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The secondary structures of polypeptides, such as an α-helix and a β-sheet, often impart specific properties and functions, making the regulation of their secondary structures of great significance. Particularly, water-soluble polypeptides bearing a β-sheet conformation are rare and challenging to achieve. Here, a series of oligo(ethylene glycol)-modified lysine N-carboxylic anhydrides (EGmK-NCA, where m= 1–3) and the corresponding polymers EGmKnare synthesized, with urethane bonds as the linker between the side-chain EG and lysine. The secondary structure of EGmKnis delicately regulated by both mand n, the length (number of repeating units) of EG and the degree of polymerization (DP), respectively. Among them, EG2Knadopts a β-sheet conformation with good water solubility at an appropriate DP and forms physically cross-linked hydrogels at a concentration as low as 1 wt %. The secondary structures of EG1Kncan be tuned by DP, exhibiting either a β-sheet or an α-helix, whereas EG3Knappears to a adopt pure and stable α-helix with no dependence on DP. Compared to previous works reporting EG-modified lysine-derived polypeptides bearing exclusively an α-helix conformation, this work highlights the important and unexpected role of the urethane connecting unit and provides useful case studies for understanding the secondary structure of polypeptides.

•Therapeutic effect of mitoxantrone on expanded and ineffective erythropoiesis in β-thalassemia was evaluated.•Significant preclinical evidence for targeting autophagy as a novel therapeutic approach for β-thalassemia has been provided.

The application potential of ferroelectric thin films largely relies on the controllability of their domain structure. Among the various proposed strategies, mechanical switching is being considered as a potential alternative to replace electrical switching for control of the domain structure of ferroelectric thin films via, e.g., the flexoelectric effect. So far, studies on mechanical switching are confined to out-of-plane polarization switching in ferroelectric thin films, which are in pristine or prepoled single-domain states. In this work, we report reversible in-plane mechanical switching of the monoclinic phase (MCphase) stripe domains in BiFeO3thin films can be realized by scanning tip force. Via controlling the fast scan direction of the scanning probe microscopy tip and the magnitude of the tip force, the effective trailing field induced by the local tip force can be rotated to consequently switch the net in-plane polarization of the two-variant stripe domain patterns by either 90° or 180°. Moreover, the monoclinic to rhombohedral (MC-R) phase transition occurs during mechanical switching with the distribution of R-phase domains dependent on the switching paths. These results extend our current understanding of the mechanical switching behavior in ferroelectric thin films and should be instructive for their future applications.

Objectives:This study examines the association between family conflict and self-efficacy in discussing end-of-life (EOL) care with family members and whether such an association differs by acculturation levels among older Chinese Americans. Method:Data were collected from 213 Chinese Americans ages 65–102 in Phoenix, AZ, and Germantown, MD. We conducted ordinary least squares regression to examine the association between family conflict, acculturation, and self-efficacy in discussing EOL care with family. Results:Family conflict was negatively associated with older adults’ self-efficacy in discussing EOL care with family. The negative association between family conflict and self-efficacy in discussing EOL care with family was more pronounced for those with higher levels of acculturation. Conclusions:As one of the first research efforts to study advance care planning among older Chinese Americans, our findings highlight differential effects of family conflict on self-efficacy of EOL care plan discussion within the context of acculturation levels. Geriatric and health social workers should assess and address acculturation to develop family-centered interventions that improve EOL care planning for older Chinese Americans.

A new homogenization kinetics prediction model for wrought superalloys based on the concept of diffusion distance was proposed. The micro-segregation and homogenization kinetics of Ni-based wrought superalloy, GH4141, were systematically studied by using the quantitative electron prob X-ray micro-analyzer (EPMA) analyses. There is a discrepancy between the predicted homogenization kinetics by the residual segregation index model and the experimental measurement. Both the experiments and theoretical analyses reveal that the homogenization kinetics can be reasonably predicted by the diffusion distance model under 1D-diffusion condition, with considering the diffusion-direction factor that is usually ignored. The new model provides a new option for predicting the homogenization kinetics with only necessarily knowing the original dendrite arm spacing and diffusion coefficient.

Purpose: In order to enhance the output performance of magnetic levitating vibration energy harvesters over a wide frequency range, this paper investigates performance enhancement strategies for the tri-magnet levitating bistable electromagnetic energy harvesters (BEEHs). Methods: The bistable nonlinear mechanism is achieved by magnetic interaction between the cylindrical and ring magnets, enabling the harvester to resonate over a wide frequency range. However, the gravity-induced asymmetric bistable potential adversely affects the output voltage response. Therefore, the bistable configuration with balanced potential well depth is proposed to improve the output performance. Results: Simulation results based on the basins of attraction show that the probability of the oscillator eventually stopping at the left and right-side potential wells is approximately the same for different initial conditions. Furthermore, the output voltage response of asymmetric and balanced BEEHs is investigated under different excitation conditions. The results show that the balanced BEEH can achieve the high-energy orbit response over a wider frequency range for the same excitation level. Two coil series connections are provided, and their performance enhancement mechanisms are analyzed. Simulation and experimental results illustrate that the series connection of coils with the same wound direction (Series 1) is more favorable for the BEEH to achieve inter-well oscillation, which is suitable for vibration environments with small excitation levels. The series connection of coils with opposite wound directions (Series 2) improves the peak output voltage but generates large electromagnetic damping forces, making it more suitable for operating conditions with high excitation levels and large load resistance. Conclusion: Balancing the potential well depth can facilitate oscillator travel across the potential barrier, and choosing the appropriate series coil solutions can exploit the BEEH advantages fully. These performance enhancement strategies have been proven to be effective in this paper.

