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Rationale Methods Results Conclusions In the era of burgeoning digital technology, healthcare is a challenging transformative change towards virtual and digital platforms. Internet‐based healthcare services are emerging as a popular trend within the medical area. User experience (UX) is paramount for the healthcare service, as it significantly influences experience satisfaction and fosters user viscosity. Gaining a profound understanding of users' demands and crafting services that align with their expectations is essential.Consequently, exploring an effective design approach for the digital healthcare service that prioritizes UX along with utilizing a comprehensive evaluation methodology to handle UX data, is of profound importance. This study introduces a design methodology for Internet‐based healthcare products grounded in the UX and mental (UX‐M) model. Aiming to refine the Internet‐based healthcare product design by integrating insights from the experience data, it employs the Delphi‐ANP and the fuzzy comprehensive evaluation to determine evaluation indexes and conduct experiential assessments.The UX evaluation results of existing schemes are compared with the proposed design scheme of the intelligent guidance and internet hospital. The findings indicate that the UX evaluation of Internet‐based medical services with the proposed method outperforms the existing schemes.On the one hand, UX research of Internet‐based healthcare products can significantly enhance service satisfaction for patients utilizing online medical treatments. On the other hand, the analysis of experience‐based evaluation empowers designers to refine and improve UX design of Internet‐based medical services. Such research endeavors are critical for enhancing the overall quality of service offerings and elevating user satisfaction in the digital healthcare landscape. [ABSTRACT FROM AUTHOR]

Background: Programmed cell death is an important mechanism for the development of hepatic ischemia and reperfusion (IR) injury, and multiple novel forms of programmed cell death are involved in the pathological process of hepatic IR. ERRFI1 is involved in the regulation of cell apoptosis in myocardial IR. However, the function of ERRFI1 in hepatic IR injury and its modulation of programmed cell death remain largely unknown. Methods: Here, we performed functional and molecular mechanism studies in hepatocyte-specific knockout mice and ERRFI1-silenced hepatocytes to investigate the significance of ERRFI1 in hepatic IR injury. The histological severity of livers, enzyme activities, hepatocyte apoptosis and ferroptosis were determined. Results: ERRFI1 expression increased in liver tissues from mice with IR injury and hepatocytes under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Hepatocyte-specific ERRFI1 knockout alleviated IR-induced liver injury in mice by reducing cell apoptosis and ferroptosis. ERRFI1 knockdown reduced apoptotic and ferroptotic hepatocytes induced by OGD/R. Mechanistically, ERRFI1 interacted with GRB2 to maintain its stability by hindering its proteasomal degradation. Overexpression of GRB2 abrogated the effects of ERRFI1 silencing on hepatocyte apoptosis and ferroptosis. Conclusions: Our results revealed that the ERRFI1-GRB2 interaction and GRB2 stability are essential for ERRFI1-regulated hepatic IR injury, indicating that inhibition of ERRFI1 or blockade of the ERRFI1-GRB2 interaction may be potential therapeutic strategies in response to hepatic IR injury. [ABSTRACT FROM AUTHOR]

This paper proposes the capacity flexibility models of transit networks to describe the ability of urban transit networks to accommodate the changes in passenger demands. In order to keep the variations of the average passenger travel time in a reasonable way, the concept of coefficient of variation (CoV) is introduced to measure and limit the deviation from a baseline time of the average passenger travel time. The CoV could transform the capacity flexibility values to non-dimensional form in order to compare the capacity flexibility characteristics of different scale transit networks on an equal basis. The genetic algorithm with deep search (GA-DS) for this problem is proposed to find the approximating optimal solution of the capacity flexibility models more effectively. The algorithm has been tested with benchmark problems reported in the existing literature. The optimal solution of the flexibility models shows that the flexibility values are further improved by reducing the number of stops for transit routes under different transit operation conditions. At last, the influence factors of the capacity flexibility of transit systems are discussed to address reliable transit services. [ABSTRACT FROM AUTHOR]

Questions: Stomata can reflect the plant's adaptation to environmental changes. However, the variation patterns of stomatal traits across different habitats and their relationships with environmental drivers are still poorly understood. Here, we assessed the extent of interspecific and intraspecific variation in stomatal traits in two typical riparian forests, and investigated how stomatal traits adapt to habitat change as well as trait–environment relationships. Location: The Irtysh River Basin in China. Methods: We measured the stomatal density (SD), stomatal size (SS), and stomatal relative area (SRA) of dominant plant species from two riparian forests: (1) a riparian forest in the valley and (2) a riparian forest in the pediment plain. We analyzed the stomatal trait variation patterns of dominant plant species in different habitats. We then quantified the magnitude of intraspecific and interspecific stomatal trait variability and evaluated the relationships between stomatal traits and environmental factors. Results: We found that SD and SRA were significantly higher in pediment plain forests than in valley forests, whereas SS was not significantly different between these habitats. The SD and SRA of trees in pediment plain forests were significantly higher than those in valley forests, whereas there were no significant differences in understory plants between habitats. The interspecific variation in each stomatal trait was significantly higher than the intraspecific variation. Stomatal traits were more related to the soil environment than to climatic factors. Conclusions: Response strategies of stomatal traits to habitat changes differed between species and functional groups, and trait–environment relationships depended on the habitat type of the riparian forest. Our analysis of stomata trait variation implies adaptive strategies in species of natural riparian forest. Insights into trait–environment relationships could be used to predict carbon and water cycling, and vegetation changes in riparian forests of arid regions, especially in the context of climate change. [ABSTRACT FROM AUTHOR]

Polymer dielectrics possessing the superiorities of easy processing and high power density are widely used in pulsed power and power electronics. However, the low energy storage density (Ue) of polymer dielectrics limits their application in the modern electronic industries. In this work, we present the sea-island structure multilayered composites based on polymethylmethacrylate (PMMA) matrix and polyvinylidene fluoride (PVDF) nanoparticles, which is constructed by the solution blending with typical solubility differences method and the layer-by-layer solution casting method. The PVDF/PMMA composite incorporated with high PVDF content is placed in the middle of the sandwich-structured composite as a non-traditional intermediate polarization layer. The PVDF/PMMA composite with low PVDF loading is placed in the outer layer to improve the insulating property of the composite. The results show that the PVDF/PMMA composites with inner and outer PVDF volume content of 30% and 10%, respectively, obtained an excellent dielectric constant value (εr ~ 4.35), which is 45% higher than that of PMMA (εr ~ 3). Meanwhile, the maximum Ue (~ 4.95 J cm−3) of the PVDF/PMMA composites at an electric field of 422.48 MV m−1 was obtained, which is 207% higher than that of PMMA (Ue ~ 1.61 J cm−3). The improved energy storage capability could be attributed to the introduction of highly polarizing particles, the increased number of heterogeneous interfaces, and the multilayered construction of composite. This work provides a strategy for the preparation of advanced all-organic dielectrics with a higher discharge energy density. [ABSTRACT FROM AUTHOR]

Friction plays a key role in the assessment of the safety and stability of mechanical systems (such as superconducting magnet quench explosion, aerospace vehicle bearing wear, etc.). Due to the closeness of the interfaces in engineering structures and the randomness of the contact surfaces, existing methods for measuring static friction force are unable to measure it at the contact interfaces of engineering structures under service conditions. In this paper, a new method for measuring the static friction force at the interface based on electrical signals is proposed. This method enables the measurement of the static friction force at interfaces of complex engineering structures under service conditions solely through electrical signals. The results indicate that the contact resistance gradually decreases with the increase in tangential load during the static friction stage until a monotonic behavior of macroscopic sliding occurs. The evolution of contact resistance is linked to the evolution of the real contact area, and this monotonic behavior can be explained as the deformation form of contact points. The accuracy of the proposed electrical measurement method is verified by comparison with experimental results (with an error of less than 9%). The indirect measurement method of friction force proposed in this paper can effectively measure the static friction force at the interfaces of engineering structures under service conditions, and it is expected to be applied to the detection of friction performance at engineering structure interfaces in extreme service environments. [ABSTRACT FROM AUTHOR]

