Identification of an Ultrathin Osteochondral Interface Tissue with Specific Nanostructure at the Human Knee Joint.

Cartilage adheres to subchondral bone via a specific osteochondral interface tissue where forces are transferred from soft cartilage to hard bone without conferring fatigue damage over a lifetime of load cycles. However, the fine structure and mechanical properties of the osteochondral interface tissue remain unclear. Here, we identified an ultrathin ∼20-30 µm graded calcified region with two-layered micronano structures of osteochondral interface tissue in the human knee joint, which exhibited characteristic biomolecular compositions and complex nanocrystals assembly. Results from finite element simulations revealed that within this region, an exponential increase of modulus (3 orders of magnitude) was conducive to force transmission. Nanoscale heterogeneity in the hydroxyapatite, coupled with enrichment of elastic-responsive protein-titin, which is usually present in muscle, endowed the osteochondral tissue with excellent mechanical properties. Collectively, these results provide novel insights into the potential design for high-performance interface materials for osteochondral interface regeneration.

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of a Monoclonal Antibody (SCTA01) Targeting SARS-CoV-2 in Healthy Adults: a Randomized, Double-Blind, Placebo-Controlled, Phase I Study.

SCTA01 is a novel monoclonal antibody with promising prophylactic and therapeutic potential for COVID-19. This study aimed to evaluate the safety, tolerability, pharmacokinetics (PK) and immunogenicity of SCTA01 in healthy adults. This was a randomized, double-blind, placebo-controlled, dose escalation phase I clinical trial. Healthy adults were randomly assigned to cohort 1 (n = 5; 3:2), cohort 2 (n = 8; 6:2), cohort 3, or cohort 4 (both n = 10; 8:2) to receive SCTA01 (5, 15, 30, and 50 mg/kg, respectively) versus placebo. All participants were followed up for clinical, laboratory, PK, and immunogenicity assessments for 84 days. The primary outcomes were the dose-limiting toxicity (DLT) and maximal tolerable dose (MTD), and the secondary outcomes included PK parameters, immunogenicity, and adverse events (AE). Of the 33 participants, 18 experienced treatment-related AEs; the frequency was 52.0% (13/25) in participants receiving SCTA01 and 62.5% (5/8) in those receiving placebo. All AEs were mild. There was no serious AE or death. No DLT was reported, and the MTD of SCTA01 was not reached. SCTA01 with a dose range of 5 to 50 mg/kg had nearly linear dose-proportional increases in Cmax and AUC parameters. An antidrug antibody response was detected in four (16.0%) participants receiving SCTA01, with low titers, between the baseline and day 28, but all became negative later. In conclusion, SCTA01 up to 50 mg/kg was safe and well-tolerated in healthy participants. Its PK parameters were nearly linear dose-proportional. (This study has been registered at ClinicalTrials.gov under identifier NCT04483375.).

Harnessing uniaxial tension to tune Poisson's ratio and wave propagation in soft porous phononic crystals: an experimental study.

Exerting mechanical loads on soft periodic porous phononic crystals provides a unique opportunity to control the propagation of waves through the peculiar band gaps. However, it is quite difficult to experimentally confirm the band gaps in soft materials owing to their viscosity and instability-prone character. We investigate here via experiments the effect of regulation of uniaxial tension on the band gaps in a 2D soft phononic crystal with criss-crossed elliptical holes which was designed based on the contrarian thinking to our previous study. The results show that the soft phononic crystal has rich initial band gaps and can be tuned by harnessing uniaxial tension to achieve continuous control of elastic band gaps. Moreover, the effect of the uniaxial tension on the effective Poisson's ratio of the structure is also studied. The present study confirms the feasibility of the design of soft tunable phononic crystals and acoustic devices by harnessing uniaxial tension.

Prescribing patterns in growing tubular soft matter by initial residual stress.

