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Chinese cherry (Prunus pseudocerasus) holds considerable importance as one of the primary stone fruit crops in China. However, artificially improving its traits and genetic analysis are challenging due to lack of high-quality genomic resources, which mainly result from difficulties associated with resolving its tetraploid and highly heterozygous genome. Herein, we assembled a chromosome-level, haplotype-resolved genome of the cultivar 'Zhuji Duanbing', comprising 993.69 Mb assembled into 32 pseudochromosomes using PacBio HiFi, Oxford Nanopore, and Hi-C. Intra-haplotype comparative analyses revealed extensive intra-genomic sequence and expression consistency. Phylogenetic and comparative genomic analyses demonstrated that P. pseudocerasus was a stable autotetraploid species, closely related to wild P. pusilliflora, with the two diverging ~18.34 million years ago. Similar to other Prunus species, P. pseudocerasus underwent a common whole-genome duplication event that occurred ~139.96 million years ago. Because of its low fruit firmness, P. pseudocerasus is unsuitable for long-distance transportation, thereby restricting its rapid development throughout China. At the ripe fruit stage, P. pseudocerasus cv. 'Zhuji Duanbing' was significantly less firm than P. avium cv. 'Heizhenzhu'. The difference in firmness is attributed to the degree of alteration in pectin, cellulose, and hemicellulose contents. In addition, comparative transcriptomic analyses identified GalAK-like and Stv1, two genes involved in pectin biosynthesis, which potentially caused the difference in firmness between 'Zhuji Duanbing' and 'Heizhenzhu'. Transient transformations of PpsGalAK-like and PpsStv1 increase protopectin content and thereby enhance fruit firmness. Our study lays a solid foundation for functional genomic studies and the enhancement of important horticultural traits in Chinese cherries.

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Solute transport during rapid and repeated thermal cycle in additive manufacturing (AM) leading to non-equilibrium, non-uniform microstructure remains to be studied. Here, a fully-coupled fluid dynamics and microstructure modelling is developed to rationalise the dynamic solute transport process and elemental segregation in AM, and to gain better understanding of non-equilibrium nature of intercellular solute segregation and cellular structures at sub-grain scale during the melting-solidification of the laser powder bed fusion process. It reveals the solute transport induced by melt convection dilutes the partitioned solute at the solidification front and promotes solute trapping, and elucidates the mechanisms of the subsequent microstructural morphology transitions to ultra-fine cells and then to coarse cells. These suggest solute trapping effect could be made used for reducing crack susceptibility by accelerating the solidification process. The rapid solidification characteristics exhibit promising potential of additive manufacturing for hard-to-print superalloys and aid in alloy design for better printability.

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BACKGROUND: Neuroimaging has played a primary role in predicting intracerebral hemorrhage (ICH) recurrence of cerebral amyloid angiopathy (CAA); however, the utilities of biomarkers in CAA-related ICH and cognitive impairment remain unexplored. OBJECTIVE: To investigate the correlations of serum levels of matrix metalloproteinase-2 (MMP-2), MMP-3, and MMP-9 with CAA-related MRI markers, ICH recurrence, and cognitive status. METHODS: 68 cases with first probable CAA-ICH and 69 controls were recruited. Clinical and imaging data were obtained at baseline and serum MMPs in the acute phase were measured by Luminex multiplex assays. Cognitive status was assessed with the Chinese version of Mini-Mental State Examination within 10-14 days after ICH onset. RESULTS: Serum MMP-2 level was significantly lower in CAA-ICH patients than controls while MMP-9 was significantly higher. In CAA-ICH patients, MMP-3 level was significantly associated with lobar cerebral microbleeds count after adjusting age, sex, and hypertension (adjusted coefficient 0.368, 95%CI 0.099-0.637, p = 0.008). During a median follow-up of 2.4 years, higher level of MMP-2 predicted lower CAA-ICH recurrence after adjusting age (adjusted HR 0.326, 95%CI 0.122-0.871, p = 0.025), ICH volume (adjusted HR 0.259, 95%CI 0.094-0.715, p = 0.009), total MRI burden of SVD score (adjusted HR 0.350, 95%CI 0.131-0.936, p = 0.037) respectively. Besides, higher level of MMP-2 was significantly associated with decreased risk of cognitive impairment independent of age and ICH volume (adjusted OR 0.054, 95%CI 0.005-0.570, p = 0.015). CONCLUSION: Serum MMP-2 in acute phase might be a promising biomarker to predict CAA-ICH recurrence and to evaluate the risk of cognitive impairment.

