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Human embryonic stem cells (hESCs) have become an ideal cell source for the ex vivo generation of megakaryocyte (MK) and platelet products for clinical applications. However, an ongoing challenge is to establish scalable culture systems to maximize the yield of stem cell‐derived MKs that release platelets. We defined a specific dynamic 3D manufacturing system in a baffled‐flow manner that could remarkably facilitate megakaryopoiesis and increase the yield of platelet‐producing MKs from hESCs within a 12‐day induction period. Additionally, an increased number of >16N ploidy MKs, proplatelets, and platelets were generated from induced cells harvested on Day 12 using the specific dynamic culture method. The specific dynamic culture method significantly enhanced endothelium‐to‐haematopoietic transition and early haematopoiesis. More importantly, MK fate was significantly facilitated in a specific dynamic manner during early haematopoiesis. Mechanistically, this dynamic culture significantly enhanced mitochondrial function via the oxidative phosphorylation pathway and caused differentiation skewing of hESCs toward megakaryopoiesis. This study can aid in the automatic and scalable production of MKs from stem cells using baffled‐flow bioreactors and assist in the manufacturing of hESC‐derived MK and platelet products. [ABSTRACT FROM AUTHOR]

Precipitation forecasting plays an important role in disaster warning, agricultural production, and other fields. To solve this issue, some deep learning methods are proposed to forecast future radar echo images and convert them into rainfall distributions. Prevailing spatiotemporal sequence prediction methods are usually based on a ConvRNN structure that combines a Convolutional Neural Network and Recurrent Neural Network. However, these existing methods ignore the image change prediction, which causes the coherence of the predicted image has deteriorated. Moreover, these approaches mainly focus on complicating model structure to exploit more historical spatiotemporal representations. Nevertheless, they ignore introducing other valuable information to improve predictions. To tackle these two issues, we propose GCMT‐ConvRNN, a multi‐ask framework of ConvRNN. Except for precipitation nowcasting as the main task, it combines the motion field estimation and sub‐regression as auxiliary tasks. In this framework, the motion field estimation task can provide motion information, and the sub‐regression task offers future information. Besides, to reduce the negative transfer between the auxiliary tasks and the main task, we propose a new loss function based on the correlation of gradients in different tasks. The experiments show that all models applied in our framework achieve stable and effective improvement. [ABSTRACT FROM AUTHOR]

Blood supply shortages, especially the shortage of rare blood types, threaten the current medical system. Research on stem cells has shed light on in vitro blood cell manufacturing. The in vitro production of universal red blood cells (RBCs) from induced pluripotent stem cells (iPSCs) has become the focus of transfusion medicine. To obtain O‐type Rh D‐negative blood, we developed O‐type Rh D‐negative human (h)iPSCs using homology‐directed repair (HDR)‐based CRISPR/Cas9. HuAiPSCs derived from human umbilical arterial endothelial cells and showing haematopoietic differentiation preferences were selected for gene modification. Guide RNAs (gRNAs) were selected, and a donor template flanked by gRNA‐directed homologous arms was set to introduce a premature stop code to RHD exon 2. CRISPR/Cas9 gene editing has resulted in the successful generation of an RHD knockout cell line. The HuAiPSC‐A1‐RHD−/− cell line was differentiated into haematopoietic stem/progenitor cells and subsequently into erythrocytes in the oxygen concentration‐optimized differentiation scheme. HuAiPSC‐A1‐RHD−/− derived erythrocytes remained positive for the RBC markers CD71 and CD235a. These erythrocytes did not express D antigen and did not agglutinate in the presence of anti‐Rh D reagents. In conclusion, taking the priority of haematopoietic preference hiPSCs, the HDR‐based CRISPR/Cas9 system and optimizing the erythroid‐lineage differentiation protocol, we first generated O‐type Rh D‐negative universal erythrocytes from RHD knockout HuAiPSCs. Its production is highly efficient and shows great potential for clinical applications. [ABSTRACT FROM AUTHOR]

PbZrO3 (PZO)‐based antiferroelectric thin films are of great interest due to their high‐power density and fast charging and discharging capability. However, the problems of low breakdown strength and inferior energy storage density of PZO films have not been well solved. In this work, the insulating MgO as the blocking interlayer is inserted into PbZrO3 films (abbreviated as P/M/P), which can inhibit the electric charge transfer and enhance the breakdown strength, as well as regulation of the polarization behavior. The results show that the maximal endurable electric field is significantly improved, and the double‐hysteresis characteristic disappeared after introducing MgO blocking interlayer. The energy storage density of P/M/P films reaches 21.97 J/cm3 under 1700 kV/cm, accompanying an ultralow efficiency of 44.01% due to the severe polarization loss. Furthermore, low‐temperature annealing is performed to suppress the polarization loss, and an energy storage density of 17.27 J/cm3 accompanying a high efficiency of 75.53% is obtained at 3100 kV/cm, still exhibiting good stability after 1 × 107 fatigue cycles. This study demonstrates that combining the insulating interlayer and the low‐temperature annealing endow the PZO‐based films significantly improved energy storage properties, having great potential to be used in the dielectric capacitors. [ABSTRACT FROM AUTHOR]