Zr-based bulk metallic glasses (BMGs) are promising for extensive industrial applications due to their superior mechanical properties, excellent glass formation ability (GFA), and low manufacturing costs. However, the wear resistance of Zr-based BMGs, especially when exposed to high-temperature service environments, is deficient and could lead to premature failure of critical components. Herein, we report an effective strategy that can significantly enhance the high-temperature wear resistance of Zr-based BMGs, referred to as pre-oxidation treatment (PT). At ambient temperature, the wear rate of the pristine Zr-based BMG samples was estimated to be ∼173.7 × 10−6 mm3 N−1 m−1, whereas the PT samples subjected to the PT strategy showed no detectable volume loss. In addition, the wear rate of the PT samples at 250 °C was ∼11.5 × 10−6 mm3 N−1 m−1. Intriguingly, even as the temperature surpassed the crystallization point of the BMG, the PT samples demonstrated a further enhancement in wear resistance, showcasing a wear rate of approximately ∼7.29 × 10−6 mm3 N−1 m−1. Our work introduces a promising and convenient strategy to enhance the high-temperature wear resistance of Zr-based BMG components, thereby promoting their application in real-world engineering scenarios.

The pitting corrosion behaviors of high-strength metastable austenitic stainless steel (MASS) 14Cr10Mn with different cold rolling reductions (0 %, 10 % and 20 %) were investigated in simulated coastal atmospheric environments by scanning electron microscope (SEM), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), electrochemical measurements and cyclic corrosion test. The cold rolling deformation noticeably increases the dislocation density in the steel. As the cold rolling reduction changes from 0 % to 20 %, the pitting potential and the polarization resistance decrease to some extent in 1 wt% NaCl solution. The cold rolling deformation increases the defect density and the contents of (Fe,Cr)-oxyhydroxides/hydroxides in the passive film on the specimen surface. After the wet-dry cyclic corrosion test, the corrosion pits initiate at the deformation band regions. The quantity, diameter and depth of the pits gradually increase with enlarging the cold rolling reduction.

ABSTRACTHigh strength structural steels have recently achieved increasing application in civil and structural engineering worldwide. For instance, the sony center tower located in Berlin were constructed through steel truss made [...]

Non-evaporable getter (NEG) films require thermal vacuum activation prior to their use in high vacuum environments. The degree of activation difficulty is influenced by the properties of the passivation layer, but there is limited information about its composition. The purpose of this study is to investigate the formation mechanism and clarify this issue. The film microstructure was investigated by scanning electron microscopy (SEM) and grazing incidence X-ray diffraction (GIXRD). The quantum chemical approach and a single-metal-atom catalytic model were used to calculate the energy barrier for the reactions between the metal atom and the gas molecule, as well as between different hydrocarbon groups. These results facilitated the deconvolution of the X-ray photoelectron spectroscopy (XPS) data and the variation analysis of the energy dispersive spectroscopy (EDS) results. It can be concluded that the presence or absence of hydrogen-proton catalysis can significantly affect the dissociation pathways of carbon dioxide, leading to the formation of different reaction products. In addition, the long-term aluminum foil wrapping and storage can significantly affect the composition of the film passivation layer. This study provides valuable insights not only into the passivation layer formation mechanism, but also into the film gettering mechanism.

Preventing metal corrosion has usually been associated with water-repellent coatings that inhibit the penetration of aggressive chloride ions. Contrary to this conventional wisdom, we engineered ultrathin superhydrophilic zwitterionic hydrogel brushes rooted in a nanoporous anodic aluminum oxide (AAO) substrate that effectively hampered the adsorption of hydrated chloride ions (Cl–·H2O) on the Al alloy surface. The hydrogel brush coating enhanced corrosion resistance by 3 orders of magnitude, with corrosion current density declining from 1.518 to 1.567 × 10–3μA cm–2. Despite suffering from long-term salt-spaying tests, zwitterionic hydrogel brush coating retained 2 orders of magnitude of corrosion resistance. Direct Raman spectroscopic evidence manifested that interfacial water comprised both highly ordered hydrogen-bonded water and disordered water containing hydrated Cl–ions. Under the hydration effect of zwitterionic hydrogel brushes, an interfacial disordered water structure dynamically transformed into a hydrogen-bonded water film. We correlated the structure and quantities of interfacial water with the corrosion current density and chloride adsorption. Hydrogen-bonded water improved by zwitterionic hydrogel brushes weakened the affinity and adsorption of hydrated Cl–ion water on the oxide film, resulting in excellent corrosion protection. Therefore, employing localized hydration tuning strategies, these findings are anticipated to generally empower ordered interfacial water to enhance metal corrosion resistance through precise interfacial engineering.

Hydrophones rely on high sensitivity to detect weak hydroacoustic signals, with the diaphragm structural design significantly impacting the sensitivity of MEMS piezoelectric hydrophones. Traditional optimization methods for hydrophone structure involve creating an equivalent circuit mathematical model or a finite-element analysis (FEA) model through simulation, starting with a structural model based on equivalent analogy or empirical knowledge, and proceeding with a parametric analysis of geometric structural parameters. However, these methods are computationally intensive and time-consuming, impeding structural design optimization. This article presents an intelligent learning (IL) algorithm-based method for optimizing MEMS hydrophone structures, which aims to simplify the design process and enhance hydroacoustic reception. Orthogonal tests and FEA models are utilized to collect the simulation data, and neural network models are developed to illustrate the relationship between the structural parameters and hydrophone performance. The diaphragm electrode thickness, piezoelectric layer thickness, diaphragm radius, and top electrode radius are optimized through a backpropagation (BP) neural network enhanced by the particle swarm optimization algorithm. The model’s accuracy is validated through simulation testing, with the optimized hydrophone sensitivity and effective electromechanical coupling coefficient averaging 99.77% and 96.03%, respectively. A MEMS hydrophone is fabricated based on the design model’s optimization results, and experimental testing confirmed the design performance. This method can meet the design requirements of MEMS hydrophones with improved efficiency and precision and can be extended to other MEMS sensors and actuators requiring structural parametric design.