In this paper, a new axial-type magnetic gear with an auxiliary flux-enhancing structure (AFS-AMG) is proposed. Compared to conventional AMGs, it has a higher torque density and higher permanent magnet (PM) utilization factor. Firstly, the design rules and operating principles of the proposed AFS-AMG are elaborated. Then, the mapping relation between the radial-type magnetic gears (RMGs) and AMGs are elucidated. Compared to its counterparts in RMGs, the AFS-AMG achieves a small size. Then, the geometrical parameters of the AFS-AMG are optimized to obtain better electromagnetic performance, where the torque density per volume and per PM volume is adopted as the evaluation standard. Finally, three different AMG topologies are constructed in finite element analysis (FEA) software for comparison. It is proven that the AFS-AMG has the largest torque density per volume and per PM volume. [ABSTRACT FROM AUTHOR]

This paper proposes an analytical model of the double-stator spoke-type permanent magnet vernier machine (DSSTVM) using the subdomain method (SDM), which can be used to calculate the magnetic field distribution and corresponding electromagnetic parameters of the DSSTVM. The whole field domain is divided into several subdomains according to the magnetic characteristics of each region, within which Laplace's and Poisson's equations are solved accordingly in terms of magnetic vector potential (MVP). Then, the corresponding magnetic flux density distribution, back electromotive force (EMF), and electromagnetic torque of the DSSTVM can be obtained. Ultimately, finite element analysis (FEA) is adopted to validate the proposed analytical model's effectiveness for quickly predicting the no-load and on-load performances of the DSSTVM. [ABSTRACT FROM AUTHOR]

Late flowering is a serious bottleneck in pumpkin (Cucurbita moschata Duch.) agriculture production. Although key genes governing flowering time have been reported in many species, the regulatory network of flowering in pumpkin remains largely obscure, thereby impeding the resolution of industry‐wide challenges associated with delayed fruit ripening in pumpkin cultivation. Here, we report an early flowering pumpkin germplasm accession (LXX‐4). Using LXX‐4 and a late flowering germplasm accession (HYM‐9), we constructed an F2 segregation population. A significant difference in FLOWERING LOCUS T‐LIKE 2 (FTL2) expression level was identified to be the causal factor of the flowering time trait discrepancy in LXX‐4 and HYM‐9. Moreover, we have shown that a 21 bp InDel in the FTL2 promoter was the key reason for the waxing and waning of its transcript level. The 21 bp deletion excluded a repressor‐AGL19 and recruited activators‐BBX7, WRKY40 and SVP to the FTL2 promoter in LXX‐4. Together, our data add a useful element to our knowledge which could be used to simplify breeding efforts for early‐maturing pumpkin. Summary statement: An InDel in FTL2 promoter exclude repressor AGL19 and recruit activators BBX7, WRKY40 and SVP to the promoter, leading to increase of FTL2 transcript level and early floral initiation under short‐day conditions. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), which is a prevailing type of dementia, presents a significant global health concern. The current therapies do not meet clinical expectations. Amyloid-beta (Aβ) has been found to induce endogenous formaldehyde (FA) accumulation by inactivating FA dehydrogenase (FDH); in turn, excessive FA triggers Aβ aggregation that eventually leads to AD onset. Hence, scavenging FA by astaxanthin (ATX, a strong exogenous antioxidant) may be pursued as a promising disease-modifying approach. Here, we report that liposomal nanoparticles coupled with PEG (PEG-ATX@NPs) could enhance water-solubility of ATX and alleviate cognitive impairments by scavenging FA and reducing Aβ deposition. To enable drug delivery to the brain, liposomes were used to encapsulate ATX and then coupled with PEG, which produced liposomal nanoparticles (PEGATX@NPs) with a diameter of <100 nm. The PEG-ATX@NPs reduced Aβ neurotoxicity by both degrading FA and reducing FA-induced Aβ assembly in vitro. Intraperitoneal administration of PEG-ATX@NPs in APPswe/PS1dE9 mice (APP/PS1, a familial model of AD), not only decreased the levels of brain FA and malondialdehyde (MDA, a typical product of oxidative stress), but also attenuated both intracellular Aβ oligomerization and extracellular Aβ-related senile plaque (SP) formation. These pathological changes were accompanied by rescued ability of spatial learning and memory. Collectively, PEG-ATX@NPs improved the water-solubility, bioavailability, and effectiveness of ATX. Thus, it has the potential to be developed as a safe and effective strategy for treating AD. [Display omitted] • Liposomal NPs of ATX with PEG enhances its bioavailability and drug delivery. • Scavenging FA by PEG-ATX@NPs decreases Aβ oligomerization and deposition. • PEG-ATX@NPs more than ATX reduce Aβ neurotoxicity by scavenging FA. • PEG-ATX@NPs may be a promising strategy for treating Alzheimer's disease. [ABSTRACT FROM AUTHOR]

In recent years, key generation schemes based on the reciprocity of wireless channels have gained widespread attention in the field of wireless physical layer security. However, due to the openness of wireless channels, eavesdroppers may obtain partial legitimate keys by eavesdropping on the wireless channel. To address this issue, this paper proposes a wireless channel coding scheme that induces an "avalanche" of errors for eavesdroppers, which could maximize eavesdropper's bit error rate. The design of this scheme is based on the significant differences between the eavesdropping channel and the legitimate channel, and the average bit key disagreement ratio of the keys generated by the legitimate channel is around 8%. The scheme selects polar codes with strong error correction capabilities and chooses a coding rate matching the error level of the legitimate channel, forcing the eavesdropping channel's error rate into an "avalanche" state, where the error rate approaches 50%. This paper presents the structure of the encoder and determines the coding rate through simulation. Simulation results demonstrate that this scheme can significantly degrade the error rate of the eavesdropping channel while ensuring the prevention of eavesdroppers from obtaining secret information transmitted through the legitimate channel. [ABSTRACT FROM AUTHOR]

Laser-induced liquid plasma is expected to be an efficient medium for a new generation of terahertz (THz) devices. However, the mechanism of interaction between liquid plasma and THz waves is currently unclear. Here, we observed two phenomena related to THz wave interaction with water plasma: THz-induced second harmonic (TISH) radiation in water plasma and THz absorption by water plasma. We established an internal relationship between these two macroscopic phenomena by utilizing a photocurrent model and the Drude model. Using liquid water and air as examples, a scheme is proposed to analyze the photonic characteristics of plasma in different physical states. This study offers an experimental basis for predicting the TISH phenomenon across various substances and states and also provides the theoretical support for the practical implementation of liquid-based detection of THz waves. [ABSTRACT FROM AUTHOR]

In situ dual‐modal detection of electrophysiology (EP) and blood oxygen (BO) during muscle–vascular activity is crucial for healthcare and human–machine interaction. It requires an integrated monitoring system: a transparent electrode for EP detection directly adhered to skin and a near‐infrared spectroscopy (NIRs) layer for BO detection. In particular, the multi‐channel, highly transparent, stretchable electrodes should be well developed. In this study, 16‐channel transparent ionotronic electrodes are fabricated based on a stretchable and printable ionogel, demonstrating excellent properties such as high transparency, large stretchability, wet adhesion, biocompatibility, softness, and long‐term stability. The electrode exhibits stable contact impedance for 24 h and a 2‐week periodic EP monitoring. The 16‐channel transparent ionotronic electrode outperforms stretchable gold electrodes by providing stable EP monitoring with minimal interference in NIRs for blood oxygen detection. An in situ negative correlation is found between EP intensity and blood oxygen level over time. This study paves the way for designing transparent ionotronics for synchronous optical‐related monitoring and highlights the potential use of an in situ dual‐modal monitoring system for the study of muscle–vascular coupling in neurocience and rehabilitation. [ABSTRACT FROM AUTHOR]

The influence mechanism of tensile load on the conductivity of thin films is a key issue in evaluating the conductivity of engineering structural thin films under complex loading conditions. How to reveal the correlation mechanisms of different physical quantities of metal films, and to predict the variation of film resistance with tensile load is a very critical and challenging problem. In this paper, a multiscale model of film resistance under tensile neching is established to describe the mechanical behavior, resistivity, and resistance of metal films under tensile load. The results show that the tensile load has a significant effect on the resistivity and conductivity of the film. This provides a reference for the evaluation and optimization of the conductivity of thin films with complex engineering structures. [ABSTRACT FROM AUTHOR]

