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By using a rigid bulky carboxylic ligand α-cyanocinnamic acid (CCA), a dinuclear dysprosium (III) complex [Dy2(CCA)6(MeOH)4] (1) was synthesized. Single crystal X-ray crystallography reveals that the two eight-coordinate dysprosium ions are bridged by four deprotonated carboxyl groups, forming a centrosymmetric paddle-wheel-like structure. Dynamic magnetic property measurements indicate that complex 1displays field-induced slow magnetic relaxation. The temperature-dependent relaxation times can be fitted using Orbach and Raman processes with parameters of n = 2.8 (2), C = 27 (8) s−1/Kn, τ0 = 5 (2) × 10−10 s and Ueff = 40 (3) cm−1. Magnetic studies on the diamagnetic YIII-diluted analogue [Dy0.206Y1.794(CCA)6(MeOH)4] (2) reveal its slow magnetic relaxation behavior without external dc field and the antiferromagnetic coupling between the DyIIIions in 1. Fits on the obtained relaxation times of 2lead to the parameters of n = 4.5 (3), C = 0.7 (2) s−1/Kn, τ0 = 2.8 (2) × 10−9 s and Ueff = 38 (2) cm−1. The results suggest that slow magnetic relaxation originates from the single-ion relaxation of DyIIIions. Moreover, the diamagnetic dilution can suppress other fast relaxation pathways at low temperature, on account of the elimination of magnetic coupling and dipolar interaction. Ab initiocalculations were then performed on the single DyIIIion species {YDy} and indicate that the first excited Kramers doublets (KDs) lie at ca.76 cm−1, which is slightly higher than the experimental Ueffvalue. The intramolecular magnetic interactions were also calculated and indicate a weak ferromagnetic dipole-diploe magnetic interaction and an antiferromagnetic exchange coupling.

With the increased deployment of power modules in demanding conditions, sintering materials, especially composite sintering materials, have raised growing interest due to their cost-effectiveness and suitability. Therefore, this study explores the viability of Cu–Ag composite sintering material, focusing on solvent influence through microstructure and mechanical behavior analysis. Micron-sized particle-based Cu–Ag composite pastes were designed and compared using eight solvents (four epoxy-free and four epoxy-added) based on fluidity and thermal stability. The sintered joints' performance, assessed through shear strength analysis, showed comparable values to pure silver sintering for both epoxy-free and epoxy-added samples. Optimized samples from each solvent system underwent reliability analysis, demonstrating that Cu–Ag joints with epoxy resin exhibited significantly higher shear strength after high-temperature storage and thermal cycling tests. Micromorphology and elemental composition analysis revealed differences in aging mechanisms, primarily attributed to variations in porosity due to oxide formation and pore filling by epoxy resin under different solvent systems. Further nanoindentation characterization of micromechanical properties, including hardness, modulus, and creep properties, during high-temperature aging, established constitutive models for insights into reliability evolution. In conclusion, the optimized epoxy-added Cu–Ag sintered joints proposed in this study demonstrated exceptional reliability and acceptable micromechanical properties, presenting a promising option for high-temperature power packaging.

A new, stable and scalable reagent based on a sulfoxide skeleton for direct deuteriodifluoromethylthiolation has been developed. The reagent displays excellent reactivities toward Tf2O promoted C–H deuteriodifluoromethylthiolation of electron-rich arenes, indoles, alkenes, and intramolecular lactonization of 2-alkynylbenzoates. Moreover, high deuteration rates and good to excellent yields were achieved under metal-free reaction conditions. As a result, a wide range of deuteriodifluoromethylthilolated compounds were prepared, enabling further applications in drug discovery.

With the rise of probiotics fermentation in food industry, fermented foods have attracted worldwide attention. In this study, protective effects of Rosa roxburghii& edible fungus fermentation broth (REFB) on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated. Results showed that REFB could improve the immune organ index, and promote the proliferation and differentiation of splenic T lymphocytes. In addition, it attenuated intestinal mucosal damage and improved intestinal cellular immunity. REFB administration also up-regulated the expression of IL-4, INF-γ, TNF-α, T-bet and GATA-3 mRNA in small intestine. Furthermore, administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus, such as Bacteroides.It also increased the production of fecal short-chain fatty acids. These indicate that REFB has the potential to improve immunity, alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.

AbstractChina’s National Sliding Center will hold the bobsleigh, skeleton and luge events during the Beijing 2022 Winter Olympics. It is the first and only bobsleigh-luge-skeleton track in China; the only track set on a mountain’s south face in the world and the Beijing Winter Olympics’ project poses the greatest design and construction difficulties. The whole track measures nearly 2000 m in length with a structural system consisting of hyperboloid concrete shell with pendulum column. Along with specially shaped beams made of laminated wood, including 210 large single-sided cantilevers, a new-type wood-steel composite structure is used for the upper sunshade. The design and construction of this sliding center’s main facilities, as well as some relevant new-type technologies are introduced and then analyzed in this paper.

ABSTRACT There is a great interest in developing and implementing new technologies for real-time evaluation of the uniformity of the construction of asphalt layers. In this study, the researchers developed [...]

