Flat silk cocoons: A candidate material for fabricating lightweight and impact-resistant composites.

The utilization of silk cocoons in the production of lightweight and tough composites has been gaining increasing attention. However, the limited applications of normal silk cocoons (NSC) are attributed to their small size and irregular shape. To overcome this deficiency, flat silk cocoons (FSC) with a similar structure and controllable size were prepared. Next, we systematically characterized and compared the microstructures, morphologies, compositions, thermal properties, and mechanical properties of FSC with NSC. Subsequently, FSC was successfully utilized to fabricate a novel silk fibroin fiber reinforced sericin matrix composite (HPFSC) using a hot pressing method, followed by the analysis of its microstructure evolution, mechanical properties, failure modes, and theoretical modeling. This composite has outstanding mechanical properties including hardness, modulus, and strength. HPFSC has a relatively low density of ~1.3 g/cm3, whose absorbed impact energy can reach a maximum value of 11.1 J/mm, exceeding that of most engineering materials, such as aluminum alloy, ceramics, glass, and carbon fiber composites. The exceptional performance of HPFSC can be attributed to the reduced porosity, enhanced bonding between silk fibroin fibers facilitated by sericin, and their structural transformation. This study offers valuable guidance for the fabrication of lightweight and impact-resistant composites using flat silk cocoons.

A PLGA/Silk Fibroin Nanofibre Membrane Loaded with Natural Flavonoid Compounds Extracted from Green Cocoons for Wound Healing.

The use of biodegradable materials combined with natural metabolites in wound dressings has received much attention. Flavonoids (FLs) from green cocoons, as metabolites, have antibacterial, antioxidant, anti-inflammatory, and other pharmacological effects. In this study, composite membranes of FL-loaded polylactic glycolic acid (PLGA)/silk fibroin (SF) were prepared by an electrospinning method. The prepared membranes, including SF, exhibited a good slow-release effect and cytocompatibility. An in vitro evaluation of the FL-loaded PLGA/SF membranes demonstrated good antioxidant, antibacterial, and anti-inflammatory properties. Animal experiments showed that the wound healing rate of PLGA/SF-2.5FL membranes within 15 days was 97.3%, and that of the control group was 72.5%. The PLGA/SF-2.5FL membranes shortened the inflammatory period of a full-layer wound model and promoted skin regeneration and wound healing by downregulating expression of the pro-inflammatory cytokines IL-1ß and TNF-α and promoting expression of the growth factors VEGF, TGF-ß, and EGF. In summary, the PLGA/SF-2.5FL composite nanofibre membrane with anti-inflammatory properties is an ideal wound dressing to promote acute wound healing.

Bioresponsive and transformable coacervate actuated by intestinal peristalsis for targeted treatment of intestinal bleeding and inflammation.

Developing an oral in situ-forming hydrogel that targets the inflamed intestine to suppress bleeding ulcers and alleviate intestinal inflammation is crucial for effectively treating ulcerative colitis (UC). Here, inspired by sandcastle worm adhesives, we proposed a water-immiscible coacervate (EMNs-gel) with a programmed coacervate-to-hydrogel transition at inflammatory sites composed of dopa-rich silk fibroin matrix containing embedded inflammation-responsive core-shell nanoparticles. Driven by intestinal peristalsis, the EMNs-gel can be actuated forward and immediately transform into a hydrogel once contacting with the inflamed intestine to yield strong tissue adhesion, resulting from matrix metalloproteinases (MMPs)-triggered release of Fe3+ from embedded nanoparticles and rearrangement of polymer network of EMNs-gel on inflamed intestine surfaces. Extensive in vitro experiments and in vivo UC models confirmed the preferential hydrogelation behavior of EMNs-gel to inflamed intestine surfaces, achieving highly effective hemostasis, and displaying an extended residence time ( > 48 h). This innovative EMNs-gel provides a non-invasive solution that accurately suppresses severe bleeding and improves intestinal homeostasis in UC, showcasing great potential for clinical applications.

FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species.

FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging.

Pollen-Modified Flat Silk Cocoon Pressure Sensors for Wearable Applications.

Microstructures have been proved as crucial factors for the sensing performance of flexible pressure sensors. In this study, polypyrrole (PPy)/sunflower pollen (SFP) (P/SFP) was prepared via the in situ growth of PPy on the surface of degreased SFP with a sea urchin-like microstructure; then, these P/SFP microspheres were sprayed onto a flat silk cocoon (FSC) to prepare a sensing layer P/SFP-FSC. PPy-FSC (P-FSC) was prepared as an electrode layer through the in situ polymerization of PPy on the FSC surface. The sensing layer P/SFP-FSC was placed between two P-FSC electrode layers to assemble a P/SFP-FSC pressure sensor together with a fork finger electrode. With 6 mg/cm2 of optimized sprayed P/SFP microspheres, the prepared flexible pressure sensor has a sensitivity of up to 0.128 KPa-1 in the range of 0-13.18 KPa and up to 0.13 KPa-1 in the range of 13.18-30.65 KPa, a fast response/recovery time (90 ms/80 ms), and a minimum detection limit as low as 40 Pa. This fabricated flexible P/SFP-FSC sensor can monitor human motion and can also be used for the encrypted transmission of important information via Morse code. In conclusion, the developed flexible P/SFP-FSC pressure sensor based on microstructure modification in this study shows good application prospects in the field of human-computer interaction and wearable electronic devices.

Multiple independent origins of the female W chromosome in moths and butterflies.

Lepidoptera, the most diverse group of insects, exhibit female heterogamy (Z0 or ZW), which is different from most other insects (male heterogamy, XY). Previous studies suggest a single origin of the Z chromosome. However, the origin of the lepidopteran W chromosome remains poorly understood. Here, we assemble the genome from females down to the chromosome level of a model insect (Bombyx mori) and identify a W chromosome of approximately 10.1 megabase using a newly developed tool. In addition, we identify 3593 genes that were not previously annotated in the genomes of B. mori. Comparisons of 21 lepidopteran species (including 17 ZW and four Z0 systems) and three trichopteran species (Z0 system) reveal that the formation of Ditrysia W involves multiple mechanisms, including previously proposed canonical and noncanonical models, as well as a newly proposed mechanism called single-Z turnover. We conclude that there are multiple independent origins of the W chromosome in the Ditrysia (most moths and all butterflies) of Lepidoptera.

Pediococcus pentosaceus ZZ61 enhances growth performance and pathogenic resistance of silkworm Bombyx mori by regulating gut microbiota and metabolites.

Probiotics have attracted considerable attention in animal husbandry due to their positive effect on animal growth and health. This study aimed to screen candidate probiotic strain promoting the growth and health of silkworm and reveal the potential mechanisms. A novel probiotic Pediococcus pentosaceus strain (ZZ61) substantially promoted body weight gain, feed efficiency, and silk yield. These effects were likely mediated by changes in the intestinal digestive enzyme activity and nutrient provisioning (e.g., B vitamins) of the host, improving nutrient digestion and assimilation. Additionally, P. pentosaceus produced antimicrobial compounds and increased the antioxidant capacity to protect the host against pathogenic infection. Furthermore, P. pentosaceus affected the gut microbiome and altered the levels of gut metabolites (e.g., glycine and glycerophospholipids), which in turn promotes host nutrition and health. This study contributes to an improved understanding of the interactions between probiotic and host and promotes probiotic utilization in sericulture.

The BTB-ZF gene Bm-mamo regulates pigmentation in silkworm caterpillars.

