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Abstract The reconstruction of damaged neural circuits is critical for neurological repair after brain injury. Classical brain-computer interfaces (BCIs) allow direct communication between the brain and external controllers to compensate for lost functions. Importantly, there is increasing potential for generalized BCIs to input information into the brains to restore damage, but their effectiveness is limited when a large injured cavity is caused. Notably, it might be overcome by transplantation of brain organoids into the damaged region. Here, we construct innovative BCIs mediated by implantable organoids, coined as organoid-brain-computer interfaces (OBCIs). We assess the prolonged safety and feasibility of the OBCIs, and explore neuroregulatory strategies. OBCI stimulation promotes progressive differentiation of grafts and enhances structural-functional connections within organoids and the host brain, promising to repair the damaged brain via regenerating and regulating, potentially directing neurons to preselected targets and recovering functional neural networks in the future.

Abstract Integrated biochemical and biophysical signals regulate embryonic development. Correct neural tube formation is critical for the development of central nervous system. However, the role of microgravity in neurodevelopment and its underlying molecular mechanisms remain unclear. In this study, the effects of stimulated microgravity (SMG) on the development of human brain organoids are investigated. SMG impairs N‐cadherin‐based adherens junction formation, leading to neural tube defects associated with dysregulated self‐renewal capacity and neuroepithelial disorganization in human brain organoids. Bulk gene expression analyses reveal that SMG alters Hippo and BMP signaling in brain organoids. The neuropathological deficits in SMG‐treated organoids can be rescued by regulating YAP/BMP/ID1 axis. Furthermore, sing‐cell RNA sequencing data show that SMG results in perturbations in the number and function of neural stem and progenitor cell subpopulations. One of these subpopulations senses SMG cues and transmits BMP signals to the subpopulation responsible for tube morphogenesis, ultimately affecting the proliferating cell population. Finally, SMG intervention leads to persistent neurologic damage even after returning to normal gravity conditions. Collectively, this study reveals molecular and cellular abnormalities associated with SMG during human brain development, providing opportunities for countermeasures to maintain normal neurodevelopment in space.

Abstract Background The effects of traumatic brain injury (TBI) can include physical disability and even death. The development of effective therapies to promote neurological recovery is still a challenging problem. 3D-printed biomaterials are considered to have a promising future in TBI repair. The injury-preconditioned secretome derived from human umbilical cord blood mesenchymal stem cells showed better stability in neurological recovery after TBI. Therefore, it is reasonable to assume that a biological scaffold loaded with an injury-preconditioned secretome could facilitate neural network reconstruction after TBI. Methods In this study, we fabricated injury-preconditioned secretome/collagen/heparan sulfate scaffolds by 3D printing. The scaffold structure and porosity were examined by scanning electron microscopy and HE staining. The cytocompatibility of the scaffolds was characterized by MTT analysis, HE staining and electron microscopy. The modified Neurological Severity Score (mNSS), Morris water maze (MWM), and motor evoked potential (MEP) were used to examine the recovery of cognitive and locomotor function after TBI in rats. HE staining, silver staining, Nissl staining, immunofluorescence, and transmission electron microscopy were used to detect the reconstruction of neural structures and pathophysiological processes. The biocompatibility of the scaffolds in vivo was characterized by tolerance exposure and liver/kidney function assays. Results The excellent mechanical and porosity characteristics of the composite scaffold allowed it to efficiently regulate the secretome release rate. MTT and cell adhesion assays demonstrated that the scaffold loaded with the injury-preconditioned secretome (3D-CH-IB-ST) had better cytocompatibility than that loaded with the normal secretome (3D-CH-ST). In the rat TBI model, cognitive and locomotor function including mNSS, MWM, and MEP clearly improved when the scaffold was transplanted into the damage site. There is a significant improvement in nerve tissue at the site of lesion. More abundant endogenous neurons with nerve fibers, synaptic structures, and myelin sheaths were observed in the 3D-CH-IB-ST group. Furthermore, the apoptotic response and neuroinflammation were significantly reduced and functional vessels were observed at the injury site. Good exposure tolerance in vivo demonstrated favorable biocompatibility of the scaffold. Conclusions Our results demonstrated that injury-preconditioned secretome/collagen/heparan sulfate scaffolds fabricated by 3D printing promoted neurological recovery after TBI by reconstructing neural networks, suggesting that the implantation of the scaffolds could be a novel way to alleviate brain damage following TBI. Graphical abstract