The Bi 2 Sr 2 CaCu 2 O 8+ x (Bi-2212) material, a high-temperature superconductor, holds significant promise for future high-field applications because of its multifilamentary, twistable production capabilities, coupled with a high upper critical field. Bi-2212 round wire (RW) is made by the powder-in-tube (PIT) technique, and Bi-2212 coils are usually being developed using the wind-and-react method and a high temperature and over-pressure (OP) heat treatment (50 atm, 890℃) is then required to achieve the high current performance. However, over-pressure (OP) heat treatment can lead to a reduction in wire diameter, compromising the stability of the coil structure. Addressing this issue, the pre-overpressure (pre-OP) heat treatment is used and proves effective in mitigating the reduction in Bi-2212 wire diameter. In this paper, to comprehensively investigate the impact of pre-OP heat treatment on the microstructure of Bi-2212 wire, a metallographic analysis of two kinds of Bi-2212 wires was carried out by the scanning electron microscope (SEM) and the ImageJ software. It was found that larger-area filaments experienced a greater reduction in area after pre-OP heat treatment, that pre-OP heat treatment increases the aspect ratio of filaments, and polygonal bundle structure helps maintain filament structure stability during pre-OP heat treatment. Additionally, the impact of pre-OP heat treatment on the performance of Bi-2212 wires was analyzed through critical current testing under high fields. [ABSTRACT FROM AUTHOR]

Current label-free surface-enhanced Raman spectroscopy (SERS) assay for the detection and analysis of organophosphorus pesticides has achieved initial success, but the application still faces constraints of substrate portability and specificity. To this end, this paper demonstrates a method for portable, rapid, and specific detection of low concentrations of fenthion pesticides based on a solid substrate of gold nanoparticle monolayers combined with molecularly imprinted polymers (MIPs). The nano-monolayers were transferred to the surface of mercapto-silicon wafers by interfacial self-assembly technique to form a stable connection with S–Au bonds and, at the same time, prevent nanoparticles from dropping off during the surfactant removal process. Then, the fenthion MIPs were directly generated on the surface of the monolayer film by spin-coating with a pre-polymerization solution and ultraviolet-induced polymerization. Tests showed that the molecular imprint was able to accurately bind to fenthion, but not other molecules, in a mixture of structural analogs, achieving a low concentration detection of 10–8 mol/L. The composite substrate maintained a signal uniformity of a relative standard deviation (RSD)  =  7.05% and a batch-to-batch reproducibility of RSD  =  10.40%, making it a potential pathway for the extended application of SERS technology. [ABSTRACT FROM AUTHOR]

• Crystal plasticity finite element model exhibits higher accuracy in evaluation of surface roughness and thickness distribution of cups fabricated by micro deep drawing. • The magnitude of surface roughness S z is almost linearly dependent on the average grain size of austenitic stainless steel foils. • The brass components are beneficial to the formation of drawn cups with uniform thickness distribution and the absence of severe defects. The present work involves the numerical simulation and experimental study on the surface roughness evolution and heterogeneous plastic deformation (strain localization and concomitant surface morphology evolution) in grain scale of micro deep drawn parts of austenitic stainless steel (ASS) 304 foils. A three-dimensional modeling framework was used to simulate the micro deep drawing (MDD) process. The simulation involved the development of a Voronoi-based polycrystalline geometry model (VPGM), a multi-stress-strain response model, and a crystal plasticity finite element methods (CPFEM) model. The results indicate that CPFEM model exhibits higher accuracy in the localized stress and strain, thickness distribution fluctuation and surface roughness evolution of the fabricated parts compared to multi-stress-strain response model. Therefore, the plastic deformation heterogeneity in MDD is in-depth discussed based on CPFEM model. The results show that the coarse-grained foils correspond to the intense strain localization, which is the main cause of surface roughening. Considering the average grain size is close to the thickness of ASS foils, mounding features on the rough surface may readily develop further into potentially fractured sites during deformation. On the other hand, crystal orientation influence plastic deformation by affecting the slip behavior of materials. The effect of crystal orientations including {011} 〈211〉 (Brass), {011} 〈100〉 (Goss), and {112} 〈110〉 components on deformation is discussed. The results indicate a strong correlation between the magnitude of the Schmid's factor and the ease of deformation. Additionally, variations in Schmid's factor across different directions result in differences in deformation accumulation, which affects the thickness distribution along the radial direction and the distribution of earrings and wrinkles along the circumferential direction of the fabricated micro parts. [ABSTRACT FROM AUTHOR]

[Display omitted] • Classical trigeminal neuralgia is associated with altered structural connections between its cerebral cortex and thalamus. • Probabilistic fiber tracking can be used for thalamic subdivisions based on connectivity of fibers. • Individualized thalamic segmentation mapping helps provide clinical treatment targets. Classical trigeminal neuralgia (CTN) refers to episodic pain that is strictly confined to the trigeminal distribution area, and the thalamus is an important component of the trigeminal sensory pathway. Probabilistic tracking imaging algorithm was used to identify specific connections between the thalamus and the cortex, in order to identify structural changes in the thalamus of patients with CTN and perform thalamic segmentation. A total of 32 patients with CTN and 32 healthy controls underwent DTI-MRI scanning (3.0 T). Differences in fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) between the groups were studied. Correlation analysis was performed with clinical course and pain level. Compared to the healthy controls, patients in the CTN group had significantly reduced FA, increased AD, RD and MD in somatosensory subregion of the bilateral thalamus, increased RD in frontal subregion, increased RD and MD in motor subregion. Correlation analysis showed that patient history was positively correlated with pain grading, and that medical history was positively correlated with significantly reduced FA in somatosensory subregion, negatively correlated with increased RD and MD in motor subregion. We used DTI-based probabilistic fiber tracking to discover altered structural connectivity between the thalamus and cerebral cortex in patients with CTN and to obtain a thalamic segmentation atlas, which will help to further understand the pathophysiology of CTN and serve as a future reference for thalamic deep brain stimulation electrode implantation for the treatment of intractable pain. [ABSTRACT FROM AUTHOR]

In recent years, NIR-II-type fluorophores with emission wavelengths within the 1000–1700 nm range have garnered widespread attention in the field of bioimaging due to their high tissue penetration ability. Here, Mn-doped BaAl 2 O 4 , Ba 3 Al 2 O 6 , and Ba 7 Al 2 O 10 with NIR-II-type luminescence were synthesized by solid-phase or liquid-phase methods. Confirmed by XPS and EDS analysis, Mn is found uniformly distributed in the structure in the valence state of + 5. The optimal doping concentration of Mn5+ in the three matrices was analyzed by PLE and PL spectroscopy. In addition, the samples exhibit a wide excitation range spanning from 600 to 900 nm, coupled with a narrow emission band peaking between 1150 and 1200 nm. As both the excitation and emission wavelengths have excellent penetration capabilities in biological tissues, the synthesized fluorescent phosphors in this study hold potential for meaningful applications in the realm of fluorescence imaging. • Mn5+-doped Ba 3 Al 2 O 6 , BaAl 2 O 4 , and Ba 7 Al 2 O 10 phosphors were synthesized. • The emission wavelengths are between 1150 and 1200 nm, in the second near-infrared window. • The phosphors have potential in fluorescence imaging. [ABSTRACT FROM AUTHOR]

[Display omitted] • The MOF-derived Fe significantly improve the polarization of PVDF-based composites. • A high breakdown strength is obtained by adjusting crystalline structure of PVDF. • The enhanced energy density of 28.9 J/cm3 is achieved at ultralow filler fractions. Polymer-based capacitors are essential energy storage components in the electronic and electrical industries, which is benefit for their high power density and fast charge–discharge capabilities. However, the low energy density of polymer-based capacitors limits their miniaturization and intelligent applications. In this study, we present the novel poly(vinylidene fluoride) (PVDF)-based composites with exceptional energy storage performance at the submicron metal filler loadings. Guided by synergistically improving the dielectric constant and breakdown strength of polymer-based composites, metal–organic framework (MOF)-derived Fe fillers and Press & Heat (P&H) cycles are mainly implemented. The polymer-based composites exhibit a superior dielectric constant of 15.3, while simultaneously maintain a high breakdown strength of 617.1 MV/m. The excellent energy density of 28.9 J/cm3 is obtained at the ultralow filler loading of 0.2 wt%. Synergistic tuning the loading content of MOF-derived Fe and optimizing the P&H cycles not only leads to a novel composite dielectrics with outstanding energy storage properties, but also presents a new strategy for exploring high-performance capacitive polymer composites. [ABSTRACT FROM AUTHOR]

