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Nanostructured amorphous composites are novel materials comprising nano-sized crystal phases embedded in an amorphous matrix, but often necessitating ultra-high-pressure molding for preparation. In this study, nanostructured amorphous ZrO 2 –Y 2 O 3 composite ceramics were rapidly prepared for the first time using flash viscous flow sintering without the application of pressure. The relative density of the ZY ceramics increased with increasing current density, and ZY composite ceramics with relative density of 86%–97 % were prepared by FS in a short time of 60 s under 700 V/cm with 0.16–0.56 A/cm2. Furthermore, the sintering activities in FS were compared between partially amorphous powder and crystalline powder. The ceramics prepared by flash sintering of partially amorphous powder show a much higher relative density than that from crystalline powder, suggesting that partially amorphous powder achieves easier densification than crystalline powder in flash sintering under given current density and power dissipation. This phenomenon was attributable to the differing sintering mechanisms between the two materials, i.e., solid-state sintering for crystalline powder and viscous flow sintering for partially amorphous powder. [ABSTRACT FROM AUTHOR]

Seasonal differences of temperature are crucial components of the Earth's climate system. However, the relatively short observational record, especially for East Asia, has limited progress in understanding seasonal differences. In this study, we identify ten tree-ring chronologies separately correlated with local winter (December–February) temperatures and twelve different tree-ring chronologies separately correlated with summer (June–August) temperatures across East Asia. Using these discrete seasonal tree-ring chronologies, we develop two independent winter and summer temperature reconstructions covering the period 1376–1995 CE for East Asia, and compare them with model simulations. Our reconstructions show a more significant volcanic cooling and earlier onset of modern warming in summer than in winter. The reconstructed summer-minus-winter temperature decreased since as early as the late 19th century, which has driven the current state of seasonal temperature difference to out of the natural variability since the 1370s. Climate models could generally reproduce the variability and trends in seasonal reconstructions, but might largely underestimate seasonal differences due to the fact that seasonal expressions on external forcing and modes of internal variability are too small. Our study highlights the importance of using proxy-based seasonal reconstructions to evaluate the performance of climate models, and implies a substantial weakening of seasonal temperature differences in the future. [ABSTRACT FROM AUTHOR]

The last millennium (LM, 1000–1850 AD) is crucial for studying historical climate change on decadal to multidecadal timescales. The summer surface air temperature (SAT) evolutions on regional scales (e.g. over China) are more uncertain than the globe/Northern Hemisphere, especially in response to external forcing factors and internal climate variability. Here, we provide one‐signal (full‐forcing) fingerprints of summer SAT in China derived from three large ensemble model archives with a multi‐proxy reconstruction during the LM, Little Ice Age (LIA, 1451–1850 AD), and Medieval Climate Anomaly (MCA, 1000–1250 AD), respectively. Our results show that (a) SATs in the northeast, southeast, northwest, and Tibetan Plateau (TP) regions of China show evident decreasing trends during the LM. External forcing response from all model archives agrees with the regional SAT reconstruction but underestimates variability in northwest China at the multidecadal timescale. (b) During the LIA, the summer regional SAT exhibits a cold condition in the reconstruction and simulations, especially in the northeast and northwest regions of China. External forcing responses in most model archives are the dominant factor on multidecadal SAT evolutions in the southeast, northeast, and TP regions of China and decadal SAT evolutions in northwest China. (c) During the MCA, detection and attribution of SAT shows that internal climate variability dominates in southeast, northeast, and TP regions of China, but external forcing dominates in northwest China at decadal to multidecadal timescales. These results contribute to a better understanding of the causes and mechanisms of regional climate change. [ABSTRACT FROM AUTHOR]

High-performance alumina-zirconia ceramics are generally sintered above 1500 °C and consume lots of energy; rapid sintering at low temperature is an ideal technique due to its economy and low-energy consumption. For the first time, flash sintering combined with phase transformation-assisted sintering techniques was reported in this work. The alumina-zirconia amorphous precursor powder was used to replace the final product powder for ceramic processing, and the one-step synthesis and rapid sintering densification of alumina-zirconia ceramics at low temperature of 849 °C for 60 s were realized. The effects of electric field on the low-temperature sintering of amorphous powders are summarized into three aspects. Firstly, the electric field reduces the viscosity of the amorphous powder and promotes liquid phase sintering. Secondly, the electric field promotes the phase transition of the amorphous powder from metastable to stable phase, and accelerates the atomic migration. Thirdly, Joule heating and defect generation in the flash sintering promotes more effective material transport. Overall, this work reduces the energy for calcination of amorphous powders, reduces the sintering temperature of ceramics, well hinders the grain coarsening and shows excellent mechanical properties. • Rapid low-temperature sintering of alumina-ziconia ceramics was achieved at 849 °C for 60 s. • For the first time, flash sintering combined with phase transformation-assisted sintering techniques was performed. • The low sintering temperature contributes to refined grain size and enhanced mechanical property of the ceramics. • This economical and low-energy consumption technique is beneficial to the achievement of carbon neutrality. [ABSTRACT FROM AUTHOR]

The trade winds cause strong upwelling in the eastern equatorial Pacific, and create the eastern Pacific Cold Tongue (EPCT) that has far‐reaching impacts on global climate. However, large discrepancies persist in quantifying 20th‐century EPCT sea surface temperature (SST) changes across different instrumental data sets. Here we synthesize four coral Sr/Ca‐SST records from the tropical central‐eastern Pacific to develop a Cold Tongue Index (CTI) reconstruction for 1887–1997. The coral CTI record shows a rapid 20th century warming of the EPCT, suggesting an underestimation of warming trends in instrumental CTI records. The decadal to multidecadal changes in reconstructed EPCT SST show an association with the Walker Circulation. Our reconstruction indicates that recent EPCT cooling during the global warming hiatus is not unusual in the context of the 20th century. Our results provide new evidence for 20th century EPCT SST changes and an observational constraint for predicting future tropical climate changes. Plain Language Summary: The tropical Pacific exhibits an asymmetric pattern of sea surface temperatures (SST) along the equator, with a warm pool in the west and a cold tongue in the east. The Eastern Pacific Cold Tongue (EPCT) plays a crucial role in influencing global climate. To date, however, considerable disagreement persists about changes and causes of the EPCT SST over the 20th century due to the sparse instrumental observations before ∼1960. Here we synthesize published coral Sr/Ca‐SST records from the tropical central‐eastern Pacific to develop a coral Cold Tongue Index (CTIcoral) for the period 1887–1997. The CTIcoral record correlates significantly with instrumental data since 1960, and thus allows reliable assessment of 20th century EPCT SST changes. Our record exhibits a rapid 20th century warming trend of the EPCT, indicating an underestimation of warming trends in instrumental CTI records. The decadal to multidecadal changes in CTIcoral also show an association with the Walker Circulation. Comparing the magnitude of the 1992–2011 trend in instrumental CTI with our reconstruction reveals that recent EPCT cooling during the global warming hiatus is not anomalous in the context of 20th century. Our findings have implications for predicting future EPCT SST changes by offering a constraint for model simulations. Key Points: Synthesizing coral Sr/Ca‐SST records yields robust estimates of 20th century warming trend in the eastern Pacific Cold Tongue (EPCT)A coral‐based reconstruction indicates an underestimation of 20th century EPCT warming trends in instrumental SST recordsRecent EPCT cooling during the global warming hiatus is not anomalous in the context of the 20th century [ABSTRACT FROM AUTHOR]

[Display omitted] Zn-Ni batteries have garnered considerable attention due to their high specific energy, consistent discharge voltage, favorable performance at low temperatures, and environmentally benign nature. Nevertheless, anode interface issues such as dendrite growth, hydrogen evolution, and interfacial side reactions lead to poor cycling stability of Zn-Ni batteries, significantly limiting their further commercial applications. In this study, we propose a facile electrolyte engineering strategy to optimize the Zn anode interfacial environment and stabilize the Zn anode by introducing tannic acid (TA) into the KOH electrolyte. The incorporated TA complexing agent addition will be used to prevent the direct contact of H 2 O with the anode surface and promote the desolvation of Zn2+ through complexation, thus suppressing the interfacial corrosion. Consequently, the Zn symmetric battery using TA electrolyte cycles stably for 178 h at 1 mA cm−2. The Zn-Ni full batteries with TA electrolyte maintain 98.08 % capacity retention after 2000 cycles at 20C. This study will be of immediate benefit in commercializing large-scale, practical energy storage applications. [ABSTRACT FROM AUTHOR]