Ordinary mixers can hardly meet the requirements in terahertz (THz) communications due to the low-power and expensive THz sources. Sensitive harmonic mixers have been widely studied to avoid this problem, owing to the fact that the higher the number of harmonics, the lower the local oscillator (LO) frequency, and the lower the cost. High-Tc superconducting (HTS) Josephson junction (JJ) mixers are performing candidates for THz receiver frontends because of the advantages of excellent sensitivity, wide bandwidth, high harmonic number and low LO power requirement. However, the normal-state resistance of HTS JJ is so low that traditional antennas are difficult to match it. In other words, it is quite a challenge to match the input impedance to a low input impedance for traditional antennas, especially for antennas fed by coplanar striplines (CPSs). In this work, based on the structure of bowtie, two types of stub tuners were integrated to decrease the impedance of the bowtie antenna so as to improve the coupling efficiency between the traditional bowtie antenna and the JJ. Furthermore, HTS YBa2Cu3O7-δ (YBCO) JJ harmonic mixers coupled with the proposed structures and fed by CPSs are fabricated and measured. The measurements show that the JJ mixer coupled with a pair of open-end stubs of the bowtie antenna achieves up to 88 harmonics, with a conversion efficiency of −69.6 dB. In contrast, the JJ mixer coupled with a pair of lumped-element stubs of the bowtie antenna only attains to 30 harmonics, with a conversion efficiency of −73.4 dB. Additional numerical simulations indicate that the coupling efficiency is enhanced when the complex impedance of the antenna is explicitly considered. Compared with other coupled traditional antennas, the JJ mixer with bowtie antenna has the largest harmonic number. This work paves the way for the future application of low-frequency and low-cost LO for THz communications.

Seed weight and number ultimately determine seed yield. Arabidopsis seed number comprised of silique number and seed number per silique (SNS). Comparing seed development and weight, determinants of seed number remain largely uncharacterized. In this study, taking advantage of 107 available Arabidopsis accessions, genome-wide association analysis (GWAS) was employed to identify the candidate genes regulating SNS. GWAS-based genotype and phenotype association analysis identified 38 most significant SNPs marker sites that were mapped to specific chromosomal positions and allowed us to screen for dozens of candidate genes. One of them (PIN3) was selected for functional validation based on gene expression analysis. It is a positive regulator of Arabidopsis SNS. Although silique length of PIN3 loss of function mutant was not significantly changed, its SNS and seed density (SD) were significantly reduced as compared with the wild type. Notably, PIN3 overexpression lines driven by a placenta-specific promoter STK exhibited significantly shorter siliques, slightly reduced SNS, but significant increased SD compared with wild type, suggesting that PIN3 positively regulates SD through inducing ovule primordia initiation regardless of the placenta size. Ovule initiation determines the maximal possibility of SNS, and new genes and mechanism regulating SNS through modulating ovule initiation is worth further investigated.

Over the past three decades, mortality from lung cancer has sharply and continuously increased in China, ascending to the first cause of death among all types of cancer. The ability to identify the actual sequence of gene mutations may help doctors determine which mutations lead to precancerous lesions and which produce invasive carcinomas, especially using next-generation sequencing (NGS) technology. In this study, we analyzed the latest lung cancer data in the COSMIC database, in order to find genomic "hotspots" that are frequently mutated in human lung cancer genomes. The results revealed that the most frequently mutated lung cancer genes are EGFR, KRAS and TP53.In recent years, EGFR and KRAS lung cancer test kits have been utilized for detecting lung cancer patients, but they presented many disadvantages, as they proved to be of low sensitivity, labor-intensive and time-consuming. In this study, we constructed a more complete catalogue of lung cancer mutation events including 145 mutated genes. With the genes of this list it may be feasible to develop a NGS kit for lung cancer mutation detection.

Research has been conducted on the 3-D coordination polymer with the helical chains of OH-bridged basic trizinc clusters. The preparation, crystal structure and luminescent properties of this polymer have been examined and the results are discussed.