Isoguanosine (isoG) is a natural structural isomer of guanosine (G) with significant potential for applications in ionophores, genetics, gel formation, and cancer therapy. However, the cost of commercially available isoG on a gram scale is relatively high. To date, a detailed method for the large‐scale preparation of high‐purity isoG has not been reported. This study presented a simple and convenient approach for the large‐scale synthesis of isoG through the diazotization of 2,6‐diaminopurine riboside with sodium nitrite and acetic acid at room temperature. Further, this method could synthesize isoG derivatives (2’‐fluoro‐isoguanosine (1) and 2’‐deoxy‐isoguanosine (2)) from 2,6‐diaminopurine nucleoside derivatives using diazotization. The structural information of natural and modified nucleosides is crucial for the modification and substitution of DNA/RNA. This study obtained the single‐crystal structure of isoG for the first time and analyzed it in detail using microcrystal electron diffraction. The three‐dimensional supramolecular structure of isoG adopted similarly base‐pair motifs from π‐π stacking interaction of diverse layers, intramolecular hydrogen bonding, and distinct hydrogen bonding interactions from sugar residues. This study has contributed to further isoG modification and its applications in medicinal chemistry and materials. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the reliability and validity of the translated Chinese version of the Communication Complexity Scale (C-CCS) in a Chinese sample of preschool-aged children with minimal verbal skills. A total of 120 children with autism spectrum disorders or children with developmental delays aged 2 to 5 years with minimal verbal skills (i.e., produced less than 20 functional words) were recruited to complete the C-CCS. First, we tested the protocol with 20 children and shortened it based on their results. Second, the interrater reliability, test-retest reliability, and concurrent validity for 100 participants were examined. C-CCS scores were compared with scores from the Chinese Communicative Development Inventories (CCDI) for concurrent validity. Ten C-CCS interactive scripts were administered to 100 participants. Intraclass correlation coefficients (ICC) between independent observers were high. The ICCs for overall optimal scores, optimal BR scores and optimal JA scores were 0.978, 0.971 and 0.977 respectively. Agreement for scores within scripted opportunities and communication level were high-Kappa coefficients 0.869 and 1.000 respectively. The test-retest reliability was high (r = 0.911). A moderate correlation was found between the C-CCS and the CCDI (r = 0.401). The results indicate that C-CCS could be used as a measurement tool in research and clinical practice to describe communication levels in children with minimal verbal skills in China. The Chinese version of the Communication Complexity Scale was developed through a rigorous cultural adaptation process. The evidence shows that the Chinese version of the Communication Complexity Scale is a reliable and valid tool for children with minimal verbal skills in China. The Chinese version of the Communication Complexity Scale can be used in research and clinical practice to assess the general level of social communication skills of Chinese children who mainly communicate using preverbal communication and develop intervention programs. [ABSTRACT FROM AUTHOR]

Dielectric elastomers (DEs) have a great potential in applications as smart materials such as artificial muscles and flexible robotics, due to their advantages of large deformation, good flexibility and fast actuation response. However, the excellent electro-actuation performance of DE materials is always achieved under high electric fields, which limits their widespread application. Herein, the synthesized acrylate-based copolymer E 8 G 2 (the molar ratio between 2-ethylhexyl acrylate and glycidyl methacrylate is 8:2) was incorporated into the polydimethylsiloxane (PDMS) matrix by solution mixing and compression molding to prepared a series of bi-network DE composites. The design of the all-organic bi-network structure not only regulates the dielectric-flexibility of E 8 G 2 /PDMS composites synchronously but also relieves the problem of plasticizer exudation. The E 8 G 2 /PDMS composites achieved a remarkable electro-actuated strain of 43.86 % at 50 V/μm, which is improved by 431.08 % compared with pure PDMS (6.95 %). Consequently, this study provides a promising approach for the preparation of advanced DE composites with outstanding electro-actuated performance in low-field driving applications. [Display omitted] • The dielectric elastomer with all-organic bi-network structures were prepared. • The electro-actuated strain of DE composite reaches 43.86 % at low-field of 50 V/μm. • The synergistic regulation on ε r and Y leads to the improved electro-actuation. • The long-standing issue of plasticizer-exudation from DE composites is relieved. [ABSTRACT FROM AUTHOR]

The high electronic conductivity and tailorable structural properties of MXene materials make them promising candidates for energy storage. However, their poor chemical instability and self‐stacking effect greatly limit their application, especially in aqueous systems. Here, using a eutectic etching approach, hydroxylated borophene is used as a trifunctional mediator to construct robust Ti3C2Tx‐based MXene/B self‐assembled film electrodes for zinc‐ion capacitors (ZICs). Due to this mediator, the as‐formed strong interfacial binding within the heterostructure can give rise to an integrated modification effect and promote high‐efficiency interface energy storage. One is to strengthen the thermodynamic stability of local Ti─O bonds and inhibit the irreversible degradation of MXene; two is to enlarge the interface space of the MXene electrode and boost the ion transport; three is to improve the interfacial Zn2+ trapping ability without affecting Zn2+ migration on the MXene surface. Thus, the MXene/B electrode exhibits a high areal capacitance (537.9 mF cm−2) at a current density of 0.2 mA cm−2 and an extraordinary cycling stability at 1 mA cm−2, with 99.64% retention after 40 000 cycles, which far surpasses that of most previous reports. This work provides a pathway for overcoming the interface storage limit of MXene electrodes to construct high‐performance ZICs. [ABSTRACT FROM AUTHOR]

Co3O4 emerges as a promising substitute in the field of anode electrode materials for the next‐generation of lithium‐ion batteries (LIBs). Nevertheless, challenges such as volumetric effects during cycling and insufficient conductivity have resulted in its subpar cycle stability, which impedes its practical application. In this study, we successfully employed a straightforward method to design and synthesize double hemispherical nano‐Co3O4/C composite materials derived from MOF‐74(Co). Benefiting from its nano‐porous structure combined with carbon materials, the resulting Co3O4/C electrode manifests outstanding electrochemical performance. Specifically, the obtained Co3O4/C electrode exhibits a notably high reversible cycle capacity (1151.9 mAh g−1 at 0.2 A g−1), exemplary rate capability, and outstanding long‐cycle performance (maintaining a capacity of 366.2 mAh g−1 at 1 A g−1 after 1400 cycles). This research introduces a novel approach for the development of innovative anode materials for LIBs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Acute LPS does not increase brain LPS levels but induces depression onset. • LPS could activate SSAO to generate FA in the midbrain vascular endothelium. • Acute injection of FA as well as LPS stimulates cytokine releases in the midbrain. • Chronic injection of FA mimics LPS-induced cytokine storm and BBB disruption. • Scavenging FA may be a novel and promising strategy for treating depression. Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1β, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO 3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood–brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment. [ABSTRACT FROM AUTHOR]

Herein, a successive energy transfer (sEnT) strategy to enable a dehydrogenative 6π‐photocyclisation, without the need for an external oxidant is reported, in which the energetically unfavourable dehydrogenation is driven by energy transfer. The valuable applicability of this method was demonstrated by the scaffold hopping of indole containing bioactive molecules, as well as by the succinct synthesis of naturally occurring tetracyclic furocarbazole alkaloids. Moreover, experimental and computational studies were conducted to elucidate the reaction mechanism. [ABSTRACT FROM AUTHOR]

• Ce and Zr stabilize the ThMn 12 structure and increase the total magnetic moment. • With Ce content increasing, the amount of soft α-(Fe,Co,Ti) phase is suppressed. • Orientation relationship of two phases: [00–1] 1:12 //[1 0 0] 1:9 and (0 2 0) 1:12 //(0 1 0) 1:9. Recently ThMn 12 -type samarium iron alloys have been promising materials for permanent magnets. Due to the high abundance and low cost, Ce as a possible stabilizer can be introduced into ThMn 12 -type alloys. The effect of Ce doping on the magnetic moment and phase stability in Ti-lean (Ce,Sm,Zr)(Fe,Co,Ti) 12 compounds were predicted by the first-principles calculations. The Ce x Sm 0.8-x Zr 0.2 (Fe 0.8 Co 0.2) 11.5 Ti 0.5 (x = 0–0.8) alloys with ThMn 12 structure were produced by strip-casting into flakes by a wheel speed of 1.5 m/s and annealed at 1000 °C for 24 h. The Ce 0.8 Zr 0.2 (Fe 0.8 Co 0.2) 11.5 Ti 0.5 annealed flake shows a high saturation magnetization value of 13.6 kGs at room temperature. With the increase of Ce substitution in the annealed flakes, the content of α-(Fe,Co,Ti) phase decreases and the saturation magnetization increases. The 1:12 phase and the 1:9 phase have an orientation relationship that can be expressed as [0 0 –1] 1:12 //[1 0 0] 1:9 and (0 2 0) 1:12 //(0 1 0) 1:9. Besides, annealing process promotes the formation of 1:12 phase transformed from 1:9 phase. Coercivity is expected to be improved by obtaining uniform microstructure and suppressing the formation of soft α-(Fe,Co,Ti) phase in the ThMn 12 -based alloys. [ABSTRACT FROM AUTHOR]