Nav1.5 sodium channels contribute to the generation of the rapid upstroke of the myocardial action potential and thereby play a central role in the excitability of myocardial cells. At present, the patch clamp method is the gold standard for ion channel inhibitor screening. However, this method has disadvantages such as high technical difficulty, high cost and low speed. In this study, novel machine learning models to screen chemical blockers were developed to overcome the above shortage. The data from the ChEMBL Database were employed to establish the machine learning models. Firstly, six molecular fingerprints together with five machine learning algorithms were used to develop 30 classification models to predict effective inhibitors. A validation and a test set were used to evaluate the performance of the models. Subsequently, the privileged substructures tightly associated with the inhibition of the Nav1.5 ion channel were extracted using the bioalerts Python package. In the validation set, the RF‐Graph model performed best. Similarly, RF‐Graph produced the best result in the test set in which the Prediction Accuracy (Q) was 0.9309 and Matthew's correlation coefficient was 0.8627, further indicating the model had high classification ability. The results of the privileged substructures indicated Sulfa structures and fragments with large Steric hindrance tend to block Nav1.5. In the unsupervised learning task of identifying sulfa drugs, MACCS and Graph fingerprints had good results. In summary, effective machine learning models have been constructed which help to screen potential inhibitors of the Nav1.5 ion channel and key privileged substructures with high affinity were also extracted. [ABSTRACT FROM AUTHOR]

We performed a meta‐analysis to evaluate the effect of platelet‐rich plasma vs standard management for the treatment of diabetic foot ulcer wounds. A systematic literature search up to March 2022 was performed and 1435 subjects with diabetic foot ulcer wounds at the baseline of the studies; 723 of them were treated with platelet‐rich plasma, and 712 used control. Odds ratio (OR) with 95% confidence intervals (CIs) was calculated to assess the effect of platelet‐rich plasma vs standard management for the treatment of diabetic foot ulcer wounds using the dichotomous method with a random or fixed‐effect model. The use of autologous platelet‐rich plasma resulted in significantly higher complete‐healed diabetic foot ulcer wounds compared with control (OR, 1.95; 95% CI, 1.49‐2.56, P < 0.001). The use of allogeneic platelet‐rich plasma resulted in significantly higher complete‐healed diabetic foot ulcer wounds compared with control (OR, 6.19; 95% CI, 2.32‐16.56, P < 0.001). The use of autologous and allogeneic platelet‐rich plasma resulted in significantly higher complete‐healed diabetic foot ulcer wounds compared with control. Though, the analysis of outcomes should be with caution because of the low number of studies in certain comparisons, for example, allogeneic platelet‐rich plasma compared with control. [ABSTRACT FROM AUTHOR]

Objectives: To estimate the coverage and willingness of pneumococcal vaccination and further explore the influencing factors of vaccination willingness among people in mainland China.Methods: Literature searches were conducted independently by two researchers in English- and Chinese-language databases from database inception to 6 October 2021. A random-effects meta-analysis model was used to derive summary vaccination coverage and willingness. Predefined subgroup analysis and meta-regression were performed to explore the sources of heterogeneity.Results: A total of 97 studies were included in this meta-analysis. The summary vaccination coverage in 76 included studies was 21.7% (95% confidence interval [CI]: 17.2%-26.5%). Subgroup analysis shows that the summary coverage was 29.0% (95% CI, 20.4%-39.1%) among the permanent residents and 20.7% (95% CI, 12.4%-35.9%) among the floating residents. The eastern and central regions presented higher coverage than the western region. Notable differences were observed between the various study populations. A total of 27 studies provided an estimation of vaccination willingness, with a summary willingness of 51.2% (95% CI, 40.4%-61.9%). In subgroup analysis, the summary willingness was 57.9% (95% CI, 48.3%-67.2%) in urban areas and 52.3% (95% CI, 40.8%-63.8%) in rural areas. Parents with children and people with a history of pneumonia were more willing to be vaccinated than the elderly. Recommendations by family members and physicians, previous pneumococcal and influenza vaccination, perceived vaccination effectiveness and severity of disease and a history of pneumonia contributed to vaccination willingness.Conclusions: Compared to global estimates and other countries, pneumococcal vaccination coverage and willingness are at a lower level in mainland China. Recommendations for vaccination by family members and doctors, a history of vaccination and the perception of pneumonia and vaccination are associated with greater willingness to be vaccinated. [ABSTRACT FROM AUTHOR]

This paper utilizes Bayesian network (BN) structure searching and scoring algorithms to identify critical nodes and investigate their reliability interdependencies for a power system under great converter penetration. As more converters are integrated into the system, reliability interactions among various converters will frequently emerge and consequently introduce system reliability concerns. However, reliability causal relations have rarely been explored and demonstrated in a clear manner. Therefore, the authors apply BN structure searching and scoring algorithms to visualize the proposed converter‐based BN structure. Moreover, reliability interactions among different nodes are quantified through information entropy theory. Numerical case studies illustrate the causal reliability relationship among various nodes while considering the reliability of all integrated converters. Critical nodes are identified such that system operators can improve the converter maintenance scheduling. [ABSTRACT FROM AUTHOR]