Initial residual stress is omnipresent in biological tissues and soft matter, and can affect growth-induced pattern selection significantly. Here we demonstrate this effect experimentally by letting soft tubes grow in the presence or absence of initial residual stress and by observing different growth pattern evolutions. These experiments motivate us to model the mechanisms at play when a growing bilayer tubular organ spontaneously displays buckling patterns on its inner surface. We demonstrate that not only differential growth, geometry and elasticity, but also initial residual stress distribution, exert a notable influence on these pattern phenomena. Prescribing an initial residual stress distribution offers an alternative or a more effective way to implement pattern selection for growable bio-tissues or soft matter. The results also show promise for the design of 4D bio-mimic printing protocols or for controlling hydrogel actuators.

Electromechanical Deformations and Bifurcations in Soft Dielectrics: A Review.

Dielectric elastomers have attracted considerable attention both from academia and industry alike over the last two decades due to their superior mechanical properties. In parallel, research on the mechanical properties of dielectrics has been steadily advancing, including the theoretical, experimental, and numerical aspects. It has been recognized that the electromechanical coupling property of dielectric materials can be utilized to drive deformations in functional devices in a more controllable and intelligent manner. This paper reviews recent advances in the theory of dielectrics, with specific attention focused on the theory proposed by Dorfmann and Ogden. Additionally, we provide examples illustrating the application of this theory to analyze the electromechanical deformations and the associated bifurcations in soft dielectrics. We compared the bifurcations in elastic and dielectric materials and found that only compressive bifurcation modes exist in elastic structures, whereas both compressive and tensile modes coexist in dielectric structures. We summarize two proposed ways to suppress and prevent the tensile bifurcations in dielectric materials. We hope that this literature survey will foster further advancements in the field of the electroelastic theory of soft dielectrics.

Efficacy and Safety of Biosimilar SCT510 Compared with Bevacizumab for the First-Line Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer: A Randomized, Double-Blind, Phase III Study.

INTRODUCTION: SCT510 is a biosimilar to bevacizumab (Avastin) reference product (RP) that is approved for various metastatic cancers. In this study, we aimed to demonstrate the equivalence of SCT510 and bevacizumab in terms of efficacy, safety, immunogenicity and pharmacokinetics (PK) in patients with advanced non-squamous non-small cell lung cancer (NSCLC). METHODS: Patients with non-squamous NSCLC were randomized equally to the SCT510 group (comprising SCT510, paclitaxel, and carboplatin) and the bevacizumab group (comprising bevacizumab, paclitaxel, and carboplatin) for 4-6 cycles, followed by maintenance monotherapy with SCT510. The primary endpoint was the objective response rate (ORR) at week 12. Secondary endpoints included 18-week ORR, disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and 1-year survival rate, as well as assessments of safety, immunogenicity, and multi-dose PK analysis. RESULTS: Between March 29, 2019, and April 27, 2021, 989 patients were screened and 567 eligible patients were randomly assigned to the SCT510 group (285 patients) and the bevacizumab group (282 patients). The ORR at week 12 was 52.6% [95% confidence interval (CI) 46.66-58.55%] in the SCT510 group and 52.5% (95% CI 46.47-58.47%) in the bevacizumab group. The ORR at week 18 was 55.4% (95% CI 49.46-61.30%) for SCT510 and 55.7% (95% CI 49.68-61.62%) for bevacizumab. The ORR risk ratio (RR) at weeks 12 and 18 was 0.99 (90% CI 0.873-1.133) and 0.99 (90% CI 0.872-1.114), respectively, both within the pre-specified equivalence margin of 0.75-1.33. There were no differences between the two groups in relation to other secondary endpoints, specifically DCR, DOR, PFS, OS, and 1-year survival rate. The overall safety findings were similar between the two treatment groups, and both SCT510 and bevacizumab RP exhibited low immunogenicity. CONCLUSIONS: SCT510 is similar to bevacizumab in clinical efficacy, safety, immunogenicity, and PK in patients with advanced non-squamous NSCLC. The totality of the evidence supports the clinical equivalence of SCT510 and bevacizumab. TRIAL REGISTRATION: NCT03792074.

