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Geogenic arsenic (As) in groundwater is widespread, affecting drinking water and irrigation supplies globally, with food security and safety concerns on the rise. Here, we present push–pull tests that demonstrate field-scale As immobilization through the injection of small amounts of ferrous iron (Fe) and nitrate, two readily available agricultural fertilizers. Such injections into an aquifer with As-rich (200 ± 52 μg/L) reducing groundwater led to the formation of a regenerable As reactive filter in situ, producing 15 m3of groundwater meeting the irrigation water quality standard of 50 μg/L. Concurrently, sediment magnetic properties were markedly enhanced around the well screen, pointing to neo-formed magnetite-like minerals. A reactive transport modeling approach was used to quantitatively evaluate the experimental observations and assess potential strategies for larger-scale implementation. The modeling results demonstrate that As removal was primarily achieved by adsorption onto neo-formed minerals and that an increased adsorption site density coincides with the finer-grained textures of the target aquifer. Up-scaled model simulations with 80-fold more Fe-nitrate reactants suggest that enough As-safe water can be produced to irrigate 1000 m2of arid land for one season of water-intense rice cultivation at a low cost without causing undue contamination in surface soils that threatens agricultural sustainability.

In social psychology, it is well known that the evolution of opinion dynamics in a society depends not only on the current opinions of individuals, but also on the past opinions stored in memory. However, it is still difficult to clearly characterize and analyze the memory influence on opinion dynamics in social networks, especially in coopetitive (cooperative and competitive) networks. In this article, we propose a novel model of opinion dynamics to describe the memory influence in coopetitive networks. In this model, memory and memoryless communication rules are simultaneously proposed for the opinion update mechanism. In terms of the network topological structure and the graph spectrum, sufficient and/or necessary conditions are, respectively, established to ensure that the opinion is nonstationary polarization, nonstationary consensus, and neutral. We employ Kahneman's seminal experiment on choices in risky and riskless contexts to interpret the results obtained in this article. Simulation analysis shows that the memory capacity of the individual is inversely proportional to the speeds of ultimate opinion formation, and the opinions reach a persistent disagreement when the individuals are very confident.

Owing to high ionic conductivity and mechanical strength, poly(vinylidene fluoride) (PVDF) electrolytes have attracted increasing attention for solid-state lithium batteries, but highly reactive residual solvents severely plague cycling stability. Herein, we report a free-solvent-capturing strategy triggered by reinforced ion–dipole interactions between Li+and residual solvent molecules. Lithium difluoro(oxalato)borate (LiDFOB) salt additive with electron-withdrawing capability serves as a redistributor of the Li+electropositive state, which offers more binding sites for residual solvents. Benefiting from the modified coordination environment, the kinetically stable anion-derived interphases are preferentially formed, effectively mitigating the interfacial side reactions between the electrodes and electrolytes. As a result, the assembled solid-state battery shows a lifetime of over 2000 cycles with an average Coulombic efficiency of 99.9% and capacity retention of 80%. Our discovery sheds fresh light on the targeted regulation of the reactive residual solvent to extend the cycle life of solid-state batteries.

An efficient PhI(OAc)2-mediated regioselective hydrothiolation of allenamides with thiophenol via a radical process was developed to create a workable route to vinyl sulfides. The reaction exhibits a good functional group tolerance and high efficiency, affording the products in good to excellent yields. Mechanistic investigations indicated that the radical cascade proceeds through an allyl radical intermediate, which is formed via the addition of the PhS radical to the central carbon of allenamides. Moreover, the reaction was also efficient with selenophenol, providing the corresponding product, vinyl selenide, in a 99% yield.

Polymer dots (PDs) have raised considerable research interest due to their advantages of designable nanostructures, high biocompatibility, versatile photoluminescent properties, and recyclability as nanophase. However, there remains a lack of in situ, real-time, and noncontact methods for synthesizing PDs. Here we report a rational strategy to synthesize PDs through a well-designed single-component precursor (an asymmetrical donor–acceptor–donor′ molecular structure) by photoirradiation at ambient temperature. In contrast to thermal processes that normally lack atomic economy, our method is mild and successive, based on an aggregation-promoted sulfonimidization triggered by photoinduced delocalized intrinsic radical cations for polymerization, followed by photooxidation for termination with structural shaping to form PDs. This synthetic approach excludes any external additives, rendering a conversion rate of the precursor exceeding 99%. The prepared PDs, as a single entity, can realize the integration of nanocore luminescence and precursor-transferred luminescence, showing 41.5% of the total absolute luminescence quantum efficiency, which is higher than most reported PD cases. Based on these photoluminescent properties, together with the superior biocompatibility, a unique membrane microenvironmental biodetection could be exemplified. This strategy with programming control of the single precursor can serve as a significant step toward polymer nanomanufacturing with remote control, high-efficiency, precision, and real-time operability.