Vibrio parahaemolyticusis a foodborne pathogenic bacterium commonly found in seafood. The emergence of drug-resistant strains poses a threat to human public health and economic development. Therefore, there are increasing needs to develop new technologies in controlling multidrug-resistant V. parahaemolyticusstrains and to evaluate their practical efficiency in seafood or mariculture. In this study, we screened two genetically related V. parahaemolyticusphages, F23s2 and H256D1, which belonged to the siphoviridaefamily and podoviridaefamily, respectively. They showed 97.13% and 96.13% identity with Vibriophage vB_Vpap_MGD1, respectively. Both phages were stable at pH 4–11 and displayed temperature tolerance (<70°C). Meanwhile they showed a broad host spectrum for multidrug-resistant V. parahaemolyticus, and Phage F23s2 lysed 16 of all 23 V. parahaemolyticusstrains, while phage H256D1 lysed 10 strains. Phage F23s2 and H256D1 had a good inhibitory effect on V. parahaemolyticusin shrimp meat. Compared with the negative group, the bacterial amount of experimental group with phage F23s2 decreased by 1.60 log colony-forming unit (CFU)/mL at 12 h. For phage H256D1, the bacterial concentration of shrimp meat contaminated with V. parahaemolyticusH256 increased to 5.65 log CFU/mL at 72 h, while the concentration of the experimental group in presence of phage H256D1 was 3.58 log CFU/mL. All live clams infected with V. parahaemolyticusdied after 96 h in the absence of phage, whereas clams with phage F23s2 and H256D1 still had a survival rate of 12% and 4%, respectively. Understanding the gene function and biology of phages facilitates its application for control of V. parahaemolyticuscontamination worldwide.

The 3-D sparse-view computed laminography (CL) is an important research issue due to its considerable potential in lowering costs. To solve the artifacts and noise caused by sparse-view scanning, the total variation (TV) method is widely used. However, TV only utilizes the prior information of the reconstructed image itself. Therefore, the prior-image-based reconstruction method (PIBR) is proposed to reduce the artifacts by using a prior image. In this study, we proposed a 3-D CL method based on the final prior image and TV for sparse-view scanning, which is divided into two subproblems corresponding to two solution steps: the novel PIBR step and the denoising step. In the first step, we devise the final prior image and its corresponding prior mask to ensure the effectiveness of the PIBR. The final prior image is obtained based on the prior images, which are reconstructed from two different oblique angle projections. The prior mask is a binary mask, which is used to record the position of the prior image information. Then, the denoising step is based on the TV minimization method using the split-Bregman (SB) frame. Soft shrinkage operations and fast Fourier transform (FFT) are used to efficiently implement the SB frame. Compared with several iterative reconstruction methods, the experimental results demonstrate the effectiveness of the proposed method in terms of preserving edges, suppressing interslices aliasing and denoising.

3-Monochloropropane-1,2-diol esters (3-MCPDE) are common food contaminants mainly formed in the edible oil refining process. Due to their potential hazards, 3-MCPDE has become a widespread food safety concern. In this study, CiteSpace and VOSviewer were used to conduct a bibliometric analysis on the 3-MCPDE research papers collected in the Web of Science Core Collection from 1998 to 2022. The results showed that the number of research publications on 3-MCPDE has increased rapidly since 2010. Analysis of the hotspots in 3-MCPDE studies showed that more attention has been paid to the exposure assessment, formation mechanism, detection methods, mitigation methods and toxicity, and toxicology of 3-MCPDE. Finally, the future trends of research on 3-MCPDE were analyzed and proposed. The mitigation methods and toxicology studies of 3-MCPDE are still the research hotspots in the future. In addition, nutritional intervention for 3-MCPDE toxicity will be an emerging trend.

Recently, nanoformulations have been widely applied in the delivery of organic photothermal agents (OPTAs) for cancer therapy to prolong blood circulation or improve tumor-targeting capacity. However, the systematic evaluations of their effects on the photothermal behavior of OPTAs are limited, especially for different types of nanoparticle systems. Herein, we prepared two kinds of nanoparticles (BSA and PEG nanoparticles (NPs)) to load an OPTA, a cyanine photosensitizer (IR780-O-TPE), and investigated their photothermal response, organelle targeting, and in vivo therapeutic efficacy. Due to different assembly forms, the two NPs showed distinct morphological changes after exposure to laser or hyperthermia. Under laser irradiation at 808 nm, BSA NPs could release IR780-O-TPE more efficiently than PEG NPs. We speculate that this phenomenon is probably caused by dual-responsive release of IR780-O-TPE from BSA NPs against light and hyperthermia. Moreover, IR780-O-TPE/BSA NPs were highly mitochondria-targeting and therefore displayed significant inhibition of cell viability. In contrast, IR780-O-TPE/PEG NPs were “shell–core” nanostructures and more stable under laser stimulation. As a consequence, the mitochondria-targeting and anticancer photothermal therapy by IR780-O-TPE/PEG NPs was less obvious. This study revealed the significance of nanocarrier design for OPTA delivery and demonstrated that BSA NPs could release IR780-O-TPE more effectively for efficient photothermal therapy. We also believe that the dual-responsive release of OPTAs from NPs can provide an effective strategy to promote anticancer photothermal treatment.

With growing concerns about travel demand management practices in overcrowded metro systems, it is considered that time-dependent pricing strategies are effective for dealing with the crowding occurring during peak commuting hours. In this study, a bi-level optimisation framework is used to consider the peak avoidance behaviour of commuters in the development of time-dependent pricing strategies. The behavioural sensitivity of commuters to pricing factors is investigated in terms of departure time and mode shift decisions based on a stated preference survey conducted in Beijing, China. The proposed bi-level programming model comprises a multi-objective optimisation model at the upper level and a nested logit-based stochastic user equilibrium model at the lower level. Based on an empirical case study of the Batong line in Beijing metro, nine optimal time-dependent pricing strategies are tailored by representative decision preferences, yielding up to 13.97% decrease in the peak ridership during rush hours.