Microstructured elastomeric surfaces with reversible adhesion and examples of their use in deterministic assembly by transfer printing.

Reversible control of adhesion is an important feature of many desired, existing, and potential systems, including climbing robots, medical tapes, and stamps for transfer printing. We present experimental and theoretical studies of pressure modulated adhesion between flat, stiff objects and elastomeric surfaces with sharp features of surface relief in optimized geometries. Here, the strength of nonspecific adhesion can be switched by more than three orders of magnitude, from strong to weak, in a reversible fashion. Implementing these concepts in advanced stamps for transfer printing enables versatile modes for deterministic assembly of solid materials in micro/nanostructured forms. Demonstrations in printed two- and three-dimensional collections of silicon platelets and membranes illustrate some capabilities. An unusual type of transistor that incorporates a printed gate electrode, an air gap dielectric, and an aligned array of single walled carbon nanotubes provides a device example.

Propagation of terahertz elastic longitudinal waves in piezoelectric semiconductor rods.

Terahertz elastic waves travelling in piezoelectric semiconductors (PSs) with the deformation-polarization-carrier coupling have a huge potential application in elastic wave-based devices. To reveal wave propagation characteristics of terahertz elastic waves in rod-like PS structures, we present three typical rod models based on the Hamilton principle and the linearization of the nonlinear current, which are extensions of the classical, Love, and Mindlin-Herrmann rod models for elastic media to those for PS materials. Using the derived equations, the analytical dispersion relations of the elastic longitudinal waves propagating in an n-type PS rod are obtained, which can be reduced to those for piezoelectric and elastic rods by sequentially dropping the corresponding electron- and piezoelectricity-related terms. The Mindlin-Herrmann rod model is more accurate for analysis of terahertz elastic longitudinal wave in rod-like PS structures. The effects of the interaction between the piezoelectricity and semiconducting properties on the dispersion behaviors of terahertz elastic longitudinal waves are investigated in detail. Numerical results show that both phase and group velocities have a 50%-60% reduction in the terahertz range in comparison with those in the low frequency range, and the effective tuning range of the initial electron concentration is different for longitudinal waves with different frequencies. It lays the theoretical foundations for the design of terahertz elastic wave-based devices.

Predictions of Dynamic Multimode-Coupling and High-Frequency Vibrations in Magneto-Electro-Elastic Heterostructures.

Mode coupling between the operation mode and unwanted eigenmodes has a significant influence on the working performance of novel thin-film magnetoelectric (ME) devices operating at high frequencies. In this article, the extended frequency spectrum quantitative prediction (FSQP) method is used to investigate mode-coupling vibrations in high-frequency ME heterostructures. This method has three key procedures. First, wave propagation in ME heterostructures is studied to determine the wavenumber and frequency of the eigenmodes. Second, the variational formulation of a general ME heterostructure is constructed. Finally, frequency spectra for predicting the coupling strength among the eigenmodes are obtained by substituting the solutions consisting of all eigenmodes into the variational formulation. Two numerical examples are presented to validate the extended FSQP method. The mode shapes of the mechanical displacements are used to thoroughly describe the mode-coupling behavior in different vibration modes. The numerical results show that the mode-coupling strength is significantly affected by the structural size and number of layers in an ME heterostructure. Furthermore, structural symmetry along the thickness direction may cause specific mode-decoupling phenomena. Effective strategies for suppressing multimode-coupling vibrations in ME heterostructures by optimizing the lateral aspect ratios based on the frequency spectra are proposed to guide device design.

Numerical studies on issues of Re-independence for indoor airflow and pollutant dispersion within an isolated building.