Summary: Heavy metal pollution poses a significant risk to human health and wreaks havoc on agricultural productivity. Phytoremediation, a plant‐based, environmentally benign, and cost‐effective method, is employed to remove heavy metals from contaminated soil, particularly in agricultural or heavy metal‐sensitive lands. However, the phytoremediation capacity of various plant species and germplasm resources display significant genetic diversity, and the mechanisms underlying these differences remain hitherto obscure. Given its potential benefits, genetic improvement of plants is essential for enhancing their uptake of heavy metals, tolerance to harmful levels, as well as overall growth and development in contaminated soil. In this study, we uncover a molecular cascade that regulates cadmium (Cd2+) tolerance in cotton, involving GhRCD1, GhbHLH12, GhMYB44, and GhHMA1. We identified a Cd2+‐sensitive cotton T‐DNA insertion mutant with disrupted GhRCD1 expression. Genetic knockout of GhRCD1 by CRISPR/Cas9 technology resulted in reduced Cd2+ tolerance in cotton seedlings, while GhRCD1 overexpression enhanced Cd2+ tolerance. Through molecular interaction studies, we demonstrated that, in response to Cd2+ presence, GhRCD1 directly interacts with GhbHLH12. This interaction activates GhMYB44, which subsequently activates a heavy metal transporter, GhHMA1, by directly binding to a G‐box cis‐element in its promoter. These findings provide critical insights into a novel GhRCD1–GhbHLH12–GhMYB44–GhHMA1 regulatory module responsible for Cd2+ tolerance in cotton. Furthermore, our study paves the way for the development of elite Cd2+‐tolerant cultivars by elucidating the molecular mechanisms governing the genetic control of Cd2+ tolerance in cotton. [ABSTRACT FROM AUTHOR]

SUMMARY Verticillium dahliae, a soil‐borne fungal pathogen, compromises host innate immunity by secreting a plethora of effectors, thereby facilitating host colonization and causing substantial yield and quality losses. The mechanisms underlying the modulation of cotton immunity by V. dahliae effectors are predominantly unexplored. In this study, we identified that the V. dahliae effector Vd6317 inhibits plant cell death triggered by Vd424Y and enhances PVX viral infection in Nicotiana benthamiana. Attenuation of Vd6317 significantly decreased the virulence of V. dahliae, whereas ectopic expression of Vd6317 in Arabidopsis and cotton enhanced susceptibility to V. dahliae infection, underscoring Vd6317's critical role in pathogenicity. We observed that Vd6317 targeted the Arabidopsis immune regulator AtNAC53, thereby impeding its transcriptional activity on the defense‐associated gene AtUGT74E2. Arabidopsis nac53 and ugt74e2 mutants exhibited heightened sensitivity to V. dahliae compared to wild‐type plants. A mutation at the conserved residue 193L of Vd6317 abrogated its interaction with AtNAC53 and reduced the virulence of V. dahliae, which was partially attributable to a reduction in Vd6317 protein stability. Our findings unveil a hitherto unrecognized regulatory mechanism by which the V. dahliae effector Vd6317 directly inhibits the plant transcription factor AtNAC53 activity to suppress the expression of AtUGT74E2 and plant defense. [ABSTRACT FROM AUTHOR]

• Largest GBS genome sequence sample of Chinese infants. • Baseline data for GBS surveillance and vaccine impact evaluation. Group B Streptococcus (GBS) is a leading cause of morbidity and mortality in young infants worldwide. This study aimed to investigate candidate GBS vaccine targets, virulence factors, and antimicrobial resistance determinants. We used whole-genome sequencing to characterize invasive GBS isolates from infants < 3 months of age obtained from a multicenter population-based study conducted from 2015 to 2021 in China. Overall, seven serotypes were detected from 278 GBS isolates, four (Ia, Ib, III, V) of which accounted for 97.8 %. We detected 30 sequence types (including 10 novel types) that were grouped into six clonal complexes (CCs: CC1, CC10, CC17, CC19, CC23 and CC651); three novel ST groups in CC17 were detected, and the rate of CC17, considered a hyperinvasive neonatal clone complex, was attached to 40.6 % (113/278). A total of 98.9 % (275/278) of isolates harbored at least one alpha-like protein gene. All GBS isolates contained at least one of three pilus backbone determinants and the pilus types PI-2b and PI-1 + PI-2a accounted for 79.8 % of the isolates. The 112 serotype III/CC17 GBS isolates were all positive for hvgA. Most of the isolates (75.2 %) were positive for serine-rich repeat glycoprotein determinants (srr1 or srr2). Almost all isolates possessed cfb (99.6 %), c1IE (100 %), lmb (95.3 %) or pavA (100 %) gene. Seventy-seven percent of isolates harboured more than three antimicrobial resistance genes with 28.4 % (79/278) gyr A quinolone resistance determinants mutation, 83.8 % (233/278) carrying tet cluster genes and 77.3 % (215/278) carrying erm genes which mediated fluoroquinolone, tetracycline and clindamycin resistance, respectively." The findings from this large whole-genome sequence of GBS isolates establish important baseline data required for further surveillance and evaluating the impact of future vaccine candidates. [ABSTRACT FROM AUTHOR]

Soil salinization is a major abiotic stress factor that negatively impacts plant growth, development, and crop yield, severely limiting agricultural production and economic development. Cotton, a key cash crop, is commonly cultivated as a pioneer crop in regions with saline-alkali soil due to its relatively strong tolerance to salt. This characteristic renders it a valuable subject for investigating the molecular mechanisms underlying plant salt tolerance and for identifying genes that confer salt tolerance. In this study, focus was placed on examining a salt-tolerant variety, E991, and a salt-sensitive variety, ZM24. A combined analysis of transcriptomic data from these cotton varieties led to the identification of potential salt stress-responsive genes within the glutathione S-transferase (GST) family. These versatile enzyme proteins, prevalent in animals, plants, and microorganisms, were demonstrated to be involved in various abiotic stress responses. Our findings indicate that suppressing GhGSTF9 in cotton led to a notably salt-sensitive phenotype, whereas heterologous overexpression in Arabidopsis plants decreases the accumulation of reactive oxygen species under salt stress, thereby enhancing salt stress tolerance. This suggests that GhGSTF9 serves as a positive regulator in cotton's response to salt stress. These results offer new target genes for developing salt-tolerant cotton varieties. [ABSTRACT FROM AUTHOR]

In this research, SCAPS-1D simulation software (Version: 3.3.10) was employed to enhance the efficiency of CsSnX3 (X = Cl, Br, I) all-inorganic perovskite solar cells. By fine-tuning essential parameters like the work function of the conductive glass, the back contact point, defect density, and the thickness of the light absorption layer, we effectively simulated the optimal performance of CsSnX3 (X = Cl, Br, I) all-inorganic perovskite solar cells under identical conditions. The effects of different X-site elements on the overall performance of the device were also explored. The theoretical photoelectric conversion efficiency of the device gradually increases with the successive substitution of halogen elements (Cl, Br, I), reaching 6.09%, 17.02%, and 26.74%, respectively. This trend is primarily attributed to the increasing size of the halogen atoms, which leads to better light absorption and charge transport properties, with iodine (I) yielding the highest theoretical conversion efficiency. These findings suggest that optimizing the halogen element in CsSnX3 can significantly enhance device performance, providing valuable theoretical guidance for the development of high-efficiency all-inorganic perovskite solar cells. [ABSTRACT FROM AUTHOR]

