Enzymatic functionalization of decellularized tilapia skin scaffolds with enhanced skin regeneration.

The decellularized tilapia skin (dTS) has gained significant attention as a promising material for tissue regeneration due to its ability to provide unique structural and functional components that support cell growth, adhesion, and proliferation. However, the clinical application of dTS is limited by its low mechanical strength and rapid biodegradability. Herein, we prepare a novel RGD (arginine-glycine-aspartic acid) functionalized dTS scaffold (dTS/RGD) by using transglutaminase (TGase) crosslinking. The developed dTS/RGD scaffold possesses excellent properties, including a medium porosity of ∼59.2%, a suitable degradation rate of approximately 80% over a period of two weeks, and appropriate mechanical strength with a maximum tensile stress of ∼46.36 MPa which is much higher than that of dTS (∼32.23 MPa). These properties make the dTS/RGD scaffold ideal for promoting cell adhesion and proliferation, thereby accelerating skin wound healing in a full-thickness skin defect model. Such an enzymatic cross-linking strategy provides a favorable microenvironment for wound healing and holds great potential for application in skin regeneration engineering.

New findings of dipteromantispids (Insecta: Neuroptera) from Upper Cretaceous Myanmar amber.

A new genus and two new species, Tholimantispa zuoae gen. et sp. nov. and Mantispidipterella curvis sp. nov. are described from the Upper Cretaceous of northern Myanmar amber collected in 2015. Tholimantispa zuoae gen. et sp. nov. is characterized by its distinct pterostigma, broad costal space, bifurcate humeral veinlets, and so forth, and Mantispidipterella curvis sp. nov. is different from Mantispidipterella longissima Liu, Lu et Zhang, 2017 in its ScP (subcosta posterior) distinctly curved at fusing point with RA (radius anterior), RP (radius posterior) abruptly and angularly curved at ra-rp (crossvein between RA and RP), AA3 (third branches of the anterior anal vein) present. The new fossil species enrich the diversity of Dipteromantispidae in the Cretaceous.

Controlled Assembly and Disassembly of Higher-Order Peptide Nanotubes.

The controlled peptide self-assembly and disassembly are not only implicated in many cellular processes but also possess huge application potential in a wide range of biotechnology and biomedicine. ß-sheet peptide assemblies possess high kinetic stability, so it is usually hard to disassemble them rapidly. Here, we reported that both the self-assembly and disassembly of a designed short ß-sheet peptide IIIGGHK could be well harnessed through the variations of concentration, pH, and mechanical stirring. Microscopic imaging, neutron scattering, and infrared spectroscopy were used to track the assembly and disassembly processes upon these stimuli, especially the interconversion between thin, left-handed protofibrils and higher-order nanotubes with superstructural right-handedness. The underlying rationale for these controlled disassembly processes mainly lies in the fact that the specific His-His interactions between protofibrils were responsive to these stimuli. By taking advantage of the peptide self-assembly and disassembly, the encapsulation of the hydrophobic drug curcumin and its rapid release upon stimuli were achieved. Additionally, the peptide hydrogels facilitated the differentiation of neural cells while maintaining low cell cytotoxicity. We believe that such dynamic and reversible structural transformation in this work provides a distinctive paradigm for controlling the peptide self-assembly and disassembly, thus laying a foundation for practical applications of peptide assemblies.

Disassembling ability of lipopeptide promotes the antibacterial activity.