The estimation of State of Health (SOH) for battery packs used in Electric Vehicles (EVs) is a complex task with significant importance, accompanied by several challenges. This study introduces a data-fusion model approach to estimate the SOH of battery packs. The approach utilizes dual Gaussian Process Regressions (GPRs) to construct a data-driven and non-parametric aging model based on charging-based Aging Features (AFs). To enhance the accuracy of the aging model, a noise model is established to replace the random noise. Subsequently, the state-space representation of the aging model is incorporated. Additionally, the Particle Filter (PF) is introduced to track the unknown state in the aging model, thereby developing the data-fusion-model for SOH estimation. The performance of the proposed method is validated through aging experiments conducted on battery packs. The simulation results demonstrate that the data-fusion model approach achieves accurate SOH estimation, with maximum errors less than 1.5%. Compared to conventional techniques such as GPR and Support Vector Regression (SVR), the proposed method exhibits higher estimation accuracy and robustness.

•High expression of AKR1C3 predicts poor prognosis in SCLC.•AKR1C3 promotes proliferation, migration and inhibits apoptosis in SCLC.•AKR1C3 regulates tumor immune microenvironment in SCLC.•AKR1C3 mediates therapy resistance through promoting tumor angiogenesis and inducing EMT process.

Root system architecture is influenced by gravity. How the root senses gravity and directs its orientation, so-called gravitropism, is not only a fundamental question in plant biology but also theoretically important for genetic improvement of crop root architecture. However, the mechanism has not been elucidated in most crops. We characterized a rice agravitropism allele, wavy root 1(war1), a loss-of-function allele in OsPIN2, which encodes an auxin efflux transporter. With loss of OsPIN2function, war1leads to altered root system architecture including wavyroot, larger root distribution angle, and shallower root system due to the loss of gravitropic perception in root tips. In the war1mutant, polar auxin transport was disrupted in the root tip, leading to abnormal auxin levels and disturbed auxin transport and distribution in columella cells. Amyloplast sedimentation, an important process in gravitropic sensing, was also decreased in root tip columella cells. The results indicated that OsPIN2controls gravitropism by finely regulating auxin transport, distribution and levels, and amyloplast sedimentation in root tips. We identified a novel role of OsPIN2in regulating ABA biosynthesis and response pathways. Loss of OsPIN2function in the war1resulted in increased sensitivity to ABA in seed germination, increased ABA level, changes in ABA-associated genes in roots, and decreased drought tolerance in the seedlings. These results suggest that the auxin transporter OsPIN2not only modulates auxin transport to control root gravitropism, but also functions in ABA signaling to affect seed germination and root development, probably by mediating crosstalk between auxin and ABA pathways.

The nucleic acid G-quadruplex (G4) has emerged as a promising therapeutic target for a variety of diseases such as cancer and neurodegenerative disease. Among small-molecule G4-binders, pyridostatin (PDS) and its derivatives (e.g., PyPDS) exhibit high specificity to G4s, but the structural basis for their specific recognition of G4s remains unknown. Here, we presented two solution structures of PyPDS and PDS with a quadruplex–duplex hybrid. The structures indicate that the rigid aromatic rings of PyPDS/PDS linked by flexible amide bonds match adaptively with G-tetrad planes, enhancing π–π stacking and achieving specific recognition of G4s. The aliphatic amine side chains of PyPDS/PDS adjust conformation to interact with the phosphate backbone viahydrogen bonding and electrostatic interactions, increasing affinity for G4s. Moreover, the N–H of PyPDS/PDS amide bonds interacts with two O6s of G-tetrad guanines viahydrogen bonding, achieving a further increase in affinity for G4s, which is different from most G4 ligands. Our findings reveal from structural perspectives that the rational assembly of rigid and flexible structural units in a ligand can synergistically improve the selectivity and affinity for G4s through spatial selective and adaptive matching.

Interval-censored failure time data frequently occur in medical follow-up studies among others and include right-censored data as a special case. Their analysis is much difficult than the analysis of the right-censored data due to their much more complicated structures and no partial likelihood. This article presents a variational Bayesian (VB) approach for analyzing such data under a proportional hazards model. The VB approach obtains a direct approximation of the posterior density. Compared to the Markov chain Monte Carlo (MCMC)-based sampling approaches, the VB approach achieves enhanced computational efficiency without sacrificing estimation accuracy. An extensive simulation study is conducted to compare the performance of the proposed methods with two main Bayesian methods currently available in the literature and the classic proportional hazards model and indicates that they work well in practical situations. [ABSTRACT FROM AUTHOR]

Heat-induced hazard 5-hydroxymethylfurfural (5-HMF) is detected in various baked foods. Although catechins and polysaccharides could inhibit 5-HMF, their inhibition efficiency was limited when used alone. Therefore, this study aimed to explore the synergistic inhibitory effect of catechins and polysaccharides on 5-HMF in biscuits. Epigallocatechin gallate (EGCG), chitosan, and sodium alginate were screened out due to their superior maximum inhibition rates (55.90%, 67.20%, and 66.62%, respectively), and their synergism were investigated by isobologram analysis. The interaction index (γ) varies inversely with the synergism. When γ < 1 or >1, it represented synergism or antagonism, respectively. The results showed that the synergism between EGCG and chitosan in the ratio of 1:1 (γ = 0.221) was better than that of 1:2 and 1:3 (γ = 0.671 and 0.523, respectively). Moreover, EGCG and sodium alginate only showed synergism in the ratio of 1:1 (γ = 0.358), while antagonism was observed in the ratios of 1:2 and 1:3 (γ = 1.12 and 1.25, respectively).The optimum inhibition rate (54.57%) on 5-HMF was reached when EGCG (0.1 g/kg) combined with sodium alginate (0.1 g/kg). Compared with those used alone, the co-addition of EGCG and chitosan could decrease the dosage of EGCG to 1/5 and that of chitosan to 1/7, indicating a significant improvement in inhibit efficiency. Finally, the concentration of inhibitors correlated negatively with 5-HMF content and browning index of biscuits, suggesting they might inhibit 5-HMF by hindering Maillardreaction or caramelization reaction. This study provided an efficient and cost-effective solution for 5-HMF control in baking products.

