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This paper develops a high-precision miniature three-dimensional Fiber Bragg Grating (FBG) force sensor designed for detecting and locating hard masses within tissues during Minimally Invasive Surgery (MIS) and robotic-assisted MIS palpation processes. The prototype consists of three FBG-etched optical fibers and an integrated elastomer. The fibers are suspended and parallel to each other within the elastomer, allowing each FBG to be directly compressed or stretched under stress. A novel model, combining segment-by-segment sensitivity and differential decoupling, is adopted for decoupling three-dimensional forces. This approach significantly reduces the crosstalk error caused by spatial forces, avoids the complexity of assembling multiple fibers in previous designs, and reduces the sensor's size, facilitating its integration into MIS procedures. Calibration experiments are conducted to determine the sensor's force sensitivity coefficients, achieving resolutions of 4.35 mN, 3.99 mN, and 3.30 mN in the X, Y, and Z directions, respectively. Through discrete and drag palpation tests on silicone with different types of hard inclusions, the results demonstrate that the proposed prototype has the ability to effectively identify the size, hardness, and depth of hard objects from the contact force information. Additionally, ex vivo porcine kidney palpation experiments are conducted to further verify the feasibility of locating hard masses during MIS palpation.

Alfalfa (Medicago sativasubsp. sativa), the “queen of forage,” is the most important perennial legume, with high productivity and an excellent nutritional profile. Medicago sativasubsp. falcatais a subspecies of the alfalfa complex and exhibits better drought tolerance. However, drought stress significantly hampers their development and yield. The molecular mechanisms underlying the aboveground and underground tissues of sativaand falcataresponding to drought stress remain obscure. Here, we performed a comprehensive comparative analysis of the physiological and transcriptomic responses of sativaand falcataunder drought stress. The results showed that photosynthesis was inhibited, and antioxidant enzymes were activated under drought stress. MsC3H29, a CCCH-type zinc finger protein, was identified as a hub gene through weighted gene coexpression network analysis (WGCNA) and was significantly induced by drought in underground tissue. The MsC3H29 protein was localized in the nucleus. Overexpression (OE) of MsC3H29can increase the primary root length and fresh weight of transgenic alfalfa hairy roots, while RNA interference (RNAi) decreases them under drought stress. The 2′,7′-dichlorodihydrofluorescein diacetate (H2DCFDA) staining revealed that MsC3H29promoted drought tolerance of alfalfa hairy roots through decreasing ROS accumulation. The targeted metabolome analysis showed that the overexpression of MsC3H29resulted in higher levels of accumulation for flavonoid monomers, including vicenin, daidzein, apigenin, isorhamnetin, quercetin, and tricin, in transgenic alfalfa hairy roots before and after drought stress, while RNAi led to a reduction. Our study provided a key candidate gene for molecular breeding to improve drought resistance in alfalfa.

Background. Transplantation and immunosuppressive therapies are the available treatments for aplastic anemia; however, each strategy has its advantages and disadvantages. Objective. The aim of this study was to find a new strategy for aplastic anemia treatment. Design. This was an experimental and comparative study. Methods. The aplastic anemia model was established by injecting rabbits with benzene and cyclophosphamide. The rabbits with aplastic anemia were divided into low-intensity pulsed ultrasound (LIPUS) and control groups. The distal femoral metaphysis of rabbits in the LIPUS group was treated with ultrasound for 30 days (20 min/d), whereas the control group received a sham treatment. Diarrhea, mortality, and blood cell count were evaluated. The levels of forkhead box P3, interleukin 17, interleukin 4, and interferon gamma were measured using an enzyme-linked immunosorbent assay. Bone marrow hyperplasia was observed by hematoxylin-eosin staining and scanning electron microscopy. Results. The numbers of red blood cells (RBCs), white blood cells (WBCs), and platelets (PLTs) were lower, the amount of hematopoietic tissue was lower, and the amount of adipose tissue was higher in the rabbit aplastic anemia model than in the normal rabbits. The numbers of RBCs, WBCs, and PLTs increased after LIPUS treatment. The interleukin 17 level decreased, whereas the forkhead box P3 level increased. The amount of hematopoietic tissue increased, whereas the amount of adipose tissue decreased. Limitations. The number of hematopoietic stem cells could not be evaluated. Conclusions. LIPUS improved the hematopoietic microenvironment, accelerated the reconstruction of bone marrow cells, and increased the quantity and quality of RBCs, WBCs, and PLTs in the peripheral blood. Hence, it can serve as a novel treatment strategy for aplastic anemia in the future., A plastic anemia is a bone marrow hematopoietic failure syndrome caused by various etiologies. It is characterized by the decreased proliferation of bone marrow hematopoietic cells and a decreased number [...]

Herein, an unprecedented cadmium-based metal–organic framework (JNU-106) fabricated by utilizing pyrazole-functionalized tetraphenylethylene ligands (Py-TPE) and rod-shaped secondary building units is reported, possessing a new (3,3,3,6,6,8)-connected topological network. Thanks to the ingeniously designed intramolecular charge transfer behavior, which originates from the congruent coplanarity between Py and TPE, JNU-106exhibits intense green luminescence with a quantum yield increased by 1.5 times. The phenomenon of remarkable fluorescence quenching of JNU-106reveals that it possesses extremely high anti-interference performance, superior sensitivity, and dedicated selectivity toward tetracycline antibiotics (TCAs) in aqueous solutions, which are comparable to those of the state-of-the-art porous sensing compounds. Taking the theoretical calculations and experimental results into account, the luminescence quenching is mainly attributed to the internal filtration effect and the static quenching effect. Considering the portable and rapid performance of JNU-106-based testing strips for sensing TCAs, the fabricated JNU-106provides an alternative for ecological monitoring and environmental governance.