Previous studies showed that ABCG11 and ABCG12, two ATP-binding-cassette (ABC) transporters, are required for cuticular lipids extracellular secretion. Here, we characterized ABCG13, a third clade member, to widen our limited knowledge regarding assembly of the plant's cuticle. We isolated an abcg13 knockout mutant and used RNAi and artificial microRNA approaches to study the effect of ABCG13 loss-of-function. These plants were subsequently used to conduct a detailed analysis of cuticular lipids composition and cytological observations. ABCG13 loss-of-function resulted in cuticle-related phenotypes that were restricted to flowers, including inter-organ post-genital fusions. Apart from a significant reduction in flower cutin monomers, the macromorphology and micromorphology of abcg13 petal epidermis was strongly affected. We also found that ABCG13 is highly expressed in flowers, predominantly in petals and carpels. The results suggest that ABCG13 is required for the transport of flower cuticular lipids. This work introduces a new component to the recently emerging genetic network that makes the archetypal exterior of Arabidopsis flowers. While the question regarding the substrate specificity of the ABCG12-clade members remains open, these findings will facilitate future investigations regarding the interaction between the half-size ABCG-type transporters that likely take part in cuticle assembly. [ABSTRACT FROM AUTHOR]

Apart from its significance in the protection against stress conditions, the cuticular cover is essential for proper development of the diverse surface structures formed on aerial plant organs. This layer mainly consists of a cutin matrix, embedded and overlaid with cuticular waxes. Following their biosynthesis in epidermal cells, cutin and waxes were suggested to be exported across the plasma membrane by ABCG-type transporters such as DSO/ABCG11 to the cell wall and further to extracellular matrix. Here, additional aspects of DSO/ABCG11 function were investigated, predominantly in reproductive organs, which were not revealed in the previous reports. This was facilitated by the generation of a transgenic DSO/ABCG11 silenced line (dso-4) that displayed relatively subtle morphological and chemical phenotypes. These included altered petal and silique morphology, fusion of seeds, and changes in levels of cutin monomers in flowers and siliques. The dso-4 phenotypes corresponded to the strong DSO/ABCG11 gene expression in the embryo epidermis as well as in the endosperm tissues of the developing seeds. Moreover, the DSO/ABCG11 protein displayed polar localization in the embryo protoderm. Transcriptome analysis of the dso-4 mutant leaves and stems showed that reduced DSO/ABCG11 activity suppressed the expression of a large number of cuticle-associated genes, implying that export of cuticular lipids from the plasma membrane is a rate-limiting step in cuticle metabolism. Surprisingly, root suberin composition of dso-4 was altered, as well as root expression of two suberin biosynthetic genes. Taken together, this study provides new insights into cutin and suberin metabolism and their role in reproductive organs and roots development. [ABSTRACT FROM PUBLISHER]

The cuticle covering every plant aerial organ is largely made of cutin that consists of fatty acids, glycerol, and aromatic monomers. Despite the huge importance of the cuticle to plant development and fitness, our knowledge regarding the assembly of the cutin polymer and its integration in the complete cuticle structure is limited. Cutin composition implies the action of acyltransferase-type enzymes that mediate polymer construction through ester bond formation. Here, we show that a member of the BAHD family of acyltransferases (DEFECTIVE IN CUTICULAR RIDGES [DCR]) is required for incorporation of the most abundant monomer into the polymeric structure of the Arabidopsis (Arabidopsis thaliana) flower cutin. DCR-deficient plants display phenotypes that are typically associated with a defective cuticle, including altered epidermal cell differentiation and postgenital organ fusion. Moreover, levels of the major cutin monomer in flowers, 9(10),16-dihydroxy-hexadecanoic acid, decreased to an almost undetectable amount in the mutants. Interestingly, dcr mutants exhibit changes in the decoration of petal conical cells and mucilage extrusion in the seed coat, both phenotypes formerly not associated with cutin polymer assembly. Excessive root branching displayed by dcr mutants and the DCR expression pattern in roots pointed to the function of DCR belowground, in shaping root architecture by influencing lateral root emergence an growth. In addition, the dcr mutants were more susceptible to salinity, osmotic, and water deprivation stress condition . Finally, the analysis of DCR protein localization suggested that cutin polymerization, possibly the oligomerization step, is partially carried out in the cytoplasmic space. Therefore, this study extends our knowledge regarding the functionality of the cuticular layer and the formation of its major constituent the polymer cutin. [ABSTRACT FROM AUTHOR]