Through a series of experiments of dynamic deformation and destruction under time series loading on an indoor real model bridge, Ground-based real-aperture radar interferometry (GB-InRAR) discovered that before the structure of the bridge was damaged, its amplitude and acceleration increased with the increase of load; After its structure was damaged or cracked, such dynamic characteristics as natural frequency, damping ratio, stiffness and bearing capacity decreased obviously. Moreover, GB-InRAR dynamic load monitoring of Xiangtan Railway Bridge and Inter-city Railway Bridge. In the process of vehicle dynamic load, such important parameters as bridge deflection, natural frequency and damping ratio conform to the bridge loading procedures and dynamic characteristics. The results show that the GB-InRAR can accurately measure the deflection changes, natural vibration frequency and spectrum characteristics of bridges, and it can be used as effective means of the dynamic characteristics analysis in the safety detection and health evaluation of bridges.

Since the 2019 novel Coronavirus disease (COVID-19) spread across the globe, risks brought by the pandemic set in and stock markets tumbled worldwide. Amidst the bleak economic outlook, investors’ concerns over the pandemic spread rapidly through social media but wore out shortly. Similarly, the crash only caused a relatively short-lived bear market, which bottomed out and recovered quickly. Meanwhile, technology stocks have grabbed the spotlight as the digitally advanced sectors seemed to show resilience in this Coronavirus-plagued market. This paper aims to examine market sentiments using social media to predict the stock market performance before, during and after the March 2020 stock market crash. In addition, using the Organisation for Economic Co-operation and Development Taxonomy of Sectoral Digital-intensity Framework, we identified market sectors that have outperformed others as the market sentiment was impacted by the unfolding of the pandemic. The daily stock performance of a usable sample of 1619 firms from 34 sectors was first examined via a combination of hierarchical clustering and shape-based distance measure. This was then tested against a time series of daily price changes through augmented vector auto-regression. Results show that market sentiments towards the pandemic have significantly impacted the price differences. More interestingly, the stock performance across sectors is characterized by the level of digital intensity, with the most digitally advanced sectors demonstrating resilience against negative market sentiments on the pandemic. This research is among the first to demonstrate how digital intensity mitigates the negative effect of a crisis on stock market performance.

Online peer-to-peer platforms have been widely utilized to facilitate sharing vast amounts of user-generated content (UGC) in the hospitality industry. However, research on the cultural impacts of the broad spectrum of UGC remains nascent and limited. This study therefore elaborates how the hospitality service dimensions that are reflected in UGC both predict service evaluation and are contingent on a reviewer’s prevailing culture. We analyzed a usable sample of 9,257 hotel reviews from 148 countries with latent Dirichlet allocation and aspect-based sentiment analysis algorithms to identify the top service features and corresponding polarity scores. Machine learning identified three dimensions of hospitality service quality: adaptability, reliable delivery, and tangibles. These three dimensions predict customers’ overall hotel ratings, and the magnitude and direction of their effects depend on alignments of cultural orientations. Following Hofstede’s cultural dimensions, reliable delivery and tangibles align with individualism and uncertainty avoidance cultures. Adaptability aligns with power distance, masculinity, long-term orientation, and indulgence cultures.

With considerable investments, mainly from local government budgets, the construction and operation of urban rail transit (URT) can exert significant spillover effects on the surrounding land use and land prices. In particular, China’s local governments are actively committed to developing their URT systems and promoting large-scale transit-oriented development (TOD) projects under the public land leasing policy. However, the connection between the land premium effects and TOD policy and practice is still lacking, particularly in the local government contexts, which exhibit significant policy and spatial heterogeneity. Thus, this research represents an attempt to better address this issue using the city of Ningbo as a case study. First, the premium effects of URT on land prices are examined, after which three crucial policy insights (land value capture [LVC], public–private cooperation [PPC], and urban regeneration) are proposed to enhance the effectiveness and efficiency of TOD, demonstrating its strong connection with the potential premium effects. The findings demonstrate that (1) local governments have adopted different innovative policies—with the ambition—to implement LVC; (2) assisted by PPC, the local rail transit authority can significantly amplify the premium effects, although it must still address the fair distribution of premiums across multiple stakeholders; and (3) transit-oriented urban regeneration can significantly influence land prices/land rents and subsequently generate significant gentrification, which will be further addressed by the TOD policy and practice.