This study conducted the numerical models validated by wind-tunnel experiments to investigate the issues of Re-independence of indoor airflow and pollutant dispersion within an isolated building. The window Reynolds number (Re w ) was specified to characterize the indoor flow and dispersion. The indicators of RRC (ratio of relative change) or DR (K_DR) (difference ratio of dimensionless concentration) ≤ 5% were applied to quantitatively determine the critical Re w for indoor flow and turbulent diffusion. The results show that the critical Re (Re crit) value is position-dependent, and Re crit at the most unfavorable position should be suggested as the optimal value within the whole areas of interest. Thus Re H,crit = 27,000 is recommended for the outdoor flows; while Re w,crit = 15,000 is determined for the indoor flows due to the lower part below the window showing the most unfavorable. The suggested Re w,crit (=15,000) for indoor airflow and cross ventilation is independence of the window size. Moreover, taking K_DR ≤ 5% as the indicator, the suggested Re w,crit for ensuring indoor pollutant diffusion enter the Re-independence regime should also be 15,000, indicating that indoor passive diffusion is completely determined by the flow structures. The contours of dimensionless velocity (U/U 0) and concentration (K) against the increasing Re w further confirmed this critical value. This study further reveals the Re-independence issues for indoor flow and dispersion to ensure the reliability of the data obtained by reduced-scale numerical or wind-tunnel models.

A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women.

The association between the CHEK2 and breast cancer risk in Chinese women is unknown. Here, we screened the full CHEK2 coding sequence in 118 Chinese familial breast cancer cases who are negative for mutations in BRCA1 and BRCA2, one recurrent mutation, CHEK2 c.1111C>T (p.H371Y), was identified in five index cases in this cohort. Functional analysis suggested that CHEK2 p.H371Y was a pathogenic mutation that resulted in decreased kinase activity. We further screened the CHEK2 p.H371Y mutation in 909 unselected breast cancer cases and 1,228 healthy individuals. The frequencies of the CHEK2 p.H371Y in familial and unselected breast cancer cases and controls were 4.24% (5/118), 1.76% (16/909), and 0.73% (9/1228), respectively. The p.H371Y mutation was significantly associated with increased breast cancer risk in unselected breast cancer (odds ratio [OR] 2.43, 95% confidence interval [CI] 1.07-5.52, P = 0.034). Our results indicate that the recurrent mutation, p.H371Y, confers a moderate risk of breast cancer in Chinese women.

The effect of an exterior electric field on the instability of dielectric plates.

We investigate the theoretical nonlinear response, Hessian stability, and possible wrinkling behaviour of a voltage-activated dielectric plate immersed in a tank filled with silicone oil. Fixed rigid electrodes are placed on the top and bottom of the tank, and an electric field is generated by a potential difference between the electrodes. We solve the associated incremental boundary value problem of superimposed, inhomogeneous small-amplitude wrinkles, signalling the onset of instability. We decouple the resulting bifurcation equation into symmetric and antisymmetric modes. For a neo-Hookean dielectric plate, we show that a potential difference between the electrodes can induce a thinning of the plate and thus an increase of its planar area, similar to the scenarios encountered when there is no silicone oil. However, we also find that, depending on the material and geometric parameters, an increasing applied voltage can also lead to a thickening of the plate, and thus a shrinking of its area. In that scenario, Hessian instability and wrinkling bifurcation may then occur spontaneously once some critical voltages are reached.

Programmable and scalable transfer printing with high reliability and efficiency for flexible inorganic electronics.