Tactile image sensors are efficient and useful in the robotics and health-care fields due to their advantage of being impervious to electromagnetic fields. The functionality and applications of the sensors have been extensively researched. Furthermore, the pattern with the arrangement of sizes, colors, shapes, and densities is like the “heart” of tactile image sensors, which immediately determines the results of detecting the position and the force. However, the effect of patterns on the resolution of tactile sensors has not been fully investigated yet. Hence, we experimentally studied the effect of different patterns on the resolution of tactile image sensors due to difficulties in theoretical analysis. Optical fibers and cameras were used to integrate flexible sensors with different features, which are divided into 61 dots. The sensors are put through their trials in various positions and forces, and the data is processed using deep learning methods. The sensors with four different patterns were all successful in distinguishing pressure, shear, and torque. More crucially, the root mean square error (RMSE) values were used to compare the impact of the various patterns on the sensors. All sensors with four types of patterns exhibited outstanding resolution for positions, normal force, shear forces, and torsion, which should be due to the optimization of the neural network and sensor structure. The seven position and force parameters of these four patterned sensors have the same order of magnitude of RMSEs, which suggests that the pattern complexity has negligible influence on the tactile image sensor resolution for these factors in our sensor structure. Moreover, we have demonstrated the outstanding resolution of the sensor with a pure color pattern. This work not only guides the pattern designs of forthcoming tactile image sensors but also enables the mass manufacture of flexible sensors for intelligent robots.

Nonstoichiometric microstructured silicon suboxide (SiOx) could be an attractive alternative to graphite as the anode materials of lithium-ion batteries (LIBs) due to its high theoretical capacity and low cost. However, practical applications of SiOxare hampered by their inferior inherent conductivity and distinct volume changes during cycling. In this work, in order to address these issues simultaneously, we designed and fabricated SiOx-based anode materials with TiO1−yNy-carbon coating layer (SiOx@TiON-C) using a scalable solvothermal and thermal reduction method. Our systematic investigations suggest that TiO1−yNyand the C coating layer could accommodate large volume variation and promote electrical conductivity of SiOxduring cycling, respectively. As a result, the as-prepared SiOx@TiON-C anode exhibits superior lithium storage performance. Specifically, the resultant SiOx@TiON-C anode could deliver an outstanding reversible capacity of 750.2 mA h g−1at 500 mA g−1after 500 cycles, high initial Coulombic efficiency of 75.1% and excellent rate capability. This work offers a promising approach to promote the practical commercialization of microstructured SiOx-based anode materials for next-generation LIBs.

ABSTRACT Low temperature thermal cracking, rutting, moisture damage and fatigue cracking are popular damages that appear in the asphalt mixture. These problems occur mainly because of the growth in the [...]

The construction of a heterojunction interface bond between LaFeO3and Li1.2Mn0.6Ni0.2O2moderating the anionic redox of Li-rich surfaces, reduces oxygen release and improves cycling stability.

Permafrost and its spatiotemporal variation considerably influence the surface and sub-surface hydrological processes, biogeochemical cycles, fauna and flora growth and cold region engineering projects in the Three-River Source Region (TRSR), Qinghai–Tibet Plateau. However, the dynamics of permafrost over a relatively long term duration (e.g. >100 years) in the TRSR is not well quantified. Thus, the spatial and temporal variations of the temperature at the top of the perennially frozen/unfrozen ground (TTOP), active layer thickness (ALT) in permafrost regions and the maximum depth of frost penetration (MDFP) in the seasonally frozen ground of the TRSR during 1901–2020 were simulated using the TTOP model and Stefan equation driven by the widely used reanalysis Climatic Research Unit 4.05 dataset. Results revealed that the permafrost in the TRSR over the past 120 years did not degrade monotonically but experienced considerable fluctuations in area with the decadal oscillations of climate warming and cooling: shrinking from 263.9 × 103 km2in the 1900s to 233.3 × 103 km2in the 1930s, expanding from 232.3 × 103 km2in the 1940s to 260.9 × 103 km2in the 1970s and shrinking again from 254.1 × 103 km2in the 1980s to 228.9 × 103 km2in the 2010s. The regional average TTOP increased from −1.34 ± 2.74 °C in the 1910s to −0.48 ± 2.69 °C in the 2010s, demonstrating the most noticeable change for the extremely stable permafrost (TTOP < −5 °C) from 8% to 1%. The regional average ALT increased from 2.68 ± 0.52 m to 2.87 ± 0.46 m, with the area proportion of ALT > 3.0 m by 12% from 1901 to 2020. Notably, minor changes were observed for the regional average MDFP, probably due to the increase in the area proportion of MDFP < 3.0 m (caused by climate warming) and MDFP > 3.5 m (owing to the transformation of permafrost to seasonally frozen ground) by 7.39% and 4.77%, respectively. These findings can facilitate an in-depth understanding of permafrost dynamics and thus provide a scientific reference for eco-environment protection and sustainable development under climate change in the TRSR.

Lithium-rich layered oxides with superior capacity over 250 mA h g–1have been regarded as one of the most promising cathode materials to address the problem of low endurance of electric vehicles. Unfortunately, their practical application has been blocked for decades by severe voltage decay and capacity fading, which mainly originate from structure evolution of layered to spinel-like phase and undesirable cathode–electrolyte interfacial reactions. Herein, the inhomogeneous distribution of LiMO2and Li2MnO3components on the surface of Li1.2Mn0.6Ni0.2O2(LMNO) is constructed by a facile NH3·H2O-assisted Mn- and Ni-treatment method, demonstrated by Raman results. As supported by dQ/dVcurves and electrochemical impedance spectroscopy data, the inhomogeneous surface improves the corrosion resistance against the electrolyte and enhances the surface–interface stability. Compared with the pristine one (P-LMNO), the Mn- and Ni-treated samples (M-LMNO and N-LMNO) deliver excellent cycling stability. After 200 cycles, the discharge capacity of the M-LMNO and N-LMNO samples is still as large as 154.5 and 174.0 mA h g–1at 200 mA g–1, respectively, which is about twice as large as that of the P-LMNO sample. This work proposes a facile and effective surface-treated strategy for Li-rich layered cathodes to alleviate structure evolution and suppress the erosion of electrolytes.

To examine the association of systolic blood pressure (SBP) and cardiovascular risk in normotensive adults.