Background: Congenital heart disease (CHD) is the most common birth defect and has high heritability. Although some susceptibility genes have been identified, the genetic basis underlying the majority of CHD cases is still undefined. Methods: A total of 1320 unrelated CHD patients were enrolled in our study. Exome‐wide association analysis between 37 tetralogy of Fallot (TOF) patients and 208 Han Chinese controls from the 1000 Genomes Project was performed to identify the novel candidate gene WD repeat‐containing protein 62 (WDR62). WDR62 variants were searched in another expanded set of 200 TOF patients by Sanger sequencing. Rescue experiments in zebrafish were conducted to observe the effects of WDR62 variants. The roles of WDR62 in heart development were examined in mouse models with Wdr62 deficiency. WDR62 variants were investigated in an additional 1083 CHD patients with similar heart phenotypes to knockout mice by multiplex PCR‐targeting sequencing. The cellular phenotypes of WDR62 deficiency and variants were tested in cardiomyocytes, and the molecular mechanisms were preliminarily explored by RNA‐seq and co‐immunoprecipitation. Results: Seven WDR62 coding variants were identified in the 237 TOF patients and all were indicated to be loss of function variants. A total of 25 coding and 22 non‐coding WDR62 variants were identified in 80 (6%) of the 1320 CHD cases sequenced, with a higher proportion of WDR62 variation (8%) found in the ventricular septal defect (VSD) cohort. WDR62 deficiency resulted in a series of heart defects affecting the outflow tract and right ventricle in mouse models, including VSD as the major abnormality. Cell cycle arrest and an increased number of cells with multipolar spindles that inhibited proliferation were observed in cardiomyocytes with variants or knockdown of WDR62. WDR62 deficiency weakened the association between WDR62 and the cell cycle‐regulated kinase AURKA on spindle poles, reduced the phosphorylation of AURKA, and decreased expression of target genes related to cell cycle and spindle assembly shared by WDR62 and AURKA. Conclusions: WDR62 was identified as a novel susceptibility gene for CHD with high variant frequency. WDR62 was shown to participate in the cardiac development by affecting spindle assembly and cell cycle pathway in cardiomyocytes. [ABSTRACT FROM AUTHOR]

Neuroblastoma (NB), an embryonic tumour originating from sympathetic crest cells, is the most common extracranial solid tumour type in children with poor overall prognosis. Accumulating evidence has demonstrated the involvement of long non‐coding RNA (lncRNA) in numerous biological processes and their associations with embryonic development and multiple diseases. Ectopic lncRNA expression is linked to malignant tumours. Previous studies by our team indicate that MEG3 attenuates NB autophagy through inhibition of FOXO1 and epithelial‐mesenchymal transition via the mTOR pathway in vitro. Moreover, MEG3 and EZH2 negatively regulate each other. In present study, we first collected 60 NB tissues and 20 adjacent tissues for Quantitative real‐time polymerase chain reaction (Q‐PCR) experiments and performed clinical correlation analysis of the results. At the same time, nude mice were used for subcutaneous tumour formation to detect the effect of MEG3 in vivo. Two NB cell lines, SK‐N‐AS and SK‐N‐BE(2)C, were overexpressed MEG3 and rescued with EZH2 and then were subjected to proliferation, migration, invasion, apoptosis and autophagy experiments. RNA‐binding protein immunoprecipitation (RIP) and Co‐Immunoprecipitation (Co‐IP) experiments were performed to explore the molecular mechanism of MEG3 and EZH2 interaction. Q‐PCR revealed that MEG3 expression was negatively correlated with INSS stage and risk grade of NB. Moreover, MEG3 overexpression was associated with inhibition of NB growth in vivo. MEG3 exerted an anti‐cancer effect via stimulatory effects on EZH2 ubiquitination leading to its degradation. Conversely, EZH2 interacted with DNMT1 and HDAC1 to induce silencing of MEG3. The EZH2 inhibitor, DZNep, and HDAC inhibitor, SAHA, displayed synergistic activity against NB. Combined treatment with DZNep and SAHA inhibited proliferation, migration and invasion of NB through suppression of the PI3K/AKT/mTOR/FOXO1 pathway. In conclusion, downregulation of MEG3 and upregulation of EZH2 forms a feedback loop that concertedly promotes the development of NB. Combined blockage of EZH2 and HDAC1 with the appropriate inhibitors may therefore present an effective treatment strategy for NB cases with low MEG3 and high EZH2 expression. [ABSTRACT FROM AUTHOR]

'Requirements for human haematopoietic stem/progenitor cells' is the first set of guidelines on human haematopoietic stem/progenitor cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, inspection methods, inspection rules, instructions for usage, labelling requirements, packaging requirements, storage requirements and transportation requirements for human haematopoietic stem/progenitor cells, which is applicable to the quality control for human haematopoietic stem/progenitor cells. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human haematopoietic stem/progenitor cells for applications. [ABSTRACT FROM AUTHOR]

The retina, the most crucial unit of the human visual perception system, combines sensing with wavelength selectivity and signal preprocessing. Incorporating energy conversion into these superior neurobiological features to generate core visual signals directly from incoming light under various conditions is essential for artificial optoelectronic synapses to emulate biological processing in the real retina. Herein, self‐powered optoelectronic synapses that can selectively detect and preprocess the ultraviolet (UV) light are presented, which benefit from high‐quality organic asymmetric heterojunctions with ultrathin molecular semiconducting crystalline films, intrinsic heterogeneous interfaces, and typical photovoltaic properties. These devices exhibit diverse synaptic behaviors, such as excitatory postsynaptic current, paired‐pulse facilitation, and high‐pass filtering characteristics, which successfully reproduce the unique connectivity among sensory neurons. These zero‐power optical‐sensing synaptic operations further facilitate a demonstration of image sharpening. Additionally, the charge transfer at the heterojunction interface can be modulated by tuning the gate voltage to achieve multispectral sensing ranging from the UV to near‐infrared region. Therefore, this work sheds new light on more advanced retinomorphic visual systems in the post‐Moore era. [ABSTRACT FROM AUTHOR]