Floods are a great threat to Pakistan with increasing concern. As the consequences of increased extreme weather related to climate change, Pakistan experiences severe floods almost every year. This study aims to explore and analysis the actual inundated situation, magnitude, the possible causes of the 2022 devastating floods, and future trends. We presented an enhanced nationwide flood mapping method and compared with other pixel-based image processing techniques including active contours and change detection. These algorithms were applied to Sentinel-1 Ground Range Detected (GRD) Synthetic Aperture Radar (SAR) imagery (10 m spatial resolution) with various land types and inundation scenarios in Pakistan, and were evaluated using other reference flood products. Accuracy evaluation analysis demonstrated that our algorithm has high robustness and accuracy, with the overall accuracy (OA) higher than 0.83 and critical success index (CSI) up to 0.91, and is suitable for automated flood monitoring in near real time. Nearly one-third of the lands were flooded in 2022, and more than half were inundated croplands. Punjab and Sindh provinces were the most severely affected regions, with the proportions of inundated area in 2022 (21.26% and 20.55%) nearly twice of that in 2010 (11.40% and 12.70%), indicating an intensified flooding trend. Analysis of possible influential factors showed that the intense and cumulative rainfall during the monsoon season (June to August) was the major cause of the 2022 flood event. Although the snow melted rapidly in June (the average change in snow depth is ∼10 mm), the overall ablation contributed insignificant amount to the flood water. The glacial lake outburst floods (GLOFs) induced by abnormal April–May heatwave provide water flowed into the tributaries of the Indus River, but are difficult to spread for thousands of kilometers from mountains to the plain downstream. The combination of the intrinsic arid climate and extreme floods exacerbate the already severe situation. • This paper presents an automated method based on tile thresholding and fuzzy logic. • The inundation in Punjab and Sindh in 2022 are nearly twice of that in 2010. • The cumulative rainfall is the major cause of the 2022 flood event. • The snow melting and GLOFs are likely small relative to the flood water gains. • These observations imply an intensified flooding and water cycle in Pakistan. [ABSTRACT FROM AUTHOR]

Plants have evolved sophisticated signaling networks to adjust flowering time, ensuring successful reproduction. Two crucial flowering regulators, FLOWERING LOCUS T (FT) and CONSTANS (CO), play pivotal roles in regulating flowering across various species. Previous studies have indicated that suppressing Gossypium hirsutum CONSTANS-LIKE 2 (GhCOL2), a homolog of Arabidopsis CO, leads to delayed flowering in cultivated cotton. However, the underlying regulatory mechanisms remain unknown. In this study, a yeast one-hybrid and dual-LUC expression assays were used to elucidate the molecular mechanism through which GhCOL2 regulates the transcription of GhHD3A. RT-qPCR was used to examine the expression of GhCOL2 and GhHD3A. Our findings reveal that GhCOL2 directly binds to CCACA cis-elements and atypical CORE (TGTGTATG) cis-elements in the promoter regions of HEADING DATE 3 A (HD3A), thereby activating GhHD3A transcription. Notably, GhCOL2 and GhHD3A exhibited high expression levels in the adult stage and low levels in the juvenile stage. Interestingly, the expression of GhCOL2 and GhHD3A varied significant between the two cotton varieties (Tx2094 and Maxxa). In summary, our study enhances the understanding of the molecular mechanism by which cotton GhCOL2-GhHD3A regulates flowering at the molecular level. Furthermore, it contributes to a broader comprehension of the GhCOL2-GhHD3A model in G. hirsutum. [ABSTRACT FROM AUTHOR]

Background: The clinical value and molecular characteristics of tumor differentiation in oral squamous cell carcinoma (OSCC) remain unclear. There is a lack of a related molecular classification prediction system based on pathological images for precision medicine. Methods: Integration of epidemiology, genomics, experiments, and deep learning to clarify the clinical value and molecular characteristics, and develop a novel OSCC molecular classification prediction system. Results: Large-scale epidemiology data (n = 118,817) demonstrated OSCC differentiation was a significant prognosis indicator (p < 0.001), and well-differentiated OSCC was more chemo-resistant than poorly differentiated OSCC. These results were confirmed in the TCGA database and in vitro. Furthermore, we found chemo-resistant related pathways and cell cycle-related pathways were up-regulated in well- and poorly differentiated OSCC, respectively. Based on the characteristics of OSCC differentiation, a molecular grade of OSCC was obtained and combined with pathological images to establish a novel prediction system through deep learning, named ShuffleNetV2-based Molecular Grade of OSCC (SMGO). Importantly, our independent multi-center cohort of OSCC (n = 340) confirmed the high accuracy of SMGO. Conclusions: OSCC differentiation was a significant indicator of prognosis and chemotherapy selection. Importantly, SMGO could be an indispensable reference for OSCC differentiation and assist the decision-making of chemotherapy. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the association between periodontitis, all‐cause and cause‐specific mortality, and its prognostic utility among adults with diabetes. Materials and Methods: Periodontal health records were retrieved from the NHANES database for 4297 participants with diabetes aged >30 years at baseline during 1988–1994, 1999–2004 and 2009–2014. Multivariable Cox proportional hazards regression model was applied to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for moderate/severe periodontitis with all‐cause and cause‐specific mortality in participants with diabetes. Area under the curve (AUC) was used to assess predictive value. Results: During a median follow‐up of 15.41 years, 1701 deaths occurred. After multivariate adjustments, moderate/severe periodontitis was significantly associated with increased risk of all‐cause (HR: 1.27; 95% CI: 1.07–1.50; p =.005) and cardiovascular disease (CVD)‐related (HR: 1.35, 95% CI: 1.03–1.76, p =.031) mortality in participants with diabetes. The absolute risk difference based on the cumulative incidence information was 0.022 (5‐year, 95% CI: 0.021–0.023) and 0.044 (10‐year, 95% CI: 0.041–0.048). Periodontitis improved the prediction of all‐cause (AUC: 0.652; 95% CI: 0.627–0.676) and CVD‐related (AUC: 0.649; 95% CI: 0.624–0.676) mortality over standard risk factors (all‐cause: AUC: 0.631; 95% CI: 0.606–0.656; CVD‐related: AUC: 0.629; 95% CI: 0.604–0.655). Conclusions: Moderate/severe periodontitis is associated with an increased risk of all‐cause and CVD‐related mortality in adults with diabetes. Periodontitis might represent a marker for residual risk. [ABSTRACT FROM AUTHOR]

Objective: Manganese ion (Mn2+) is reported to promote the antitumor immune response by activating the cGAS‐STING pathway, but it is unknown whether Mn2+ can prevent the malignant transformation of precancerous lesions. The effects of Mn2+ in treating oral leukoplakia (OLK) were explored in this work. Methods: Peripheral blood Mn analysis of the patients was performed using inductively coupled plasma atomic emission spectroscopy (ICP–AES). A coculture model of dendritic cells (DCs)/macrophages, CD8+ T cells, and dysplastic oral keratinocytes (DOKs) was employed to analyze the role and mechanism of Mn2+ in a simulated OLK immune microenvironment. Western blot, RT–PCR, flow cytometry, enzyme‐linked immunosorbent assay (ELISA), and lactate dehydrogenase (LDH) assays were adopted to detect the mechanism of Mn2+ in this model. 4‐nitroquinoline oxide (4NQO)‐induced OLK mice were used to assess the role of Mn2+ in suppressing OLK progression, and a novel Mn2+‐loaded guanosine‐tannic acid hydrogel (G‐TA@Mn2+ hydrogel) was fabricated and evaluated for its advantages in OLK therapy. Results: The content of Mn in patients' peripheral blood was negatively related to the progression of OLK. Mn2+ promoted the maturation and antigen presentation of DCs and macrophages and enhanced the activation of CD8+ T cells in the coculture model, resulting in effective killing of DOKs. Mechanistic analysis found that Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway. Moreover, Mn2+ suppressed the development of 4NQO–induced carcinogenesis in the mouse model. In addition, the G‐TA@Mn2+ hydrogel had better anti‐OLK effects. Conclusions: Mn2+ enhanced the anti‐OLK immune response by activating the cGAS‐STING pathway, and the G‐TA@Mn2+ hydrogel is a potential novel therapeutic approach for OLK treatment. [ABSTRACT FROM AUTHOR]