Alfalfa is the most widely cultivated perennial legume forage crop worldwide. Drought is one of the major environmental factors influencing alfalfa productivity. However, the molecular mechanisms underlying alfalfa responses to drought stress are still largely unknown. This study identified a drought-inducible gene of unknown function, designated as Medicago sativa DROUGHT-INDUCED UNKNOWN PROTEIN 1(MsDIUP1). MsDIUP1 was localized to the nucleus, chloroplast, and plasma membranes. Overexpression of MsDIUP1in Arabidopsisresulted in increased tolerance to drought, with higher seed germination, root length, fresh weight, and survival rate than in wild-type (WT) plants. Consistently, analysis of MsDIUP1over-expression (OE) alfalfa plants revealed that MsDIUP1also increased tolerance to drought stress, accompanied by physiological changes including reduced malondialdehyde (MDA) content and increased osmoprotectants accumulation (free proline and soluble sugar), relative to the WT. In contrast, disruption of MsDIUP1expression by RNA interference (RNAi) in alfalfa resulted in a drought-hypersensitive phenotype, with a lower chlorophyll content, higher MDA content, and less osmoprotectants accumulation than that of the WT. Transcript profiling of alfalfa WT, OE, and RNAi plants during drought stress showed differential responses for genes involved in stress signaling, antioxidant defense, and osmotic adjustment. Taken together, these results reveal a positive role for MsDIUP1in regulating drought tolerance.

Image and video based human motions can be regarded as the deformation processes of person appearances, so motion transfer is usually treated as a pose guided image generation task and implemented in the 2D image plane. However, the 2D plane image generation lacks guidance of the original 3D motion information, which results in blur and shape distortions of the generated motion images. Therefore, we propose to simulate the generation process of real motion images by projecting the 3D human models, which are reconstructed from the training motion images and driven with target poses, into the 2D plane. We then take the 2D projections as the pose representations and input them into the generation model as they naturally inherit the 3D information from the original motions. Considering the unreliability on the invisible surface of the single image based human model reconstruction, we propose a sequential image based human model refinement module which exploits the complementary information between adjacent motion frames to refine the 3D human model. Furthermore, we propose a face-attention GAN model to conduct the final motion transfer, in which we use the Gaussian distribution to match the elliptical face region and design a face enhancement loss function since the faces in the generated motion images influence the performances very much. The generated motion images with reliable depth information, accurate shapes and clear faces demonstrate the effectiveness of the proposed method.

As an important device for energy conversion, insulated-gate bipolar transistor (IGBT) modules are widely used in various applications. Generally, IGBT power modules work in a harsh environment, and their reliable operation is of high importance. However, most of the existing package design methods fail to provide sufficient reliability for IGBT modules. To address this, an optimal package design method for IGBT modules is proposed in this article. In the proposed design method, the vapor chamber is embedded in the copper substrate. Based on this, a satisfactory performance of spreading heat is accordingly achieved. Moreover, a thermal stress analysis of the IGBT power module with the proposed design method is then provided. The analysis under the high load working state reveals the proposed design method can reduce the chip junction temperature by 12 °C. The optimized structure brings lower thermal stress and a more uniform temperature and consequently maintains the reliability of the IGBT power modules. Experimental tests have verified the performance of the proposed optimization design method.

Lycium barbarumpolysaccharide (LBP) is a substance with various biological activities extracted from Lycium barbarum. LbGPs are peptidoglycans with a short peptide backbone and a complex, branched glycan moiety, which is further extracted and isolated from LBPs. Previous studies have shown that LbGP can inhibit cancer cell growth, but its specific mechanism is not completely clear. In this study, we found that LbGP could inhibit the proliferation of glioma cells and promote the expression of period 2 (PER2) through the PKA-CREB pathway. In addition, LbGP could inhibit the de novo synthesis of lipids by downregulating SREBP1c and its target genes, which depended on the expression of PER2. Moreover, PER2 negatively regulated the expression of SREBP1c via suppressing PI3K/AKT/mTOR pathway. In summary, LbGP may upregulate the expression of PER2 to reduce the expression of SREBP1c, inhibit lipid synthesis in glioblastoma, and inhibit glioblastoma cell proliferation. This study provides an alternative drug for the treatment of glioma and elucidates its potential mechanism.

Civil infrastructure systems are prone to environmental deterioration processes that gradually reduce their mechanical properties and their capability to sustain severe natural hazards, such as earthquakes. The rate of occurrence of major seismic events, the time-variant seismic vulnerability of single bridges, and the indirect economic losses due to traffic flow redistribution related to the closure of key routes within the highway network are affected by uncertainties to be addressed by modelling their constitutive parameters as random variables and processes. This paper presents an integrated simulation-based methodology to estimate the user cost-based risk and system robustness of spatially distributed bridge networks subjected to prescribed deterioration and regional seismic hazard scenarios. Life-cycle seismic risk metrics are evaluated in terms of bridges failure rates and exceedance rates of indirect monetary losses based on free-flow traffic analysis and user cost assessment. The lifetime system robustness is also evaluated based on appropriate probabilistic performance indicators.

When grabbing an object, a robot needs to be installed with a sensor on its finger to sense the position of the object and the intensity of the contact force. Therefore, the accuracy of the tactile sensor’s recognition is very important to grasp the object successfully. In our work, we design a data acquisition scheme and establish the corresponding deep-learning dataset taking the optical-fiber-based tactile sensor as the research object. This kind of sensor is composed of different layers. Those layers are deformed when the force is applied to the surface. Since the extent of deformation is proportional to the value of the force, the color and brightness of the collected pictures will change according to the Poisson effect. A novel multiscale (MS) ResNet is proposed and compared with some mainstream networks such as AlexNet, ResNet, VGG, DenseNet, and GoogLeNet under the same dataset. The dataset we collected contains normal force, shear force, and torsion. It can provide better calibrations between the image change and force value. The proposed network is investigated experimentally. The results demonstrate that it can achieve enhanced performance by extracting image features of different scales. This MS ResNet can be widely applied to the deep-learning training of mechanic sensors based on the image and is also well-suited for the calibration tasks such as classification and regression prediction of mechanics sensors based on multiple data features.

