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Lightweight aluminum (Al) alloys have been widely used in frontier fields like aerospace and automotive industries, which attracts great interest in additive manufacturing (AM) to process high-value Al parts. As a mainstream AM technique, laser-directed energy deposition (LDED) shows good scalability to meet the requirements for large-format component manufacturing and repair. However, LDED Al alloys are highly challenging due to their inherent poor printability (e.g. low laser absorption, high oxidation sensitivity and cracking tendency). To further promote the development of LDED high-performance Al alloys, this review offers a deep understanding of the challenges and strategies to improve printability in LDED Al alloys. The porosity, cracking, distortion, inclusions, element evaporation and resultant inferior mechanical properties (worse than laser powder bed fusion) are the key challenges in LDED Al alloys. Processing parameter optimizations, in-situ alloy design, reinforcing particle addition and field assistance are the efficient approaches to improving the printability and performance of LDED Al alloys. The underlying correlations between processes, alloy innovation, characteristic microstructures, and achievable performances in LDED Al alloys are discussed. The benchmark mechanical properties and primary strengthening mechanism of LDED Al alloys are summarized. This review aims to provide a critical and in-depth evaluation of current progress in LDED Al alloys. Future opportunities and perspectives in LDED high-performance Al alloys are also outlined.

Hepatotoxicity is a common side effect for patients treated with gefitinib, but the related pathogenesis is unclear and lacks effective predictor and management strategies. A multi-omics approach integrating pharmacometabolomics, pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution. Here, we found that patients with rs4946935 AA, located in Forkhead Box O3 (FOXO3) which is a well-known autophagic regulator, had a higher risk of hepatotoxicity than those with the GA or GG variant (OR = 18.020, 95%CI = 2.473 to 459.1784, P = 0.018) in a gefitinib-concentration dependent pattern. Furthermore, functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity, increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury. In contrast, erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3. This study reveals that FOXO3 mutation, leading to autophagic imbalance, plays important role in gefitinib-induced hepatotoxicity, especially for patients with high concentration of gefitinib. In conclusion, FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA.

Abstract In complex networks, the role of a node is based on the aggregation of structural features and functions. However, in real networks, it has been observed that a single node can have multiple roles. Here, the roles of a node can be defined in a case-by-case manner, depending on the graph data mining task. Consequently, a significant obstacle to achieving multiple-role discovery in real networks is finding the best way to select datasets for pre-labeling. To meet this challenge, this study proposes a flexible framework that extends a single-role discovery method by using domain adversarial learning to discover multiple roles for nodes. Furthermore, we propose a method to assign sub-networks, derived through community extraction methods, to a source network and a validation network as training datasets. Experiments to evaluate accuracy conducted on real networks demonstrate that the proposed method can achieve higher accuracy and more stable results.

Highlights The first phosphoproteome profiling of mouse livers during normal aging. A total of 5,685 phosphosites in 2,335 proteins were quantified in this study. A phosphorylation-regulated pathway network was constructed. Metabolism, secretion, and the cell cycle might be dysregulated during normal aging.

IntroductionCochlear implantation is currently the most successful intervention for severe-to-profound sensorineural hearing loss, particularly in deaf infants and children. Nonetheless, there remains a significant degree of variability in the outcomes of CI post-implantation. The purpose of this study was to understand the cortical correlates of the variability in speech outcomes with a cochlear implant in pre-lingually deaf children using functional near-infrared spectroscopy (fNIRS), an emerging brain-imaging technique.MethodsIn this experiment, cortical activities when processing visual speech and two levels of auditory speech, including auditory speech in quiet and in noise with signal-to-noise ratios of 10 dB, were examined in 38 CI recipients with pre-lingual deafness and 36 normally hearing children whose age and sex matched CI users. The HOPE corpus (a corpus of Mandarin sentences) was used to generate speech stimuli. The regions of interest (ROIs) for the fNIRS measurements were fronto-temporal-parietal networks involved in language processing, including bilateral superior temporal gyrus, left inferior frontal gyrus, and bilateral inferior parietal lobes.ResultsThe fNIRS results confirmed and extended findings previously reported in the neuroimaging literature. Firstly, cortical responses of superior temporal gyrus to both auditory and visual speech in CI users were directly correlated to auditory speech perception scores, with the strongest positive association between the levels of cross-modal reorganization and CI outcome. Secondly, compared to NH controls, CI users, particularly those with good speech perception, showed larger cortical activation in the left inferior frontal gyrus in response to all speech stimuli used in the experiment.DiscussionIn conclusion, cross-modal activation to visual speech in the auditory cortex of pre-lingually deaf CI children may be at least one of the neural bases of highly variable CI performance due to its beneficial effects for speech understanding, thus supporting the prediction and assessment of CI outcomes in clinic. Additionally, cortical activation of the left inferior frontal gyrus may be a cortical marker for effortful listening.