Osteoporosis is one of the leading forms of systemic diseases related to bone metabolism in the world. STARD3 N‐terminal like (STARD3NL) showed robust association with osteoporosis‐related traits. Yet, the molecular functional mechanisms of STARD3NL in osteoblasts is still obscure. In this study, we demonstrated a high level of STARD3NL expression in the bone tissues from the patients with low bone mass and ovariectomized (OVX)‐induced osteoporotic mice. We identified Stard3nl as a potent factor that negatively and positively regulates osteoblast differentiation and cell proliferation, respectively. Furthermore, inhibition of Stard3nl induced β‐catenin gene expression and the nuclear translocation of β‐catenin, as well as Wnt signalling activities, contributing to the activation of Wnt/β‐catenin signalling. Mechanistic studies revealed that Stard3nl bound with Annexin A2 (Anxa2) to suppress β‐catenin expression, resulting into the suppression of Wnt signalling and downstream osteogenic differentiation. Moreover, adeno‐associated virus 9 (AAV9)‐mediated silencing of Stard3nl reversed bone loss in OVX‐induced osteoporotic mice by the injection into the knee joints. Collectively, our study revealed that Stard3nl suppressed osteogenesis via binding with Anxa2, resulting into the inactivation of Wnt signalling. It also highlights the preventive and therapeutic potential of STARD3NL as a specific and novel target for osteoporotic patients. [ABSTRACT FROM AUTHOR]

Lipid and fatty acid datasets are commonly used to assess the nutritional composition of organisms, trophic ecology, and ecosystem dynamics. Lipids and their fatty acid constituents are essential nutrients to all forms of life because they contribute to biological processes such as energy flow and metabolism. Assessment of total lipids in tissues of organisms provides information on energy allocation and life‐history strategies and can be an indicator of nutritional condition. The analysis of an organism's fatty acids is a widely used technique for assessing nutrient and energy transfer, and dietary interactions in food webs. Although there have been many published regional studies that assessed lipid and fatty acid compositions, many only report the mean values of the most abundant fatty acids. There are limited individual records available for wider use in intercomparison or macro‐scale studies. This dataset consists of 4856 records of individual and pooled samples of at least 470 different marine consumer species sampled from tropical, temperate, and polar regions around Australia and in the Southern, Indian, and Pacific Oceans from 1989 to 2018. This includes data for a diverse range of taxa (zooplankton, fish, cephalopods, chondrichthyans, and marine mammals), size ranges (0.02 cm to ~13 m), and that cover a broad range of trophic positions (2.0–4.6). When known, we provide a record of species name, date of sampling, sampling location, body size, relative (%) measurements of tissue‐specific total lipid content and abundant fatty acids, and absolute content (mg 100 g−1 tissue) of eicosapentaenoic acid (EPA, 20:5n3) and docosahexaenoic acid (DHA, 22:6n3) as important long‐chain (≥C20) polyunsaturated omega‐3 fatty acids. These records form a solid basis for comparative studies that will facilitate a broad understanding of the spatial and temporal distribution of marine lipids globally. The dataset also provides reference data for future dietary assessments of marine predators and model assessments of potential impacts of climate change on the availability of marine lipids and fatty acids. There are 480 data records within our data file for which the providers have requested that permission for reuse be granted, with the likely condition that they are included as a coauthor on the reporting of the dataset. Records with this condition are indicated by a "yes" under "Conditions_of_data_use" in Data S1: Marineconsumer_FAdata.csv (see Table 2 in Metadata S1 for more details). For all other data records marked as "No" under "Conditions_of_data_use," there are no copyright restrictions for research and/or teaching purposes. We request that users acknowledge use of the data in publications, research proposals, websites, and other outlets via formal citation of this work and original data sources as applicable. [ABSTRACT FROM AUTHOR]

Efficient utilization of solar energy to generate steam is a green and promising technology because of its great potential applications in seawater desalination and industrial wastewater purification. However, the practical application of high‐efficiency solar steam generation devices is largely overshadowed due to their complex process, high cost, low life‐span, and poor thermal performance. Here, novel meat and bonemeal biochar (MBB) with high solar steam generation efficiency is produced by pyrolyzing dead carp at 300, 400, and 500 °C under anoxic conditions. Attributed to its typical hydrophilic pore structure, the photon trapping ability of MBB500 is up to 97% and 84.1% in the ultraviolet and visible regions and near‐infrared light regions, respectively. Meanwhile, hydrophilic pore structural provides a strong capillary force for the rapid transmission of water. As a result, under 1 sun illumination (1 kW m−2), the water evaporation rate and the apparent energy conversion efficiency of MBB500 reach 1.48 kg m−2 h−1 and 131.2%, respectively. In addition, MBB500 also exhibits excellent seawater and heavy metal wastewater evaporation effects, providing a new manufacturing strategy for photo‐thermal materials, which greatly benefit their practical application in pure water regeneration. [ABSTRACT FROM AUTHOR]

Dielectric capacitors play a key role in high power electronics, electric vehicles, and medical devices. Due to the biodegradability, high thermal stability, and ease of processing, poly(lactic acid)‐based (PLA) films are widely used in applications of tissue engineering, actuators, and sensors. In this investigation, PLA films are prepared using a solution casting method for high energy density capacitor applications. It is found that the stretched poly(d‐lactic acid) (PDLA) film exhibits an energy density and charge discharge efficiency of 18.5 J cm−3 and 95%, respectively, at room temperature. Furthermore, after a heating time of 30 min at 100 °C, it is found that the energy density and chargedischarge efficiency of the stretched PDLA films are maintained at 11.2 J cm−3 and 76%, respectively. In comparison, the energy density and efficiency of the stretched PDLA film are 1.03‐fold and 53% higher, respectively, than those of the stretched poly(vinylidene fluoride‐hexafluoropropylene) film at 100 °C with the same heat treatment. Compared with a high temperature polyimide material, the energy density of the stretched PDLA film is 1.98‐fold higher at 100 °C. The PLA‐based material shows great promise for application in high energy density capacitors operating at a high temperature (100 °C). [ABSTRACT FROM AUTHOR]