Lipopeptides have become one of the most potent antibacterial agents, however, there is so far no consensus about the link between their physic-chemical properties and biological activity, in particular their inherent aggregation propensity and antibacterial potency. To this end, we here de novo design a series of lipopeptides (CnH(2n-1)O-(VVKK)2V-NH2), in which an alkyl chain is covalently attached onto the N-terminus of a short cationic peptide sequence with an alternating pattern of hydrophobic VV (Val) and positively charged KK (Lys) motifs. By varying the alkyl chain length (ortho-octanoic acid (C8), lauric acid (C12), and palmitic acid (C16)), the lipopeptides show distinct physicochemical properties and self-assembly behaviors, which have great effect on their antibacterial activities. C8H15O-(VVKK)2V-NH2, which contains the lowest hydrophobicity and surface activity has the lowest antibacterial activity. C12H23O-(VVKK)2V-NH2 and C16H31O-(VVKK)2V-NH2 both have high hydrophobicity and surface activity, and self-assembled into long nanofibers. However, the nanofibers formed by C12H23O-(VVKK)2V-NH2 disassembled by dilution, resulting in its high antibacterial activity via bacterial membrane disruption. Comparatively, the nanofibers formed by C16H31O-(VVKK)2V-NH2 were very stable, which can closely attach on bacterial surface but not permeate bacterial membrane, leading to its low antibacterial activity. Thus, the stability other than the morphologies of lipopeptides' nanostructures contribute to their antibacterial ability. Importantly, this study enhances our understanding of the antibacterial mechanisms of self-assembling lipopeptides that will be helpful in exploring their biomedical applications.

Amyloid-like aggregates of short self-assembly peptide selectively induce melanoma cell apoptosis.

With the rising global incidence of melanoma, new anti-melanoma drugs with low-inducing drug resistance and high selectivity are in urgent need. Inspired by the physiological events in which fibrillar aggregates formed by amyloid proteins are toxic to normal tissues, we here rationally design a tyrosinase responsive peptide, I4K2Y* (Ac-IIIIKKDopa-NH2). Such peptide self-assembled into long nanofibers outside the cells, while it was catalyzed into amyloid-like aggregates by tyrosinase which was rich in melanoma cells. The newly formed aggregates concentrated around the nucleus of melanoma cells, blocking the exchange of biomolecules between the nucleus and cytoplasm and finally leading to cell apoptosis via the S phase arrest in cell cycle distribution and dysfunction of mitochondria. Furthermore, I4K2Y* effectively inhibited B16 melanoma growth in a mouse model but with minimal side effects. We believe that the strategy of combining the usage of toxic amyloid-like aggregates and in-situ enzymatic reactions by specific enzymes in tumor cells will bring profound implications for designing new anti-tumor drugs with high selectivity.

A novel 1.38-kb deletion combined with a single nucleotide variant in KIAA0586 as a cause of Joubert syndrome.

BACKGROUND: KIAA0586, also known as Talpid3, plays critical roles in primary cilia formation and hedgehog signaling in humans. Variants in KIAA0586 could cause some different ciliopathies, including Joubert syndrome (JBTS), which is a clinically and genetically heterogeneous group of autosomal recessive neurological disorders. METHODS AND RESULTS: A 9-month-old girl was diagnosed as JBTS by the "molar tooth sign" of the mid-brain and global developmental delay. By whole-exome sequencing, we identified a single nucleotide variant c.3303G > A and a 1.38-kb deletion in KIAA0586 in the proband. These two variants of KIAA0586 were consistent with the mode of autosomal recessive inheritance in the family, which was verified using Sanger sequencing. CONCLUSIONS: This finding of a compound heterozygote with a 1.38-kb deletion and c.3303G > A gave a precise genetic diagnosis for the patient, and the novel 1.38-kb deletion also expanded the pathogenic variation spectrum of JBTS caused by KIAA0586.

Self-Assembly of Short Amphiphilic Peptides and Their Biomedical Applications.

A series of functional biomaterials with different sizes and morphologies can be constructed through self-assembly, among which amphiphilic peptide-based materials have received intense attention. One main possible reason is that the short amphiphilic peptides can facilitate the formation of versatile materials and promote their further applications in different fields. Another reason is that the simple structure of amphiphilic peptides can help establish the structure-function relationship. This review highlights the recent advances in the self-assembly of two typical peptide species, surfactant-like peptides (SLPs) and peptides amphiphiles (PAs). These peptides can self-assemble into diverse nanostructures. The formation of these different nanostructures resulted from the delicate balance of varied non-covalent interactions. This review embraced each non-covalent interaction and then listed the typical routes for regulating these non-covalent interactions, then realized the morphologies modulation of the self-assemblies. Finally, their applications in some biomedical fields, such as the stabilization of membrane proteins, templating for nanofabrication and biomineralization, acting as the antibacterial and antitumor agents, hemostasis, and synthesis of melanin have been summarized. Further advances in the self-assembly of SLPs and PAs may focus on the design of functional materials with targeted properties and exploring their improved properties.