Wearable intelligent health monitoring devices with on-device biomedical AI processor can be used to detect the abnormity in users’ biomedical signals (e.g., ECG arrythmia classification, EEG-based seizure detection). This requires ultra-low power and reconfigurable biomedical AI processor to support battery-supplied wearable devices and versatile intelligent health monitoring applications while achieving high classification accuracy. However, existing designs have issues in meeting one or more of the above requirements. In this work, a reconfigurable biomedical AI processor (named BioAIP) is proposed, mainly featuring: 1) a reconfigurable biomedical AI processing architecture to support versatile biomedical AI processing. 2) an event-driven biomedical AI processing architecture with approximate data compression to reduce the power consumption. 3) an AI-based adaptive-learning architecture to address patient-to-patient variation and improve the classification accuracy. The design has been implemented and fabricated using a 65nm CMOS process technology. It has been demonstrated with three typical biomedical AI applications, including ECG arrythmia classification, EEG-based seizure detection and EMG-based hand gesture recognition. Compared with the state-of-the-art designs optimized for single biomedical AI tasks, the BioAIP achieves the lowest energy per classification among the designs with similar accuracy, while supporting various biomedical AI tasks.

This paper is concerned with the input delay compensation problem for neutral-type systems with both state and input delays. Single/various cascaded-observers based output feedback controllers are designed to predict the future states such that the input delay that can be arbitrarily large yet exactly known is compensated completely. Compared with the existing techniques, some more simple necessary and sufficient conditions guaranteeing the stability of the closed-loop systems are offered in terms of the stability of retarded-type time-delay systems referred to as observer-error systems. Finally, the lossless transmission line control system is worked out to illustrate the effectiveness of the proposed controllers.

Nowadays, infections caused by methicillin-resistant Staphylococcus aureus(MRSA) have constituted a new challenge for anti-infective treatment. Precise identification and rapid clinical diagnostics of MRSA from other methicillin-sensitive strains entail assays with robust diagnostic efficiency and simple operation steps. Sensitive detection of MecA gene is promising to indicate MRSA infection, but it is challenged by the lack of isothermal and simple strategies. A visual assay based on isothermal rolling circular amplification and G-quadruplex/hemin (G4/hemin) DNAzyme proximity assembly was proposed for the immediate, efficient, and cost-effective detection of MecA in simple operation steps and in a single tube. The presence of MecA specifically drove the formation of circular templates, which further triggered isothermal amplification. The amplified product offered abundant binding sites for DNA-grafted hemin probes to form a novel proximity-assembled G4/hemin DNAzyme structure for colorimetric changing diagnosis. This tandem-repeated novel DNAzyme possessed higher catalytic activity and a lower background signal than traditional G4/hemin DNAzyme, ensuring sensitive discrimination of MRSA (limit of detection: 9.6 pM). Assay stability and antimatrix interference capability enable clinical application, which shows compared diagnostic ability with classic methods (100% sensitivity and 100% specificity) but possesses more simplified procedures and shorter turnaround time (<6 h). This colorimetric strategy in a nonsite-specific and hypersensitive manner holds foreseeable prospects in clinical diagnostic and research applications.

Machine learning approaches have introduced an urgent need for large datasets of materials properties. However, for mechanical properties, current high-throughput measurement methods typically require complex robotic instrumentation, with enormous capital costs that are inaccessible to most experimentalists. A quantitative high-throughput method using only common lab equipment and consumables with simple fabrication steps is long desired. Here, we present such a technique that can measure bulk mechanical properties in soft materials with a common laboratory centrifuge, multiwell plates, and microparticles. By applying a homogeneous force on the particles embedded inside samples in the multiwell plate using centrifugation, we show that our technique measures the fracture stress of gels with similar accuracy to a rheometer. However, our method has a throughput on the order of 103samples per run and is generalizable to virtually all soft material systems. We hope that our method can expedite materials discovery and potentially inspire the future development of additional high-throughput characterization methods.