Objectives: Anti‐microbial peptides (AMPs) have been comprehensively investigated as a novel alternative to traditional antibiotics against microorganisms. Meanwhile, Tetrahedral DNA nanostructures (TDNs) have gained attention in the field of biomedicine for their premium biological effects and transportation efficiency as delivery vehicles. Hence, in this study, TDN/Histatin 5 (His‐5) was synthesized and the transport efficiency and anti‐fungal effect were measured to evaluate the promotion of His‐5 modified by TDNs. Materials and Methods: Tetrahedral DNA nanostructures/His‐5 complex was prepared via electrostatic attraction and characterized by transmission electron microscopy (TEM), polyacrylamide gel electrophoresis (PAGE), dynamic light scattering (DLS) and electrophoretic light scattering (ELS). The anti‐fungal effect of the TDN/His‐5 complex was evaluated by determining the growth curve and colony‐forming units of C. albicans. The morphological transformation of C. albicans was observed by light microscope and scanning electron microscope (SEM). Immunofluorescence was performed, and potassium efflux was detected to mechanistically demonstrate the efficacy of TDN/His‐5. Results: The results showed that Histatin 5 modified by TDNs had preferable stability in serum and was effectively transported into C. albicans, leading to the increased formation of intracellular reactive oxygen species, higher potassium efflux and enhanced anti‐fungal effect against C. albicans. Conclusions: Our study showed that TDN/His‐5 was synthesized successfully. And by the modification of TDNs, His‐5 showed increased transport efficiency and improved anti‐fungal effect. [ABSTRACT FROM AUTHOR]

Flexoelectricity is an electromechanical coupling effect in which electric polarization is generated by a strain gradient. In this investigation, a potassium sodium niobite/poly(vinylidene fluoride‐trifluoroethylene) (KNN/PVDF‐TrFE)‐based nanocomposite is fabricated, and the flexoelectric effect is used to enhance the photovoltaic current (Ipv) in the nanocomposite. It is found that both a pyroelectric current and photovoltaic current can be generated simultaneously in a light illumination process. However, the photovoltaic current (Ipv) in this process contributes ≈85% of the total current. When assessing the effect of flexoelectricity with a curvature of 1/20, the Ipv of the curved KNN/PVDF‐TrFE (20%) (K/P‐20) composite increased by ≈13.9% compared to that of the flat K/P‐20 nanocomposite. Similarly, at a curvature of 1/20, the Ipv of the K/P‐20 nanocomposite is 71.6% higher than that of the PVDF‐TrFE film. However, the photovoltaic effect induced by flexoelectricity is much higher than the increased polarization from flexoelectricity, so this effect is called as the flexophotovoltaic effect. Furthermore, the calculated energy conversion efficiency of the K/P‐20 film is 0.017%, which is comparable to the previous research result. This investigation shows great promise for PVDF‐based nanocomposites in ferroelectric memory device applications. [ABSTRACT FROM AUTHOR]

Objectives: Ex vivo engineered production of megakaryocytes (MKs) and platelets (PLTs) from human pluripotent stem cells is an alternative approach to solve shortage of donor‐donated PLTs in clinics and to provide induced PLTs for transfusion. However, low production yields are observed and the generation of clinically applicable MKs and PLTs from human pluripotent stem cells without genetic modifications still needs to be improved. Materials and Methods: We defined an optimal, stepwise and completely xeno‐free culture protocol for the generation of MKs from human embryonic stem cells (hESCs). To generate MKs from hESCs on a large scale, we improved the monolayer induction manner to define three‐dimensional (3D) and sphere‐like differentiation systems for MKs by using a special polystyrene CellSTACK culture chamber. Results: The 3D manufacturing system could efficiently generate large numbers of MKs from hESCs within 16‐18 days of continuous culturing. Each CellSTACK culture chamber could collect on an average 3.4 × 108 CD41+ MKs after a three‐stage orderly induction process. MKs obtained from hESCs via 3D induction showed significant secretion of IL‐8, thrombospondin‐1 and MMP9. The induced cells derived from hESCs in our culture system were shown to have the characteristics of MKs as well as the function to form proPLTs and release PLTs. Furthermore, we generated clinically applicable MKs from clinical‐grade hESC lines and confirmed the biosafety of these cells. Conclusions: We developed a simple, stepwise, 3D and completely xeno‐free/feeder‐free/transgene‐free induction system for the generation of MKs from hESCs. hESC‐derived MKs were shown to have typical MK characteristics and PLT formation ability. This study further enhances the clinical applications of MKs or PLTs derived from pluripotent stem cells. [ABSTRACT FROM AUTHOR]

Topological nodal‐line semimetal SrAs3 hosts a simple nodal loop on the verge of Fermi level without distracting trivial states, providing a good platform for further investigations of electronic quantum states. Here, a report on pressure‐driven superconductivity in SrAs3 single crystal is provided and the interplay between the crystal structure, electronic state, and superconductivity is clarified therein. The comprehensive high‐pressure experiments, i.e., synchrotron X‐ray diffraction, electrical transport, and Raman spectroscopy, consistently reveal a critical pressure Pc ≈ 25 GPa. Around Pc, a superconducting transition appears, concomitant with the formation of high‐pressure cubic Pm‐3m phase. Meanwhile, the superconducting transition temperature Tc and hole carrier density increase synchronously above Pc. This finding demonstrates that the emerging superconductivity in SrAs3 stems from the high‐pressure cubic phase on the one hand, and shows that the evolution of Tc(P) is intimately correlated with the enhanced density of states near the Fermi level on the other hand. [ABSTRACT FROM AUTHOR]