Characterization and Fine Mapping of qRPR1-3 and qRPR3-1, Two Major QTLs for Rind Penetrometer Resistance in Maize.

Stalk strength is one of the most important traits in maize, which affects stalk lodging resistance and, consequently, maize harvestable yield. Rind penetrometer resistance (RPR) as an effective and reliable measurement for evaluating maize stalk strength is positively correlated with stalk lodging resistance. In this study, one F2 and three F2:3 populations derived from the cross of inbred lines 3705I (the low RPR line) and LH277 (the high RPR line) were constructed for mapping quantitative trait loci (QTL), conferring RPR in maize. Fourteen RPR QTLs were identified in four environments and explained the phenotypic variation of RPR from 4.14 to 15.89%. By using a sequential fine-mapping strategy based on the progeny test, two major QTLs, qRPR1-3 and qRPR3-1, were narrowed down to 4-Mb and 550-kb genomic interval, respectively. The quantitative real-time PCR (qRT-PCR) assay was adopted to identify 12 candidate genes responsible for QTL qRPR3-1. These findings should facilitate the identification of the polymorphism loci underlying QTL qRPR3-1 and molecular breeding for RPR in maize.

Comparative Analysis of Transcriptomes of Diploid and Tetraploid Miscanthus lutarioriparius under Drought Stress.

Miscanthus lutarioriparius is a species of bioenergy crop unique to China. It is widely distributed in the south of China with high resistance to drought and salt stress. To date, the molecular mechanism of the adaption to drought stress in M. lutarioriparius is little known. In this study, RNA-seq technology was employed to analyze the transcriptome changes of diploid and tetraploid M. lutarioriparius after drought treatment. It was found that the number of differentially expressed genes in diploid M. lutarioriparius was much higher than tetraploid, whereas the tetraploid M. lutarioriparius may require fewer transcriptional changes. While the transcriptional changes in drought-tolerant tetraploid M. lutarioriparius are less than that of diploid, more known drought-tolerant pathways were significantly enriched than drought-sensitive diploid M. lutarioriparius. In addition, many drought-tolerance-related genes were constitutively and highly expressed in tetraploid under either normal condition or drought stress. These results together demonstrated that drought-tolerant tetraploid M. lutarioriparius, on the one hand, may preadapt to drought by constitutively overexpressing a series of drought-tolerant genes and, on the other hand, may adapt to drought by actively inducing other drought-tolerant-related pathways. Overall, this study could deepen our understanding of the molecular mechanism of drought-tolerance in bioenergy plants.

Enzymatically functionalized RGD-gelatin scaffolds that recruit host mesenchymal stem cells in vivo and promote bone regeneration.

Critical-size bone defects are imposing a substantial biomedical burden. Despite being long regarded as a potential approach to mitigate this burden or an alternative to bone grafts, bone tissue engineering (BTE) has virtually not proceeded to widespread clinical practices. In the BTE field, it is highly required to find a facile method to prepare active scaffolds with tailored biological functions. Here, we immobilized cell adhesive RGD motifs onto gelatin sponge (GS) scaffolds through enzymatic linking. On the basis of the resulting RGD-functionalized GS (RGD/GS) scaffolds, we developed a new and convenient strategy for bone defect repair, in which the scaffolds were first used to recruit mesenchymal stem cells (MSCs) from skeletal muscle, immediately followed by their engraftment into bone defect. We demonstrated significantly enhanced host cells homing into RGD/GS scaffolds as a result of specific RGD-integrin interactions, and the recruited host cells showed a strong osteogenic differentiation potential. After ectopic implantation of cell-laden RGD/GS scaffolds into critical-size mouse bone defects, marked bone tissue regeneration occurred. The presented strategy not only provides an agile route for the preparation of bioactive scaffolds and the construction of osteoinductive bone-graft substitutes, but also avoids or minimizes the complicated and laborious cell isolation, in vitro expansion and cell seeding procedures used in the conventional BTE.