Background: Tea contains many polyphenols with biological properties such as antithrombosis and antioxidation. Recent observational studies on tea consumption concerning cerebral hemorrhage risk have reported inconsistent results. This meta-analysis aimed to summarize the accumulated evidence on the association between tea consumption and cerebral hemorrhage risk. Methods: Web of Science, PubMed, Embase, and Scopus databases were searched to identify relevant studies through December 2021. Relative risks (RRs) or odds ratios (ORs) from observational studies were synthesized. Results: Ten studies involving over 721,827 participants were included. Higher tea consumption was correlated with a 23% (RR = 0.77; 95% CI 0.66–0.89) lower risk of cerebral hemorrhage. Subgroup meta-analyses indicated higher tea consumption was beneficial in preventing cerebral hemorrhage risk for green tea, alcohol-adjusted, fruit/vegetables-adjusted, and physical activity-adjusted subgroups, respectively (P&lt; 0.01). Dose–response analysis indicated each one-cup (120 ml/cup) increment in tea or green tea intake/day was correlated with an average of 2% (RR = 0.98, 95% CI 0.976–0.990), or 6% (RR = 0.94; 95% CI 0.92–0.97) lower cerebral hemorrhage risk. Conclusions: This study suggests that daily tea consumption is related to a lower risk of cerebral hemorrhage among adults. Green tea consumption appears to be more beneficial in preventing cerebral hemorrhage. Physical activity, fruit/vegetables, and alcohol may affect the relationship between tea consumption and hemorrhagic stroke. Future studies should investigate the interplay of tea with these factors.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The relationship between the 5-hydroxytryptamine transporter gene-linked polymorphic region (5-HTTLPR) and depression in Parkinson's disease (PD) has remained controversial. Therefore, we conducted this meta-analysis to evaluate the relationship between 5-HTTLPR polymorphisms and depression in PD. Relevant online databases were searched for cross-sectional, case–control or cohort studies examining relations between 5-HTTLPR polymorphisms (S/L) and the risk of developing depression of PD using a meta-analysis. Odd ratios (ORs) of 5-HTTLPR polymorphisms (S/L allele genotype) were calculated between depression in PD and PD for each study. Five observational studies were identified. Overall ORs for 5-HTTLPR S-Allele genotype was 1.98 (95% CI 0.92–4.26) in the dominant model, 1.43 (95% CI 1.08–1.90) in the recessive model, 2.64 (95% CI 1.01–6.88) in the additive model, independently. The overall ORs of S-Allele genotype was 1.51 (95% CI 0.63–3.64) for the Caucasian subgroup, and 1.44 (95% CI 1.05–1.98) for the non-Caucasian subgroup in the recessive model. This meta-analysis indicates that the 5-HTTLPR genotype (S/S-Allele) is correlated with an increased depression risk in PD, and this highlights the needs for these people to take some effective approaches (if any) in prevention of depression of PD before its onset.

Organic pollutants in aqueous solutions may potentially be adsorbed on biochar. In this study, biochar was derived from the pyrolysis of chitosan at 800°C. The removal rate of 2,4-dichlorophenol (DCP) exceeded 80%. Investigations by Fourier transform infrared spectroscopy and Brunauer– Emmett–Teller indicated that the adsorption of organic pollutants on biochar tends to be a physical process. The optimized pH was 5. All three isotherm models involved (Freundlich, Koble–Corrigan, and Henry) could describe the adsorption process of 2,4-DCP well on chitosan-biochar, which was non-uniform surface adsorption in a diluted solution. The adsorption was an endothermic process. It took 40 min to reach the adsorption equilibrium, and kinetics of the Elovich equation and intraparticle diffusion (IPD) model indicated that the adsorption rate at the rapid adsorption stage was simultaneously controlled by surface diffusion and IPD and that at slow adsorption stage was controlled by surface diffusion. The ionic strengths suggested that electrostatic interaction was not the dominant mechanism during this process.

The response of plant functional diversity to external disturbances not only effectively predicts changes in the ecosystem but it also reflects how plant communities use external environmental resources. However, research on how different herbivore assemblages affect plant functional diversity is limited. Therefore, this study systematically explored the effects of three typical herbivore assemblages (yak grazing, Tibetan sheep grazing, and mixed grazing by yaks and Tibetan sheep) on species richness, plant functional diversity, and soil physicochemical properties in alpine grasslands on the Qinghai-Tibet Plateau. This study further investigated the primary mechanisms driving the changes in plant functional diversity. The results indicate four key aspects of this system: (1) Grazing significantly enhanced plant functional diversity, particularly when the mixed grazing by yaks and Tibetan sheep was applied at a ratio of 1:2. This ratio showed the most substantial improvement in the functional dispersion index and Rao's quadratic entropy index. (2) Compared to enclosed treatments, grazing increased species richness and β-diversity, contributing to higher plant functional diversity. (3) Grazing treatments affected various plant traits, such as reducing plant community height and leaf thickness while increasing specific leaf area. However, the impact on plant functional diversity was most pronounced under the mixed grazing by yaks and Tibetan sheep at a ratio of 1:2. (4) Species α-diversity was positively correlated with plant functional diversity. Changes in plant functional diversity were primarily regulated by variations in soil physicochemical properties. Specifically, increases in soil available nitrogen significantly promoted changes in plant functional diversity, while increases in soil available potassium and bulk density had a significant inhibitory effect on these changes. Long-term grazing significantly reduced the height of plant communities in alpine meadows, while a balanced mixture of yak and Tibetan sheep grazing, especially at a ratio of 1:2, enhanced plant functional diversity the most. This suggests that, under these conditions, the use of external environmental resources by the plant community is optimized.

Using the on-the-fly machine learning force field, simulations were performed to study the atomic structure evolution of the liquid-Al/solid-TiB2interface with two different terminations, aiming to deepen the understanding of the mechanism of TiB2as nucleating particles in an aluminum alloy. We conducted simulations using MLFF for up to 100 ps, enabling us to observe the interfacial properties from a deeper and more comprehensive perspective. The nucleation potential of TiB2particles is determined by the formation of various ordered structures at the interface, which is significantly influenced by the termination of the TiB2(0001) surface. The evolution of the interface during heterogeneous nucleation processes with different terminations is described using structural information and dynamic characteristics. The Ti-terminated surface is more prone to forming quasi-solid regions compared to the B-termination. Analysis of mean square displacement and vibrational density of states indicates that the liquid layer at the Ti-terminated interface is closer in characteristics to a solid compared to the B-terminated interface. We also found that on the TiB2(0001) surface different terminations give rise to distinct ordered structures at the interfaces, which is ascribed to their different diffusion abilities.