Vision enables both image-forming perception, driven by a contrast-based pathway, and unconscious non-image-forming circadian photoentrainment, driven by an irradiance-based pathway1,2. Although two distinct photoreceptor populations are specialized for each visual task3–6, image-forming photoreceptors can additionally contribute to photoentrainment of the circadian clock in different species7–15. However, it is unknown how the image-forming photoreceptor pathway can functionally implement the segregation of irradiance signals required for circadian photoentrainment from contrast signals required for image perception. Here we report that the DrosophilaR8 photoreceptor separates image-forming and irradiance signals by co-transmitting two neurotransmitters, histamine and acetylcholine. This segregation is further established postsynaptically by histamine-receptor-expressing unicolumnar retinotopic neurons and acetylcholine-receptor-expressing multicolumnar integration neurons. The acetylcholine transmission from R8 photoreceptors is sustained by an autocrine negative feedback of the cotransmitted histamine during the light phase of light–dark cycles. At the behavioural level, elimination of histamine and acetylcholine transmission impairs R8-driven motion detection and circadian photoentrainment, respectively. Thus, a single type of photoreceptor can achieve the dichotomy of visual perception and circadian photoentrainment as early as the first visual synapses, revealing a simple yet robust mechanism to segregate and translate distinct sensory features into different animal behaviours.

The exceptional electrochemical performance of lithium-ion batteries has spurred considerable interest in advanced battery technologies, particularly those utilizing ternary nickel–cobalt–manganese (NCM) cathode materials, which are renowned for their robust electrochemical performance and structural stability. Building upon this research, investigators have explored doping additional elements into NCM cathode materials to further enhance their electrochemical performance and structural integrity. However, the multitude of doping strategies available for NCM battery systems presents a challenge in determining the most effective approach. In this study, we elucidate the potential of ternary NCM systems as cathode materials for lithium-ion batteries. We compile a comprehensive database of lithium-ion batteries employing NCM systems from various sources of prior research and develop a corresponding data-driven model utilizing graph neural networks to predict optimal doping strategies. Our aim is to provide insights into the NCM-based battery systems for both fundamental understanding and practical applications.

Molecular imaging is a non‐invasive imaging method that is widely used for visualization and detection of biological events at cellular or molecular levels. Stimuli‐responsive linkers that can be selectively cleaved by specific biomarkers at desired sites to release or activate imaging agents are appealing tools to improve the specificity, sensitivity, and efficacy of molecular imaging. This review summarizes the recent advances of stimuli‐responsive linkers and their application in molecular imaging, highlighting the potential of these linkers in the design of activatable molecular imaging probes. It is hoped that this review could inspire more research interests in the development of responsive linkers and associated imaging applications. Stimuli‐responsive linkers are appealing tools to improve the specificity, sensitivity, and efficacy of molecular imaging. In this review, the recent examples and progress toward the development of stimuli‐responsive linkers and their application in molecular imaging are systematically summarized, highlighting the potential of these linkers in the design of activatable molecular imaging probes.

The Beijing genotype is the most common type of tuberculosis in Jiangxi Province, China. The association of population characteristics and their prevalence in the development of recent transmission is still unclear. 1,433 isolates were subjected to drug-resistant tests and MIRU-VNTR analysis. We compared differences in demographic characteristics and drug resistance patterns between the Beijing and non-Beijing family strains. We also explored the association of the clustering rate with the Beijing genotype of Mycobacterium tuberculosis. The Beijing genotype was dominant (78.16%). The results of MIRU-VNTR showed that 775 of 1,433 strains have unique patterns, and the remaining gather into 103 clusters. A recent transmission rate was 31.54% (452/1,433). The Beijing genotype strains were more likely to spread among the recurrent population (p= 0.004), people less than 50 years of age (p= 0.02 or 0.003), and the personnel in the northern regions (p= 0.03). Drug resistance patterns did not show significant differences between Beijing and non-Beijing genotype isolates. Furthermore, we found that HIV-positive cases had a lower clustering rate (p= 0.001). Our results indicated that the recurrent population and people under 50 years of age were more likely to be infected with the Beijing genotype of M. tuberculosis. The strains from the Beijing family were easier to cluster compared to strains isolated from the non-Beijing family. Social activity and AIDS substantially impacted the clustering rate of the Beijing genotype of M. tuberculosis. Multidrug resistant M. tuberculosisaffected Beijing genotype transmission.

As the second most abundant natural polymer, accounting for approximately 30% of the organic carbon in the biosphere, lignin plays an essential role in plant development. However, a high lignin content affects the nutritional quality of alfalfa (Medicago sativaL.), the most widely cultivated perennial legume forage crop. Histological analysis indicated that G-lignin and S-lignin were present in the stem, leaf, and petiole of alfalfa, and the deposition of lignin increased gradually in descending internodes. Neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid detergent lignin (ADL) contents continually increased from the top to the bottom of the stem, and ADL content showed a similar trend in leaves. Alfalfa leaves and stems from five different nodes (1, 2, 4, 6, and 8) were used as materials to investigate molecular regulatory mechanisms in lignin synthesis by RNA sequencing. Respectively 8074 and 7752 differentially expressed genes (DEGs) were identified in leaves and stems, and 1694 DEGs were common to the two tissues. “Phenylpropanoid biosynthesis” was the most enriched pathway in both leaves and stems, and 134 key regulatory genes in lignin synthesis were identified by a weighted gene co-expression network analysis. The NAC family transcription factor MsNST1gene was highly expressed in old leaf and stem tissues. The deposition pattern of G- and S-lignin differed among M. truncatulawild-type, nst1mutants, and overexpression lines, and the transcription levels of lignin synthesis genes such as HCT, F5H, and COMTin these three materials also differed. These results suggest that MsNST1affects lignin synthesis in alfalfa. These findings provide a genetic basis and abundant gene resources for further study of the molecular mechanisms of lignin synthesis, laying a foundation for low-lignin alfalfa breeding research.

Bioinspired metal–organic frameworks (MOFs) serve as suitable crystalline models for recognition and sensing of biomolecules mimicking natural processes, providing new ideas and concepts for cutting-edge biomedical applications. Here, we have successfully prepared a robust biological metal–organic framework with periodic docking grooves resembling the major and minor grooves in the DNA double helix structure, which can be used as unique recognition sites for selectively identifying l-/d-tryptophan (l-/d-Trp). Notably, successful encapsulation of Trp could be observed by single-crystal X-ray diffraction for the first time. Trp has matched size and shape to fit snugly into the major groove. Combined with isothermal titration calorimetry, it was found that ZnBTCHx could spontaneously capture l-/d-Trp through two different thermodynamic pathways: enthalpy-driven for encapsulating l-Trp and entropy-driven for uptaking d-Trp. Furthermore, molecular dynamics and density functional theory verified the role of hydrogen bonding and π–π/C–H···π interactions in the host–guest interface. This work provides unique insight for the construction of bionic models to mimic the natural binding properties, which is of great significance for the fields of pharmaceutical chemistry and biomedical science.