City modeling and generation have attracted an increased interest in various applications, including gaming, urban planning, and autonomous driving. Unlike previous works focused on the generation of single objects or indoor scenes, the huge volumes of spatial data in cities pose a challenge to the generative models. Furthermore, few publicly available 3D real-world city datasets also hinder the development of methods for city generation. In this paper, we first collect over 3,000,000 geo-referenced objects for the cities of New York, Zurich, Tokyo, Berlin, Boston, and several other large cities. Based on this dataset, we propose AETree, a tree-structured auto-encoder neural network, for city generation. Specifically, we first propose a novel Spatial-Geometric Distance (SGD) metric to measure the similarity between building layouts and then construct a binary tree over the raw geometric data of the building based on the SGD metric. Next, we present a tree-structured network whose encoder learns to extract and merge spatial information from the bottom-up iteratively. The resulting global representation is reversely decoded for reconstruction or generation. To address the issue of long-dependency as the level of the tree increases, a Long Short-Term Memory (LSTM) Cell is employed as a basic network element of the proposed AETree. Moreover, we introduce a novel metric, Overlapping Area Ratio (OAR), to quantitatively evaluate the generation results. Experiments on the collected dataset demonstrate that the proposed model outperforms baseline models, such as LayoutTransformer and LayoutVAE, in terms of key metrics. Specifically, the proposed model achieves a Jensen–Shannon Divergence (JSD) of 0.0033, compared to 0.0041 and 0.0061 for LayoutTransformer and LayoutVAE, respectively. Similarly, for the Overall Accuracy Rate (OAR), the proposed model scores 1.66, significantly better than 28.24 and 19.01 for the baseline models Furthermore, the latent features learned by AETree can serve downstream urban planning applications. Project webpage is available at https://ai4ce.github.io/RealCity3D. [ABSTRACT FROM AUTHOR]

PA28γ overexpression is aberrant and accompanied by poor patient prognosis in various cancers, the precise regulatory mechanism of this crucial gene in the tumor microenvironment remains incompletely understood. In this study, using oral squamous cell carcinoma as a model, we demonstrated that PA28γ exhibits high expression in cancer-associated fibroblasts (CAFs), and its expression significantly correlates with the severity of clinical indicators of malignancy. Remarkably, we found that elevated levels of secreted IGF2 from PA28γ+ CAFs can enhance stemness maintenance and promote tumor cell aggressiveness through the activation of the MAPK/AKT pathway in a paracrine manner. Mechanistically, PA28γ upregulates IGF2 expression by stabilizing the E2F3 protein, a transcription factor of IGF2. Further mechanistic insights reveal that HDAC1 predominantly mediates the deacetylation and subsequent ubiquitination and degradation of E2F3. Notably, PA28γ interacts with HDAC1 and accelerates its degradation via a 20S proteasome-dependent pathway. Additionally, PA28γ+ CAFs exert an impact on the tumor immune microenvironment by secreting IGF2. Excitingly, our study suggests that targeting PA28γ+ CAFs or secreted IGF2 could increase the efficacy of PD-L1 therapy. Thus, our findings reveal the pivotal role of PA28γ in cell interactions in the tumor microenvironment and propose novel strategies for augmenting the effectiveness of immune checkpoint blockade in oral squamous cell carcinoma. • PA28γ in CAFs correlates with malignancy indicators and poor outcomes in OSCC. • PA28γ+ CAFs release IGF2, boosting stemness, tumor aggression via the MAPK/AKT pathway and rebuilding immunosuppressive TME. • PA28γ promotes HDAC1 degradation, stabilizing E2F3 and consequently orchestrating IGF2 production. • Targeting PA28γ+ CAFs or IGF2 enhances the effectiveness of PD-L1 therapy in OSCC. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disorder that poses a significant global health challenge. There is a lack of safe and effective medications to treat AD. Astragalus membranaceous is a traditional Chinese medicine widely used in clinical treatment of skin diseases. Calycosin (CA), derived from the root of Astragalus membranaceous , exhibits dual attributes of anti-inflammatory and antioxidant properties, suggesting its promise for addressing cutaneous inflammation. Nonetheless, the precise mechanisms underlying CA's therapeutic actions in AD remain elusive. This study aimed to evaluate the efficacy and safety of CA in treating AD while also delving into the mechanistic underpinnings of CA's action in AD. The cell viability and anti-inflammatory impacts of CA in vitro were first gauged using CCK-8 and RT-qPCR. The potential mechanisms of CA were then probed using modular pharmacology. Flow cytometry was employed to ascertain the differentiation of Treg and Th17 cells derived from naïve T cells, as well as the proportions and mean fluorescence intensity (MFI) of human iTreg cells. The expressions of IL-10 and TGF-β1 were measured and Treg suppression assay was performed. The in vivo therapeutic efficacy of topical CA application was assessed using a calcipotriol (MC903)-induced AD mouse model. The expression metrics of inflammatory cytokines, IL-17A, FOXP3, and RORγt were authenticated via immunohistochemistry, RT-qPCR, Western blot, and ELISA. CA exhibited a favorable safety profile and reduced the mRNA expressions of Th2 inflammatory cytokines in HaCaT cells. Modular pharmacology analysis pinpointed Th17 differentiation as the pivotal mechanism behind CA's therapeutic effect on AD. In vitro , CA fostered the differentiation of naïve T cells into Tregs while inhibiting their differentiation into Th17 cells. Furthermore, CA augmented the proliferation of human iTregs. In vivo, CA alleviated skin manifestations and decreased the levels of inflammatory mediators (IL-4, IL-5, IL-13, TSLP, and NF-κB related cytokines) in AD-like mouse models. Simultaneously, it regulated Treg/Th17 balance through suppressing IL-17A and RORγt expressions and bolstering FOXP3 expression. The study provides insights into the mechanistic pathways through which CA exerts its anti-inflammatory effects, particularly through promoting Treg cell differentiation and inhibiting Th17 cell differentiation. Furthermore, CA emerges as an alternative or adjunctive treatment strategy for managing AD. [Display omitted] [ABSTRACT FROM AUTHOR]

Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are ambiguous. More worsely, the developed medicines targeting amyloid-beta (Aβ) and/or tau hyperphosphorylation did not approach the clinical expectations in patients with moderate or severe AD until now. This review unveils the role of a vicious cycle between Aβ-derived formaldehyde (FA) and FA-induced Aβ aggregation in the onset course of AD. Document evidence has shown that Aβ can bind with alcohol dehydrogenase (ADH) to form the complex of Aβ/ADH (ABAD) and result in the generation of reactive oxygen species (ROS) and aldehydes including malondialdehyde, hydroxynonenal and FA; in turn, ROS-derived H 2 O 2 and FA promotes Aβ self-aggregation; subsequently, this vicious cycle accelerates neuron death and AD occurrence. Especially, FA can directly induce neuron death by stimulating ROS generation and tau hyper hyperphosphorylation, and impair memory by inhibiting NMDA-receptor. Recently, some new therapeutical methods including inhibition of ABAD activity by small molecules/synthetic polypeptides, degradation of FA by phototherapy or FA scavengers, have been developed and achieved positive effects in AD transgenic models. Thus, breaking the vicious loop may be promising interventions for halting AD progression. [Display omitted] • Aβ can bind with alcohol dehydrogenase (ADH) to form the complex of Aβ/ADH. • ADH inactivation induces FA generation; in turn, FA promotes Aβ self-aggregation. • Vicious cycle between Aβ-derived FA and FA-induced Aβ assembly elicits AD onset. • Degradation of FA alleviates Aβ neurotoxicity and Alzheimer-related phenotypes. • Breaking the vicious cycle is promising interventions for halting AD progression. [ABSTRACT FROM AUTHOR]

This work aims to study the ammonia/methanol blended fuel with ammonia cracking in lean-burn condition. Ammonia on-line cracking to produce hydrogen production has the potential to realize the high-efficiency combustion. A new ammonia/methanol/hydrogen mechanism was updated and simplified using several reduction methods to optimize the computation time in 3D simulation. Visualization measurements in constant volume combustion chamber (CVCC) for flame propagation and NO generation were conducted, and 3D computational fluid dynamics (CFD) modeling was also established with the simplified mechanism simultaneously to investigate the impact of methanol addition and ammonia cracking in the lean-burn mode. The findings showed that methanol addition and ammonia cracking can significantly improve the combustion rate, and 60%ammonia/40%methanol with ammonia cracking ratio of 90% (N60R90) at equivalence ratio (ER) of 0.7 yields the similar LBV as pure methanol at ER of 1.0 in laminar burning condition. Its ER can be extended to 0.4 to obtain the similar level of LBV as pure ammonia at 1.0. The experiments and 3D simulations revealed that N60R90 at 0.4 yields the equivalent level of combustion rate as N60R0 at 0.8, while obtaining much lower NO emission. In addition, N60R100 at 0.4 without fuel-NO formation during the combustion can get ultra-low NO emission. This study provides the insights on low-carbon combustion strategy for ammonia cracking with low NO. [ABSTRACT FROM AUTHOR]