Zeolitic imidazolate framework-8 (ZIF-8) is extensively researched and used because of its exclusive structural and excellent physicochemical properties; however, significant challenges of alleviating the adverse effects of its particle form in many aspects are still faced by the scientific community. In this study, in situ growth of ZIF-8 within the pore channels and surfaces of green cellulose-based wood sponge was attempted through polydopamine-mediated incubation. The wood sponge was prepared by eliminating lignin and hemicellulose from natural balsa wood. Then, the sponge was impregnated with dopamine aqueous solution to yield polydopamine-covered wood sponge (PWS). ZIF-8 crystals were ultimately in situ grown in the substrate after sequential impregnation with zinc nitrate hexahydrate and 2-methylimidazole aqueous solutions at room temperature. Additionally, the effects of the deposition concentration of the dopamine aqueous solution and ZIF-8 incubation time were investigated. The obtained ZIF-8@PWS was characterized using Fourier transform infrared spectroscopy, scanning electron microscopy, X-ray diffraction, Brunauer–Emmett–Teller analysis and thermogravimetric analysis. Finally, the toluene adsorption performance of porous ZIF-8@PWS in aqueous solution was also briefly evaluated, and it was demonstrated that the maximum adsorption capacity was 106.4 mg/g and the removal rate was as high as 94.2%. This work validates the envisioned universal protocol of preparing ZIF-8-decorated porous substrates through the integrated mediating role of polydopamine.

Viral nervous necrosis (VNN) caused by a betanodavirus (NNV) is one of the major diseases in Asian seabass (Lates calcarifer) hatcheries. Our previous studies showed that the tbx21gene was in a QTL for NNV resistance in linkage group 23 in Asian seabass. The expression of this gene was changed in tissues of Asian seabass challenged with NNV. However, the role of tbx21in NNV resistance remains largely unknown. In this study, tbx21of Asian seabass was characterized. This gene consists of an ORF of 1866 bp, a 5′ UTR of 357 bp, and a 3′ UTR of 4674 bp. The TBX21 protein showed substantial amino acid similarity (70–96%) with other fish but exhibited lower identity (47–52%) with mammals. One SNP identified in the first intron was significantly associated with NNV resistance. In healthy fish, tbx21was expressed in all tissues examined, and was highly expressed in the kidney and liver. The expression of tbx21increased in the eye, gills, heart, kidney and gut, but decreased in the brain and spleen at five days after NNV challenge. Overexpression of tbx21reduced the replication of NNV, whereas knockdown increased viral expression and virus titers. These results suggest that tbx21plays a key role in NNV resistance. The SNP in this gene could be used as a marker to facilitate marker-assisted selection for NNV resistance. Further investigation of polymorphisms in the 5’ and 3’ UTRs of tbx21may provide additional insights into the gene's role in NNV resistance.

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies, including Alzheimer’s disease (AD). We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase, thus specifically facilitating tau dephosphorylation and removal. Here, we sought to optimize the construction of tau dephosphorylating-targeting chimera (DEPTAC) and obtained a new chimera D14, which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models, while showing limited cytotoxicity. Moreover, D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K18 fragments, and improved cognitive functions of tauopathy mice. These results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

The uniaxial compression tests are conducted on single-fissured sandstone with different angles, and the effect of fissure angle (β) on mechanical properties, acoustic emission (AE) features, crack propagation characteristics, and failure mode of sandstone are studied with the AE monitoring and photographic system. The research results reveal that as the βincreases, the uniaxial compressive strength (UCS) exhibits an asymmetric inverted “U” shape and the minimum is only 33.14 MPa when β= 30°, while the elastic modulus increases monotonously from 8.98 to 15.14 GPa. During the loading process, the AE parameters demonstrate obvious stage characteristics, while tension cracks dominate and the shear cracks significantly increase. As βincreases, the AE activity gradually shifts to the post-peak destruction stage, and the effect of shear crack on the final failure mode of the specimens becomes more significant. The stress–strain relationship, AE features, and real-time photographic system are sufficient to comprehensively depict the crack evolution process in each stage, and there is a good correlation between each parameter. Increase in βmakes the crack initiation stress and its ratio to UCS increase, from 68.74% to 79.92%, which makes it more difficult for crack initiation, and the secondary crack propagation gradually transforms from tension to shear. The macroscopic failure mode of fissured sandstone gradually changes from tension failure to mixed tension–shear failure and finally to shear failure, the angle between the propagation direction of initial cracks and fissure gradually decreases, and the surface spalling zone becomes more obvious.

Lysosomal compartments undergo extensive remodeling during dendritic cell (DC) activation to meet the dynamic functional requirements of DCs. Instead of being regarded as stationary and digestive organelles, recent studies have increasingly appreciated the versatile roles of lysosomes in regulating key aspects of DC biology. Lysosomes actively control DC motility by linking calcium efflux to the actomyosin contraction, while enhanced DC lysosomal membrane permeability contributes to the inflammasome activation. Besides, lysosomes provide a platform for the transduction of innate immune signaling and the intricate host-pathogen interplay. Lysosomes and lysosome-associated structures are also critically engaged in antigen presentation and cross-presentation processes, which are pivotal for the induction of antigen-specific adaptive immune response. Through the current review, we emphasize that lysosome targeting strategies serve as vital DC-based immunotherapies in fighting against tumor, infectious diseases, and autoinflammatory disorders.In this study, we highlight that lysosomes undergo extensive remodeling amid the functional maturation of dendritic cells (DCs). In turn, lysosomes actively regulate the motility, inflammasome activation, and innate immune sensing of DCs. Lysosomes also mediate the intricate host-pathogen interplay, while lysosomes and lysosome-associated structures are critically engaged in antigen presentation and cross-presentation pathways, rendering lysosome-targeting an appealing strategy for DC-based immunotherapies.