Calothrixin A (CAA) is a dual Topo I and II inhibitor but exhibits poor antiproliferative activities and water solubility. Herein, a library of novel CAAanalogues was synthesized. Among them, compound F16exhibited superior water solubility (>5 mg/mL) as compared to CAA(<5 μg/mL). The mechanism of action studies confirmed that F16acted as a dual Topo I and II poison. Furthermore, F16displayed potent antiproliferative activities against high Topo I and II expression cell lines A375 and HCT116, with IC50values of 20 and 50 nM, respectively. In xenograft models, F16reduced the tumor growth at a dose of 10 or 20 mg/kg without apparent effect on the mouse weight, while the clinically used Topo II inhibitor VP-16dramatically reduced the mouse weight. Collectively, our data demonstrated that F16could be a promising lead for the development of novel dual Topo I and II antitumor agents.

Charged metal-organic cages generally produce aggregates with various morphologies and different properties through the multiple supramolecular interactions in solution. Herein, a luminescent hexahedral metal-organic cage containing pyrene chromophores is successfully constructed through coordination-driven subcomponent self-assembly. The cage exhibits novel spontaneous aggregation in a dilute solution and time-dependent luminescence enhancement behavior during the subsequent incubation process. Dynamic light scatter (DLS) and transmission electron microscopy (TEM) results prove that the metal-organic cages can form blackberry-like aggregates in methanol dilute solution. Unexpectedly, the luminescent intensity of this system shows a linear increase with the extension of the incubation time in methanol, and this process is also reflected in the change in the quantum yield of the system (2% to over 80% after 5 days incubation time). Ultraviolet-visible (UV-vis), 1H nuclear magnetic resonance (1H NMR) and mass spectra show that metal-organic cages can stably exist in dilute solution. Time-depended DLS and TEM data reveal that the aggregates of metal-organic cages are gradually changed from the dense state to the loose one, which may involve the transition of the system from an energy unstable state to a stable one, probably leading to the unusual time-dependent luminescent property. This unique time-dependent luminescent cage aggregate can be potentially applied as a “supramolecular time meter”.

IMPORTANCE: Induction chemotherapy added to concurrent chemoradiotherapy significantly improves survival for patients with locoregionally advanced nasopharyngeal carcinoma, but the optimal induction regimen remains unclear. OBJECTIVE: To determine whether induction chemotherapy with paclitaxel, cisplatin, and capecitabine (TPC) improves survival vs cisplatin and fluorouracil (PF) prior to chemoradiotherapy for patients with stage IVA to IVB nasopharyngeal carcinoma. DESIGN, SETTING, AND PARTICIPANTS: This randomized, open-label, phase 3 clinical trial recruited 238 patients at 4 hospitals in China from October 20, 2016, to August 29, 2019. Patients were 18 to 65 years of age with treatment-naive, nonkeratinizing stage IVA to IVB nasopharyngeal carcinoma and an Eastern Cooperative Oncology Group performance status of 0 to 1. INTERVENTIONS: Patients were randomly assigned (1:1) to receive induction chemotherapy with two 21-day cycles of TPC (intravenous paclitaxel [150 mg/m2, day 1], intravenous cisplatin [60 mg/m2, day 1], and oral capecitabine [1000 mg/m2 orally twice daily, days 1-14]) or PF (intravenous cisplatin [100 mg/m2, day 1] and fluorouracil [800 mg/m2 daily, days 1-5]), followed by chemoradiotherapy. MAIN OUTCOMES AND MEASURES: The primary end point was failure-free survival in the intention-to-treat population. Secondary end points included distant metastasis–free survival, locoregional relapse–free survival, overall survival, tumor response, and safety. RESULTS: Overall, 238 eligible patients (187 men [78.6%]; median age, 45 years [range, 18-65 years]) were randomly assigned to receive TPC (n = 118) or PF (n = 120). The median follow-up duration was 48.4 months (IQR, 39.6-53.3 months). Failure-free survival at 3 years was 83.5% (95% CI, 77.0%-90.6%) in the TPC group and 68.9% (95% CI, 61.1%-77.8%) in the PF group (stratified hazard ratio [HR] for recurrence or death, 0.47; 95% CI, 0.28-0.79; P = .004). Induction with the TPC regimen resulted in a significant reduction in the risk of distant metastases (stratified HR, 0.49 [95% CI, 0.24-0.98]; P = .04) and locoregional recurrence (stratified HR, 0.40 [95% CI, 0.18-0.93]; P = .03) compared with the PF regimen. However, there was no effect on early overall survival (stratified HR, 0.45 [95% CI, 0.17-1.18]; P = .10). The incidences of grade 3 to 4 acute adverse events and late-onset toxicities were 57.6% (n = 68) and 13.6% (16 of 118), respectively, in the TPC group and 65.8% (n = 79) and 17.9% (21 of 117), respectively, in the PF group. One treatment-related death occurred in the PF group. CONCLUSIONS AND RELEVANCE: This randomized clinical trial found that induction chemotherapy with 2 cycles of TPC for patients with stage IVA to IVB nasopharyngeal carcinoma improved failure-free survival compared with 2 cycles of PF, with no increase in the toxicity profile. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02940925

Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer’s disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg−1· d−1, ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1β, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.