The Yangtze River Economic Belt and the Yellow River Basin are important economic regions and ecological barriers in China. Promoting the development of the Yangtze River Economic Belt and promoting ecological protection and high-quality development in the Yellow River Basin are major regional strategies implemented by the Chinese government, and the green growth of the two regions is important for the high-quality sustainable development of the whole China. To investigate the regional differences in green growth efficiency of the same type of geographical units, this paper measures the green growth efficiency and decomposition indicators of the Yangtze River Economic Belt and the Yellow River Basin from 2010 to 2020 using a three-stage DEA model and the Malmquist index method and establishes a panel Tobit model to identify the influencing factors of green growth efficiency. The results show that: ①After using the three-stage DEA model to remove the influence of external environment and stochastic factors, the mean values of green growth efficiency of Yangtze River Economic Zone and Yellow River Basin from 2010 to 2020 are 0.996 and 1.089, respectively. The change of green growth efficiency of Yangtze River Economic Zone is slightly higher than that of Yellow River Basin. ②The Malmquist indexes of the Yangtze River Economic Belt and the Yellow River Basin have generally increased, with the Technological Progress Index, which characterizes technological innovation, being the main endogenous driver of green growth efficiency in the Yellow River Basin, while the technical efficiency index, which characterizes factor mix and management level, is more significant in the Yangtze River Economic Belt. ③The Tobit model regression results show that the factors influencing green growth efficiency are also different in the two regions. Among them, the urbanization rate has a significantly positive effect on the two regions, while the effects of environmental regulation and research intensity are not significant. External openness has a suppressive effect on green growth efficiency in the Yangtze River Economic Belt, while the level of financial development and human capital negatively affect green growth efficiency in the Yellow River Basin. Therefore, green development in the new era should pay attention to the differences between different regions, and make appropriate development policies according to the local conditions of the development status of different regions.

This paper investigates the strength development of fly ash (FA)-based geopolymer paste cured by thermal and microwave radiations, together with microstructural characterisations. The results indicate that both the two methods can significantly increase the compressive strength compared to room temperature curing. Higher microwave power can promote the strength development without changing the reaction products and the final strength, owing to the accelerated formation of N-A-S-H in the reaction product under the raised temperature, characterised by the increased Si–O Q2-3 bonds and decreased Si/Al ratio. Over-time microwave radiation weakens the strength due to the formation of micro-cracks. Microwave presents higher curing efficiency than heating, producing a compressive strength of 37 MPa within 15 min. Moreover, microwave radiation can accelerate the setting progress of the fresh paste without compromising its final strength after curing. The present work can guide the preparation of FA-based geopolymers with high early strength in practice.

Directional axon regeneration and remyelination are crucial for repair of spinal cord injury (SCI), but existing treatments do not effectively promote those processes. Here, we propose a strategy for construction of niche-specific spinal white matter-like tissue (WMLT) using decellularized optic nerve (DON) loaded with neurotrophin-3 (NT-3)-overexpressing oligodendrocyte precursor cells. A rat model with a white matter defect in the dorsal spinal cord of the T10 segment was used. The WMLT transplantation group showed significant improvement in coordinated motor functions compared with the control groups. WMLT transplants integrated well with host spinal cord white matter, effectively addressing several barriers to directional axonal regeneration and myelination during SCI repair. In WMLT, laminin was found to promote development of oligodendroglial lineage (OL) cells by binding to laminin receptors. Interestingly, laminin could also guide linear axon regeneration via interactions with specific integrins on the axon surface. The WMLT developed here utilizes the unique microstructure and bioactive matrix of DON to create a niche rich in laminin, NT-3 and OL cells to achieve significant structural repair of SCI. Our protocol can help to promote research on repair of nerve injury and construction of neural tissues and organoids that form specific cell niches.

Historical land use impacts climate by biogeophysical and biogeochemical effects. Their combined effects on mean and extreme temperature may harm economically disadvantaged countries but benefit those in rich countries, raising questions of equality.

Abstract Background A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. Methods We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. Results The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8–65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. Conclusions GOHI—subject to rigorous validation—would represent the world’s first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge. Graphical Abstract

At present, chitosanase used to prepare chito-oligosaccharides has the disadvantage of low enzyme activity and poor acid stability. In this study, chitosanase-producing strain was screened from mud samples from Lianyungang Haizhou Bay, the highest chitosanase-producing strain was identified, and the acid stability and enzyme properties of the strain were studied. The screening was carried out by using the transparent zone method, and shaking flask fermentation. The chitosanase producing strain CLT08 was obtained. Then, the strain CLT08 was identified as Paenibacillus chitinolyticus with morphological characteristics, physiological and biochemical determination and 16S rDNA sequence amplification and analysis. The optimum temperature and pH for chitosanase production of strain CLT08 were 45 ℃ and pH4.0; Zn2+ had a significant activation effect on the enzyme, and Ba2+, Co2+, Fe2+ had significant effects inhibition. The degree of polymerization of chitosan was≥6 after being hydrolyzed by CLT08 chitosanase. The results of this study laid the foundation for further research on the enzyme.