Micro- and nano-structures are a new type of material structures that combines micrometer- and nanometer-scale structures in a single material, which confers special properties on the material. Designing and fabricating micro- and nano-structures on glass surfaces hold great importance for achieving desired functionalities. However, the inherent hardness and brittleness of glass pose challenges for preparing micro-structures using traditional fabrication methods. Thus, developing a simple and controlled manufacturing strategy becomes imperative to prepare micro- and nano-structured glasses with functional applications. In this work, an innovative approach that employed soluble NaCl particles as precursor templates was presented, allowing the formation of customizable porous structures on glass surfaces. Using the pioneering molding strategy proposed here, the potential of soluble NaCl particles as templates was successfully harnessed, thereby facilitating the fabrication of tailorable porous glass surfaces. By tuning the size and combination of these particles, porous glasses ranging from superhydrophilic (1°) to superhydrophobic (142°) were achieved. Notably, the prepared porous glass surfaces demonstrated remarkable lipophilicity, highlighting its great potential for diverse applications, such as oil–water separation and self-cleaning. Importantly, even after undergoing 10 fabrication iterations, the hydrophobic–oleophilic functionality of the glass surface remained intact, underscoring the durability and repeatability of our strategy. This approach offers a convenient and cost-effective means to achieve special functions in glass, paving the way for advancements across various fields.

ABSTRACTObjectivesTo explore the relationship between serum uric acid (UA) and high-density lipoprotein cholesterol (HDL-C) ratio (UHR) and metabolic syndrome (MetS) in nondiabetic individuals.MethodsA total of 15,760 nondiabetic participants were screened from the China National Diabetes and Metabolic Disorders Study. Pearson correlation was used to determine the correlation between the components of MetS and UHR, HDL-C, and UA. Receiver operating characteristic curves were used to evaluate the ability of UHR, HDL-C, and UA to identify MetS in the nondiabetic population.ResultsA total of 6,386 men and 9,374 women were enrolled in this study. There were 1,480 (23.2%) men and 1,828 (19.5%) women with MetS. UHR significantly correlated with the components of MetS in men and women, especially with waist circumference  and triglyceride. In men, although HDL-C showed a higher specificity index, UHR presented higher sensitivity index and area under the curve (AUC) than HDL-C (P = 0.0001) and UA (P < 0.0001), with AUC (95% CI) of 0.762 (0.752–0.773). Higher AUCs of UHR relative to HDL-C and UA were also observed in the age groups <40 and 40–59 years. There was no significant difference in AUC between UHR and HDL-C in the age group ≥60 years (P = 0.370). However, similar results were not observed in women.ConclusionUHR significantly correlated with the components of MetS and could serve as a novel and reliable marker for identifying the population at a high risk of MetS in nondiabetic men, especially in younger adults.

Self-sensing soft robotics that mimic the proprioception and exteroception abilities of natural biological systems have shown great potential in challenging applications. However, current add-on strategies that simply combine sensors with actuators by post processing generally suffer from poor compatibility in mechanical properties, interfacing problems, complex manufacturing, and high cost. Herein, we present knitted soft robotics with build-in textile-integrated multimodal sensors, where the knit structure is used not only as a physical actuating layer but also as a sensing functional component. Based on different knit-stitch arrangements, an all-in-one knitted electronic skin with functions of neurons, sensing, and actuation in a single knit-structured fabric layer is constructed. The knitted electronic skin is then integrated into knitted soft robotics, enabling a proprioceptive sense of actuation deformation and an exteroceptive perception of ambient stimuli with minimized interferences for actuation. In addition, the tuck stitches serve as an anisotropic strain-limiting layer to increase the actuating energy efficiency, which resolves the key conflict of softness and volumetric power density in soft actuators. This design strategy provides a convenient, low-cost, and customized method to bring about structural and functional integrability into soft actuators, greatly extending the adaptability of current soft robotics for real-world applications.

• The high temperature wear behavior and wear mechanisms of a novel Ir-Ta-Ni-Nb bulk metallic glass were investigated. • The superior high temperature wear resistance of Ir-Ta-Ni-Nb bulk metallic glass compared to other reported metallic glass systems was demonstrated. • The oxidation behavior of Ir-Ta-Ni-Nb bulk metallic glass during high temperature wear was studied. Wear resistance is a critical consideration in engineering applications. In this study, we demonstrated an Ir-Ta-Ni-Nb bulk metallic glass (BMG) with outstanding high-temperature wear resistance and revealed its promising applications in extreme environments. The wear behavior and mechanism were systematically investigated from room temperature (RT) to 750 °C. The results show that the wear rate increases from ∼2.65 × 10−6 mm3 N−1 m−1 to ∼10.56 × 10−6 mm3 N−1 m−1 in the temperature span RT to 400 °C, following abrasive wear and flash temperature-induced oxidative wear during the friction. However, at the higher temperature of 600 °C, further heating due to frictional heat leads to a softening of the wear surface, resulting in a maximum wear rate of ∼20.99 × 10−6 mm3 N−1 m−1 under softness-driven abrasive wear as well as oxidative wear. Interestingly, the wear resistance at an even higher temperature of 750 °C shows a paradoxical improvement of ∼7.08 × 10−6 mm3 N−1 m−1, which is attributed to the formation of an oxide layer with a thickness of several microns, avoiding violent wear of BMG. The results demonstrate the unreported outstanding high-temperature wear resistance of the Ir-Ta-Ni-Nb BMG, especially its excellent capability to resist wear at 750 °C, leading to the promising applications of BMG in the fields of aerospace, metallurgy, and nuclear industries. [ABSTRACT FROM AUTHOR]

LINE-1s are the major clade of retrotransposons with autonomous retrotransposition activity. Despite the potential genotoxicity, LINE-1s are highly activated in early embryos. Here we show that a subset of young LINE-1s, L1Md_Ts, are marked by the RNA polymerase II elongation factor ELL3, and function as enhancers in mouse embryonic stem cells. ELL3 depletion dislodges the DNA hydroxymethylase TET1 and the co-repressor SIN3A from L1Md_Ts, but increases the enrichment of the Bromodomain protein BRD4, leading to loss of 5hmC, gain of H3K27ac, and upregulation of the L1Md_T nearby genes. Specifically, ELL3 occupies and represses the L1Md_T-based enhancer located within Akt3, which encodes a key regulator of AKT pathway. ELL3 is required for proper ERK activation and efficient shutdown of naïve pluripotency through inhibiting Akt3during naïve-primed transition. Our study reveals that the enhancer function of a subset of young LINE-1s controlled by ELL3 in transcription regulation and mouse early embryo development.