Cobalt-free Li-rich layered oxides (LLOs) such as Li1.2Mn0.6Ni0.2O2have attracted extensive attention owing to their high specific capacity and low cost. Nonetheless, numerous problems such as continuous voltage fading and capacity decay have become stumbling blocks in its commercial application. In this study, we propose an effective dual-site doping strategy by choosing Mo as the cation and F as the anion to enhance the capacity and cycling performance. The research demonstrates that the cycling stability of LLOs enhances with the doping ratio of Mo, and their capacity increases with the doping ratio of F. It is because Mo as a pillar enhances the structural stability and F doping is conducive to the activation of Li2MnO3. What's more, dual-site doping also promotes the diffusion of Li+and reduces the internal resistance of the electrode. Due to these improvements, the 5F3M sample still maintains a discharge capacity of 190.98 mAh g-1after 100 cycles at 200 mA g-1, which is much higher than 165.29 mAh g-1of the Pristine sample. This discovery provides a new way to develop advanced layered oxide cathodes for both Na- and Li-ion batteries.

Post-synthetic installation strategy is an effective approach to improve the functions of metal-organic frameworks (MOFs). Herein, a pair of chiral MOFs is successfully constructed through solvothermal subcomponent self-assembly and exhibit circularly polarized luminescence (CPL). These MOFs contain coordinatively unsaturated Zn sites and channels, which allow the installation of pyridyl-terminated pillars into the original structure. Such a post-synthetic installation process reinforces the MOFs’ rigidity and increases the photoluminescence quantum yields (PLQYs). Furthermore, the luminescence dissymmetry factors (glum) of these post-modified MOFs are amplified after installing the pillars. This work provides an appealing strategy for boosting the CPL performance of chiral MOFs.

For Landsat land cover classification, the time series observations are typically irregular in the number of observations in a period (e.g., a year) and acquisition dates due to cloud cover variations over large areas and acquisition plan variations over long periods. Compositing or temporal percentile calculation are usually used to transform the irregular time series to regular temporal variables so that the machine and deep learning classifiers can be applied. Recognizing that the composite and percentile calculations have information loss, this study presents a method directly Classifying the Raw Irregular Time series (CRIT) (‘raw’ means irregular good-quality surface reflectance time series without any composite or temporal percentile derivation) by adapting Transformer. CRIT uses the acquisition day of year as classification input to align time series and also takes the Landsat satellite platform (Landsat 5, 7 and 8) as input to address the inter-sensor reflectance differences.

Type 1 diabetes is an autoimmune disease in which the insulin-secreting β-cells of the pancreas are destroyed. Circulating islet autoantibodies and autoreactive T-cells are hallmarks of this islet cell specific [...], Autoantibodies to the 65-kDa isoform of GAD (GAD65Abs) are associated with type 1 diabetes development, but the conformational nature of the GAD65Ab epitopes complicates the evaluation of disease risk. Six GAD65-specific recombinant Fabs (rFabs) were cloned from monoclonal antibodies b96.11, DP-C, DP-A, DPD, 144, and 221-442. The binding of GAD65Abs in 61 type 1 diabetic patients to GAD65 was analyzed by competitive radioimmunoassays with the six rFabs to ascertain disease-specific GAD65Ab binding specificities. The median binding was reduced significantly by rFab b96.11 (72%) (P < 0.0001), DP-A (84%) (P < 0.0001), DP-C (84%) (P < 0.0001), 221-442 (79%) (P < 0.0001), and DP-D (80%) (P < 0.0001). The competition pattern in type 1 diabetic patients differed from that in GAD65Ab-positive late autoimmune diabetes in adults (LADA) patients (n = 44), first-degree relatives (n = 38), and healthy individuals (n = 14). Whereas 87 and 72% of the type 1 diabetic sera were competed by rFab b96.11 and DP-C, respectively, only 34 and 26% of LADA patients, 18 and 25% of first-degree relatives, and 7 and 28% of healthy individuals showed competition (P < 0.0001). These findings support the view that type 1 diabetes is associated with disease- and epitope-specific GAD65Abs and supports the notion that the middle epitope is disease associated. These GAD65-specific rFabs should prove useful in predicting type 1 diabetes and in the study of conformational GAD65Ab epitopes.

As a new cement-based composite material, the ultra-high-performance concrete (UHPC) has attracted wide attention because of its excellent mechanical properties and durability; and it has been applied successfully in the engineering field. As an important way to sustain engineering practice, the combination of prefabricated building and UHPC presents a great economic benefit and is worthy of further exploration. Based on the research and application status of UHPC materials in prefabricated construction, the engineering application classifications of UHPC are introduced; the advantages of using UHPC in prefabricated construction are summarized; the progress on UHPC research and its application in prefabricated construction is also summarized; the potential issues on the application of UHPC in prefabricated construction are pointed out; the possible solution strategies and development directions are proposed for promoting UHPC application in prefabricated construction.

Systemic corticosteroids for the treatment of COPD exacerbations decrease treatment failure and shorten the length of hospitalization. However, the optimal dose is unclear.

Li-rich layered oxiges with high initial coulombic efficiency not only have to construct suitable oxygen vacancies, but also require other components with Li-poor structure to stabilize oxygen.

The Nanwenghe Wetlands Reserve in the Yile'huli Mountains is a representative region of the Xing'an permafrost. The response of permafrost to climate change remains unclear due to limited field investigations. Thus, longer-term responses of the ground thermal state to climate change since 2011 have been monitored at four sites with varied surface characteristics: Carex tatowetland (P1) and shrub-C. tatowetland (P2) with a multi-year average temperatures at the depth of zero annual amplitude (TZAA) of −0.52 and −1.19 °C, respectively; Betula platyphylla-Larix gmelinii(Rupr.) Kuzen mixed forest (P3) with TZAAof 0.17 °C, and; the forest of L. gmelinii(Rupr.) Kuzen (P4) with TZAAof 1.65 °C. Continuous observations demonstrate that the ecosystem-protected Xing'an permafrost experienced a cooling under a warming climate. The temperature at the top of permafrost (TTOP) rose (1.8 °C per decade) but the TZAAdeclined (−0.14 °C per decade), while the active layer thickness (ALT) thinned from 0.9 m in 2012 to 0.8 m in 2014 at P1. Both the TTOP and TZAAincreased (0.89 and 0.06 °C per decade, respectively), but the ALT thinned from 1.4 m in 2012 to 0.7 m in 2016 at P2. Vertically detached permafrost at P3 disappeared in summer 2012, with warming rates of +0.42 and + 0.17 °C per decade for TTOP and TZAA, respectively. However, up to date, the ground thermal state has remained stable at P4. We conclude that the thermal offset is crucial for the preservation and persistence of the Xing'an permafrost at the southern fringe.