The temperature variability over multidecadal and longer timescales (e.g., the cold epochs in the late 15th, 17th, and early 19th centuries) is significant and dominant in the millennium-long, large-scale reconstructions and model simulations; however, their temporal patterns in the reconstructed and simulated temperature series are not well understood and require a detailed assessment and comparison. Here, we compare the reconstructed and simulated temperature series for the Northern Hemisphere (NH) at multidecadal and longer-term timescales (>30 years) by evaluating their covariance, climate sensitivity and amplitude of temperature changes. We found that covariances between different reconstructions or between reconstructions and simulations are generally high for the whole period of 850–1999 CE, due to their similar long-term temporal patterns. However, covariances between different reconstructions or between reconstructions and simulations steadily decline as time series extends further back in time, becoming particularly small during Medieval times. This is related to the large uncetainties in the reconstructions caused by the decreased number of proxy records and sample duplication during the pre-instrumental periods. Reconstructions based solely on tree-ring data show higher skill than multiproxy reconstructions in capturing the amplitude of volcanic cooling simulated by models. Meanwhile, climate models have a shorter recovery (i.e., lag) in response to the cooling caused by volcanic eruptions and solar activity minima, implying the lack of some important feedback mechanisms between external forcing and internal climate processes in climate models. Amplitudes of temperature variations in the latest published tree-ring reconstructions are comparable to those of the multiproxy reconstructions. We found that the temperature difference between the Medieval Climate Anomaly (950–1250 CE) and the Little Ice Age (1450–1850 CE) is generally larger in proxy-based reconstructions than in model simulations, but the reason is unclear. [ABSTRACT FROM AUTHOR]

The influence of external forcings on surface temperature is not fully understood at decadal to multi-centennial timescales. This study uses simulation results from the Community Earth System Model (CESM) forced by total solar irradiation (TSI), greenhouse gases (GHGs) concentrations, volcanic eruptions (VOL), and land use and land covers (LULC) to investigate the possible impacts of external forcing on decadal to multi-centennial timescales over the past 2000 years. The simulated global annual mean surface temperature (GMST) variations show a good coherence with observations over the past 150 years and proxy-based reconstructions over the past 2000 years. Ensemble empirical mode decomposition (EEMD) is used to isolate the GMST variations on decadal to multi-centennial timescales. We found that the VOL forcing has a significant effect on GMST at decadal to multi-decadal timescales, but its effect weakens gradually as the timescale lengthens. The TSI forcing is a major factor of GMST on multi-decadal to sub-millennial timescales, and its effect strengthens as the timescale lengthens. The GHGs is the dominant driver of recent warming, but its effect is weak in the pre-industrial times. The LULC could lead to a slight cooling trend over the past 2000 years but has no large impact on GMST at decadal to multi-centennial timescales. This study reports a 2000-year length climate simulation and may contribute to better understanding external drivers of GMST at different timescales. [ABSTRACT FROM AUTHOR]

We report a 1556 year-long tree-ring width chronology for the Hexi Corridor, in the arid Northwestern China, established by applying the signal-free regional curve standardization method to 416 juniper ring-width series. We found that drought in early summer (May–June) is the primary controlling factor for tree growth in this area. We then developed an early summer moisture (i.e., scPDSI) reconstruction from 455 CE to present. Our reconstruction captures multi-centennial scale moisture variations, showing two long-term dry periods during 800–950 CE and 1000–1200 CE, and two long-term wet periods during 1200–1450 CE and 1510–1620 CE. We found strong similarities between hydroclimatic changes in the Hexi Corridor and Qaidam Basin from interannual to centennial timescales; however, at multi-centennial (>300 years) timescales, hydroclimatic variations in the two regions showed significant regional differences. The Hexi Corridor witnessed a generally dry Medieval Climate Anomaly (MCA, here 800–1200 CE) and the drying 20th century, whereas the Qaidam Basin experienced high-precipitation periods during the MCA and 20th century. The different correlation pattern with Northern Hemisphere temperature suggest that the Qaidam Basin will receive more precipitation under global warming, whereas the Hexi Corridor will become dryer in the future. [ABSTRACT FROM AUTHOR]

In this study, agarose was chemically modified with ethylene oxide, 1,2-epoxypropane and 1,2-epoxybutane, to prepare hydroxyethyl agarose (HEAG), hydroxypropyl agarose (HPAG), and hydroxybutyl agarose (HBAG). The structures and properties of the products were characterized by Fourier transform infrared spectroscopy (FTIR), 1 H NMR spectroscopy, X-ray diffractometry (XRD), rheology measurement and gel electrophoresis. The results showed that the gelling temperature (T g ) of HEAG, HPAG, and HBAG were decreased to 28.3 °C, 29.0 °C and 28.7 °C respectively, with the melting temperature (T m ) simultaneously declined to 64.2 °C, 63.8 °C and 63.0 °C, respectively. Meanwhile, the gel strength of HBAG, HEAG, and HPAG were dramatically reduced to 194 g/cm 2 , 312 g/cm 2 and 279 g/cm 2 , respectively. Furthermore, HEAG and HPAG showed excellent separation efficiency which is in accordance with commercialized low-melting-point (LMP) agarose (Amersco 0815). These results indicated that oxyalkylation is a promising and economical method for the preparation of LMP agarose. [ABSTRACT FROM AUTHOR]

Tetraspanins are commonly believed to act as 'molecular facilitators', not directly involved in signal transduction. Tetraspanin 31 (TSPAN31), recently discovered to be linked to cancer, has not yet been studied in hepatocellular carcinoma ( HCC). Here, we show that TSPAN31 is the natural antisense transcript of cyclin dependent kinase 4 (CDK4), and regulates the expression of CDK4 mRNA and protein. Target analysis indicates that miR-135b can directly regulate TSPAN31 expression. miR-135b-induced TSPAN31 silencing increases CDK4 protein levels. Interestingly, p53 negatively regulates TSPAN31 expression. si RNA-induced TSPAN31 knockdown reduces the expression of Akt signaling pathway components phosphorylated Akt, p- GSK3β and β-catenin, and restrains β-catenin migration to cell nucleus. TSPAN31 knockdown also significantly inhibits HCC cell invasion and migration. These findings thus point to TSPAN31 as a novel regulator in transduction of intracellular survival and apoptotic signals. [ABSTRACT FROM AUTHOR]

Previous studies have suggested that preindustrial climate epochs such as the Medieval Climate Anomaly (MCA) and Little Ice Age (LIA) did not occur synchronously across large areas of the globe. However, it is still unclear whether and to what extent this conception is independent on the space and time scales considered. Here, we assess the agreement of MCA and LIA peak temperatures at various timescales (i.e., from 51 to 351 years) by analyzing proxy-based temperature reconstructions at local, regional, and continental scales across the Northern Hemisphere. We show that the synchronization of the MCA and LIA peak temperatures tends to be more coherent at longer time and larger space scales. At local and regional scales, the timing of MCA and LIA peak temperatures differs substantially, in line with previous findings. At continental scale, there is still no rigorous synchronization of these climate epochs, but the differences of the timing of the MCA/LIA peak temperatures are mostly smaller than five decades at multi-centennial timescales. The time and space dependent synchronization is related to the relative contribution of variations in external forcing and internal variability at these different scales. These results on the synchronization are robust across several different proxy-based reconstructions used in this study, but the precise timing of the MCA maximum and LIA minimum temperatures detected is largely influenced by the uncertainties in temperature reconstructions. Our results support the relevance of the terms MCA and LIA at long time and large space scales, and suggest that both external forcing and internal variability played roles in driving these climatic epochs. [ABSTRACT FROM AUTHOR]