Zero thermal expansion materials are important for the practical applications due to their shape stability as changing temperature. The reported concept of average atomic volume is an available method to hunt new zero thermal expansion materials. Here, according to this concept, a tetragonal tungstate Cs2W3O10with zero expansion has been found. There is no structure phase transition as increasing temperature from 150 K to 573 K. The coefficient of thermal expansion of axes and volume are αa = 0.0074 × 10−6K−1, αc = 1.63 × 10−6K−1, and αV = 1.60 × 10−6K−1, respectively, in the temperature range of 150 ∼ 573 K. The temperature- and pressure-dependent Raman spectra reveal that the vibrations of WO6octahedra libration modes with positive total anharmonicity and W-O-W bending mode with negative Grüneisen parameter are possibly the origin of zero thermal expansion in Cs2W3O10.

The critical pathogenesis of type 1 diabetes (T1D)/type 2 diabetes (T2D) is the physical status, mass, and function of pancreatic β cells. Mammalian STE20-like protein 1 kinase (MST1) plays vital roles in the apoptosis and insulin secretion of β cells. Here, we discovered a novel, potent, and selective MST1 inhibitor 19(IC50= 23 nM), which inhibited the phosphorylation of MST1-protected β cells from the damage of inflammatory cytokines in vitro. In vivo, it displayed acceptable pharmacokinetic properties in different species. In the STZ-induced T1D/T2D mouse models, both monotherapy of 19and in combination with metformin led to the decline of fasting blood glucose and showed protective effect of β cells. In addition, the combination of 19and metformin decreased the hemoglobin A1c level. Together, our study suggested that 19might be a useful pharmacological tool to study MST1-mediated physiology and pathology as well as a potential drug candidate for diabetes.

A series of novel 1,3-benzodioxole-pyrimidine derivatives were designed and synthesized. The in vitrobioassay indicated that compounds 4e, 4g, 4n, 5c, and 5edisplayed excellent fungicidal activities against test fungal strains. Especially, in the in vitroexperiments, 5cexhibited a broad spectrum of fungicidal activity against Botrytis cinerea, Rhizoctonia solani, Fusarium oxysporum, Alternaria solani, and Gibberella zeaewith EC50values of 0.44, 6.96, 6.99, 0.07, and 0.57 mg/L, respectively, which were significantly more potent than those of positive control boscalid (EC50: 5.02, >50, >50, 0.16, and 1.28 mg/L). In vivotesting on tomato fruits and leaves showed that 5cdisplayed considerable protective and curative efficacy against A. solani. Scanning electron microscopy analysis indicated that 5cpossessed a strong ability to destroy the surface morphology of mycelia and seriously interfere with the growth of the fungal pathogen. In the in vitroenzyme inhibition assay, 5cexhibited pronounced succinate dehydrogenase (SDH) inhibitory activity with an IC50value of 3.41 μM, equivalent to that of boscalid (IC50: 3.40 μM). In addition, fluorescence quenching experiment further confirmed the strong interaction of 5cwith SDH. Through chiral resolution, 5cwas separated into two enantiomers. Among them, (S)-5cexhibited stronger fungicidal activity (EC50: 0.06 mg/L) and SDH inhibitory (2.92 μM) activity than the R-enantiomer (EC50: 0.17 mg/L and SDH IC50: 3.68 μM), which was in accordance with the molecular docking study (CDOCKER Interaction Energy for (R)-5cand (S)-5c: −28.23 and −29.98 kcal/mol, respectively). These results presented a promising lead for the discovery of novel SDHIs as antifungal pesticides.