Objectives:In China, the high prevalence of cognitive impairment among older adults affects millions of family caregivers and raises concerns for caregiver burden, depression, and other mental health problems. The purpose of this study is to examine the association between coping strategies and caregiver burden and depression among Chinese caregivers of older adults with cognitive impairment. Method:Data came from structured interviews with 300 primary family caregiver–care recipient dyads in Wuhan, China. Coping strategies were measured by the Brief COPE (Coping Orientation to Problems Experienced) survey, caregiver burden was measured by the Zarit Burden Interview, and depression was measured by the Center for Epidemiologic Studies Depression Scale. We used ordinary least squares regression to examine the association between coping strategies and caregiver burden and depression. Results:More positive reframing and acceptance were associated with lower caregiver burden, whereas more self-distraction was associated with higher caregiver burden. More positive reframing was associated with lower caregiver depression, whereas higher self-distraction and religion were associated with higher caregiver depression. Conclusions:Findings are of particular importance in developing and refining mental health interventions to prevent and reduce caregiver burden and stress by advocating for resources and training to facilitate effective positive reframing.

We investigated the ferrite recrystallization behavior of pure iron with different dislocation characters. Two types of specimens with almost the same dislocation densities and different dislocation characters were prepared. The edge dislocation density in specimen A was larger than that in specimen B, whereas the screw dislocation density in specimen B was larger than that in specimen A. Ferrite recrystallization progressed faster in specimen A than in specimen B. Furthermore, cellular automaton simulation proved that changes in ferrite recrystallization behavior due to the dislocation character are attributed to the difference in the driving force for recrystallization and the activation energy for recovery in each specimen. Thus, we found that the difference in the dislocation character can affect the ferrite recrystallization behavior of pure iron.

Purpose: The existing Nonlinear Dynamic Vibration Absorbers (NLDVAs) have the disadvantages of complex structure, high cost, high installation space requirements and difficulty in miniaturization. And most of the NLDVAs have not been applied to reality. To address the above issues, a novel Triple-magnet Magnetic Dynamic Vibration Absorber (TMDVA) with tunable stiffness, only composed of triple cylindrical permanent magnets and an acrylic tube, is designed, modeled and tested in this paper. Design/methodology/approach: (1) A novel TMDVA is designed. (2) Theoretical and experimental methods. (3) Equivalent dynamics model. Findings: It is found that adjusting the magnet distance can effectively optimize the vibration reduction effect of the TMDVA under different resonance conditions. When the resonance frequency of the cantilever changes, the magnet distance of the TMDVA with a high vibration reduction effect shows an approximately linear relationship with the resonance frequency of the cantilever which is convenient for the design optimization of the TMDVA. Originality/value: Both the simulation and experimental results prove that the TMDVA can effectively reduce the vibration of the cantilever even if the resonance frequency of the cantilever changes, which shows the strong robustness of the TMDVA. Given all that, the TMDVA has potential application value in the passive vibration reduction of engineering structures.

In maize, prolificacy, the number of ears per plant, is a trait of interest to maize breeders for breeding high grain-yielding cultivars or specialty corn, as well as being a model trait for decoding the molecular mechanism of maize evolution. Its genetic basis remains largely unknown. We identified a stable quantitative trait locus, qEN7, for ear number on chromosome 7 in both F2and F2:3populations derived from a single cross between the nonprolific inbred line Mo17 and the prolific inbred line LAN404 derived from the landrace PI217404. qEN7explained 10.7%–11.9% of phenotypic variation, and the LAN404 allele at this locus was associated with an increase of around one ear per plant. qEN7was confined by fine-mapping to a 0.56-Mb region containing eight annotated genes. Analysis of selection, gene expression patterns in various maize tissues, and sequence polymorphisms between the two parental lines suggested that Zm00001d020683, which encodes a putative INDETERMINATE DOMAIN (IDD) transcription factor, is the most likely candidate gene underlying qEN7. Zm00001d020683is expressed mainly in the vegetative meristem, immature ears, and internodes and has undergone selection during maize improvement. The identification of qEN7and the prediction of its candidate gene sheds some light on the evolution of maize ear number and provides a novel resource for breeding of multi-ear maize cultivars.

Aging research has shifted from studying phenotypes to studying in-depth mechanisms in recent decades. However, extrapolating cellular and molecular bases of aging from studying traditional model systems to humans has been challenging. The advent of organoids holds promise for overcoming the limitations of monolayer cell culture and bridging the gap between animal models and humans. Here, we mainly discuss recent paradigms for using organoid models in studying organ aging. Pluripotent stem cells–derived organoid provides a promising platform for simulating the pathophysiology of several aging-related diseases, especially neurodegenerative diseases, and adult stem cells organoids derived from different age groups have been applied to detect aging-related functional changes. We also assess the value of organoid model systems in understanding human aging and aging-related diseases, and identify challenges to be addressed in the future, such as the immaturity of organoids, and effective methods of inducing aging.

AbstractPerformance evaluations often convey values promoted by the government. However, it is unclear in the Chinese context what ‘performance’ means when referring to appraised values because little empirical evidence exists, particularly regarding the relations between values. This study examines Hangzhou, a pioneering case among Chinese municipalities of comprehensive performance evaluation, to analyze the relations between values. We examined 2,422 performance evaluation reports and policies released to the public. After conducting content and social network analyses, we theorized the public values structure were composed of relations of hierarchy, proximity, and causality. Our findings indicate prime values were listed prior to instrumental or market-driven values. The proximity between public interest and quality is demonstrated by the highest correlation coefficients. Each value cluster contains a causal relationship, indicating one value is the means to another. We discuss the values-oriented approach to performance evaluation, the contextual nature of public values studies, and the limits of using public satisfaction in performance evaluation. As an exploratory study, this work identifies values advocated by local governments in China; such findings are absent from existing research. Moreover, this study provides a practical method for empirically studying public values.