Although tree-ring-width-based temperature reconstructions of centennial-to-millennial length have previously been published for many parts of the eastern Tibetan Plateau (ETP), a millennium-long regional-scale composite reconstruction with annual resolution has so far been lacking. Here, the authors present a reconstruction of June-August (JJA) temperature variability over the ETP for the period AD 1000-2005 using a nested composite-plus-scale (CPS) approach to 12 temperature-sensitive tree-ring width chronologies, including 946 individual tree-ring width series. The composite reconstruction reveals warm episodes occurring during much of the sixteenth, nineteenth, and twentieth centuries and cold episodes during much of the eleventh, seventeenth, and eighteenth centuries. The period AD 1996-2005 is likely the warmest decade in the context of the past millennium. The authors explore the influence of possible forcings, finding only a weak direct relationship of temperature changes over the ETP with solar forcing at multidecadal time scales but a robust in-phase relationship with the Atlantic multidecadal oscillation (AMO) during the past millennium. This suggests that the AMO may play an important role in controlling summer temperature variability over the ETP at multidecadal time scales. A comparison with temperature reconstructions from the higher latitudes of East Asia, central-eastern China, and the whole of the Northern Hemisphere shows that the cold eleventh century and the warm nineteenth century prevailing over ETP are somewhat unique, suggesting regional specific characteristics of the temperature variability in this region. This result highlights the need to further increase the number of millennium-long, high-resolution temperature records from East Asia. [ABSTRACT FROM AUTHOR]

Here we report the design of a uniquematrix, assembled from engineered M13 phage bionanofibers with specificcues of nanotopographies and versatile signal peptides to simulatenative niche for directing the fate of induced pluripotent stem cells(iPSCs). By independently varying the peptide sequences and nanotopographies,we find that the resident iPSCs on the phage matrix are first differentiatedinto mesenchymal progenitor cells (MPCs), which are further differentiatedinto osteoblasts in the absence of osteogenic supplements due to theelongation induced by phage nanofibers. The phage-based matrix representsnot only a biomimetic stem cell niche enabling independently varyingbiochemical and biophysical cues in one system but also a substratefor generating a safe and efficient cell source for tissue engineering. [ABSTRACT FROM AUTHOR]

We present two tree-ring chronologies for the southeastern Tibetan Plateau (TP), established by applying the signal-free regional curve standardization and standard dendrochronological methodologies to a set of ring-width series of Tibetan juniper. The relationship between tree growth and climate shows that temperature variability in the previous year is the primary factor controlling tree growth at the upper portion of the forest belt. Accordingly, we developed a mean annual temperature reconstruction covering the period A.D. 984-2009 and explaining 50 % of the instrumental variance. The spatial correlation patterns suggest that our temperature reconstruction is a reasonable proxy for temperature change over the TP. At long time scales, the temperature reconstruction shows similar warm-cold patterns to those in temperature records from other regions of the TP, indicating that decadal and multidecadal temperature variations were generally synchronous across the TP during the past millennium. The periods 1140-1350 and 1600-1800 were common warm and cold episodes over the TP, respectively. Comparison of our reconstruction with four Northern Hemisphere (NH) temperature series indicates that temperature changes on the southeastern TP have generally followed the NH temperature patterns during the past millennium. Our results also suggest that temperature variability over the TP is affected by the Atlantic Multidecadal Oscillation (AMO), with the warm (cool) phases of the AMO associated with above-average (below-average) temperatures over the TP. [ABSTRACT FROM AUTHOR]

Abstract: The self-assembly of apatite and proteins is a critical process to induce the formation of the bones and teeth in vertebrates. Although hierarchical structures and biomineralization mechanisms of the mineralized tissues have been intensively studied, most researches focus on the self-assembly biomimetic route using one single-molecular template, while the natural bone is an outcome of a multi-molecular template co-assembly process. Inspired by such a mechanism in nature, a novel strategy based on multi-molecular template co-assembly for fabricating bone-like hybrid materials was firstly proposed by the authors. In this review article we have summarized the new trends from single-molecular template to bi-/multi-molecular template systems in biomimetic fabrication of apatite hybrid materials. So far, many novel apatite hybrid materials with controlled morphologies and hierarchical structures have been successfully achieved using bi-/multi-molecular template strategy, and are found to have multiple common features in comparison with natural mineralized tissues. The carboxyl, carbonyl and amino groups of the template molecules are identified to initiate the nucleation of calcium phosphate during the assembling process. For bi-/multi-molecular templates, the incorporation of multiple promotion sites for calcium and phosphate ions precisely enables to regulate the apatite nucleation from the early stage. The roles of acidic molecules and the synergetic effects of protein templates have been significantly recognized in recent studies. In addition, a specific attention is paid to self-assembling of apatite nanoparticles into ordered structures on tissue regenerative scaffolds due to their promising clinical applications ranging from implant grafts, coatings to drug and gene delivery. [Copyright &y& Elsevier]

ABSTRACT Spatial and temporal variations in moisture across the Tibetan Plateau ( TP) during the years 1300-2005 were investigated using 50 gridded Palmer drought severity index ( PDSI) series extracted from the newly developed Monsoon Asia Drought Atlas ( MADA). The first four spatial patterns of moisture variations were identified by empirical orthogonal function analysis. They represent coherent moisture variations on the northern, southern, northwestern and southeastern TP, respectively. Similar spatial patterns were seen for the reconstructed and observational PDSI series. Comparisons between the first four principal components ( PCs) of 50 MADA-PDSI and Dai- PDSI series confirmed that the PCs based on the MADA-PDSI are reasonable proxies for regional moisture variations over the TP during the past 700 years. During the last century, wetness has generally increased on the northern and southern TP, which is in accord with the simulation of the global monsoon rainfall and paleoclimate records from Monsoonal Asia. The results of spatial correlation analysis indicated that the North Atlantic Oscillation is a primary cause of the contrasting moisture conditions between the northern and southern TP on a decadal time scale. Decadal moisture variations are also closely associated with the Pacific decadal oscillation which contributes to the difference in moisture conditions between the eastern and western TP. Moreover, interannual moisture variations over the TP were found to be closely linked to the El Niño southern oscillation. Large-scale dryness and wetness are possibly caused by the joint effects of each of these three atmospheric oscillation modes. © 2013 Royal Meteorological Society [ABSTRACT FROM AUTHOR]

Abstract: Heparinized biomaterials exhibit great anticoagulant properties. However, they promote proliferation of Staphylococcus aureus (S. aureus) and therefore cause infection within the bloodstream upon implantation in vivo. In the present study, an interesting dual-functional composite with anticoagulant and antibacterial properties based on heparinized silk fibroin and chitosan was synthesized. First, heparin was grafted onto the silk fibroin by covalent immobilization with N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (EDC) and N-hydroxysuccinimide (NHS). All data gathered from Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and elemental analysis (EA) indicated that the heparin was successfully immobilized onto the silk fibroin. The dual-functional composite of heparinized silk fibroin and chitosan was then fabricated by a blending method. The anticoagulant activity of the heparinized materials was evaluated using the prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT). The results showed that both heparinized silk fibroin and the composite material exhibited better hemocompatibility in comparison with single silk fibroin or chitosan. The antibacterial property of the materials was investigated by the pour-plate method. Results further suggested that the composite antibacterial property with respect to S. aureus was significantly enhanced. The dual-functionality of the composite material may supply a potential choice in blood contact devices. [Copyright &y& Elsevier]