Activating mutations in EZH2, the catalytic component of PRC2, promote cell proliferation, tumorigenesis, and metastasis through enzymatic or non-enzymatic activity. The EZH2-Y641 gain-of-function mutation is one of the most significant in diffuse large B-cell lymphoma (DLBCL). Although EZH2 kinase inhibitors, such as EPZ-6438, provide clinical benefit, certain cancer cells are resistant to the enzymatic inhibition of EZH2 because of the inability to functionally target mutant EZH2, or because of cells’ dependence on the non-histone methyltransferase activity of EZH2. Consequently, destroying mutant EZH2 protein may be more effective in targeting EZH2 mutant cancers that are dependent on the non-catalytic activity of EZH2. Here, using extensive selectivity profiling, combined with genetic and animal model studies, we identified USP47 as a novel regulator of mutant EZH2. Inhibition of USP47 would be anticipated to block the function of mutated EZH2 through induction of EZH2 degradation by promoting its ubiquitination. Moreover, targeting of USP47 leads to death of mutant EZH2-positive cells in vitro and in vivo. Taken together, we propose targeting USP47 with a small molecule inhibitor as a novel potential therapy for DLBCL and other hematologic malignancies characterized by mutant EZH2 expression.

In the present paper, we propose a novel opinion dynamics model referred to as nucleus Hegselmann-Krause (NHK) model, which depicts the influence of the neighbor is directly proportional to the opinion distance in the first similarity interval and is inversely proportional to the opinion distance in the second similarity interval. The convergence of the NHK opinion dynamics model is analysed by the property of weight matrix. Moreover, the NHK model with cognitive neighbor and spatial neighbor are respectively studied by the scale-free networks and the small-world networks. Finally, the NHK model with stubborn individuals is considered, it is disclosed that the larger the proportion of the similar individuals in the community is, the faster the opinion of individuals reaching consensus.

The mechanism of silk fiber formation in silkworms, Bombyx mori, is of particular scientific interest because it is closely related to the mechanical properties of silk fibers. However, there are still substantial knowledge gaps in understanding the details of this mechanism. Studies have found a pH gradient in the silk gland of silkworms. A vacuolar-type ATPase (V-ATPase) is thought to be involved in establishing this pH gradient. Although it is reported that the pH gradient plays a role in silk fibrillogenesis, the direct relationship between V-ATPase and silk mechanical properties is unclear. Thus, this study aims to clarify this relationship. We found that V-ATPase is highly and stably expressed in the anterior silk gland (ASG) and maintains the pH gradient and the fine structure of ASG. Inhibition of V-ATPase activity increased the β-sheet content and crystallinity of silk fibers. Tensile testing showed that the mechanical properties of silk fibers improved after inhibiting V-ATPase activity. All the data suggest that V-ATPase is a key factor in regulating silk fibrillogenesis and is related to the final mechanical properties of the silk fibers. V-ATPase is a potential target for silk mechanical property improvement.

ABSTRACTThe Segregation Index quantifies the degree of segregation of social groups or classes. Because of the increasing use of fine-grained spatiotemporal activity and flow data, the conventional segregation measurements’ inclusiveness is challenged. We add population flow to the conventional place-based spatial exposure index to identify spatiotemporal segregation changes. Specifically, we considered the population-flow network, hierarchical structure, and time. In Chicago’s demonstration case study, we first used the time-dependent Twitter Origin-Destination flow matrices and their hierarchical structure information to estimate interactions between areal units at the neighborhood level. Then we computed the new population composition of units based on their interactions with other units and estimated the proposed spatiotemporal exposure index for different times. Finally, we systematically compared their differences with the conventional indices at global and local scales to see how population-flow patterns affect the exposure index. The results show that the population-flow patterns reflect valuable information in neighborhood interactions in temporal and spatial dimensions, but it is missing information in the conventional segregation computations. Furthermore, we emphasize that the hierarchical structures of flow patterns and the choice of appropriate parameters are also important factors for a rational segregation evaluation.

The enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 that catalyzes methylation of histone H3 lysine 27 (H3K27). Overexpression or mutation of EZH2 has been identified in hematologic malignancies and solid tumors. Based on the structure of EPZ6438 (1) and the binding model with PRC2, we designed a series of analogues aiming to improve the activities of EZH2 mutants. Structure–activity relationship (SAR) exploration at both enzymatic and cellular levels led to the discovery of inhibitor 29. In the biochemical assay, 29inhibited EZH2 (IC50= 26.1 nM) with high selectivity over other histone methyltransferases. It was also potent against EZH2 mutants (EZH2 Y641F, IC50= 72.3 nM). Furthermore, it showed no apparent inhibitory activity against the human ether-á-go-go related gene (hERG) (IC50> 30 μM). In vivo, 29exhibited favorable pharmacokinetic properties for oral administration and showed better efficacy than 1in both Pfeiffer and Karpas-422 cell-mediated xenograft mouse models, indicating that it might be a new potential therapeutic candidate for EZH2 mutant cancers.