Cryo-electron tomography (cryo-ET) has become a powerful approach to study the high-resolution structure of cellular macromolecular machines in situ. However, the current correlative cryo-fluorescence and electron microscopy lacks sufficient accuracy and efficiency to precisely prepare cryo-lamellae of target locations for subsequent cryo-ET. Here we describe a precise cryogenic fabrication system, ELI-TriScope, which sets electron (E), light (L) and ion (I) beams at the same focal point to achieve accurate and efficient preparation of a target cryo-lamella. ELI-TriScope uses a commercial dual-beam scanning electron microscope modified to incorporate a cryo-holder-based transfer system and embed an optical imaging system just underneath the vitrified specimen. Cryo-focused ion beam milling can be accurately navigated by monitoring the real-time fluorescence signal of the target molecule. Using ELI-TriScope, we prepared a batch of cryo-lamellae of HeLa cells targeting the centrosome with a success rate of ~91% and discovered new in situ structural features of the human centrosome by cryo-ET.

ABSTRACTInfertility is rarely life threatening, however, it poses a serious global health issue posing far-reaching socio-economic impacts affecting 12–15% of couples worldwide where male factor accounts for 70%. Functional spermatogenesis which is the result of several concerted coordinated events to produce sperms is at the core of male fertility, Alternative splicing and microRNA (miRNA) mediated RNA silencing (RNAi) constitute two conserved post-transcriptional gene (re)programming machinery across species. The former by diversifying transcriptome signature and the latter by repressing target mRNA activity orchestrate a spectrum of testicular events, and their dysfunctions has several implications in male infertility. This review recapitulates the knowledge of these mechanistic events in regulation of spermatogenesis and testicular homoeostasis. In addition, miRNA payload in sperm, vulnerable to paternal inputs, including unhealthy diet, infection and trauma, creates epigenetic memory to initiate intergenerational phenotype. Naive zygote injection of sperm miRNAs from stressed father recapitulates phenotypes of offspring of stressed father. The epigenetic inheritance of paternal pathologies through miRNA could be a tantalizing avenue to better appreciate ‘Paternal Origins of Health and Disease’ and the power of tiny sperm.

ABSTRACTBackgroundFasting glucose variability (FGV) extensively promotes the onset and development of diabetic complications. This study aimed to evaluate the FGV in type 2 diabetes mellitus (T2DM) patients administered basal insulin using a needle-free insulin injector (NFII).Research design and methodsThis was a prospective randomized multicenter open-label crossover study. We randomly assigned 48 T2DM patients to receive basal insulin by NFII or conventional insulin pen (CIP) for 7–14 days and were then crossed over after washout. We conducted continuous glucose monitoring to investigate the FGV, our primary outcome was a composite parameter of the FGV with a fasting blood glucose target between 4.4 and 6.1 mmol/L.ResultsThe coefficient of variation for sensor glucose at 6 a.m. with CIP was 11.67 (8.70,14.81)% vs. 9.48 (6.48,12.24)% with NFII (p= 0.003), and the coefficient of variation for mean sensor glucose at 5–6 a.m. with CIP was 12.70 (9.17,16.56)% vs. 9.23 (7.01,11.98)% with NFII (p< 0.001). The overall basal insulin dosage with CIP injection was 18.00 (16.00, 20.00) IU vs. 16.00 (12.00, 19.00) IU during NFII (p< 0.003).ConclusionCompared with CIP, the use of the NFII to inject basal insulin improved FGV in T2DM.Clinical trial registrationhttps://www.chictr.org.cnIdentifier isChiCTR2000034674.

4-methylimidazole (4-MI), a derivative of imidazole, is a widely used component in caramel-colored food products such as soy sauce, beer and other soft drinks. The present study is aimed to investigate the effects of 4-MI on the male reproduction. The results revealed that 8 weeks of 4-MI exposure did not significantly alter the body weight and testicular weight of male mice. However, testicular morphology and computer-assisted sperm analysis showed that exposed to 4-MI caused irregular arrangement of spermatogenic cells in the testes and weakened sperm motility. Consistently, we observed the decreased fertilization ability in vivo of 4-MI-treated male mice. We further demonstrated that 4-MI disrupted the blood-testis barrier (BTB) integrity by decreasing the protein expression of BTB-related junction with permeability assay and western blot. In addition, the apoptosis of Sertoli cells (TM4) occurred in 4-MI treated mice, which might be caused by the generation of oxidative stress. Collectively, our findings document that 4-MI exposure damages the sperm mobility via disruption of BTB integrity.

Small-molecule prodrug nanoassembly technology with a unique advantage in off-target toxicity reduction has been widely used for antitumor drug delivery. However, prodrug activation remains a rate-limiting step for exerting therapeutic actions, which requires to quickly reach the minimum valid concentrations of free drugs. Fortunately, we find that a natural compound (BL-193) selectively improves the chemotherapy sensitivity of breast cancer cells to podophyllotoxin (PPT) at ineffective dose concentrations. Based on this, we propose to combine prodrug nanoassembly with chemotherapy sensitization to fully unleash the chemotherapeutic potential of PPT. Specifically, a redox-sensitive prodrug (PSSF) of PPT is synthesized by coupling 9-fluorenyl-methanol (Fmoc-OH) with PPT linked via disulfide bond. Intriguingly, PSSF with a π-conjugated structure readily co-assembles with BL-193 into stable nanoassembly. Significantly, BL-193 serves as an excellent chemosensitizer that creates an ultra-low-dose chemotherapeutic window for PPT. Moreover, prodrug design and precise hybrid nanoassembly well manage off-target toxicity. As expected, such a BL-193-empowered prodrug nanoassembly elicits potent antitumor responses. This study offers a novel paradigm to magnify chemotherapy efficacy-toxicity benefits.