The spatiotemporal variations of the climate of the last millennium provide the context for understanding the recent climate. However, there are few 1000‐year‐long spatiotemporally continuous climate reconstructions at hemispheric to global scales. Here, a millennial, spatiotemporally continuous and annually resolved air temperature dataset for the Northern Hemisphere (NH) was reconstructed using paleoclimate data assimilation (PDA) approach based on an expanded tree ring proxy dataset and artificial neural network‐based proxy system models. Verifications show the PDA‐based reconstruction agrees well with instrumental temperature, previous proxy‐based reconstructions and the Last Millennium Climate Reanalysis version 2 (LMRv2) dataset in space and time domains. Since the PDA‐based reconstruction is spatiotemporally continuous fields without missing value over the whole NH, which is a distinct advantage of the PDA‐based reconstruction over other proxy‐based NH‐averaged temperature reconstructions, we focussed on analysing the spatial variations of the NH temperature during the last millennium, for example, the primary modes of temperature variabilities and the spatial variabilities of the NH temperature in three typical climatic epochs of the millennium. Results show that the first‐leading mode (explained variance of 72.50%) of the NH temperature variability is a spatially consistent mode, while the second‐leading mode (explained variance of 10.60%) exhibits a different pattern that is different from the first‐leading empirical orthogonal function mode, particularly in the Arctic, which shows a dipole structure anomaly. The 20th century was the warmest, with 94.17% of the NH displaying positive anomalies. The 11th century was the second warmest century in the record, with 70.26% of the NH showing a positive anomaly. The 19th century was the coldest, with negative anomalies covering 86.97% of the NH. Northwest North America and the Northern Europe‐Barents Sea are two distinctly anomalous centres during these three centuries. Overall, the reconstructed air temperatures provide a new and reliable dataset for studying the millennial NH temperature variations. [ABSTRACT FROM AUTHOR]

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs. [ABSTRACT FROM AUTHOR]

The challenge of preparing dense ultrafine-grained high-entropy ceramics through conventional pressureless sintering is hereby addressed by a simple two-step sintering method. Ultrafine-grained (Ce 0.2 Nd 0.2 Sm 0.2 Eu 0.2 Gd 0.2) 2 Zr 2 O 7 high-entropy zirconate with 99.2 % theoretical density and 135 nm grain size has been fabricated by pressureless two-step sintering for the first time. Compared to the conventional sintering, two-step sintering provides finer grain sizes and better microstructural uniformity, which yield excellent comprehensive mechanical properties with high hardness of 16.0 GPa, large elastic modulus of 262 GPa and high fracture toughness of 2.8 MPa·m1/2. It is believe that pressureless two-step sintering can be utilized to prepare other high-entropy ceramics with fine grain size and high quality. [ABSTRACT FROM AUTHOR]

[Display omitted] Angiogenesis plays a pivotal role in tissue development and regeneration, but few safe and efficient pro-angiogenic factors are available for long-term clinical therapy. Although stem cell-derived exosomes exhibit excellent biocompatibility and considerable pro-angiogenic capacity, their low yield extremely limits their clinical potential. Exosome-mimetics (EMs) employ similar features to exosomes and can be produced in a higher yield. In this study, the HY-EMs were produced to enhance in vitro and in vivo pro-angiogenic ability from hypoxia-preconditioned bone marrow mesenchymal stem cells (BMSCs) using a serial extrusion method. The yield of EMs was over 10 times greater than that of exosomes. Furthermore, compared with the EMs group, the tube number of human umbilical vein endothelial cells (HUVECs) in vitro doubled in the HY-EMs treated group, and the number of blood vessels increased by 186% in subcutaneously implanted scaffold with HY-EMs. More importantly, the HY-EMs effectively promoted vascularized osteogenesis in a critical-sized cranial defect model, with the new bone volume and vessel number in regenerated bone increased to 120% and 175%, respectively. Consequently, our current work provides a promising strategy to customize and mass-produce functional EMs for vascularized osteogenesis. [ABSTRACT FROM AUTHOR]

Preparation of high-entropy ceramics (HECs) requires long duration at high temperatures, which limits their wide application. In this study, high-entropy (La 0.2 Ce 0.2 Nd 0.2 Sm 0.2 Eu 0.2) 2 Zr 2 O 7 ceramics was prepared at low temperatures of 762–885 °C in very short time of 60 s using the flash sintering. The effects of electric field strength and current limit on the densification and grain growth, as well as the phase transformation were systematically investigated. Both density and grain size were increased with the increase of the electric field strength and current limit. The phase transformation from defective fluorite to pyrochlore occurred at large current limit. The flash-sintered bulks exhibited good mechanical properties. This study demonstrates that flash sintering is an effective method for rapid preparation of HECs at low temperatures. Moreover, the microstructure of HECs can be controlled by adjusting the electric field strength and current limit. [ABSTRACT FROM AUTHOR]

Preparation of high-entropy ceramics (HECs) requires long duration at high temperatures, which limits their wide application. In this study, high-entropy (La 0.2 Ce 0.2 Nd 0.2 Sm 0.2 Eu 0.2) 2 Zr 2 O 7 ceramics was prepared at low temperatures of 762–885 °C in very short time of 60 s using the flash sintering. The effects of electric field strength and current limit on the densification and grain growth, as well as the phase transformation were systematically investigated. Both density and grain size were increased with the increase of the electric field strength and current limit. The phase transformation from defective fluorite to pyrochlore occurred at large current limit. The flash-sintered bulks exhibited good mechanical properties. This study demonstrates that flash sintering is an effective method for rapid preparation of HECs at low temperatures. Moreover, the microstructure of HECs can be controlled by adjusting the electric field strength and current limit. [ABSTRACT FROM AUTHOR]

The drivers of multidecadal‐ to centennial‐scale variability in East Asian temperature, apparent in temperature reconstructions, are poorly understood. Here we apply a multivariate regression analysis to distinguish the influences of large‐scale modes of internal variability (Atlantic Multidecadal Oscillation and Pacific Multidecadal Oscillation) and external natural (orbital, solar, and volcanic) and anthropogenic (greenhouse gas concentrations, aerosols, and land use changes) forcings on East Asian warm‐season temperature over the period 850–1999 CE (Common Era). We find that ~80% of the temperature change on time scales longer than 30 years can be explained including all drivers over the full‐length period. The Pacific Multidecadal Oscillation was the most important driver of multidecadal temperature variability during the Medieval Climate Anomaly (here 950–1250), while solar contribution was important during the Little Ice Age (here 1350–1850). Since 1850, two thirds of temperature change can be explained with anthropogenic forcing, whereas one third was related mainly to the Atlantic Multidecadal Oscillation and volcanic forcing. Plain Language Summary: The Atlantic Multidecadal Oscillation (AMO) and Pacific Multidecadal Oscillation (PMO) are suggested to be key components of internal temperature variability globally and in the Northern Hemisphere. However, the contribution of the AMO and PMO to temperature at regional/continental scales in preindustrial times is still unclear. Here we use a multivariate regression analysis to distinguish the AMO and PMO contributions to the East Asian temperature multidecadal (> 30 years) changes from the influence of external (orbital solar, volcanic, and anthropogenic) forcings. We find that the contribution of the AMO and PMO is of similar magnitude as solar and volcanic forcing during the period 850–1999 CE (Common Era). We apply the same approach to three subperiods and find that the PMO, solar forcing, and anthropogenic forcing contributed most during the periods 950–1250, 1350–1850, and 1850–1999, respectively. Key Points: Atlantic and Pacific Multidecadal Oscillations (AMO and PMO) are important contributors to East Asian temperature variabilityThe combined contribution of the AMO and PMO is of similar magnitude as solar and volcanic forcing during 850–1999The most important drivers change between subperiods: for 950–1250 it is the PMO, and for 1350–1850 it is solar forcing [ABSTRACT FROM AUTHOR]

Biophysical cues of the cellular microenvironment tremendously influence cell behavior by mechanotransduction. However, it is still unclear how cells sense and transduce the mechanical signals from 3D geometry to regulate cell function. Here, the mechanotransduction of human mesenchymal stem cells (MSCs) triggered by 3D micropatterns and its effect on the paracrine of MSCs are systematically investigated. Our findings show that 3D micropattern force could influence the spatial reorganization of the cytoskeleton, leading to different local forces which mediate nucleus alteration such as orientation, morphology, expression of Lamin A/C and chromatin condensation. Specifically, in the triangular prism and cuboid micropatterns, the ordered F-actin fibers are distributed over and fully transmit compressive forces to the nucleus, which results in nuclear flattening and stretching of nuclear pores, thus enhancing the nuclear import of YES-associated protein (YAP). Furthermore, the activation of YAP significantly enhances the paracrine of MSCs and upregulates the secretion of angiogenic growth factors. In contrast, the fewer compressive forces on the nucleus in cylinder and cube micropatterns cause less YAP entering the nucleus. The skin repair experiment provides the first in vivo evidence that enhanced MSCs paracrine by 3D geometry significantly promotes tissue regeneration. The current study contributes to understanding the in-depth mechanisms of mechanical signals affecting cell function and provides inspiration for innovative design of biomaterials. [ABSTRACT FROM AUTHOR]