A general understanding of the nature of the charge motions at the organic/dielectric interface requires an accurate examination on the influence from the Coulomb interactions among carriers. However, difficulties on this substantial issue are due to complicated interpretation and extraction of the intrinsic electrical parameters for the organic films. Here, the carrier transport in highly ordered, few‐layer organic crystalline semiconductors is studied by a geometry‐independent gated van der Pauw method, confining the charge carrier distribution at the precision of molecular layers and minimizing the effects of extrinsic factors. The characteristics of carrier transport are varied in different film layers and show nonideal features. The Fröhlich polaron model well explains the features and suggests that the Coulomb interactions among carriers should be considered at a high carrier density, which is manifested by the characteristic parameter 〈ξ 〉/2 measuring the extra potential for polaron transport. This understanding of the physical process between Coulomb interactions and polaron transport in organic crystalline semiconductors can enable promising strategies for achieving more ideal transistor performance and new device physics. [ABSTRACT FROM AUTHOR]

Tetralogy of Fallot (TOF) is the most common complex congenital heart disease (CHD) with uncertain cause. Although long non‐coding RNAs (lncRNAs) have been implicated in heart development and several CHDs, their role in TOF is not well understood. This study aimed to investigate how dysregulated lncRNAs contribute to TOF. Using Gene Expression Omnibus data mining, bioinformatics analysis and clinical heart tissue sample detecting, we identified a novel antisense lncRNA TBX5‐AS1:2 with unknown function that was significantly down‐regulated in injured cardiac tissues from TOF patients. LncRNA TBX5‐AS1:2 was mainly located in the nucleus of the human embryonic kidney 293 (HEK293T) cells and formed an RNA‐RNA double‐stranded structure in the overlapping region with its sense mRNA T‐box transcription factor 5 (TBX5), which is an important regulator in heart development. Knock‐down of lncRNA TBX5‐AS1:2 via promoter hypermethylation reduced TBX5 expression at both the mRNA and protein levels by affecting its mRNA stability through RNA‐RNA interaction. Moreover, lncRNA TBX5‐AS1:2 knock‐down inhibited the proliferation of HEK293T cells. In conclusion, these results indicated that lncRNA TBX5‐AS1:2 may be involved in TOF by affecting cell proliferation by targeting TBX5. [ABSTRACT FROM AUTHOR]

Organic UV photodetectors using a transistor architecture can yield higher photoresponsivity than diode‐based devices because of the presence of a gate electrode. However, a long‐term issue of these phototransistor devices is the slow response speed, which hinders their practical applications. Here, organic UV phototransistors are constructed using few‐layer organic crystalline van der Waals (vdW) heterojunctions as the photoactive layers. The thickness of the photoactive layers is even less than the exciton diffusion length, thus removing the exciton‐diffusion bottleneck and giving rise to the confinement of charge separation and recombination within the adjacent molecular layers across the heterojunction interface. Hence, the phototransistor devices can exhibit a remarkably enhanced response speed (rise and decay times as short as only ≈4 and 6 ms, respectively). The layer‐dependent photoresponse characteristics are also observed, reinforcing the great importance of few‐layer organic heterostructures in phototransistor devices. This work not only provides a promising avenue toward fast response optoelectronic devices but also presents an in‐depth understanding on the microscopic nature of photogenerated charge carriers at the precision of molecular layers. [ABSTRACT FROM AUTHOR]

Quasi‐1D transition metal tetrachalcogenide TaTe4 exhibits charge‐density waves (CDW), large anisotropic magnetoresistance, and nontrivial Berry phase at ambient pressure. Pressure‐induced superconductivity is reported in pristine TaTe4 via electrical transport experiments. It is shown that the superconductivity, first observed at Pc ≈ 8.0 GPa, is robust up to 50.6 GPa. No structural transition is detected up to 21.4 GPa, which indicates the tetragonal structure of TaTe4 is stable across Pc. Hall resistivity measurements reveal that both electron and hole densities increase sharply upon compression up to Pc and level off at higher pressures, suggesting that the emergent superconductivity of pressurized TaTe4 can be attributed to the enhancement of the charge carrier density. This finding may provide a new platform to investigate the interplay among superconducting, CDW, and topological orders. [ABSTRACT FROM AUTHOR]

Pathological cardiac hypertrophy (CH) is a key factor leading to heart failure and ultimately sudden death. Long non‐coding RNAs (lncRNAs) are emerging as a new player in gene regulation relevant to a wide spectrum of human disease including cardiac disorders. Here, we characterize the role of a specific lncRNA named cardiac hypertrophy‐associated regulator (CHAR) in CH and delineate the underlying signalling pathway. CHAR was found markedly down‐regulated in both in vivo mouse model of cardiac hypertrophy induced by pressure overload and in vitro cellular model of cardiomyocyte hypertrophy induced by angiotensin II (AngII) insult. CHAR down‐regulation alone was sufficient to induce hypertrophic phenotypes in healthy mice and neonatal rat ventricular cells (NRVCs). Overexpression of CHAR reduced the hypertrophic responses. CHAR was found to act as a competitive endogenous RNA (ceRNA) to down‐regulate miR‐20b that we established as a pro‐hypertrophic miRNA. We experimentally established phosphatase and tensin homolog (PTEN), an anti‐hypertrophic signalling molecule, as a target gene for miR‐20b. We found that miR‐20b induced CH by directly repressing PTEN expression and indirectly increasing AKT activity. Moreover, CHAR overexpression mitigated the repression of PTEN and activation of AKT by miR‐20b, and as such, it abrogated the deleterious effects of miR‐20b on CH. Collectively, this study characterized a new lncRNA CHAR and unravelled a new pro‐hypertrophic signalling pathway: lncRNA‐CHAR/miR‐20b/PTEN/AKT. The findings therefore should improve our understanding of the cellular functionality and pathophysiological role of lncRNAs in the heart. [ABSTRACT FROM AUTHOR]