Transfer printing that enables heterogeneous integration of materials in desired layouts offers unprecedented opportunities for developing high-performance unconventional electronic systems. However, large-area integration of ultrathin and delicate functional micro-objects with high yields in a programmable fashion still remains as a great challenge. Here, we present a simple, cost-effective, yet robust transfer printing technique via a shape-conformal stamp with actively actuated surface microstructures for programmable and scalable transfer printing with high reliability and efficiency. The shape-conformal stamp features the polymeric backing and commercially available adhesive layer with embedded expandable microspheres. Upon external thermal stimuli, the embedded microspheres expand to form surface microstructures and yield weak adhesion for reliable release. Systematic experimental and computational studies reveal the fundamental aspects of the extraordinary adhesion switchability of stamp. Demonstrations of this protocol in deterministic assemblies of diverse challenging inorganic micro-objects illustrate its extraordinary capabilities in transfer printing for developing high-performance flexible inorganic electronics.

BRCA1 germline mutations and tumor characteristics in Chinese women with familial or early-onset breast cancer.

The data related to BRCA1 germline mutation in Chinese women with familial breast cancer is increasing. However, little is known the frequency of BRCA1 mutations in Chinese women with familial or early-onset breast cancer from Northern China, and few studies are available to investigate the clinicopathological characteristics of BRCA1 tumors in Chinese women. In this study, we detected germline mutations in BRCA1 in a cohort of 139 breast cancer patients who either have a family history of breast cancer (n = 68) or whose tumors are diagnosed at or before the age of 35 (n = 71) from Northern China. A total of 6 deleterious BRCA1 mutations were identified in this cohort, 4 of which (5587-1 del8, 3887 del AG, IVS21 + 1delG, and 2129 ins TG) are novel and one mutation (3478del5) detected in this study was only reported in Chinese population. The frequency of BRCA1 mutations in women with familial or early-onset breast cancer was 5.9% (4/68) or 2.8% (2/71) in this cohort, respectively; but the mutations were detected in 4 of 16(25.0%) familial breast cancer patients whose tumors were diagnosed before the age of 40. Moreover, BRCA1 mutation tumors tended to be high histological grade, and to be negative for ER, PgR, and Her-2 compared with tumors without BRCA1 mutations. Our study suggests that Chinese women with a family history of breast cancer whose tumors are diagnosed before age of 40 would be a suitable candidate for BRCA1 testing; and BRCA1 tumors in Chinese women exhibit an aggressive phenotype.

Influence of Initial Residual Stress on Growth and Pattern Creation for a Layered Aorta.

Residual stress is ubiquitous and indispensable in most biological and artificial materials, where it sustains and optimizes many biological and functional mechanisms. The theory of volume growth, starting from a stress-free initial state, is widely used to explain the creation and evolution of growth-induced residual stress and the resulting changes in shape, and to model how growing bio-tissues such as arteries and solid tumors develop a strategy of pattern creation according to geometrical and material parameters. This modelling provides promising avenues for designing and directing some appropriate morphology of a given tissue or organ and achieve some targeted biomedical function. In this paper, we rely on a modified, augmented theory to reveal how we can obtain growth-induced residual stress and pattern evolution of a layered artery by starting from an existing, non-zero initial residual stress state. We use experimentally determined residual stress distributions of aged bi-layered human aortas and quantify their influence by a magnitude factor. Our results show that initial residual stress has a more significant impact on residual stress accumulation and the subsequent evolution of patterns than geometry and material parameters. Additionally, we provide an essential explanation for growth-induced patterns driven by differential growth coupled to an initial residual stress. Finally, we show that initial residual stress is a readily available way to control growth-induced pattern creation for tissues and thus may provide a promising inspiration for biomedical engineering.

Nanoscale Insights into Photovoltaic Hysteresis in Triple-Cation Mixed-Halide Perovskite: Resolving the Role of Polarization and Ionic Migration.