Airborne mineral dust is sensitive to climatic changes, but its response to orbital forcing is still not fully understood. Here, we present a reconstruction of dust input to the Subarctic Pacific Ocean covering the past 190 kyr. The dust composition record is indicative of source moisture conditions, which were dominated by precessional variations. In contrast, the dust flux record is dominated by obliquity variations and displays an out‐of‐phase relationship with a dust record from the mid‐latitude North Pacific Ocean. Climate model simulations suggest precession likely drove changes in the aridity and extent of dust source regions. Additionally, the obliquity variations in dust flux can be explained by meridional shifts in the North Pacific westerly jet, driven by changes in the meridional atmospheric temperature gradient. Overall, our findings suggest that North Pacific dust input was primarily modulated by orbital‐controlled source aridity and the strength and position of the westerly winds. Glacial‐interglacial climate variations can affect dust transport to the ocean, but the controls on past dust fluxes to the North Pacific Ocean remain poorly constrained. This region is important because fertilization of phytoplankton growth by dust‐borne iron may have contributed to lower glacial atmospheric CO2, and dust records could also constrain the past dynamics of the North Pacific westerly winds. Here, we highlight the dominance of obliquity cycles in modulating latitudinal shifts of the westerly winds and, in turn, dust inputs. In contrast, precession regulates the aridity of the dust source regions, which determines both dust emission rates and composition. Such orbital‐scale fluctuations in the dust flux could influence ocean‐atmosphere interactions in the middle and high northern latitudes, with implications for global atmospheric circulation and ocean carbon storage. Moisture availability in Asian dust source regions to the North Pacific Ocean were controlled by precessionNorth Pacific dust flux reveals dominant obliquity variations, but is out‐of‐phase at different latitudesThe westerlies in the Northern Hemisphere were primarily modulated by obliquity cycles in the late Pleistocene Moisture availability in Asian dust source regions to the North Pacific Ocean were controlled by precession North Pacific dust flux reveals dominant obliquity variations, but is out‐of‐phase at different latitudes The westerlies in the Northern Hemisphere were primarily modulated by obliquity cycles in the late Pleistocene

PI3Kγ and PI3Kδ plays critical roles in exerting immunosuppression by targeting regulatory T cells and myeloid cells. Dual inhibition of PI3Kγ and PI3Kδ has emerged as a novel therapeutic strategy for cancer immunotherapy. We herein report a series of pyrazolopyridine derivatives with distinct scaffolds as potent and selective dual inhibitors of PI3Kγ and PI3Kδ. Among them, 20e(IHMT-PI3K-315) displays an IC50value of 4.0 and 9.1 nM against PI3Kγ and PI3Kδ respectively in biochemical assays. Meanwhile, it potently inhibits PI3Kγ and PI3Kδ-mediated phosphorylation of AKT S473 with EC50values of 0.028 and 0.013 μM in cellular assays. In addition, 20eexhibits a favorable selectivity profile in protein kinases at 1 μM. In bone marrow-derived macrophages (BMDM), 20ecan repolarize the M2 phenotype to the M1 phenotype. In vivo, 20edemonstrates acceptable pharmacokinetic properties and suppresses tumor growth in a MC38 syngeneic mouse model.

Six new nardosinane-type sesquiterpenoids, clavukoellians A–F (1–6), together with one new neolemnane-type sesquiterpene, 4-O-deacetylparalemnolin D (7), were isolated from the marine soft coral Clavularia koellikeri. The structures of compounds 1–7were elucidated by NMR spectroscopy, ECD analysis, and quantum chemical calculation methods. Compounds 1and 7demonstrated significant antiangiogenic activities in wound healing assays on HUVECs.