The nuclear pore complex (NPC), one of the largest protein complexes in eukaryotes, serves as a physical gate to regulate nucleocytoplasmic transport. Here, we determined the 8 Å resolution cryo-electron microscopic (cryo-EM) structure of the outer rings containing nuclear ring (NR) and cytoplasmic ring (CR) from the Xenopus laevisNPC, with local resolutions reaching 4.9 Å. With the aid of AlphaFold2, we managed to build a pseudoatomic model of the outer rings, including the Y complexes and flanking components. In this most comprehensive and accurate model of outer rings to date, the almost complete Y complex structure exhibits much tighter interaction in the hub region. In addition to two copies of Y complexes, each asymmetric subunit in CR contains five copies of Nup358, two copies of the Nup214 complex, two copies of Nup205 and one copy of newly identified Nup93, while that in NR contains one copy of Nup205, one copy of ELYS and one copy of Nup93. These in-depth structural features represent a great advance in understanding the assembly of NPCs.

A facile, precise, and controllable manufacturing technology is desired for hierarchical functional surfaces. In this work, we successfully manufactured porous metallic glass using a water-dissolution material as template and the excellent thermoplastic property of metallic glass. The prepared micro/nanostructures have excellent tunability, and the proposed approach can be used to prepare large-area disordered porous structures and ordered regular arrays with nanoscale replication accuracy. In particular, the disordered porous structure prepared by the dissolvable template strategy exhibits a water contact angle of ∼140° and an oil contact angle of ∼0°, making it suitable for oil/water separation. It also shows stable wettability after being soaked in strong acid or alkali environments and maintains a ∼130° water contact angle and a ∼4° oil contact angle even after severe wear. The proposed strategy also possesses excellent recycling properties. We reconstructed porous structures on the same surface three times and found no significant change in wettability for each reconstructed porous structure. Our research provides a facile and controllable approach for the preparation of hierarchical porous structures and paves the way for the design of other functional surfaces.

Fe3O4nanoparticles are the most widely used magnetic nanoparticles in the biomedicine field. The biodistribution of most nanoparticles in vivo is determined by the capture of macrophages; however, the effects of nanoparticles on macrophages remain poorly understood. Here, we demonstrated that Fe3O4nanoparticles could reduce macrophage viability after 48 h of treatment and induce a shift in macrophage polarization toward the M1 phenotype; RNA sequencing revealed the activation of the ferroptosis pathway and p53upregulation compared to the control group. The expression in p53, xCT, glutathione peroxidase 4 (GPX4), and transferrin receptor (TFR) in macrophages was similar to that in erastin-induced ferroptosis in macrophages, and the ultrastructural morphology of mitochondria was consistent with that of erastin-treated cells. We used DCFH-DA to estimate the intracellular reactive oxygen species content in Fe3O4nanoparticles treated with Ana-1 and JC-1 fluorescent probes to detect the mitochondrial membrane potential change; both showed to be time-dependent. Fer-1 inhibited the reduction of the glutathione/oxidized glutathione (GSH/GSSG) ratio and inhibited intracellular oxidative stress states; therefore, Fe3O4nanoparticles induced ferroptosis in macrophages. Finally, we used pifithrin-α hydrobromide (PFT) as a p53 inhibitor to verify whether the high expression of p53 is involved in mediating this process. After PFT treatment, the live/dead cell rate, TFR, p53 expression, and GPX4 consumption were inhibited and mitigated the GSH/GSSG ratio reduction as well. This indicates that p53 may contribute to Fe3O4nanoparticle-induced ferroptosis of macrophages. We provide a theoretical basis for the molecular mechanisms of ferroptosis in macrophages and the biotoxicity in vivo induced by Fe3O4nanoparticles.

Hierarchically porous activated coke is widely applied in pollutant removal due to its excellent molecule adsorption and transportation ability. Catalytic activation with the participation of alkali/alkaline earth metal salt has been reported to be effective for constructing hierarchical pore configuration; however, the technical condition remains to be explored for providing guidance to practical preparation process. Herein, the relationship between the porous structure of Zhundong coal-based activated coke and the technical condition during catalytic activation is systematically discussed. Based on comparisons of porous structures obtained under different carbonization–activation conditions, one-step catalytic activation is demonstrated to be more favorable for pore development than traditional carbonization–activation process. Physicochemical structural analyses of the precursor and the prepared activated coke reveal that pore development during catalytic activation is also related to the surface chemistry of the precursor and particle size. Amplified preparation experiments in rotary kiln further verify the potential of one-step catalytic activation in industrial production. As a proof of application, selective catalytic reduction tests show that the prepared hierarchically porous activated coke viaone-step catalytic activation exhibits high efficiency in NO removal. This work highlights the promoting role of one-step catalytic activation in pore development, providing guidance for preparing high-performance activated coke under practical industrial conditions.

Levels of cotinine, a major metabolite of nicotine, have been positively correlated with risks of cigarette smoking-related diseases. Melatonin is synthesized by the pineal gland and has been demonstrated to be beneficial to oocyte maturation due to its antioxidative activity. In this study, we investigated the effects of cotinine on mouse oocyte meiosis and the protective roles of melatonin in vitro and in vivo. The results showed that cotinine exposure caused defects in the first polar body extrusion and reduced parthenogenetic activation in in vitro-matured oocytes. Additionally, cotinine exposure increased the level of oxidative stress, which resulted in aberrant actin distribution, abnormal spindle morphology, chromosome misalignment, and even oocyte aneuploidy. Simultaneously, cotinine exposure decreased the mitochondrial membrane potential and antioxidant gene expression and increased apoptosis-related gene expression. However, all these toxic effects of cotinine could be reversed after the addition of melatonin, and the mechanism may be a decrease in reactive oxygen species production. In conclusion, cotinine causes poor oocyte quality, which could be rescued by melatonin supplementation during meiotic maturation in mouse oocytes.Cotinine, the major metabolite of nicotine and a key component in cigarette smoke, causes poor oocyte quality, which could be rescued by melatonin supplementation during meiotic maturation in mouse oocytes.