Triple-cation mixed-halide perovskites of composition Csx (FAy MA1- y )1 -x Pb(Iz Br1 -z )3 (CsFAMA) have been reported to possess excellent photovoltaic efficiency with minimal hysteresis; in this work, nanoscale insight is shed into the roles of illumination-induced polarization and ionic migration in photovoltaic hysteresis. By examining the concurrent evolution of ionic distribution and spontaneous polarization of CsFAMA under light illumination using dynamic-strain-based scanning probe microscopy, strong linear piezoelectricity arising from photoenhanced polarization is observed, while ionic migration is found to be not significantly increased by lightening. Nanoscale photocurrents are mapped under a series of biases using conductive atomic force microscopy, revealing negligible difference between forward and backward scans, and local IV curves reconstructed from principal component analysis show minimal hysteresis of just 1%. These observations at the nanoscale are confirmed in a macroscopic perovskite solar cell made of CsFAMA, exhibiting a high efficiency of 20.11% and with hysteresis index as small as 3%. Ionic migration, polarization, and photocurrent hysteresis are thus directly correlated at the nanoscale, and photoenhanced polarization in triple-cation mixed-halide perovskites is established, which does not contribute to the photovoltaic hysteresis.

Soft Ultrathin Electronics Innervated Adaptive Fully Soft Robots.

Soft robots outperform the conventional hard robots on significantly enhanced safety, adaptability, and complex motions. The development of fully soft robots, especially fully from smart soft materials to mimic soft animals, is still nascent. In addition, to date, existing soft robots cannot adapt themselves to the surrounding environment, i.e., sensing and adaptive motion or response, like animals. Here, compliant ultrathin sensing and actuating electronics innervated fully soft robots that can sense the environment and perform soft bodied crawling adaptively, mimicking an inchworm, are reported. The soft robots are constructed with actuators of open-mesh shaped ultrathin deformable heaters, sensors of single-crystal Si optoelectronic photodetectors, and thermally responsive artificial muscle of carbon-black-doped liquid-crystal elastomer (LCE-CB) nanocomposite. The results demonstrate that adaptive crawling locomotion can be realized through the conjugation of sensing and actuation, where the sensors sense the environment and actuators respond correspondingly to control the locomotion autonomously through regulating the deformation of LCE-CB bimorphs and the locomotion of the robots. The strategy of innervating soft sensing and actuating electronics with artificial muscles paves the way for the development of smart autonomous soft robots.

Buckling of a stiff thin film on an elastic graded compliant substrate.

The buckling of a stiff film on a compliant substrate has attracted much attention due to its wide applications such as thin-film metrology, surface patterning and stretchable electronics. An analytical model is established for the buckling of a stiff thin film on a semi-infinite elastic graded compliant substrate subjected to in-plane compression. The critical compressive strain and buckling wavelength for the sinusoidal mode are obtained analytically for the case with the substrate modulus decaying exponentially. The rigorous finite element analysis (FEA) is performed to validate the analytical model and investigate the postbuckling behaviour of the system. The critical buckling strain for the period-doubling mode is obtained numerically. The influences of various material parameters on the results are investigated. These results are helpful to provide physical insights on the buckling of elastic graded substrate-supported thin film.

Time-dependent response of laminated isotropic strips with viscoelastic interfaces.

The two dimensional problem of simply supported laminated isotropic strips with viscoelastic interfaces and under static loading was studied. Exact solution was derived based on the exact elasticity equation and the Kevin-Voigt viscoelastic interfacial model. Numerical computations were performed for a strip consisting of three layers of equal thickness. Results indicated that the response of the laminate was very sensitive to the presence of viscoelastic interfaces.

Potential theory method for 3D crack and contact problems of multi-field coupled media: a survey.

This paper presents an overview of the recent progress of potential theory method in the analysis of mixed boundary value problems mainly stemming from three-dimensional crack or contact problems of multi-field coupled media. This method was used to derive a series of exact three dimensional solutions which should be of great theoretical significance because most of them usually cannot be derived by other methods such as the transform method and the trial-and-error method. Further, many solutions are obtained in terms of elementary functions that enable us to treat more complicated problems easily. It is pointed out here that the method is usually only applicable to media characterizing transverse isotropy, from which, however, the results for the isotropic case can be readily obtained.