Lymphocyte activation gene 3 (LAG-3) has attracted much attention as a potentially valuable immune checkpoint. Individual identification of LAG-3 expression at screening and during treatment could improve the successful implementation of anti-LAG-3 therapies. HuL13 is a human IgG1 monoclonal antibody that binds to the LAG-3 receptor in T cells. Here, we used [89Zr]Zr-labeled HuL13 to delineate LAG-3+T-cell infiltration into tumors via positron emission tomography (PET) imaging. A549/LAG-3 cells, which stably express LAG-3, were generated by infection with lentivirus. The uptake of [89Zr]Zr-DFO-HuL13 in A549/LAG-3 cells was greater than that in the negative control (A549/NC) cells at each time point. The equilibrium dissociation constant (Kd) of [89Zr]Zr-DFO-HuL13 for the LAG-3 receptor was 8.22 nM. PET imaging revealed significant uptake in the tumor areas of A549/LAG-3 tumor-bearing mice from 24 h after injection (SUVmax = 2.43 ± 0.06 at 24 h). As a proof of concept, PET imaging of the [89Zr]Zr-DFO-HuL13 tracer was further investigated in an MC38 tumor-bearing humanized LAG-3 mouse model. PET imaging revealed that the [89Zr]Zr-DFO-HuL13 tracer specifically targets human LAG-3 expressed on tumor-infiltrating lymphocytes (TILs). In addition to the tumors, the spleen was also noticeably visible. Tumor uptake of the [89Zr]Zr-DFO-HuL13 tracer was lower than its uptake in the spleen, but high uptake in the spleen could be reduced by coinjection of unlabeled antibodies. Coinjection of unlabeled antibodies increases tracer activity in the blood pool, thereby improving tumor uptake. Dosimetry evaluation of the healthy mouse models revealed that the highest absorbed radiation dose was in the spleen, followed by the liver and heart wall. In summary, these studies demonstrate the feasibility of using the [89Zr]Zr-DFO-HuL13 tracer for the detection of LAG-3 expression on TILs. Further clinical evaluation of the [89Zr]Zr-DFO-HuL13 tracer may be of significant help in the stratification and management of patients suitable for anti-LAG-3 therapy.

Near-infrared (NIR) fluorescent probes can deeply penetrate through tissues with little damage. To facilitate image-guided theranostics, researchers usually apply a desired amount of photosensitizers to achieve effective photothermal responses. However, these probes could easily suffer from low photostability and aggregated-caused quenching effect in high concentrations. In this paper, the rational incorporation of an aggregated-induced emission (AIE) unit into the structure of heptamethine cyanine IR-780 is reported. Using tetraphenylethene (TPE) as an AIE core, we synthesize three TPE-modified IR-780 probes (IR-780 AIEgens) via different linkages. The IR-780 derivatives all show enhanced AIE features, in which the probe with an ether linkage (IR780-O-TPE) is superior in rapid cell uptake, high targeting capacity, and good photostability. Moreover, IR780-O-TPE exhibits the strongest cytotoxicity to HeLa cells (IC50= 3.3 μM). The three IR-780 derivatives displayed a photothermal response in a concentration-dependent manner, in which IR-780 AIEgens are more cytotoxic than IR-780, with IC50of 0.3 μM under 808 nm laser irradiation. In tumor-bearing mice, the optimal probe IR780-O-TPE also showed a more effective photothermal response than IR-780. By illustrating the relationship between aggregation state with photophysical properties, cell imaging, and cytotoxicity, this work is helpful in modulating NIR-based photosensitizers into AIE features for efficient image-guided theranostics.

In this study, three amorphous B4C structures (α-B12CCC, α-B11Ce-CBC, α-B11Cp-CBC) were modeled with W(110), W(200) and W(211) layers to establish W/α-B4C interfaces. The interface characteristics, such as the adhesion work, electronic structure, and tensile mechanical properties, was calculated using the first-principles method. In order to precisely investigate the role of C atoms in interfacial bonding, the properties of the interfaces formed between W and α-B11Cp-CBC with B-top and C-top (labeled as α-Btop-B11Cp-CBC and α-Ctop-B11Cp-CBC) was also studied respectively. It reports that W/α-B11Cp-CBC interfaces obtain the highest adhesion work, where W(200)/α-B11Cp-CBC interface has the most robust atomic bonding ability. The chemical bonding at the interface consists of ionic bonds, which makes it easier to form a stable interfacial structure. However, the reconstruction of W atoms in the W(200)/α-B11Cp-CBC interface occurred as the strain increased, while W(110)/α-B11Cp-B4C maintained excellent structural stability and toughness. W(110)/α-Btop-B11Cp-CBC and W(110)/α-Ctop-B11Cp-CBC interfaces performed excellent tensile strength of 26.7 GPa and 27.4 GPa, respectively, corresponding strains were 24 % and 16 %. The W-C bonding in the W(110)/α-Ctop-B11Cp-CBC interface significantly reduces its plasticity. Therefore, W(110)/α-Btop-B11Cp-CBC interface combines outstanding toughness and plasticity with maximum tensile strength. The tensile strength of the interface cannot be explained only by the work of adhesion.