Infertility affects 8–12% of couples globally, and the male factor is a primary cause in ~50% of couples. Male infertility is a multifactorial reproductive disorder, which can be caused by paracrine and autocrine factors, hormones, genes, and epigenetic changes. Recent studies in rodents and most notably in humans using multiomics approach have yielded important insights into understanding the biology of spermatogenesis. Nonetheless, the etiology and pathogenesis of male infertility are still largely unknown. In this review, we summarized and critically evaluated findings based on the use of advanced technologies to compare normal and obstructive azoospermic versus nonobstructive azoospermic men, including whole-genome bisulfite sequencing, single-cell RNA-seq, whole-exome sequencing, and transposase-accessible chromatin using sequencing. It is obvious that the multiomics approach is the method of choice for basic research and clinical studies including clinical diagnosis of male infertility.This review summarizes findings of the past 20 years published in literature listed in PubMed including our laboratory, utilizing multiomics approach to study the etiology and pathogenesis of male infertility.Graphical Abstract

Background This study aims to assess the efficacy and safety of Endostar in the management of locally advanced cervical cancer.Methods This retrospective, 2-center study enrolled 41 patients with locally advanced cervical cancer between June 2017 and December 2020. The patients were subjected to a combination of Endostar and chemoradiotherapy until they experienced disease progression or an unacceptable level of toxicity. The patients in the Endostar combined chemoradiotherapy (E + CRT) and CRT groups were matched 1:1 based on clinical features, including age, disease stage, and pathological type. The therapeutic efficacy and safety outcomes were compared between the 2 groups.Results Early treatment response: the CR rates in E + CRT and CRT groups were 48.8% and 26.8%, respectively (χ2= 4.20, P < .05). The ORR and DCR were not significantly different between the 2 groups. Long-term efficacy: there was no significant difference in the 1-year and 2-year PFS rates and OS rates between 2 groups. However, in patients with stage IIB, subgroup analyses revealed a significant difference in PFS between the 2 groups (P < .05). Prognostic factors: stage, Eastern Cooperative Oncology Group (ECOG) score, and tumor size were independent predictive factors for PFS, while ECOG score and tumor size were those of OS in patients with locally advanced cervical cancer. Safety: The incidence of grade III-IV myelosuppression was significantly lower in E + CRT group than in CRT group (P < .05).Conclusions The combination of Endostar and concurrent CRT exhibited greater efficacy in treating locally advanced cervical cancer with no severe adverse reactions, when compared to simple CRT. It is expected that this approach will evolve into a new treatment alternative for patients with locally advanced cervical cancer.

Fat (FAT atypical cadherin) and Dchs (Dachsous cadherin–related protein) in adjacent Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interfaces create an important intercellular bridge whose adhesive function is in turn supported by Fjx1, a nonreceptor Ser/Thr protein kinase. This concept is derived from earlier studies of Drosophila, which has been confirmed in this and earlier reports as well. Herein, we use the approach of knockdown of Fat1 by RNAi using primary cultures of Sertoli cells that mimicked the blood–testis barrier (BTB) in vivo, and a series of coherent experiments including functional assays to monitor the Sertoli cell tight junction (TJ) permeability barrier and a functional in vitro TJ integrity assay to assess the role of Fat1 in the testis. It was shown that planar cell polarity (PCP) protein Fat1 affected Sertoli cell function through its modulation of actin and microtubule cytoskeletal function, altering their polymerization activity through the Fat1/Fjx1 complex. Furthermore, Fat1 is intimately associated with β-catenin and α-N-catenin, as well as with Prickle 1 of the Vangl1/Prickle 1 complex, another PCP core protein to support intercellular interactions to confer PCP. In summary, these findings support the notion that the Fat:Dchs and the Vangl2:Fzd PCP intercellular bridges are tightly associated with basal ES/TJ structural proteins to stabilize PCP function at the Sertoli:Sertoli, Sertoli:spermatid, and spermatid:spermatid interface to sustain spermatogenesis.

Seminal extracellular vesicles (EVs) contain different subgroups that have diverse effects on sperm function. However, the effect of seminal EVs—especially their subgroups—on endometrial receptivity is largely unknown. Here, we found that seminal EVs could be divided into high-density EVs (EV-H), medium density EVs, and low-density EVs after purification using iodixanol. We demonstrated that EV-H could promote the expression and secretion of leukemia inhibitor factor (LIF) in human endometrial cells. In EV-H–treated endometrial cells, we identified 1274 differentially expressed genes (DEGs). DEGs were enriched in cell adhesion and AKT and STAT3 pathways. Therefore, we illustrated that EV-H enhanced the adhesion of human choriocarcinoma JAr cell spheroids to endometrial cells through the LIF-STAT3 pathway. Collectively, our findings indicated that seminal EV-H could regulate endometrial receptivity through the LIF pathway, which could provide novel insights into male fertility.

Purpose: In order to improve the comprehensive evaluation level of shield tunnel structure health, taking a subway tunnel section as an example, and combined with the onsite measured data, such as regular inspection, health monitoring and disease remediation, this paper introduces the variable weight theory to improve the traditional fixed-weight evaluation method from structural deformation, current durability and disease status. Design/methodology/approach: Considering the influence of the fluctuation of each index value on the index weight, a comprehensive structural health evaluation model of shield tunnel based on an improved variable weight matter-element extension model is proposed. Findings: Compared with the traditional fixed-weight evaluation method, this model can correct the evaluation distortion caused by the fluctuation of index value and has optimal effect. Originality/value: The sensitive analysis shows that several key indicators of the main threats to tunnel structure are obtained to improve the efficiency of operation, maintenance and management of shield tunnel structure.

Information-rich molecules provide opportunities for evolution. Genetically engineered materials are superior in that their properties are coded within genetic sequences and could be fine-tuned. In this review, we elaborate the concept of genetically engineered materials (GEMs) using examples ranging from engineered protein materials to engineered living materials. Protein-based materials are the materials of choice by nature. Recent progress in protein engineering has led to opportunities to tune their sequences for optimal material performance. Proteins also play a central role in living materials where they act in concert with other biological components as well as nonbiological cofactors, giving rise to living features. While the existing GEMs are often limited to those constructed by building blocks of biological origin, being genetically engineerable does not preclude nonbiologic or synthetic materials, the latter of which have yet to be fully explored.