence of electric energy substitution and operation strategy, the optimal configuration of multi-energy storage devices was modeled as a MILP formulation and solved with the Gurobi optimizer. Finally, a case study verified the effectiveness of the proposed model and the method. Furthermore, the sensitivity analysis was carried out to quantify the influence degree of each factor (such as price, etc.) on the energy storage configuration. [ABSTRACT FROM AUTHOR]

In order to build an active distribution system with multi virtual power plants (VPP), a decentralized two-stage stochastic dispatching model based on synchronous alternating direction multiplier method (SADMM) was proposed in this paper. Through the integration of distributed energy and large-scale electric vehicles (EV) in the distribution network by VPP group, coordinative complementarity, and global optimization were realized. On the premise of energy autonomy management of active distribution network (AND) and VPP, after ensuring the privacy of stakeholders, the power of tie-line was taken as decoupling variable based on SADMM. Furthermore, without the participation of central coordinators, the optimization models of VPPs and distribution networks were decoupled to achieve fully decentralized optimization. Aiming at minimizing their own operating costs, the VPPs aggregate distributed energy and large-scale EVs within their jurisdiction to interact with the upper distribution network. On the premise of keeping operation safe, the upper distribution network formulated the energy interaction plan with each VPP, and then, the global energy optimization management of the entire distribution system and the decentralized autonomy of each VPP were achieved. In order to improve the stochastic uncertainty of distributed renewable energy output, a two-stage stochastic optimization method including pre-scheduling stage and rescheduling stage was adopted. The pre-scheduling stage was used to arrange charging and discharging plans of EV agents and output plans of micro gas turbines. The rescheduling stage was used to adjust the spare resources of micro gas turbines to deal with the uncertainty of distributed wind and light. An example of active distribution system with multi-VPPs was constructed by using the improved IEEE 33-bus system, then the validity of the model was verified. [ABSTRACT FROM AUTHOR]

Multidrug bacterial resistance endangers clinically effective antimicrobial therapy and continues to cause major public health problems, which have been upgraded to unprecedented levels in recent years, worldwide. β-Lactam antibiotics have become an important weapon to fight against pathogen infections due to their broad spectrum. Unfortunately, the emergence of antibiotic resistance genes (ARGs) has severely astricted the application of β-lactam antibiotics. Of these, New Delhi metallo-β-lactamase-1 (NDM-1) represents the most disturbing development due to its substrate promiscuity, the appearance of variants, and transferability. Given the clinical correlation of β-lactam antibiotics and NDM-1-mediated resistance, the discovery, and development of combination drugs, including NDM-1 inhibitors, for NDM-1 bacterial infections, seems particularly attractive and urgent. This review summarizes the research related to the development and optimization of effective NDM-1 inhibitors. The detailed generalization of crystal structure, enzyme activity center and catalytic mechanism, variants and global distribution, mechanism of action of existing inhibitors, and the development of scaffolds provides a reference for finding potential clinically effective NDM-1 inhibitors against drug-resistant bacteria.

Cholesteryl ester transfer protein (CETP) has been identified as a potential target for cardiovascular disease (CVD) for its important role in the reverse cholesteryl transfer (RCT) process. In our previous work, compound 5 was discovered as a moderate CETP inhibitor. The replacement of the amide linker by heterocyclic aromatics and then a series of N , N -substituted-4-arylthiazole-2-methylamine derivatives were designed by utilizing a conformational restriction strategy. Thirty-six compounds were synthesized and evaluated for their CETP inhibitory activities. Structure-activity relationship studies indicate that electron donor groups substituted ring A, and electron-withdrawing groups at the 4-position of ring B were critical for potency. Among these compounds, compound 30 exhibited excellent CETP inhibitory activity (IC 50 = 0.79 ± 0.02 μM) in vitro and showed an acceptable metabolic stability.