Cancer recurrence and metastasis after surgical resection is a vital reason of treatment failure. The modification of immune cells through implanted biomaterials is a promising postoperative immunotherapy. Herein, an injectable hydrogel scaffold loaded with engineered exosome mimetics that in vivo recruits and programs endogenous macrophages into M1 binding with anti‐CD47 antibody (M1‐aCD47 macrophages) for postoperative cancer immunotherapy is developed. Briefly, M1 macrophages‐derived exosome mimetics co‐modified with vesicular stomatitis virus glycoprotein (VSV‐G) and aCD47 (V‐M1EM‐aCD47) are encapsulated in injectable chitosan hydrogel. Such hydrogel recruits inherent macrophages in situ and releases V‐M1EM‐aCD47 that programs M2 to M1‐aCD47 macrophages. M1‐aCD47 macrophages own dual‐functions of tumor‐homing and enhanced phagocytosis. They can actively target to tumor cells for delivery of aCD47 that blocks the "don't eat me" signal, thereby promoting phagocytosis of macrophages to cancer cells. Furthermore, V‐M1EM‐aCD47 hydrogel implanted into resection site of 4T1 breast tumor inhibits tumor recurrence and metastasis by phagocytosis of M1‐aCD47 macrophages and T cell‐mediated immune responses. The findings demonstrate that biomaterials can be designed in vivo to program inherent macrophages, thereby activating the innate and adaptive immune systems for prevention of postoperative tumor recurrence and metastasis. [ABSTRACT FROM AUTHOR]

Tissue engineering heart valve (TEHV) offers great potential to overcome the limitations of commercial artificial valves used in clinical practice as a permanent prosthetic valve. Currently, decellularized heart valve (DHV) is the most widely used scaffold for TEHV, but showed suboptimal performance due to difficulty of endothelialization. Facilitating endothelialization of DHV is indispensable for better valve performance, and excellent hemocompatibility guarantees enough time windows for endothelialization process. Herein, a dual‐functional TEHV scaffold with improving hemocompatibility and accelerating endothelialization is constructed by modifying DHV with copper ions (Cu) and growth differentiation factor 11 (GDF11). Results show the newly‐constructed scaffold successfully generates endogenous nitric oxide (NO) through catalysis of Cu, and possesses improved hemocompatibility by down‐regulating platelets activation and adhesion. Furthermore, GDF11 immobilization significantly accelerates scaffold endothelialization through facilitating recruitment, supporting growth, and alleviating apoptosis of endothelial progenitor cells. This TEHV scaffold shows favorable performance under in vivo hemodynamic environment with intact endothelial coverage and adaptive ECM remodeling, and without thrombus or calcification formation. This newly‐constructed TEHV scaffold is expected to make up for the shortcomings of currently available prosthetic valves in clinical practice and has the potential possibility of rapid translation to the clinic as a better prosthetic valve. [ABSTRACT FROM AUTHOR]

The reconstruction of global annual mean temperatures made by the PAGES 2k Consortium in 2019 represents one of the most influential sequences of global climate variability over the Common Era. However, it is still not clear how the reconstruction can be influenced by the selection of reconstruction methods and the selection of proxy records with different temporal resolutions over different regions. We adopt a widely used Composite-Plus-Scale method to elucidate the effects of the selection of the proxy records on temperature reconstruction. To ensure the uniformity of data, different types of proxy records spanning the past ∼2000 years from the PAGES 2k proxy network were used to investigate the potential effects of proxy selection in hemispheric and global temperature reconstructions during the past two millennia. The long-term trends, spectral characteristics, and volcanic responses of the annual temperatures were studied based on the reconstructions. Our results reveal a significant cooling trend in the global annual mean temperature using both tree-ring and non-tree-ring records during the 1–1850 CE period, and show that the cooling exhibits a stronger trend in the Southern Hemisphere (SH) than that in the Northern Hemisphere (NH). Yet, the long-term trends vary according to different combinations of proxy records. Different reconstructions based on different types of proxies also exhibit different features in terms of volcanic responses and spectral properties. Tree-ring-based temperature reconstructions show stronger cooling responses to tropical volcanic eruptions, while non-tree-ring-based reconstructions suggest less robust volcanic responses, which may be related to dating uncertainties and low temporal resolution of the proxies. Tree-ring width records tend to preserve a substantial proportion of high-frequency (<200 years) variability, whereas non-tree-ring proxies tend to capture a larger fraction of low-frequency (>200 years) variations. Efforts are needed to reduce uncertainties of the temperature reconstruction over the Common Era associated with the insufficient spatiotemporal coverage of the current proxy network, especially for the first millennium and for the SH and tropics, also to develop statistical methods and to improve the signal strength and constrain uncertainties in existing proxy records. [ABSTRACT FROM AUTHOR]

Lung cancer remains one of the leading causes of death in humans. Gefitinib is an inhibitor of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) commonly used to suppress tumour growth. However, constantly use of gefitinib results in drug-resistance, reduced efficacy and undesired side effects. To circumvent these drawbacks, targeted and photothermal therapies have emerged as effective strategies. Herein, we are first to adopt a black phosphorus (BP) nanoparticle-based novel delivering strategy by combining gefitinib and cancer cytomembrane to treat non-small cell lung cancer (NSCLC). In these gefitinib-containing nano-carriers, cyanine 5 (Cy5) biotin-labelled BP was incorporated with cancer membrane and then consists of a nanomaterial (BPGM), which enabled to deliver gefitinib to the tumours effectively. The combination of BPGM showed reinforcing effects to suppress NSCLC cells and xenograft tumours without apparent adverse effects both in vitro and in vivo. BPGM facilitated the delivery of gefitinib to tumour tissue and extended its retention time within tumours. These studies thus suggest that BP may serve as novel delivery strategy for lung cancer. [ABSTRACT FROM AUTHOR]

Epigenetic modifications viz. DNA methylation, histone modifications, and RNA-based alterations play a crucial role in the development of cardiovascular diseases. In this study, we investigated DNA methylation with an aim to reveal the epigenetic etiology of heart failure. Sprague–Dawley rats surviving myocardial infarction developed acute heart failure in 1 week. Genomic DNA methylation changes were profiled by bisulfite sequencing, and gene expression levels were analyzed by RNA-seq in failing and sham-operation hearts. A total of 3480 differentially methylated genes in the promoter regions including transcriptional start site and 1934 transcriptome-altered genes were identified in the defected hearts. Common differential genes were enriched by the gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein–protein interaction for HF phenotypes. Among these, Mettl11b, HDAC3, HDAC11, ubiquitination-related genes, and snoRNAs are new epigenetic classifiers that had not been reported yet, which may be important regulators in HF. [ABSTRACT FROM AUTHOR]

• The zinc anode protection layer comprising cost-effective zinc saponite. • The interlayer with negative charge structure of NLZS ensures uniform Zn2+ flux. • The NLZS layers exhibit excellent desolvation ability, inhibiting zinc corrosion. • Zn metal batteries and capacitor based on NLZS layer show stable cycling. The performance of zinc anode in aqueous zinc metal batteries is severely challenged by dendritic growth and side reactions. Here, a zinc saponite (NLZS) protective layer strategy with "cation-regulation" is explored to realize dendrite-free zinc metal anode. The abundant negative charge channels confer unique cation selectivity to the NLZS protective layer, homogenizing the interfacial electric field while regulating zinc-ion flux, ensuring uniform zinc deposition and inhibiting interfacial side reactions. Consequently, the functional NLZS protective layer enables the zinc anode to deliver an average coulombic efficiency of more than 99.5 % at 5 mA cm−2 and a cycle life of more than 1600 h at 0.5 mA cm−2. Furthermore, both MnO 2 -based full batteries and zinc-ion capacitors exhibit outstanding rate performance and cycling stability. This work not only provides a simple and cost-effective protection strategy for the zinc anode but also holds promise for practical applications. [ABSTRACT FROM AUTHOR]