Background: The aim of the study was to explore whether plasma stromal cel l-derived factor 1 (SDF-1) levels are associated with the EZSCAN score an d its derived indicators in patients with type 2 diabetes (T2D). Methods: From July 2020 to December 2020, a total of 253 patients with T2D were consecutively recruited. Serum SDF-1 levels were measured by sa ndwich ELISA. EZSCAN test was applied to evaluate the sudomotor function of each pat ient, and based on the results, EZSCAN score, cardiac autonomic neuropathy risk sc ore (CANRS) and cardiovascular risk score (CVDRS) were calculated by particular algorithms. In addition, other relevant clinical data were also collected. Results: With increasing tertiles of serum SDF-1 levels, the CANRS and CVDRS significantly increased (both P for trend

Edible insects are a highly nutritious source of protein and are enjoyed by people all over the world. Insects contain various other nutrients and beneficial compounds, such as lipids, vitamins and minerals, chitin, phenolic compounds, and antimicrobial peptides, which contribute to good health. The practice of insect farming is far more resource-efficient compared to traditional agriculture and animal husbandry, requiring less land, energy, and water, and resulting in a significantly lower carbon footprint. In fact, insects are 12 to 25 times more efficient than animals in converting low-protein feed into protein. When it comes to protein production per unit area, insect farming only requires about one-eighth of the land needed for beef production. Moreover, insect farming generates minimal waste, as insects can consume food and biomass that would otherwise go to waste, contributing to a circular economy that promotes resource recycling and reuse. Insects can be fed with agricultural waste, such as unused plant stems and food scraps. Additionally, the excrement produced by insects can be used as fertilizer for crops, completing the circular chain. Despite the undeniable sustainability and nutritional benefits of consuming insects, widespread acceptance of incorporating insects into our daily diets still has a long way to go. This paper provides a comprehensive overview of the nutritional value of edible insects, the development of farming and processing technologies, and the problems faced in the marketing of edible insect products and insect foods to improve the reference for how people choose edible insects.

A novel interlaminar elastic screw spacer technique was designed to maintain lumbar mobility in treating lumbar degenerative diseases. A validated finite element model of L4/5 was used to establish an ISES-1/2 model and an ISES-1/3 model based on different insertion points, a unilateral fixation model and a bilateral fixed model based on different fixation methods, and a Coflex-F model based on different implants. The elastic rods were used to fix screws. Under the same mechanical conditions, we compared the biomechanical characteristics to investigate the optimal entry point for ISES technology, demonstrate the effectiveness of unilateral fixation, and validate the feasibility of the ISES technique. Compared to ISES-1/3, the ISES-1/2 model had lower intradiscal pressure, facet cartilage stress, and posterior structural stress. Compared to the ISES-BF model, the ISES-UF model had lower intervertebral pressure, larger mobility, and smaller stress on the posterior structures. The ISES model had a similar intervertebral pressure and limitation of extension as the Coflex-F model. The ISES model retained greater mobility and reduced the stress on the facet cartilage and posterior structure compared with the Coflex-F model. Our study suggests that the ISES technique is a promising treatment of lumbar degenerative diseases, especially those with osteoporosis.

Hizikia fusiforme has a long history of consumption and medicinal use in China. It has been found that natural plants containing polyphenol–polysaccharide complexes have better activity compared with polyphenols and polysaccharides. Therefore, in this study on enzymatic hydrolysis and fractional alcohol precipitation, two kinds of polyphenol–polysaccharide complexes (PPC), PPC1 and PPC2, were initially obtained from Hizikia fusiforme, while the dephenolization of PPC1 and PPC2 produced PPC3 and PPC4. Through in vitro assays, PPC2 and PPC4 were found to have higher antioxidant activity, and thus were selected for testing the PPCs’ anti-aging activity in a subsequent in vivo experiment with D-gal-induced aging in mice. The results indicated that PPCs could regulate the expressions of antioxidant enzymes and products of oxidation, elevate the expressions of genes and proteins related to the Nrf2 pathway in the mouse brain, enrich the gut microbiota species and increase the Bacteroidota–Firmicute (B/F) ratio. Above all, the Hizikia fusiforme polyphenol–polysaccharide complex has potential in the development of natural anti-aging drugs.