The protection of historic buildings has drawn increasing attention and usually requires a sound nondestructive testing (NDT) technique. This paper first describes the significance of and the status on the protection of historic structures followed by a summary of common damage and repair measures for such structures. Lastly, the principles, characteristics, and applications of NDT techniques for historic wooden and masonry structures, including ultra-CT testing, stress wave testing, micro-drilling resistance meter, radar detection, and X-ray diffraction, are described and compared. This study concludes by providing a guide for studying the structural damage of historic structures and for the selection of a detection technique.

To explore the ameliorating effects of low‐intensity pulsed ultrasound (LIPUS) on Sprague Dawley rat myelosuppression induced by cell cycle specificity drugs (docetaxel, mitotic phase sensitive; and etoposide, gap 2 phase sensitive). Rats were respectively administered docetaxel (100 mg/kg) or etoposide (110 mg/kg) by intraperitoneal injection for 4 consecutive days. Then the rats were divided randomly into a LIPUS group and a non‐LIPUS group. In the LIPUS group, the right femoral metaphysis of rats was treated by LIPUS (acoustic intensity, 200 mW/cm2; frequency, 0.3 MHz; and duty cycle, 20%) for 20 minutes on 7 consecutive days from day 5. The rats of the non‐LIPUS group were treated without ultrasound output. A blood cell count, an enzyme‐linked immunosorbent assay, a real‐time quantitative polymerase chain reaction, and hematoxylin–eosin staining were applied to detect the results. Low‐intensity pulsed ultrasound significantly promoted the counts of bone marrow nucleated cells, white blood cells, immunoglobulin A (IgA), IgG, granulocyte colony‐stimulating factor, stem cell factor, and intercellular cell adhesion molecule 1 and reduced the counts of vascular cell adhesion molecule 1 whether in the docetaxel or etoposide group (P< .05). Low‐intensity pulsed ultrasound only increased the expression level of IgM in the docetaxel group but decreased the level of interleukin 6 in the etoposide group (P< .05). Low‐intensity pulsed ultrasound has potential to be a noninvasive treatment for myelosuppression caused by different cell cycle–sensitive chemotherapy drugs.

The exploration of highly efficient materials for the degradation of chemical warfare agents has been a longstanding task for preventing human exposure. Herein, we report a series of metal–organic frameworks (MOFs) M-TCPP-La based on metallo-tetra(4-carboxyphenyl)porphyrin and LaIII, which were applied to selectively oxidize 2-chloroethyl ethyl sulfide (CEES, a sulfur mustard simulant) as heterogeneous photocatalysts. After irradiation from a commercial blue light-emitting diode (LED), both superoxide ion and singlet oxygen were generated by M-TCPP-La and involved in selective oxidization of CEES to 2-chloroethyl ethyl sulfoxide (CEESO). Notably, a very short half lifetime (2.5 min) was achieved using Fe-TCPP-La as the photocatalyst. In comparison to currently utilizing singlet oxygen and hydrogen peroxide as oxidizing agents, this work employing both singlet oxygen and superoxide ion represents a new and effective strategy of detoxification of mustard gas.

The common vetch (Vicia sativaL.) is a self-pollinated annual forage legume that is widely distributed worldwide. It has wide adaptability and high nutritional value and is commonly used as an important protein source for livestock feed. However, pod shattering seriously limits the yield of common vetch. To clarify the mechanism of pod shattering in common vetch, the pod walls of three shattering-resistant (SR) accessions (B65, B135, and B392) and three shattering-susceptible (SS) accessions (L33, L170, and L461) were selected for transcriptome sequencing. A total of 17190 differentially expressed genes (DEGs) were identified in the pod wall of B135 and L461 common vetch at 5, 10, 15, 20, and 25 days after anthesis. KEGG analysis showed that “phenylpropanoid biosynthesis” was the most significantly enriched pathway, and 40 structural genes associated with lignin biosynthesis were identified and differentially expressed in B135 and L461 common vetch. We analysed the DEGs in the pod wall of three SR and three SS accessions at 15 days after anthesis, and most of the DEGs were consistent with the significant enrichment pathways identified in B135 and L461 common vetch. The total lignin content of SR accessions was significantly lower than the SS accessions. The present study lays a foundation for understanding the molecular regulatory mechanism of pod shattering related to lignin biosynthesis in common vetch and provides reference functional genes for breeders to further cultivate shattering-resistant common vetch varieties.

S-acylation of proteins allows their association with membranes. Here, we present a protocol for establishing a platform for membrane affinity evaluation of S-acylated proteins in vitro. We describe steps for preparing lipid-maleimide compounds, mCherry-p62 recombinant proteins, and total cellular membranes. We then detail procedures for synthesizing protein-lipid conjugates using lipid-maleimide compounds and recombinant proteins and evaluating the membrane affinity of protein-lipid conjugates.

Polycyclic aromatic hydrocarbons (PAHs) play an important role in the industry, and the development of new materials for the selective separation of PAHs is of great significance. In this work, we report a hexahedral metal-organic cage with low symmetry by subcomponent self-assembly. In this cage, the eight ZnIIcenters adopt an interesting ΛΛ/ΔΔΔΔΔΔ or ΛΛΛΛΛΛ/ΔΔ configuration. This cage with a cavity volume of 520 Å3can bind anthracene, phenanthrene, and pyrene to form 1:1 host-guest complexes, while the bigger triphenylene, chrysene, perylene, and coronene cannot be encapsulated. The binding constant Kaof pyrene is about 1.110 × 103(mol/L)−1,which is more than an order of magnitude larger than that of anthracene and phenanthrene (111 (mol/L)−1, 277 (mol/L)−1, respectively). X-ray structure studies reveal that the pyrene is located in the cavity and stabilized by multiple CH⋅⋅⋅πinteractions. After separation from a mixture of PAHs, pyrene with >96.1% purity can be obtained. This work provides a useful method for the first time for the selective separation of pyrene from PAHs mixture by utilizing a metal-organic cage as the material, making it a useful tool for purifying and separating specific compounds from complex mixtures.