Abstract: The fine structure of zinc substituted hydroxyapatite was studied using experimental analysis and first-principles calculations. The synthetic hydroxyapatite nanoparticles containing low Zn concentration show rod-like morphology. The crystallite sizes and unit-cell volumes tended to decrease with the increased Zn concentration according to X-ray diffraction patterns. The Zn K-edge X-ray absorption spectra and fitting results suggest that the hydroxyapatite doped with 0.1 mole% zinc is different in the zinc coordination environments compared with that containing more zinc. The density function theory calculations were performed on zinc substituted hydroxyapatite. Two mechanisms included replacing calcium by zinc and inserting zinc along the hydroxyl column and were investigated, and the related substitution energies were calculated separately. It is found that the substitution energies are negative and lowest for inserting zinc between the two oxygen atoms along the hydroxyl column (c-axis). Combined with the spectral analysis, it is suggested that the inserting mechanism is favored for low concentration zinc substituted hydroxyapatite. [Copyright &y& Elsevier]

Almost all proxy-based temperature reconstructions for East Asia have hitherto been designed to resolve summer or annual temperature variability. Reconstruction for the winter temperature is still lacking. Here, we report an annually resolved, winter-season (December-February, DJF) temperature field reconstruction for East Asia covering the period 1300–2000 CE, based on 260 temperature-sensitive tree-ring records. The most striking feature of our new reconstruction is a significant long-term warming trend since the 14th century, which is associated with winter solar insolation at mid-latitudes of the Northern Hemisphere and the global anthropogenic impact. The amplitude of reconstructed winter temperature change over the study period was ~4.7 times greater than that for summer temperature, and the rate of winter temperature increase was ∼6 times as much as that of summer temperature. The results from climate model simulations were consistent with the reconstruction, showing that the amplitude and rate of temperature change in winter were greater than those in summer. The reconstruction also suggests the possible influence of volcanic eruptions, anthropogenic activities and winter solar insolation on the winter temperature variations. Our result also suggests a long-term decrease in summer-to-winter temperature difference occurred in 1625 (±24 years) CE. [ABSTRACT FROM AUTHOR]

Alignment system, with large stroke, high accuracy, and deviation automatic correction properties, is really attractive for performing the task of wafer-level flip-chip packaging. The motivation for this work is enabling a common packaging system to run in a manner of deviation automatic correction. To this end, in this article, three parallel kinematic flexure limbs with lever displacement amplifier are designed to construct a 3-RRR (R is revolute) XY θ deviation corrector. After a series of kinematics theoretic analyses and dimension optimizations, the mechanism is evaluated. Given the dynamic coupling linear and angular motion of the corrector are hard to be acquired simultaneously by common commercial displacement sensors, a “coarse-precise” composite visual inspection algorithm is designed to capture the precise motion in XY θ directions at the same time. Then, a series of validation experiments are successfully carried out, including visual inspection test, kinematics characterization, open-loop and closed-loop tracking tests, and flip-chip deviation correction test. The results indicate that the resolution and the absolute positioning accuracy of the developed alignment system are achieved up to 40 nm/10 μrad and 0.3  μm/30  μrad, respectively, and the positioning period under maximum range is kept within two control cycles (0.7 s). Finally, in association with the deviation corrector, the accuracy of the alignment system is improved up to 0.3  μm/0.03 mrad, which proved that the proposed strategy provides an effective solution for the one-step accurate alignment operation of advanced chip packaging. [ABSTRACT FROM AUTHOR]

• A SeO 3 2−-based strategy is developed for ROS/RNS burst and NADPH depletion. • An injectable Alg@SLGA hydrogel achieves synergistic therapy for breast cancer. • Alg@SLGA hydrogel triggers ROS/RNS generation and NADPH exhaustion. • Alg@SLGA hydrogel acts as an ICD inducer to boost systemic anti-tumor immunity. The anti-cancer effect of selenite (SeO 3 2−) is limited by its short half-life and narrow therapeutic window. Peroxynitrite (ONOO−), the most active reactive nitrogen species (RNS) derived from nitric oxide (NO) reacting with superoxide anion (O 2 •−), is still not fully exploited in the combination therapy against cancers. Herein, an injectable hydrogel is developed to trigger intracellular reactive oxygen species (ROS)/RNS bursts and disrupt nicotinamide adenine dinucleotide phosphate (NADPH) homeostasis via an innovative SeO 3 2−-based strategy. Calcium selenite/ L -Arginine (L -Arg) nanospheres (SL NPs) are synthesized as the donor of NO and SeO 3 2−. The injectable Alg@SLGA sol composed of SL NPs, glucose oxidase (GOx), 6-aminonicotinamide (6-AN, an inhibitor of the pentose phosphate pathway (PPP)), and sodium alginate (Alg) can convert to gel in a physiological environment. Peritumoral injection of Alg@SLGA hydrogel is performed for safe and targeted treatment. The loaded GOx catalyzes glucose oxidation to produce acidic H 2 O 2 , initiating the release of NO and SeO 3 2− from Alg@SLGA. SeO 3 2− reacts with intracellular GSH and H 2 O 2 to generate •OH and O 2 •−, which further interacts with NO to form ONOO−. The SeO 3 2− and 6-AN synergistically trigger intracellular NADPH exhaustion by promoting cystine metabolism-mediated NADPH consumption and inhibiting NADPH generation, respectively. Moreover, Alg@SLGA effectively induces immunogenic cell death (ICD) of tumor cells, further provoking systemic antitumor immune responses. As a consequence, the injectable Alg@SLGA hydrogel achieves enhanced ROS/RNS-mediated combination therapy by synergistically disrupting NADPH homeostasis and improving antitumor immunity. [ABSTRACT FROM AUTHOR]

[Display omitted] • The ZnSe protective layer is constructed on porous ZnO by hydrothermal method. • ZnO@ZnSe has a unique layered porous structure and an outstanding specific surface area. • ZnO@ZnSe electrodes can achieve long-term cycling stability at high rates. • ZnO@ZnSe still has a specific capacity of 577.5 mAh·g−1 after 1460 cycles. Zinc anodes suffer from self-corrosion, deformation and dendrite growth, which greatly limit the commercial application of zinc-nickel batteries. For this purpose, zinc oxide microspheres with porous surfaces are synthesized by a simple hydrothermal method, and ZnSe protective layer is constructed on their surfaces. The uniform coverage of ZnSe improves the corrosion resistance of the anode material and alleviates the polarization phenomenon during the cycle, thus ensuring the stability of the electrode material. Moreover, the prominent specific surface area optimizes the interface contact between anode and electrolyte, improving the ion transport efficiency while homogenizing the current distribution around the interface. Therefore, the discharge specific capacity of ZnO@ZnSe electrode can still reach 577.5 mAh·g−1 after 1460 cycles at a high rate. There is almost no attenuation compared with the initial discharge capacity, demonstrating an extremely excellent electrochemical performance. [ABSTRACT FROM AUTHOR]

[Display omitted] • ZnO@CaC 2 O 4 prepared by water bath method is firstly introduced into Zn-Ni batteries. • ZnO@CaC 2 O 4 solves the problems of zinc dendrite and hydrogen precipitation reactions. • The ZnO@CaC 2 O 4 achieves ultra-long cycle stability of 2100 cycles. • The average discharge-specific capacity of this work can attain 570.7 mAh·g−1. Alkaline zinc-nickel batteries have attracted the attention of many researchers because of their low cost, environmental friendliness, and safety. However, the notorious zinc dendrite and hydrogen evolution issues have seriously hindered the commercialization progress. Herein, ZnO@CaC 2 O 4 microspheres are constructed with a two-step water bath method. It has a dual inhibition of dendrite growth due to the significant interaction of carbonyl oxygen and the regulation of zincate concentration by calcium ions, favoring ion transport and inducing zinc deposition efficiently. Besides, the hydrogen bond formed by carbonyl oxygen and water molecule can inhibit water activity at the reaction interface, thus suppressing side reactions such as hydrogen evolution. Consequently, the ZnO@CaC 2 O 4 anode achieves a high specific capacity (Average value 570.7 mAh·g−1), high rate performance (10C), and long cycle stability (2100 cycles). This method of dendrite suppression and hydrogen evolution control provides a new approach to designing high-performance zinc-nickel electrode materials. [ABSTRACT FROM AUTHOR]