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Histone deacetylases 3 (HDAC3) modulates the acetylation state of histone and non-histone proteins and could be a powerful regulator of the inflammatory process in stroke. Inflammasome activation is a ubiquitous but poorly understood consequence of acute ischemic stroke. Here, we investigated the potential contributions of HDAC3 to inflammasome activation in primary cultured microglia and experimental stroke models. In this study, we documented that HDAC3 expression was increased in microglia of mouse experimental stroke model. Intraperitoneal injection of RGFP966 (a selective inhibitor of HDAC3) decreased infarct size and alleviated neurological deficits after the onset of middle cerebral artery occlusion (MCAO). In vitro data indicated that LPS stimulation evoked a time-dependent increase of HDAC3 and absent in melanoma 2 (AIM2) inflammasome in primary cultured microglia. Interestingly, AIM2 was subjected to spatiotemporal regulation by RGFP966. The ability of RGFP966 to inhibit the AIM2 inflammasome was confirmed in an experimental mouse model of stroke. As expected, AIM2 knockout mice also demonstrated significant resistance to ischemia injury compared with their wild-type littermates. RGFP966 failed to exhibit extra protective effects in AIM2-/- stroke mice. Furthermore, we found that RGFP966 enhanced STAT1 acetylation and subsequently attenuated STAT1 phosphorylation, which may at least partially contributed to the negative regulation of AIM2 by RGFP966. Together, we initially found that RGFP966 alleviated the inflammatory response and protected against ischemic stroke by regulating the AIM2 inflammasome.

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The nucleation pathway plays an important role in vitrification, preparation of glass-ceramic composites and synthesis of metastable materials. In this paper, we studied the nucleation pathway of a novel ferroelectric BaTi2O5 (BT2) during crystallization from undercooled liquid by aerodynamic levitation (ADL) containerless processing and structural analysis. An interesting polymorphic transition of BT2 regulated by the undercooling was observed during the crystallization process: the ferroelectric monoclinic phase (γ-BT2) was fabricated at low undercoolings and the paraelectric orthorhombic metastable phase (ß-BT2) was obtained from hypercooled liquid. This polymorphic transition phenomenon corresponds to a non-classical nucleation pathway: metastable ß-BT2 preferentially nucleates from undercooled melt and γ-BT2 is generated from ß phase by solid-state phase transition. The two-step nucleation pathway stems from the structural heredity between the undercooled liquid and crystals. A stronger structural homology exists between the undercooled melt and ß-BT2 than γ-BT2 based on diffraction data and atomic configurations analysis. This structural homology coupled with nucleation barrier calculation was used to elucidate the non-classical nucleation pathway of BT2 crystallization: the similarity of the structural unit (Ti-O polyhedra) between the undercooled liquid and the metastable ß-BT2 reduces the nucleation barrier and contributes to the preferential precipitation of ß-like clusters. This work reveals the formation route of BT2 from cooling melt, which not only benefits the synthesis and application of this novel functional material but also provides a guideline of the crystallization process of titanates from melt at atomic level.

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HDAC3 has been shown to regulate inflammation. However, the role of HDAC3 in primary microglia is largely unknown. RGFP966 is a newly discovered selective HDAC3 inhibitor. In this study, we used protein mass spectrometry to analyze protein alterations in LPS-treated primary microglia with the application of RGFP966. Generally, about 2000 proteins were studied. 168 of 444 (37.8%) LPS-induced proteins were significantly reduced with the treatment of RGFP966, which mainly concentrated on Toll-like receptor signaling pathway. In this regard, we selected Toll-like receptor 2 (TLR2), TLR3, TLR6, MAPK p38, CD36, and spleen tyrosine kinase (SYK) for further validation and found that they were all significantly upregulated after LPS stimulation and downregulated in the presence of RGFP966. Additionally, RGFP966 inhibited supernatant tumor necrosis factor (TNF)-α and Interleukin 6 (IL-6) concentrations. Activation of STAT3 and STAT5 was partially blocked by RGFP966 at 2 h after LPS-stimulation. The fluorescence intensity of CD16/32 was significantly decreased in LPS + RGFP966-treated group. In conclusion, our data provided a hint that RGFP966 may be a potential therapeutic medication combating microglia activation and inflammatory response in central nervous system, which was probably related to its repressive impacts on TLR signaling pathways and STAT3/STAT5 pathways.