This paper is concerned with the consensus problem for high-order continuous-time multiagent systems with both state and input delays. A novel approach referred to as pseudo-predictor feedback protocol is proposed. Unlike the predictor-based feedback protocol which utilizes the open-loop dynamics to predict the future states, the pseudo-predictor feedback protocol uses the closed-loop dynamics of the multiagent systems to predict the future agent states. Full-order/reduced-order observer-based pseudo-predictor feedback protocols are proposed, and it is shown that the consensus is achieved and the input delay is compensated by the proposed protocols. Necessary and sufficient conditions guaranteeing the stability of the integral delay systems are provided in terms of the stability of the series of retarded-type time-delay systems. Furthermore, compared with the existing predictor-based protocols, the proposed pseudo-predictor feedback protocol is independent of the input signals of the neighboring agents and is easier to implement. Finally, a numerical example is given to demonstrate the effectiveness of the proposed approaches.

Accumulated pieces of evidence have shown that PI3Kδ plays a critical role in chronic obstructive pulmonary disease (COPD). Using a fragment-hybrid approach, we discovered a potent and selective PI3Kδ inhibitor (S)-18. In the biochemical assay, (S)-18inhibits PI3Kδ (IC50= 14 nM) with high selectivity over other class I PI3Ks (56∼83 fold). (S)-18also achieves good selectivity over other protein kinases in the kinome (S-score (35) = 0.015). In the cell, (S)-18selectively and potently inhibits the PI3Kδ-mediated phosphorylation of AKT T308 but not other class I PI3K-mediated signaling. Additionally, (S)-18exhibits no apparent inhibitory effect on CYP isoforms except for a moderate effect on CYP2C9. Furthermore, it shows no apparent inhibitory activity against hERG (IC50> 10 μM). In vivo, (S)-18displays favorable PK properties for inhaled delivery and improves lung function in a rodent model of pulmonary inflammation. These results suggest that (S)-18might be a new potential therapeutic candidate for COPD.

Plenoptic cameras are increasingly gaining attention in various fields due to their ability to capture both spatial and angular information of light rays. Accurate geometric calibration can lay a solid foundation for the applications that use the plenoptic camera. In this paper, to the best of our knowledge, we first introduce an accurate corner detection method based on a novel selection and refinement strategy. The detected-corner candidates on raw images are selected by a random sample consensus (RANSAC)-based algorithm and optimized by the photometric similarity, as well as the sub-pixel refinement. In addition, a robust and accurate stepwise calibration method is proposed based on separated intrinsic parameters, including parameters related to the pinhole model and those unique to the plenoptic camera. Experiments on both simulated and real data demonstrate that our method outperforms the state-of-the-art methods and is able to support a more accurate calibration of plenoptic cameras.

There are two distinctly different views on Quaternary sedimentation rates in the central Arctic Ocean, namely, that they were on cm/kyr or on mm/kyr scales, largely as a result of divergent interpretations of magnetic reversal stratigraphy. This study provides new evidence to help resolve this controversy in the form of an almost 1‐m‐thick negative polarity interval located at ~1.15 m below the seafloor in a 4.15‐m‐long sediment core from the Lomonosov Ridge, central Arctic Ocean. This thick polarity anomaly was first revealed through alternating field demagnetization of natural remanent magnetization on u‐channel samples. It was subsequently confirmed to be an authentic signal of a syndepositional geomagnetic field by integrating detailed rock magnetic studies, transmission electron microscopy with energy‐dispersive X‐ray spectroscopy analyses of magnetic extracts, and both alternating field and thermal demagnetization of discrete paleomagnetic samples. Here we conclude that it is more reasonable to interpret the reversed interval as a record of the Matuyama Chron rather than a Brunhes‐aged excursion, which yields mean sedimentation rates of ~1.5 mm/kyr and ~0.5 mm/kyr in the Brunhes and Matuyama Chrons, respectively. These estimates are remarkably lower than assumed in most recent studies, but in good agreement with both previous magnetostratigraphic and recent geochemical studies relative to the decay of Be and U‐series isotopes, which might indicate “sediment‐starved” environments at least in some parts of this region. Overall, our results not only imply that chronostratigraphy in the central Arctic Ocean remains open to debate but also warrant further investigations in this microfossil‐barren region. The effects of self‐reversed CRM of diagenetic titanomaghemite are probably only regional in the central Arctic sedimentsThe "reversal" interpretation supports "sediment starved" environments at least in some regions of the central Arctic OceanThe chronostratigraphy and usability of paleomagnetism in the central Arctic Ocean remains open to debate and further studies are warranted