Conductive hydrogel scaffolds have important applications for electroactive tissue repairs. However, the development of conductive hydrogel scaffolds tends to incorporate nonbiodegradable conductive nanomaterials that will remain in the human body as foreign matters. Herein, a biodegradable conductive hybrid hydrogel is demonstrated based on the integration of black phosphorus (BP) nanosheets into the hydrogel matrix. To address the challenge of applying BP nanosheets in tissue engineering due to its intrinsic instability, a polydopamine (PDA) modification method is developed to improve the stability. Moreover, PDA modification also enhances interfacial bonding between pristine BP nanosheets and the hydrogel matrix. The incorporation of polydopamine‐modified black phosphorous (BP@PDA) nanosheets into the gelatin methacryloyl (GelMA) hydrogels significantly enhances the electrical conductivity of the hydrogels and improves the cell migration of mesenchymal stem cells (MSCs) within the 3D scaffolds. On the basis of the gene expression and protein level assessments, the BP@PDA‐incorporated GelMA scaffold can significantly promote the differentiation of MSCs into neural‐like cells under the synergistic electrical stimulation. This strategy of integrating biodegradable conductive BP nanomaterials within a biocompatible hydrogel provides a new insight into the design of biomaterials for broad applications in tissue engineering of electroactive tissues, such as neural, cardiac, and skeletal muscle tissues. [ABSTRACT FROM AUTHOR]

Bone tissue engineering utilizes three critical elements – cells, scaffolds, and bioactive factors – to recapitulate the bone tissue microenvironment, inducing the formation of new bone. Recent advances in materials development have enabled the production of scaffolds that more effectively mimic the hierarchical features of bone matrix, ranging from molecular composition to nano/micro-scale biochemical and physical features. This review summarizes recent advances within the field in utilizing these features of native bone to guide the hierarchical design of materials and scaffolds. Biomimetic strategies discussed in this review cover several levels of hierarchical design, including the development of element-doped compositions of bioceramics, the usage of molecular templates for in vitro biomineralization at the nanoscale, the fabrication of biomimetic scaffold architecture at the micro- and nanoscale, and the application of external physical stimuli at the macroscale to regulate bone growth. Developments at each level are discussed with an emphasis on their in vitro and in vivo outcomes in promoting osteogenic tissue development. Ultimately, these hierarchically designed scaffolds can complement or even replace the usage of cells and biological elements, which present clinical and regulatory barriers to translation. As the field progresses ever closer to clinical translation, the creation of viable therapies will thus benefit from further development of hierarchically designed materials and scaffolds. [ABSTRACT FROM AUTHOR]

• Nano monetite particles with good dispersion can exist as hydrosol. • Compared with nano hydroxyapatite hydrosol and bioactive glass, dentin tubule can be effectively occluded by nano monetite hydrosol in short time. • Supersaturated ionic environment (Ca2+ and PO 4 3− ions) and remineralization activity supported from nano monetite hydrosol were beneficial to acid erosion resistance of dentin tubule. We aim to investigate the dentin tubule occlusion and remineralization potential of a novel nano-monetite hydrosol (nMH). First, nano-monetite hydrosol (nMH) was fabricated by homogeneous precipitation method. Then, the effectiveness of toothpaste with nMH on improving remineralization was evaluated by the measurement of tubule occluding ratio and acid-resistant stability compared with dentifrices comprising nano-hydroxyapatite hydrosol (nHH) and bioactive glass (BG). To explain this result, we studied the ions releasing and remineralization based on gelatin scaffold among nMH, nHH and BG. Finally, the cytotoxicity of these three minerals on Human dental pulp stem cells (HDPSCs) was evaluated. Processing for more than 7 days, the toothpaste containing nMH exhibited the significant remineralization potential and acid-resistant compared with two commercial de-sensitive dentifrices comprising nHH and BG. In addition, cytotoxicity test resulted that nMH has good cell compatibility to HDPSCs below extracts concentration of 3.12 mg/mL. Small size, the release of Ca2+ and PO 4 3− with high concentration, strongly binding on dental surface, and fast transformation to HAp, were all needed in the preparation of effective dentin tubule occluding biomaterials. [ABSTRACT FROM AUTHOR]

• We have broadened the biomedical application of erythrocyte membrane as a multifunctional biological vesicle in the treatment of osteoarthritis. • The modification of the erythrocyte membrane avoids acute inflammatory reactions caused by injection of nanocarriers into joint cavities and meanwhile enhancing targeted therapy. • The injectable core–shell nanocarrier carrying two drug molecules can achieve double-factor sequential release, providing a feasible and effective method for early inflammation inhibition and later remodeling of damaged cartilage. Osteoarthritis is a commonly severe joint disease featured by the progressive loss of cartilage and reduction in lubricating synovial fluid, which currently lacks the effective treatment in clinic. Herein, we designed an erythrocyte membrane-camouflaged and double-factor sequential delivery of shell-core nanocarrier to deliver two diverse drugs. The interior core of nanocarriers was loaded with the transforming growth factor-β3 (TGF-β3), and subsequently modified with a natural anti-inflammatory drug of curcumin, and finally encapsulated with erythrocyte membrane as a protective and regulation shell. The as-prepared engineered nanocarriers were injected into joint capsule to play a dual function on inflammation modulation and cartilage remodeling. The curcumin absorbed on the internal surface of shell membrane was firstly released in large quantities to tune the inflammatory microenvironment whereas the TGF-β3 in the interior core was released subsequently with the nanoparticle degradation to alleviate chondrocyte senescence. Overall, our current work creates an engineered nanocarrier to control macrophage type and induce cartilage restoration on postponing the progression of osteoarthritis. [ABSTRACT FROM AUTHOR]

Considerable progress has been made in dendroclimatological research in China during the period 2000–2017, including a significant increase in the spatial coverage of tree-ring chronologies developed for paleoclimatic research. New tree-ring sampling sites have been established across the Tibetan Plateau, as well as the northeastern and sub-tropical eastern parts of China. Most of the studies use coniferous trees, although different plant functional types (e.g., broadleaf species and shrubs) have also been increasingly investigated. Tree-ring chronologies longer than 600 years, however, are mostly found on the Tibetan Plateau, with the longest one extending back to 2637 BCE (before Common Era). Most tree-ring records in the eastern parts of China are <400 years long. Tree-ring width is the most commonly studied parameter, although stable isotope ratios and wood density data have also been obtained for specific sites. Stable oxygen isotope data frequently shares a common hydroclimate signal, whereas the climate or environmental signals remain inconsistent for the few available stable carbon isotope records. In general, tree-ring width-based temperature reconstructions originate from higher elevation sites (i.e., treeline) compared to hydroclimate reconstructions. Precipitation or drought reconstructions are mainly obtained from regions with an annual precipitation of <800 mm. Most of the tree-ring reconstructions are based on individual site or local-scale chronologies, although a limited number of regional-scale and field reconstructions have been produced. The most prominent identified characteristics of the recent advances in dendroclimatological research for China have manifested in aspects such as an expanded network of sampling sites, improved climate reconstruction methodology, and improved uncertainty estimations in the latter. Furthermore, the traditional statistical-based tree growth–climate relationships have been supplemented by monitoring and modeling approaches. Based on the progress from 2000 to 2017, and on the research potential of the country in this field, we expect additional widening of the dendroclimatological investigations in China during the coming years. [ABSTRACT FROM AUTHOR]