Ionospheric disturbance is one of the most serious factors that limit the accuracy of deformation measurement of interferometric synthetic aperture radar (InSAR) especially for spaceborne SAR systems in low frequency such as L-band. Especially in imaging modes with a large coverage, ScanSAR mode for example, ionospheric disturbance phase screen almost submerges other useful geographical information. In this study, two ALOS-2 (L-band) full-aperture ScanSAR images (October 2015 and October 2016) are used to study ground deformation in Beijing from 2015 to 2016. The split range-spectrum technique is adopted to extract ionospheric distortion. The authors splice the differential interferograms of adjacent subswaths by resampling them to perform the overall ionospheric extraction. Also non-local filtering is used to improve the coherence of interferograms. Spatial deformation distribution that was obtained by differential interferometric synthetic aperture radar (D-InSAR) technique using the two ALOS-2 ScanSAR images is highly consistent with the result obtained by persistent scatterer interferometric synthetic aperture radar (PS-InSAR) technique using Sentinel Tops mode images (October 2015–February 2017). The comparison results show the effectiveness of the ionospheric distortion extraction method used in this study. Moreover, the spatial distribution is also highly consistent with the results before 2014, which means that the deformation trend in Beijing continues. [ABSTRACT FROM AUTHOR]

As a donor and acceptor separately, Nb5+ and Al3+ are used to substitute Ti4+ in the ixiolite ZnTiNb2O8 system for the first time. The dielectric responses in the terahertz range of this system are initially studied based on the data from terahertz time‐domain transmitted spectroscopy. Combined with ligand field theory, the formation of a secondary phase of ZnAl2O4 is reasonably explicated. Then, the origins of the lower dielectric loss and the terahertz wave absorption coefficient are determined to be the high chemical bond covalency and effective phase control. For the composition of ZnTi0.85(Al0.5Nb0.5)0.15Nb2O8 sintered at 1180°C, a low dielectric loss (<5 × 10−3 @ 0.5 THz) and absorption coefficient (<10/cm @ 0.5 THz) are obtained, which make this kind of material propitious for developing terahertz dielectric devices. [ABSTRACT FROM AUTHOR]

Hereditary spherocytosis (HS) is the most common inherited haemolytic anaemia disorder. ANK1 mutations account for most HS cases, but pathogenicity analysis and functional research have not been widely performed for these mutations. In this study, in order to confirm diagnosis, gene mutation was screened in two unrelated Chinese families with HS by a next‐generation sequencing (NGS) panel and then confirmed by Sanger sequencing. Two novel heterozygous mutations (c.C841T, p.R281X and c.T290G, p.L97R) of the ANK1 gene were identified in the two families respectively. Then, the pathogenicity of the two new mutations and two previously reported ANK1 mutations (c.C648G, p.Y216X and c.G424T, p.E142X) were studied by in vitro experiments. The four mutations increased the osmotic fragility of cells, reduced the stabilities of ANK1 proteins and prevented the protein from localizing to the plasma membrane and interacting with SPTB and SLC4A1. We classified these four mutations into disease‐causing mutations for HS. Thus, conducting the same mutation test and providing genetic counselling for the two families were meaningful and significant. Moreover, the identification of two novel mutations enriches the ANK1 mutation database, especially in China. [ABSTRACT FROM AUTHOR]

Paleoclimate records identified a severe drought lasting approximately a decade on the Mongolian Plateau during the 2000s, the severity of which was only exceeded by a single drought during the last two millennia. Under high‐emission scenarios, arid and semiarid areas are projected to continue to experience a drying trend over the coming decades; therefore, understanding how ecosystems respond to long‐lasting drought has global implications. Here we used a process‐based ecosystem model to examine the interannual and intra‐annual variations in net ecosystem productivity in response to climate extremes across the Mongolian Plateau. We find that the recent‐decade drought caused Mongolian terrestrial ecosystems to shift from a carbon (C) sink to a C source, canceling 40% of climate‐induced C accumulation over the entire twentieth century. Our study details a shortened C sequestering season, increased summer C source, and accelerated C depletion during the 2000s drought. Plain Language Summary: Multiple lines of evidence have shown detrimental effects of drought events on ecosystem production and carbon dynamics, but it remains uncertain how arid and semiarid ecosystems respond to long‐lasting drought. Here we reveal that a severe drought during the first decade of the 2000s on the Mongolian Plateau considerably weakened C sequestration capacity and accelerated C depletion. This work has broad implications for understanding impacts of persistent droughts on terrestrial C dynamics as a drying trend, in many arid and semiarid areas, is projected to continue over the coming decades. Key Points: The recent decade (2000–2009) has been identified as one of the driest periods on the Mongolian Plateau over the most recent ~2,000 yearsThis long‐duration drought shortened the C sequestration season, increased the summer C source, and led to a net annual C releaseThe NEP amplitude in this dry decade increased due to reduced C uptake and increased C emissions, implying an accelerated C depletion [ABSTRACT FROM AUTHOR]