N,N-Substituted amine derivatives were designed by utilizing a bioisosterism strategy. Consequently, twenty-two compounds were synthesized and evaluated for their inhibitory activity against CETP. Structure-activity relationship (SAR) studies indicate that hydrophilic groups at the 2-position of the tetrazole and 3,5-bistrifluoromethyl groups on the benzene ring provide important contributions to the potency. Among these compounds, compound 17 exhibited excellent CETP inhibitory activity (IC 50 = 0.38 ± 0.08 μM) in vitro. Furthermore, compound 17 was selected for an in vitro metabolic stability study., Competing Interests: The authors declare no conflict of interest.

Abnormality of fibroblast growth factor receptor (FGFR)-mediated signaling pathways were frequently found in various human malignancies, making FGFRs hot targets for cancer treatment. To address the consistent need for a new chemotype of FGFR inhibitors, here, we started with a hit structure identified from our internal hepatocyte growth factor receptor (also called c-Met) inhibitor project, and conducted a chemical optimization. After exploring three parts of the hit compound, we finally discovered a new series of pyrrolo[2,3- b ]pyrazine FGFR inhibitors, which contain a novel scaffold and unique molecular shape. We believe that our findings can help others to further develop selective FGFR inhibitors.

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1 H -indazole derivatives as potent FGFR inhibitors. The compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)- N -phenyl-1 H -indazole-4-carboxamide ( 10a ) was identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that 6-(2,6-dichloro-3,5-dimethoxyphenyl)- N -(3-(4-methylpiperazin-1-yl)phenyl)-1 H -indazole-4-carboxamide ( 13a ) is the most potent FGFR1 inhibitor in this series, with an enzyme inhibitory activity IC 50 value of about 30.2 nM.

We have identified a novel series of substituted N,N'-diarylurea p38α inhibitors. The inhibitory activity of the target compounds against the enzyme p38α, MAPKAPK2 in BHK cells, TNF-α release in LPS-stimulated THP-1 cells and p38α binding experiments were tested. Among these compounds, 25a inhibited the p38α enzyme with an IC50 value of 0.47 nM and a KD value of 1.54 × 10(-8) and appears to be the most promising one in the series.

A novel series of substituted N,N'-diaryl ureas that act as p38α inhibitors have been designed and synthesized based on two key residues (Gly110 and Thr106) that are different in p38α MAPK than in other kinases. Preliminary biological evaluation indicated that most compounds possessed good p38α inhibitory potencies. Among these compounds, 9g appeared to be the most powerful and is the main compound that we will study in the future.

The goal of the present work was to study the feasibility of 10-hydroxycamptothecin (HCPT) nanoparticle preparation using supercritical antisolvent (SAS) precipitation. The influences of various experimental factors on the mean particle size (MPS) of HCPT nanoparticles were investigated. The optimum micronization conditions are determined as follows: HCPT solution concentration 0.5 mg/mL, the flow rate ratio of CO(2) and HCPT solution 19.55, precipitation temperature 35 °C and precipitation pressure 20 MPa. Under the optimum conditions, HCPT nanoparticles with a MPS of 180 ± 20.3 nm were obtained. Moreover, the HCPT nanoparticles obtained were characterized by Scanning electron microscopy, Dynamic light scattering, Fourier-transform infrared spectroscopy, High performance liquid chromatography-mass spectrometry, X-ray diffraction and Differential scanning calorimetry analyses. The physicochemical characterization results showed that the SAS process had not induced degradation of HCPT. Finally, the dissolution rates of HCPT nanoparticles were investigated and the results proved that there is a significant increase in dissolution rate compared to unprocessed HCPT.

In this study, folic-dextran-camptothecin (Fa-DEX-CPT) tumor-targeted nanoparticles were produced with a supercritical antisolvent (SAS) technique by using dimethyl sulfoxide (DMSO) as a solvent and carbon dioxide as an antisolvent. A factorial design was used to reveal the effect of various process parameters on the mean particle size (MPS) and morphology of the particles formed. Under the optimum operation conditions, Fa-DEX-CPT nanoparticles with a MPS of 182.21 nm were obtained. Drug encapsulation efficiency and loading efficiency were 62.13% and 36.12%, respectively. It was found that the concentrations of the camptothecin (CPT) and dextran solution had a major influence upon morphology and shape of the final product. In addition, the samples were characterized by Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) with the purpose of developing a suitable targeted drug delivery system for cancer chemotherapy.