Tuning the shell structure of peptide nanotubes with sodium tartrate: From monolayer to bilayer.

Though the function of peptide based nanotubes are well correlated with its shape and size, controlling the dimensions of nanotubes still remains a great challenge in the field of peptide self-assembly. Here, we demonstrated that the shell structure of nanotubes formed by a bola peptide Ac-KI3VK-NH2 (KI3VK, in which K, I, and V are abbreviations of lysine, isoleucine, and valine) can be regulated by mixing it with the salt sodium tartrate (STA). The ratio of KI3VK and STA had a great impact on shell structure of the nanotubes. Bilayer nanotubes can be constructed when the molar ratio of KI3VK and STA was less than 1:2. Both the two hydroxyls and the negative charges carried by STA were proved to play important roles in the bilayer nanotubes formation. Observations of different intermediates provided obvious evidence for the varied pathway of the bilayer nanotubes formation. Based on these experimental results, the possible mechanism for bilayer nanotubes formation was proposed. Such a study provides a simple and effective way for regulating the shell structure of the nanotubes and may expand their applications in different fields.

Ordered Packing of ß-Sheet Nanofibrils into Nanotubes: Multi-hierarchical Assembly of Designed Short Peptides.

Although it is well-known proteins and their complexes are hierarchically organized and highly ordered structures, it remains a major challenge to replicate their hierarchical self-assembly process and to fabricate multihierarchical architectures with well-defined shapes and monodisperse characteristic sizes via peptide self-assembly. Here we describe an amphiphilic short peptide Ac-I3GGHK-NH2 that first preassembles into thin, left-handed ß-sheet nanofibrils, followed by their ordered packing into right-handed nanotubes. The key intermediate morphology and structures featuring the hierarchical process are simultaneously demonstrated. Further mechanistic exploration with the variants Ac-I3GGGK-NH2, Ac-I3GGFK-NH2, and Ac-I3GGDHDK-NH2 reveals the vital role of multiple His-His side chain interactions between nanofibrils in mediating higher-order assembly and architectures. Altogether, our findings not only advance current understanding of hierarchical assembly of peptides and proteins but also afford a paradigm of how to take advantage of side chain interactions to construct higher-order assemblies with enhanced complexities.

Optimal strategic pandemic control: human mobility and travel restriction.

This paper presents a model for finding optimal pandemic control policy considering cross-region human mobility. We extend the baseline susceptible-infectious-recovered (SIR) epidemiology model by including the net human mobility from a severely-impacted region to a mildly-affected region. The strategic optimal mitigation policy combining testing and lockdown in each region is then obtained with the goal of minimizing economic cost under the constraint of limited resources. We parametrize the model using the data of the COVID-19 pandemic and show that the optimal response strategy and mitigation outcome greatly rely on the mitigation duration, available resources, and cross-region human mobility. Furthermore, we discuss the economic impact of travel restriction policies through a quantitative analysis.

The reference genome of Miscanthus floridulus illuminates the evolution of Saccharinae.

Miscanthus, a member of the Saccharinae subtribe that includes sorghum and sugarcane, has been widely studied as a feedstock for cellulosic biofuel production. Here, we report the sequencing and assembly of the Miscanthus floridulus genome by the integration of PacBio sequencing and Hi-C mapping, resulting in a chromosome-scale, high-quality reference genome of the genus Miscanthus. Comparisons among Saccharinae genomes suggest that Sorghum split first from the common ancestor of Saccharum and Miscanthus, which subsequently diverged from each other, with two successive whole-genome duplication events occurring independently in the Saccharum genus and one whole-genome duplication occurring in the Miscanthus genus. Fusion of two chromosomes occurred during rediploidization in M. floridulus and no significant subgenome dominance was observed. A survey of cellulose synthases (CesA) in M. floridulus revealed quite high expression of most CesA genes in growing stems, which is in agreement with the high cellulose content of this species. Resequencing and comparisons of 75 Miscanthus accessions suggest that M. lutarioriparius is genetically close to M. sacchariflorus and that M. floridulus is more distantly related to other species and is more genetically diverse. This study provides a valuable genomic resource for molecular breeding and improvement of Miscanthus and Saccharinae crops.