Micheliolide (MCL), derived from parthenolide (PTL), is known for its antioxidant and anti-inflammatory effects and has multiple roles in inflammatory diseases and tumours. To investigate its effect on renal disease, we intragastrically administrated DMAMCL, a dimethylamino Michael adduct of MCL for in vivo use, in two renal fibrosis models–the unilateral ureteral occlusion (UUO) model and an ischaemia-reperfusion injury (IRI) model and used MCL in combination with transforming growth factor beta 1 (TGF-β1) on mouse tubular epithelial cells (mTEC) in vitro. The expression of fibrotic markers (fibronectin and α-SMA) was remarkably reduced, while the expression of the epithelial marker E-cadherin was restored after DMAMCL treatment both in the UUO and IRI mice. MCL function in TGF-β1-induced epithelial-mesenchymal transition (EMT) in mTEC was consistent with the in vivo results. Metadherin (Mtdh) was activated in the fibrotic condition, suggesting that it might be involved in fibrogenesis. Interestingly, we found that while Mtdh was upregulated in the fibrotic condition, DMAMCL/MCL could suppress its expression. The overexpression of Mtdh exerted a pro-fibrotic effect by modulating the BMP/MAPK pathway in mTECs, and MCL could specifically reverse this effect. In conclusion, DMAMCL/MCL treatment represents a novel and effective therapy for renal fibrosis by suppressing the Mtdh/BMP/MAPK pathway. Micheliolide (MCL) is known for its antioxidant and anti-inflammatory effects and has multiple effects in inflammatory diseases and tumors. The authors studied the effects of an MCL derivative in two renal fibrosis models. They found that the metastasis adhesion protein metadherin (Mtdh) was activated under fibrotic conditions and that MCL suppressed its expression via the BMP/MAPK pathway.

Two glycoside hydrolases encoded by the mannan utilization gene cluster of alkaliphilic Bacillussp. N16-5 were studied. The recombinant Gal27A (rGal27A) hydrolyzed both galactomannans and oligo-galactomannans to release galactose, while the recombinant Man113A (rMan113A) showed poor activity toward galactomannans, but it hydrolyzed manno-oligosaccharides to release mannose and mannobiose. rGal27A showed synergistic interactions with rMan113A and recombinant β-mannanase ManA (rManA), which is also from Bacillussp. N16-5, in galactomannan degradation. The synergy degree of rGal27A and rManA on hydrolysis of locust bean gum and guar gum was 1.13 and 2.21, respectively, and that of rGal27A and rMan113A reached 2.00 and 2.68. The main products of galactomannan hydrolyzed by rGal27A and rManA simultaneously were galactose, mannose, mannobiose, and mannotriose, while those of galactomannan hydrolyzed by rGal27A and rMan113A were galactose and mannose. The yields of mannose, mannobiose, and mannotriose dramatically increased compared with the hydrolysis in the presence of rManA or rMan113A alone.

Although genome-wide association studies have greatly advanced our understanding of the contribution of common noncoding variants to leprosy susceptibility, protein-coding variants have not been systematically investigated. We carried out a three-stage genome-wide association study of protein-coding variants in Han Chinese, of whom were 7,048 leprosy patients and 14,398 were healthy control subjects. Seven coding variants of exome-wide significance were discovered, including two rare variants: rs145562243 in NCKIPSD(P = 1.71 × 10–9, odds ratio [OR] = 4.35) and rs149308743 in CARD9(P = 2.09 × 10–8, OR = 4.75); three low-frequency variants: rs76418789 in IL23R(P = 1.03 × 10–10, OR = 1.36), rs146466242 in FLG(P = 3.39 × 10–12, OR = 1.45), and rs55882956 in TYK2(P = 1.04 × 10–6, OR = 1.30); and two common variants: rs780668 in SLC29A3(P = 2.17 × 10–9, OR = 1.14) and rs181206 in IL27(P = 1.08 × 10–7, OR = 0.83). Discovered protein-coding variants, particularly low-frequency and rare ones, showed involvement of skin barrier and endocytosis/phagocytosis/autophagy, in addition to known innate and adaptive immunity, in the pathogenesis of leprosy, highlighting the merits of protein-coding variant studies for complex diseases.

ABSTRACTIn this work, Al2O3honeycomb ceramics with unidirectionally aligned channels were fabricated by the ionotropic gelation process of alginate/Al2O3suspensions. By heating the bottom of the suspension container during the gelation step, the heat energy conducted upward from foot to the top surface of the slurry, which has shortened the gelation time from 48 to 10 h and improved efficiency dramatically. Meanwhile, as the heating temperature increased from 25 to 40°C, the porosity of Al2O3honeycomb ceramics remained unchangeable with the pore size decreasing from 163 to 79 μm for the increasing opportunities for forming capillaries in the primary membrane. By the integrated effect of unidirectional pore channels and dense pore walls, both the compressive strength and water permeability of the sintered samples were higher than those of Al2O3foam ceramics.

In 2013, the Texas Department of Transportation completed development of its total pavements acceptance device (TPAD), which contains the next generation of rolling deflectometer integrated with ground penetrating radar and video logging. TPAD collects data at 2 mph and provides deflections measurement at 2-in. intervals from three rolling geophones. In this paper, the development of TPAD is described with typical outputs from the data processing software. How TPAD deflections can be used to determine the load transfer efficiencies of joints and cracks is described, along with the correlation with falling weight deflectometer measurements. Four case studies are presented illustrating typical TPAD data on a range of problem concrete pavements in Texas. These case studies include pavements with a debonded concrete overlay, pavements with voids beneath the slab, and a section that has full-depth patching. The TPAD data collected on US-75, which is a jointed concrete pavement in very poor condition, are presented. TPAD provides highly useful data for planning the rehabilitation of concrete pavements in Texas. Since its development, TPAD has been used on 15 major rehabilitation projects. A popular application is to determine if an upcoming project is a good candidate for an engineered thin asphalt overlay or if more major structural improvements are required.