[Display omitted] • An innovative method has been developed for creating metal ion-chelated silk fibroin coatings using a binary-solvent system. • Increased β -sheet content (45.4%) and crystallinity in silk fibroin result in enhanced corrosion resistance. • A universal mechanism for stepwise nucleation induced by binary solvent has been proposed. • The chelation of Ca2+ and Sr2+ into silk fibroin facilitates controlled release, thereby enhancing osteogenic activity. The development of biofunctional coating is vital for the clinical application of implants. A persistent challenge with magnesium alloys implants, which are inherently prone to rapid degradation, is the simultaneously enhancement of corrosion resistance and bioactivity. This study introduces a novel protein coating for magnesium alloys, incorporating calcium and strontium ions with silk fibroin. By utilizing the microcrystal nucleation facilitated by a binary solvent system, the β -sheet content is significantly increased to 45.4 % in silk fibroin. The increased β -sheet bolsters the "labyrinth effect" at the nanoscale, resulting in a substantial improvement in corrosion resistance. This is evidenced by a three-order-of-magnitude reduction in the corrosion current density (I corr) to 3.65 × 10−7 A cm−2, compared to that of the uncoated alloys. The meticulous doping of Ca2+ and Sr2+ ions ensures stable chelation with amorphous segments of silk fibroin. The controlled release activates the Wnt signaling pathway, boosting osteogenic activity. Such silk fibroin coating system, prepared through a straightforward method, enables a concurrent enhancement of both corrosion resistance and osteogenic potential in biomedical magnesium alloys. [ABSTRACT FROM AUTHOR]

The chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol has attracted increasing attentions in recent years in the field of pharmaceuticals because of its important use as a building block in the synthesis of novel anti-tumor drugs targeting tropomyosin receptor kinases. In the present study, a ω-transaminase (ωTA) library consisting of 21 (R)-enantioselective enzymes was constructed and screened for the asymmetric biosynthesis of (R)-2-(1-aminoethyl)-4-fluorophenol from its prochiral ketone. Using (R)-α-methylbenzylamine, D-alanine, or isopropylamine as amino donor, 18 ωTAs were identified with target activity and the enzyme AbTA, which was originally identified from Arthrobacter sp. KNK168, was found to be a potent candidate. The E. coli whole cells expressing AbTA could be used as catalysts. The optimal temperature and pH for the activity were 35–40 °C and pH8.0, respectively. Simple alcohols (such as ethanol, isopropanol, and methanol) and dimethyl sulfoxide were shown to be good cosolvents. High activities were detected when using ethanol and dimethyl sulfoxide at the concentrations of 5–20%. In the scaled-up reaction of 1-liter containing 13 mM ketone substrate, about 50% conversion was achieved in 24 h. 6.4 mM (R)-2-(1-aminoethyl)-4-fluorophenol was generated. After a simple and efficient process of product isolation and purification (with 98.8% recovery), 0.986 g yellowish powder of the product (R)-2-(1-aminoethyl)-4-fluorophenol with high (R)-enantiopurity (up to 100% enantiomeric excess) was obtained. This study established an overall process for the biosynthesis of the high value pharmaceutical chiral amine (R)-2-(1-aminoethyl)-4-fluorophenol by ωTA. Its applicable potential was exemplified by gram-scale production. • An enzymatic way for synthesizing (R)-2-(1-aminoethyl)-4-fluorophenol was reported. • 21 (R)-type ω-transaminases were screened. • Gram-scale production was achieved. • Product exhibited high (R)-enantiopurity (up to 100% e.e.). [ABSTRACT FROM AUTHOR]

• We synchronize gas hydration with membrane permeation to improve mass transfer for gas separation. • An accurate formula was developed to calculate the gas consumption during stable growth of hydrate. • We built a dynamic matching model to describe hydrate-membrane synergistic action. • We simulated the separation of H 2 -containing gas mixture by hydrate-membrane coupling method. • Simulation results indicate that the coupling method greatly improves the gas separation effect. The recovery of hydrogen (H 2) form H 2 -containing gas mixtures, such as petrochemical refinery tail gas, plays a important role in energy conservation and cost reduction. The hydrate-membrane coupling separation process has been demonstrated as a more efficient and energy-saving approach for H 2 recovery. This study aims to achieve the synergistic matching of hydration and permeation, so as to explore the underlying mechanisms of coupling and facilitate subsequent experimental studies. In this work, an effective method was developed to calculate the gas consumption rate during the stable growth stage of hydrates. Furthermore, a dynamic matching model of the hydrate-membrane coupling mechanism was employed to simulate the variations in the separation process using infinitesimal methods. The simulations indicate that the H 2 concentration of product gas and the feed gas treatment capacity of the coupling method outperform those of hydrate separation and membrane separation alone. Overall, this study provides valuable insights into an efficient and energy-saving method for H 2 recovery from H 2 -containing gas mixtures, utilizing the hydrate-membrane coupling method. These findings hold promising prospects for practical application in the future. [ABSTRACT FROM AUTHOR]

The presence of carbon tetrachloride in groundwater raises concerns for human health and the environment. Thus, there is an urgent need for a faster and more efficient groundwater remediation method. Our study found that the EHC remedial agent can achieve promising pilot remediation results quickly, as demonstrated in laboratory tests. During the pilot test, the contaminated groundwater was subjected to injection with the EHC remedial agent using in-situ high-pressure rotary jet technology. It was observed that indicators such as alkalinity and SO 4 2− can signify the occurrence of biological reduction, with the presence of ZVI significantly shortening the beginning time of biological action within the EHC. The pilot test results reveal that the initial four days following the injection of the EHC witnessed only chemical reduction, with chemical and biological reduction coexisting from day 4 to day 45. Post the 45-day mark, the removal of contaminants solely relied on biological reduction. While chemical reduction displayed a rapid rate but limited duration, insufficient for ensuring long-term effectiveness in the remediation process, bioremediation offered sustained efficacy for continuous contaminant reduction. These findings signify a more eco-friendly and efficient approach to groundwater remediation, offering both human health and environmental benefits. [Display omitted] • EHC injected using high-pressure rotary jet efficiently remediated CCl 4 -contaminated groundwater. • Alkalinity and SO 4 2− indicators demonstrated the initiation of biological reduction. • Chemical-Biological Coexistence ensure rapid and sustained remediation. • Bioremediation shows a continuous improvement in removal efficiency over 268 d. [ABSTRACT FROM AUTHOR]

Mixed traffic flow involving connected and automated vehicles (CAVs) and human-driven vehicles (HDVs) will be a new state in the future traffic pattern. However, the inherent "stop-and-go" mode of existing traffic signal control seriously weakens the advantage of CAV cooperative operation in mixed traffic. To handle this problem, this study proposes a novel traffic signal control scheme that addresses a mixed traffic scenario at a typical intersection. Specifically, the control scheme can precisely match traffic demand and space-time supply. Then, a protocol of white phases is proposed to decrease the crossing time of CAVs. Finally, the traffic signals and vehicle trajectories are optimized in a unified control framework that minimizes the travel delay of all vehicles. The proposed scheme is verified in SUMO-based simulation considering various penetration rates of the CAVs, different input traffic volumes, and different proportions of left-turning traffic. The experimental results show that the proposed scheme is superior to existing actuated signal control regarding stability when facing different input traffic volumes and proportions of left-turning traffic. Moreover, it is observed that the travel delay decreases with the penetration rates of the CAVs, indicating the potential of the proposed method in the near future mixed traffic scenario. • Matching traffic demand and space-time supply improves intersection efficiency. • Reservation-based phase can improve the control stability in dynamic traffic flow. • Average vehicle delay decreases with the increased number of CAVs. • Introducing white phases can decrease the crossing time of CAVs. [ABSTRACT FROM AUTHOR]