series of light-emitting group 14 element-containing organometallic platinum polyynes of the form trans-[-Pt(PBu)C≡ CArC≡ C(ER)C≡ CArC≡ C-] (Ar = 9-butylcarbazole-3,6-diyl, ER = SiMe, SiPh, GeMe, GePh) were synthesized and spectroscopically characterized. The solution properties and regiochemical structures of this new structural class of organosilicon- and organogermanium-based metallopolyynes were studied by IR and NMR (H, C, Si, and P) spectroscopies. The optical absorption and photoluminescence spectra of these metallopolymers were examined and compared with their well-defined dinuclear model complexes trans-[Pt(Ph)(PEt)C≡ CArC≡ C(ER)C≡ CArC≡ CPt(Ph)(PEt)]. The influence of the heavy platinum atom and the group 14 silyl or germyl structural unit possessing different side group substituents on the thermal and phosphorescence properties were investigated in detail. We have also established the goal for studying the evolution of the lowest singlet and triplet excited states with the nature of ER unit in these metallopolymers. The present work indicates that the phosphorescence emission efficiency harnessed through the heavy-atom effect of platinum in the main chain changes significantly with the identity of ER in the general orders GeR > SiR (R = Me, Ph) and EMe > EPh (E = Si, Ge). [ABSTRACT FROM AUTHOR]

The plant cell cuticle serves as the first barrier protecting plants from mechanical injury and invading pathogens. The cuticle can be breached by cutinase-producing pathogens and the degradation products may activate pathogenesis signals in the invading pathogens. Cuticle degradation products may also trigger the plant's defense responses. Botrytis cinerea is an important plant pathogen, capable of attacking and causing disease in a wide range of plant species. Arabidopsis thaliana shn1-1D is a gain-of-function mutant, which has a modified cuticular lipid composition. We used this mutant to examine the effect of altering the whole-cuticle metabolic pathway on plant responses to B. cinerea attack. Following infection with B. cinerea, the shn1-1D mutant discolored more quickly, accumulated more H2O2, and showed accelerated cell death relative to wild-type (WT) plants. Whole transcriptome analysis of B. cinerea-inoculated shn1-1D vs. WT plants revealed marked upregulation of genes associated with senescence, oxidative stress and defense responses on the one hand, and genes involved in the magnitude of defense-response control on the other. We propose that altered cutin monomer content and composition of shn1-1D plants triggers excessive reactive oxygen species accumulation and release which leads to a strong, unique and uncontrollable defense response, resulting in plant sensitivity and death.

Floral organs display tremendous variation in their exterior that is essential for organogenesis and the interaction with the environment. This diversity in surface characteristics is largely dependent on the composition and structure of their coating cuticular layer. To date, mechanisms of flower organ initiation and identity have been studied extensively, while little is known regarding the regulation of flower organs surface formation, cuticle composition, and its developmental significance. Using a synthetic microRNA approach to simultaneously silence the three SHINE (SHN) clade members, we revealed that these transcription factors act redundantly to shape the surface and morphology of Arabidopsis flowers. It appears that SHNs regulate floral organs' epidermal cell elongation and decoration with nanoridges, particularly in petals. Reduced activity of SHN transcription factors results in floral organs' fusion and earlier abscission that is accompanied by a decrease in cutin load and modified cell wall properties. SHN transcription factors possess target genes within four cutin- and suberin-associated protein families including, CYP86A cytochrome P450s, fatty acyl-CoA reductases, GSDL-motif lipases, and BODYGUARD1-like proteins. The results suggest that alongside controlling cuticular lipids metabolism, SHNs act to modify the epidermis cell wall through altering pectin metabolism and structural proteins. We also provide evidence that surface formation in petals and other floral organs during their growth and elongation or in abscission and dehiscence through SHNs is partially mediated by gibberellin and the DELLA signaling cascade. This study therefore demonstrates the need for a defined composition and structure of the cuticle and cell wall in order to form the archetypal features of floral organs surfaces and control their cell-to-cell separation processes. Furthermore, it will promote future investigation into the relation between the regulation of organ surface patterning and the broader control of flower development and biological functions.