Many observations in and model simulations for northern basins have confirmed an increased streamflow from degrading permafrost, while the streamflow has declined in the source area of the Yellow River (SAYR, above the Tanag hydrological station) on the northeastern Qinghai-Tibet Plateau, West China. How and to what extent does the degrading permafrost change the flow in the SAYR? According to seasonal regimes of hydrological processes, the SAYR is divided into four sub-basins with varied permafrost extents to detect impacts of permafrost degradation on the Yellow River streamflow. Results show that permafrost degradation may have released appreciable meltwater for recharging groundwater. The potential release rate of ground-ice melt-water in the Sub-basin 1 (the headwater area of the Yellow River (HAYR), above the Huangheyan hydrological station) is the highest (5.6 mm per year), contributing to 14.4% of the annual Yellow River streamflow at Huangheyan. Seasonal/intra- and annual shifts of streamflow, a possible signal for the marked alteration of hydrological processes by permafrost degradation, is observed in the HAYR, but the shifts are minor in other sub-basins in the SAYR. Improved hydraulic connectivity is expected to occur during and after certain degrees of permafrost degradation. Direct impacts of permafrost degradation on the annual Yellow River streamflow in the SAYR at Tanag, i.e., from the meltwater of ground-ice, is estimated at 4.9% that of the annual Yellow River discharge at Tanag, yet with a high uncertainty, due to neglecting of the improved hydraulic connections from permafrost degradation and the flow generation conditions for the ground-ice meltwater. Enhanced evapotranspiration, substantial weakening of the Southwest China Autumn Rain, and anthropogenic disturbances may largely account for the declined streamflow in the SAYR.

Alfalfa (Medicago sativaL.) is a globally important forage crop. It also serves as a vegetable and medicinal herb because of its excellent nutritional quality and significant economic value. Multi-omics data on alfalfa continue to accumulate owing to recent advances in high-throughput techniques, and integrating this information holds great potential for expediting genetic research and facilitating advances in alfalfa agronomic traits. Therefore, we developed a comprehensive database named MODMS (multi-omics database of M. sativa) that incorporates multiple reference genomes, annotations, comparative genomics, transcriptomes, high-quality genomic variants, proteomics, and metabolomics. This report describes our continuously evolving database, which provides researchers with several convenient tools and extensive omics data resources, facilitating the expansion of alfalfa research. Further details regarding the MODMS database are available at https://modms.lzu.edu.cn/.

Dynamics of the frozen ground are key to understand the changes of eco-environment in cold regions, especially for areas with limited field observations. In this study, we analyzed the spatial and temporal variations of the ground surface freezing and thawing indices from 1900 to 2017 for the upper Brahmaputra River (also called the Yarlung Zangbo River in China) Basin (UBRB), southwestern Tibetan Plateau, with the air freezing and thawing indices using the University of Delaware (UDEL) monthly gridded air temperature dataset. The abrupt change years for air freezing index (AFI) and ground surface freezing index (GFI) were detected in 1999 and 2002, respectively, and for both air thawing index (ATI) and ground surface thawing index (GTI) were 2009. With the air temperature rising at a rate of 0.006 °C per year over 1900–2017, the AFI and GFI decreased at a rate of −0.1 °C d per year, while the ATI and GTI increased at rates of 0.3 and 0.5 °C d per year before the abrupt change year, respectively; all changing trends of freezing/thawing indices increased after the abrupt year, which was −2.9, −0.8, 7.3, and 21.7 °C d per year for the AFI, GFI, ATI, and GTI, respectively. We utilized the surface frost number model to obtain the dynamics of the frozen ground over the UBRB. When the empirical coefficient of Ewas assigned to 1.2, the simulated frozen ground occupied about 53.2% of the whole UBRB in the 1990s, which agreed well with the existing permafrost map published in 1996. The area of frozen ground accounts for 51.5%–54.5% of the UBRB during 1900–2017. This result may facilitate further studies of the multi-interactions among the frozen ground and relevant eco-environment, such as the air-ground surface energy exchange, hydrological cycles, and changes of the active layer thickness over the UBRB.

Under a warming climate, degrading permafrost profoundly and extensively affects arctic and alpine ecology. However, most existing relevant studies are more focused on the hydrothermal impacts of vegetation on the underlying permafrost, or symbiosis between vegetation and permafrost, only very few on ecological impacts of permafrost degradation. Additionally, there are much more pertinent investigations in arctic and boreal regions than those in alpine and high-plateau regions at mid- and low latitudes. This study emphasizes on the impact mechanisms of permafrost degradation on vegetation both at high and mid-to low latitudes, addressing vegetation succession trajectories and associated changes in soil hydrology and soil nutrient above degrading permafrost. Permafrost degradation influences vegetation by altering soil hydrology, soil biogeochemical processes and microbial communities, which further improve soil nutrient availability. Furthermore, under a warming climate, vegetation may take two successional trajectories, towards a wetter or drier ecosystem within a certain time period, but to a drier ecosystem in the end upon the thaw of permafrost in case of permeable soils and good drainage. Thus, with rapidly developing remote-sensing and other space- and ground-based and air-borne observational networks and numerical predictive models, the impacting mechanisms of permafrost degradation on vegetation should be timely and better monitored, evaluated and modeled at desired spatiotemporal scales and resolutions by terrestrial or integrated ecosystem models.

Nanoparticles offer great opportunities for precision medicine. However, the use of nanoparticles as smart photosensitizers that target tumor biomarkers and are responsive to the tumor microenvironment has yet to be explored. Herein, prostate cancer (PCa)-selective theranostic gold nanoparticles (AuNPs) for precise cancer imaging and therapy are developed. Silicon phthalocyanine, Pc158, was synthesized and deactivated by conjugating it to AuNPs viaa biocleavable linker. In vitroand in vivo, the targeted AuNPs show excellent selectivity for PSMA-positive tumor cells. Triggered release of the therapeutic, Pc158, followed by sequential photodynamic therapy (PDT) results in significant inhibition of tumor growth. Further, we demonstrate that multiple sequential PDT greatly enhances nanoparticle uptake and therapeutic efficacy. PSMA is highly expressed in the neovasculature of most other solid tumors in humans, as well as PCa, making this approach of great practical interest for precision PDT in a wide range of cancers.