Water-induced parasitic reaction and zinc dendrite growth caused by uneven electric field distribution on the surface of the zinc anode are the most controversial problems in the practical application of zinc-nickel rechargeable batteries in large-scale energy storage. Herein, Bi 2 O 3 /In 2 O 3 doped ZnO@C synthesized by MOF pyrolysis with good cycle stability. The ability to inhibit hydrogen evolution and achieve uniform deposition of zinc is characterized by CV, Tafel, and scanning electron microscopy (SEM). Benefiting from the high hydrogen evolution overpotential and high electrical conductivity, Bi 2 O 3 doped ZnO@C (BCZ) and In 2 O 3 doped ZnO@C (ICZ) electrodes deliver high capacity of 640 mA h g−1 and 580 mA h g−1 at 10 C after 1200 and 3400 cycles, respectively, and reveals long-term cyclic stability with capacity retention over 90%. This work provides new ideas for the anode synthesis of aqueous rechargeable zinc metal batteries and other batteries. • Bi 2 O 3 /In 2 O 3 doped ZnO@C are synthesized in one step by a simple MOF-5 pyrolysis route. • Bi 2 O 3 /In 2 O 3 doped ZnO@C anode achieves ultra-long cycle stability at a high rate. • The dual regulation mechanism of MOF and Bi 2 O 3 /In 2 O 3 inhibit the growth of dendrites and the occurrence of HER. [ABSTRACT FROM AUTHOR]

Excessive ethanol (EtOH) intake, especially to prenatal exposure, can significantly affect cognitive function and cause permanent learning and memory injures in children. As a result, how to protect children from EtOH neurotoxicity has gained increasing attention in recent years. Piracetam (Pir) is a nootropic drug derived from c-aminobutyric acid and can manage cognition impairments in multiple neurological disorders. Studies have shown that Pir can exert therapeutic effects on EtOH-induced memory impairments, but the underlying mechanism is still unknown. In this study, we found that Pir inhibited ethanol-induced memory deficit by mediating multiple pathways. Treatment with EtOH could cause cognitive deficit in juvenile rats, and triggered the alteration of synaptic plasticity. Administration with Pir significantly increased long-term potentiation and protected hippocampus neurons from EtOH neurotoxicity. Pir intervention ameliorated EtOH-induced cell apoptosis and inhibited the activation of Caspase-3 in vitro , suggesting that Pir protected neurons by anti-apoptotic effects. Pir could decrease the expression of LC3-II and Beclin-1 induced by EtOH, and increase the phosphorylation of mTOR and reduce the phosphorylation of Akt, which suggested that the protective effect of Pir was involved in regulation of autophagic process and mTOR/Akt pathways. In conclusion, we speculate that Pir reduces EtOH-induced neuronal damage by regulation of apoptotic action and autophagic action, and our research offers preclinical evidence for the application of Pir in ethanol toxicity. [ABSTRACT FROM AUTHOR]

Osteochondral defects cannot be adequately self-repaired due to the presence of the sophisticated hierarchical structure and the lack of blood supply in cartilage. Thus, one of the major challenges remaining in this field is the structural design of a biomimetic scaffold that satisfies the specific requirements for osteochondral repair. To address this hurdle, a bio-inspired multilayer osteochondral scaffold that consisted of the poly(ε-caprolactone) (PCL) and the hydroxyapatite (HA)/PCL microspheres, was constructed via selective laser sintering (SLS) technique. The SLS-derived scaffolds exhibited an excellent biocompatibility to support cell adhesion and proliferation in vitro . The repair effect was evaluated by implanting the acellular multilayer scaffolds into osteochondral defects of a rabbit model. Our findings demonstrated that the multilayer scaffolds were able to induce articular cartilage formation by accelerating the early subchondral bone regeneration, and the newly formed tissues could well integrate with the native tissues. Consequently, the current study not only achieves osteochondral repair, but also suggests a promising strategy for the fabrication of bio-inspired multilayer scaffolds with well-designed architecture and gradient composition via SLS technique. [ABSTRACT FROM AUTHOR]

Nitric Oxide Generation and Endothelial Progenitor Cells Recruitment for Improving Hemocompatibility and Accelerating Endothelialization of Tissue Engineering Heart Valve (Adv. Funct. Endothelialization, growth differentiation factor 11, hemocompatibility, nitric oxide generation, tissue engineering heart valves Keywords: endothelialization; growth differentiation factor 11; hemocompatibility; nitric oxide generation; tissue engineering heart valves EN endothelialization growth differentiation factor 11 hemocompatibility nitric oxide generation tissue engineering heart valves 1 1 1 02/27/23 20230223 NES 230223 B Next-Generation Tissue Engineering Heart Valves b In article number 2211267, Nianguo Dong, Weihua Qiao, and co-workers report a newly-constructed copper ion coated and GDF11 immobilized scaffold to successfully generate endogenous nitric oxide and improve hemocompatibility by down-regulating platelets activation and adhesion, meanwhile significantly accelerating endothelialization through facilitating recruitment and alleviating apoptosis of endogenous endothelial progenitor cells, promising for clinical application as an ideal prosthetic valve. [Extracted from the article]

Diltiazem has been used for post-transplant hypertension, but the mechanism underlying its protective effect of endothelial cells against angiotensin II (Ang II) – induced impairment remains unclear. Human umbilicus vein endothelial cells (HUVECs) were cultured and divided into seven groups: control, Ang II (10 −6 M), diltiazem (10 −6 M), [D-Lys3]-GHRP-6(25 μM), diltiazem (10 −6 M) + Ang II (10 −6 M), losartan (10 −6 M) + Ang II (10 −6 M), [D-Lys3]-GHRP-6 (25 μM) + Dil(10 −6 M) + Ang II (10 −6 M) groups. Nitric oxide (NO) production, intracellular reactive oxygen species (ROS) levels, protein and mRNA expressions of endothelial nitric oxide synthase (eNOS) and p47 phox subunit of NADPH were evaluated. Results indicated that pre- treatment with diltiazem significantly decreased the intracellular ROS levels and increased NO production. Treatment with 10 −6 M Ang II for 24 h induced a significant decrease in the mRNA and protein levels of eNOS, which was significantly increased by the pre-incubated with diltiazem (10 −6 M). Treatment with 10 −6 M Ang II for 24 h induced a significant increase in the mRNA and protein levels of p47 phox subunit of NADHP oxidase, which was significantly decreased by the pre-incubated with diltiazem. However, all of these protective roles of diltiazem were attenuated by pre-incubation of [D-Lys3]-GHRP-6. The results reveal that diltiazem inhibits the Ang II – induced oxidative stress in HUVECs, which may be partly mediated by GHSR1a. [ABSTRACT FROM AUTHOR]

• Ti 3 C 2 T x MXene provides zincophilic sites for dendrite-Free zinc deposition. • The ZnO@MXene anode achieves ultra-long cycle stability at a high rate. • The average discharge specific capacity of this work can attain 625 mAh·g−1. Although Zn-Ni battery is a potential energy storage system, the anode zinc electrode often faces dendrite, passivation and deformation problems, which tend to be exacerbated at high current densities particularly, and severely hamper its practical applications. Zinc oxide was modified with 2D transition metal carbides/nitride (ZnO@MXene) firstly for the purpose of broadening the application scenarios of zinc alkaline secondary batteries. A variety of characterizations and density functional theory (DFT) calculations certify that highly conductive MXene matrix provides a high-speed electron transfer channel and its low ionic diffusion barrier and excellent ionic diffusion mobility of MXene can quickly reduce the ion concentration gradient at the solid–liquid interface, which weakens the concentration polarization. Also, MXene can tune the diffusion behavior to induce homogeneous deposition of zinc via the zinc-oriented-O groups, forming well-dispersed "seed points" to realize uniform nucleation and inhibiting dendrite growth. Therefore, ZnO@MXene as the anode of a Zn-Ni battery can keep its capacity of 594mAh·g−1 after 1500 cycles at 10C. That reaches 90% of its initial capacity (596mAh·g−1), suggesting superb specific capacity, rate performance, and cycle life span. [ABSTRACT FROM AUTHOR]