Hybrid electric vehicles (HEVs) provide a promising alternative to conventional engine‐powered vehicles, with less emission and better fuel economy. This study proposes a hierarchical control for a power‐split HEV over a driving cycle, featuring pre‐trip optimisation and en‐route speed adaption. Constraints including vehicle powertrain boundaries, road gradients, and speed limits, are taken into consideration. In the first stage, the HEV operating conditions, including the optimal vehicle SOC, speed profiles, and total driving time, are generated for the entire trip before departure. Based on the pre‐trip results, the second stage adapts the vehicle speed for a short horizon when driving, while taking the safety spacing to the preceding vehicle into consideration, which acts as an indicator of actual traffic conditions and guarantees safe driving. Both optimisations are conducted under the distance domain for realising localisation in the optimal speed profile due to frequent changes in traffic conditions. An estimation of distribution algorithm is used to run the simulation so that the feasibility, robustness, and effectiveness of the proposed hierarchical control can be demonstrated. [ABSTRACT FROM AUTHOR]

Abstract: Band engineering in layered metal dichalcogenides leads to a variety of physical phenomena and has obtained considerable attention recently. In this work, pressure‐induced metallization and superconductivity in pristine 1T‐SnSe2 is reported via electrical transport and synchrotron X‐ray diffraction experiments. Electrical transport results show that the metallization emerges above 15.2 GPa followed by appearance of superconducting transition at 18.6 GPa. The superconductivity is robust with a nearly constant Tc ≈ 6.1 K between 30.1 and 50.3 GPa. High‐pressure synchrotron X‐ray diffraction experiments indicate that the 1T‐SnSe2 phase maintains up to 46.0 GPa. Although the theoretical predicted structural transition and decomposition of SnSe2 into Sn3Se4 and Se are not detected, it is argued that the structural instability under high pressure might be crucial for the superconductivity. These findings demonstrate that 1T‐SnSe2 is a very rare system from which superconductivity can be driven via multiple ways. [ABSTRACT FROM AUTHOR]

Highly compact and conductive Cu films are successfully fabricated by introducing mechanically robust and highly conductive metal nanowires (NWs) as fillers and optimizing amine‐based ligands in Cu complex inks. The metal NWs (AgNWs and CuNWs) dispersed in the complex inks provide networks of nucleation sites for the in situ formed Cu particles and thereby control the decomposition of Cu complex inks at low temperatures to realize Cu films with high uniformity and integrality. The high affinity between metal NWs and the in situ formed Cu element enables the growth of Cu particles along the metal NWs to create a compact structure. Besides, the amine‐based ligands such as 2‐amino‐2‐methyl‐1‐propanol (AMP), 2‐ethylhexylamine (Ethy), and hexylamine (Hexy) are varied to adjust the size of Cu particles and further improve the microstructure and conductivity of the sintered Cu films. The Cu‐Ethy complex/metal NW inks sintered at 140 °C exhibit the lowest resistivity of 14.9 µΩ cm, which is about one‐third that fabricated from the pure Cu‐AMP complex inks. The flexible light‐emitting diode circuits and V‐shaped dipole antennas prepared from the Cu complex/metal NW inks have excellent performance due to their outstanding conductivity and flexibility, showing great potential in the fabrication of cost‐effective, flexible printed electronic devices. [ABSTRACT FROM AUTHOR]

The microstructure of printed Cu wirings fabricated from air‐stable Cu complex inks is greatly modified by low‐temperature curing followed by intense pulsed light densification enhancement treatment. The resulting almost full densification of printed Cu wirings enables them to possess a high electrical conductivity of 50% bulk Cu. The dense structure also largely prevents the permeation of oxygen and water into the inner side of the Cu wirings, thereby improving their oxidation resistance and maintaining a stable resistance (R/R0 < 1.5) even after 1000 h aging at 85 °C‐85% RH. In addition, the dense and robust structure can improve the resistance to crack generation and propagation in Cu wirings during the bending, so as to improve their flexibility. The relative resistance of Cu wirings can be kept below 1.2 after 1000 bending cycles. All the results indicate that these highly densified Cu wirings fabricated from air‐stable Cu complex inks can be used to replace the noble metallic Au and Ag wirings for practical application in flexible electronics. In order to address the oxidation problem of Cu inks and enhance the oxidation resistance of printed Cu wirings, air‐stable Cu complex ink is used, and almost full densification of printed Cu wirings is successfully achieved by a two‐step sintering process consisting of low‐temperature curing and intense pulsed light treatment. [ABSTRACT FROM AUTHOR]

Na v 1.5 sodium channels contribute to the generation of the rapid upstroke of the myocardial action potential and thereby play a central role in the excitability of myocardial cells. At present, the patch clamp method is the gold standard for ion channel inhibitor screening. However, this method has disadvantages such as high technical difficulty, high cost and low speed. In this study, novel machine learning models to screen chemical blockers were developed to overcome the above shortage. The data from the ChEMBL Database were employed to establish the machine learning models. Firstly, six molecular fingerprints together with five machine learning algorithms were used to develop 30 classification models to predict effective inhibitors. A validation and a test set were used to evaluate the performance of the models. Subsequently, the privileged substructures tightly associated with the inhibition of the Na v 1.5 ion channel were extracted using the bioalerts Python package. In the validation set, the RF-Graph model performed best. Similarly, RF-Graph produced the best result in the test set in which the Prediction Accuracy (Q) was 0.9309 and Matthew's correlation coefficient was 0.8627, further indicating the model had high classification ability. The results of the privileged substructures indicated Sulfa structures and fragments with large Steric hindrance tend to block Na v 1.5. In the unsupervised learning task of identifying sulfa drugs, MACCS and Graph fingerprints had good results. In summary, effective machine learning models have been constructed which help to screen potential inhibitors of the Na v 1.5 ion channel and key privileged substructures with high affinity were also extracted., (© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)