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Studies of abnormal regional homogeneity (ReHo) in Parkinson's disease (PD) have reported inconsistent results. Therefore, we conducted a meta-analysis using the Seed-based d Mapping software package to identify the most consistent and replicable findings. A systematic literature search was performed to identify eligible whole-brain resting-state functional magnetic resonance imaging studies that had measured differences in ReHo between patients with PD and healthy controls between January 2000 and June 4, 2016. A total of ten studies reporting 11 comparisons (212 patients; 182 controls) were included. Increased ReHo was consistently identified in the bilateral inferior parietal lobules, bilateral medial prefrontal cortices, and left cerebellum of patients with PD when compared to healthy controls, while decreased ReHo was observed in the right putamen, right precentral gyrus, and left lingual gyrus. The results of the current meta-analysis demonstrate a consistent and coexistent pattern of impairment and compensation of intrinsic brain activity that predominantly involves the default mode and motor networks, which may advance our understanding of the pathophysiological mechanisms underlying PD.

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The design of chemical compositions containing potent nuclei for the enhancement of heterogeneous nucleation in aluminium, especially cast alloys such as Al-Si alloys, is a matter of importance in order to achieve homogeneous properties in castings with complex geometries. We identified that Al3Nb/NbB2 compounds are effective heterogeneous nuclei and are successfully produced in the form of Al-2Nb-xB (x = 0.5, 1 and 2) master alloys. Our study shows that the inoculation of Al-10Si braze alloy with these compounds effectively promotes the heterogeneous nucleation of primary α-Al crystals and reduces the undercooling needed for solidification to take place. Moreover, we present evidences that these Nb-based compounds prevent the growth of columnar crystals and permit to obtain, for the first time, fine and equiaxed crystals in directionally solidified Al-10Si braze alloy. As a consequence of the potent heterogeneous particles, the size of the α-Al crystals was found to be less dependent on the processing conditions, especially the thermal gradient. Finally, we also demonstrate that the enhanced nucleation leads to the refinement of secondary phases such as eutectic silicon and primary silicon particles.

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INTRODUCTION: Human umbilical cord mesenchymal stem cells (HUC-MSCs) are one of the typical adult stem cells; they have superiorities including low immunogenicity, non-invasive harvest procedure, easy expansion in vitro, and ethical access compared with stem cells from other sources. Therefore, HUC-MSCs are a promising candidate for cell-based therapy. AREAS COVERED: Here we reviewed the development of stem cell-based therapy, the manufacturing and banking process of HUC-MSCs, the emerging clinical studies in the field of cancer, central nervous system diseases, liver diseases and graft-versus-host disease, the potential therapeutic mechanisms, as well as challenges of HUC-MSCs in clinical translation. EXPERT OPINION: HUC-MSCs seem to be an optimal choice for stem cell-based therapy. However, before the cells translate from basic to clinical research, some problems still remain to be solved: i) building regulatory guidelines as well as an efficient and safe manufacturing procedure; ii) establishing donor's genetic testing and long-term closely monitoring system; iii) conducting further clinical trials to determine the optimum and standard dosage, time, route, frequency and many other technical issues of HUC-MSCs transplantation.

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Chronic asthma is one of the most common respiratory diseases, characterized by airway inflammation. However, little is known whether asthma-induced airway inflammation might influence the brain. We found that chronic asthma not only resulted in peripheral inflammation, but also induced neuroinflammation which was characterized by microglial activations and increased levels of TNFα and IL-1ß in the hippocampus and prefrontal cortex. Simultaneously, we found that there was significant neuronal loss in the asthmatic mouse brain. Inhaled budesonide, the classic therapeutic drug for chronic asthma, could inhibit asthma-induced microglial activation, down-regulate TNFα and IL-1ß but up-regulate TGFß and IL-10 of mouse brain, and thereby attenuate neuronal loss. Further study showed that chronic asthma increased the expressions of TLR4 and p65/NFκB in the brain, which could be reversed by budesonide treatment. Therefore, the present study reveals that inhaled budesonide protects against asthma-induced neuroinflammation in mouse brain, which might be contributed to attenuate neuronal loss.

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