Clinical heterogeneity and intrafamilial variability of Joubert syndrome in two siblings with CPLANE1 variants.

BACKGROUND: Joubert syndrome (JBTS) is a rare genetic disorder that is characterized by midbrain-hindbrain malformations. Multiple variants in genes that affect ciliary function contribute to the genetic and clinical heterogeneity of JBTS and its subtypes. However, the correlation between genotype and phenotype has not been elucidated due to the limited number of patients available. METHODS: In this study, we observed different clinical features in two siblings from the same family. The older sibling was classified as a pure JBTS patient, whereas her younger sibling displayed oral-facial-digital defects and was therefore classified as an oral-facial-digital syndrome type VI (OFD VI) patient. Next, we performed human genetic tests to identify the potential pathogenic variants in the two siblings. RESULTS: Genetic sequencing indicated that both siblings harbored compound heterozygous variants of a missense variant (c.1067C>T, p.S356F) and a frameshift variant (c.8377_8378del, p.E2793Lfs*24) in CPLANE1 (NM_023073.3). CONCLUSION: This study reports that two novel CPLANE1 variants are associated with the occurrence of JBTS and OFD VI. These results help elucidate the intrafamilial phenotypic variability associated with CPLANE1 variants.

Mutation analysis of TCOF1 gene in Chinese Treacher Collins syndrome patients.

BACKGROUND: Treacher Collins syndrome (TCS) is a rare autosomal dominant or recessive disorder, that involves unique bilateral craniofacial malformations. The phenotypes of TCS are extremely diverse. Interventional surgery can improve hearing loss and facial deformity in TCS patients. METHOD: We recruited seven TCS families. Variant screening in probands was performed by targeted next-generation sequencing (NGS). The variants identified were confirmed by Sanger sequencing. The pathogenicity of all the mutations was evaluated using the guidelines of the American College of Medical Genetics and Genomics (ACMG) and InterVar software. RESULTS: Three frameshift variants, two nonsense variants, one missense variant, and one splicing variant of TCOF1 were identified in the seven TCS probands. Five variants including c.1393C > T, c.4111 + 5G>C, c.1142delC, c.2285_2286delCT, and c.1719delG had not been previously reported. Furthermore, we report the c.149A > G variant for the first time in a Chinese TCS patient. We provided prenatal diagnosis for family 4. Proband 7 chose interventional surgery. CONCLUSION: We identified five novel variants in TCOF1 in Chinese patients with TCS, which expands the mutation spectrum of TCOF1 in TCS. Bone conduction hearing rehabilitation can improve hearing for TCS patients and prenatal diagnosis can provide fertility guidance for TCS families.

Rapid Hemostasis Resulting from the Synergism of Self-Assembling Short Peptide and O-Carboxymethyl Chitosan.

The development of novel hemostatic agents with distinct modes of action from traditional ones remains a formidable challenge. Self-assembling peptide hydrogels have emerged as a new hemostatic material, not only because of their inherent biocompatibility and biodegradability but also their designability. Especially, rational molecular design can make peptides and their hydrogelation responsive to biological cues. In this study, we demonstrated that transglutaminase-catalyzed reactions not only occurred among designed short peptide I3QGK molecules but also between the peptide and a natural polysaccharide O-carboxymethyl chitosan. Because Factor XIII in the blood can rapidly convert into activated transglutaminase (Factor XIIIa) upon bleeding, these enzymatic reactions, together with the electrostatic attraction between the two hemostatic agents, induced a strong synergetic effect in promoting hydrogelation, blood coagulation, and platelet adhesion, eventually leading to rapid hemostasis. The study presents a promising strategy for developing alternative hemostatic materials and methods.