In the underground laboratory of Meuse/Haute-Marne (Bure) in France, different fracture types have been intensively investigated. Within a co-operative project between BGR and ANDRA, geophysical measurements and borehole gas tests were conducted in three well-designed boreholes in the gallery GRM to characterize the fracture structure and to determine the gas tracer velocity within fracture networks.On the basis of seismic measurements and nitrogen gas interference tests, helium was injected into an interval of borehole OHZ3003, where an unloading joint has been identified. The injection took place in the form of a 10 min ‘pulse’ with an injection pressure of 2 bar. The other two boreholes, OHZ3002, where an upper part of the shear-mode fractures (‘chevron’ pattern) dominate, and OHZ3001, where shear-mode fractures (subvertical ‘oblique’ fractures and ‘chevron’ pattern) exist, served as observation holes. To maintain the pressure gradient between the injection hole and the observation holes, nitrogen gas was subsequently flushed into the injection hole. Two breakthrough curves of helium concentration and pressure developments in the two observation holes were continuously monitored using two helium leakage detectors and pressure gauges.To interpret the measured pressure and concentration data, numerical models were constructed. A 3D model was used to simulate nitrogen gas flow and 2D models were applied to simulate a helium transport process. The real volume of the injection interval was considered in the model and the experimental process was simulated. Using the calibrated transport parameter data for a helium tracer from previous studies in the Mont Terri Rock Laboratory, the calculated breakthrough curves agreed well with those obtained from measuring the variation in permeability. The permeability derived from the helium tracer test agrees well with the estimation obtained from the nitrogen gas tests.

The molecular and pathogenic mechanisms of esophageal squamous cell carcinoma (ESCC) development are still unclear, which hinders the development of effective treatments. In this study, we report that DUSP4 is highly expressed in human ESCC and is negatively correlated with patient prognosis. Knockdown of DUSP4 suppresses cell proliferation and patient-derived xenograft (PDX)-derived organoid (PDXO) growth and inhibits cell-derived xenograft (CDX) development. Mechanistically, DUSP4 directly binds to heat shock protein isoform β (HSP90β) and promotes the ATPase activity of HSP90β by dephosphorylating HSP90β on T214 and Y216. These dephosphorylation sites are critical for the stability of JAK1/2-STAT3 signaling and p-STAT3 (Y705) nucleus translocation. In vivo, Dusp4knockout in mice significantly inhibits 4-nitrochinoline-oxide-induced esophageal tumorigenesis. Moreover, DUSP4 lentivirus or treatment with HSP90β inhibitor (NVP-BEP800) significantly impedes PDX tumor growth and inactivates the JAK1/2-STAT3 signaling pathway. These data provide insight into the role of the DUSP4-HSP90β-JAK1/2-STAT3 axis in ESCC progression and describe a strategy for ESCC treatment.

Low-temperature photothermal therapy (PTT) has the advantage of causing less damage to normal tissues and has attracted great attention in recent years. However, the efficacy of low-temperature PTT is restricted by the overexpression of heat shock proteins (HSPs), specifically HSP70 and HSP90. Inhibiting the function of these HSPs is a major strategy used in the development of new cancer therapies. Herein, we designed four T780T-containing thermosensitive nanoparticles to interrupt the energy supply for HSP expression using their TPP-based mitochondrial targeting action. The reversal behavior of the nanoparticles on the gambogic acid (GA)-induced compensatory increase of HSP70 was investigated in vitroby Western blot and in vivoby immunohistochemistry. The in vivoanticancer efficacy of the low-temperature PTT based on these thermosensitive nanoparticles was also systematically examined. The design proposes for the first time to utilize and elucidate the mechanism of the mitochondrial targeting of T780T-containing NPs in synergy with the HSP90 inhibition of GA to achieve an effective low-temperature PTT. This work not only provides a novel pathway for the dual inhibition of HSP70 and HSP90 but also opens up a new approach for low-temperature PTT of tumors.

Gastric ulcers are a common clinical presentation affecting anyone, regardless of their age or gender. Nanoparticles (NPs) containing Bletilla striatapolysaccharide (BSP) and omeprazole (OME) were investigated in the study for their therapeutic effect on gastric ulcers. Ethanol-induced gastric ulcers in rats (240 ± 30 g) were established. Our OME-BSP NPs were more stable than free OME in the acidic environment and can increase the absorption of OME in rat stomach, which was confirmed by in situ gastric absorption and distribution experiments. The extended blood circulation of OME-BSP NPs was also observed in rats with gastric ulcer. More importantly, OME-BSP NPs not only decreased the area of gastric ulcer and inhibited gastric acid secretion but also reversed gastric tissue damage and cell apoptosis, as revealed by HE and TUNEL staining. Subsequent SOD, MDA, PGE2, IL-6, and TNF-α tests further verified the superiority of OME-BSP NPs against rat gastric ulcer, which properly originated from superior antioxidant and anti-inflammatory effects. As a result, our OME-BSP NPs’ drug delivery system improved the stability and absorption of OME in the rat stomach and achieved targeted treatment of gastric ulcers.

Graphical Abstract:

Cultivating rice will get both obvious economic and social benefits, but extending the paddy field area blindly and extensive irrigation water management mode have also brought some negative effects. Therefore, determining the scale of paddy field development reasonably has become an important issue in the planning of regional farming. The future of the paddy field appropriate development scale was analyzed and forecasted in Jiansanjiang Administration, and indicates that the local soil and water resources have the condition to develop the paddy field area. In addition, we calculated the rice comprehensive gross irrigation quota of different planning years, and showed that the Jiansanjiang Administration should reduce paddy field area appropriately to 2010–2015 level; the local paddy field area and the proportion will show a trend of gradual increase during 2015–2030. By 2030, the local suitable development scale of paddy field will reach 386,153 ha, back to 78.6 % of the paddy field area of 2009, which fully illustrates the constraint effect of water resources on rice production. The suitable area of paddy field and its growing proportion put forward in this paper offered macroscopic guidance for the local development of water-saving agriculture and the adjustment of agricultural planting structure.