The color pattern of insects is one of the most diverse adaptive evolutionary phenotypes. However, the molecular regulation of this color pattern is not fully understood. In this study, we found that the transcription factor Bm-mamo is responsible for black dilute (bd) allele mutations in the silkworm. Bm-mamo belongs to the BTB zinc finger family and is orthologous to mamo in Drosophila melanogaster. This gene has a conserved function in gamete production in Drosophila and silkworms and has evolved a pleiotropic function in the regulation of color patterns in caterpillars. Using RNAi and clustered regularly interspaced short palindromic repeats (CRISPR) technology, we showed that Bm-mamo is a repressor of dark melanin patterns in the larval epidermis. Using in vitro binding assays and gene expression profiling in wild-type and mutant larvae, we also showed that Bm-mamo likely regulates the expression of related pigment synthesis and cuticular protein genes in a coordinated manner to mediate its role in color pattern formation. This mechanism is consistent with the dual role of this transcription factor in regulating both the structure and shape of the cuticle and the pigments that are embedded within it. This study provides new insight into the regulation of color patterns as well as into the construction of more complex epidermal features in some insects.

Disruption of Zfh3 abolishes mulberry-specific monophagy in silkworm larvae.

Feeding behavior is critical for insect survival and fitness. Most researchers have explored the molecular basis of feeding behaviors by identifying and elucidating the function of olfactory receptors (ORs) and gustatory receptors (GRs). Other types of genes, such as transcription factors, have rarely been investigated, and little is known about their potential roles. The silkworm (Bombyx mori) is a well-studied monophagic insect which primarily feeds on mulberry leaves, but the genetic basis of its monophagy is still not understood. In this report, we focused on a transcription factor encoded by the Zfh3 gene, which is highly expressed in the silkworm central and peripheral nervous systems, including brain, antenna, and maxilla. To investigate its function, Zfh3 was abrogated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9) mutagenesis. Since Zfh3 knockout homozygotes are not viable, we studied feeding behavior in heterozygotes, and found that disruption of Zfh3 affects both gustation and olfaction. Mutant larvae lose preference for mulberry leaves, acquire the ability to consume an expanded range of diets, and exhibit improved adaptation to the M0 artificial diet, which contains no mulberry leaves. These results provide the first demonstration that a transcription factor modulates feeding behaviors in an insect.

Effects of reactive oxygen species and mitochondrial dysfunction on reproductive aging.

Mitochondria, the versatile organelles crucial for cellular and organismal viability, play a pivotal role in meeting the energy requirements of cells through the respiratory chain located in the inner mitochondrial membrane, concomitant with the generation of reactive oxygen species (ROS). A wealth of evidence derived from contemporary investigations on reproductive longevity strongly indicates that the aberrant elevation of ROS level constitutes a fundamental factor in hastening the aging process of reproductive systems which are responsible for transmission of DNA to future generations. Constant changes in redox status, with a pro-oxidant shift mainly through the mitochondrial generation of ROS, are linked to the modulation of physiological and pathological pathways in gametes and reproductive tissues. Furthermore, the quantity and quality of mitochondria essential to capacitation and fertilization are increasingly associated with reproductive aging. The article aims to provide current understanding of the contributions of ROS derived from mitochondrial respiration to the process of reproductive aging. Moreover, understanding the impact of mitochondrial dysfunction on both female and male fertility is conducive to finding therapeutic strategies to slow, prevent or reverse the process of gamete aging, and thereby increase reproductive longevity.

Mulberry Leaf Lipid Nanoparticles: a Naturally Targeted CRISPR/Cas9 Oral Delivery Platform for Alleviation of Colon Diseases.

Oral treatment of colon diseases with the CRISPR/Cas9 system has been hampered by the lack of a safe and efficient delivery platform. Overexpressed CD98 plays a crucial role in the progression of ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC). In this study, lipid nanoparticles (LNPs) derived from mulberry leaves are functionalized with Pluronic copolymers and optimized to deliver the CRISPR/Cas gene editing machinery for CD98 knockdown. The obtained LNPs possessed a hydrodynamic diameter of 267.2 nm, a narrow size distribution, and a negative surface charge (-25.6 mV). Incorporating Pluronic F127 into LNPs improved their stability in the gastrointestinal tract and facilitated their penetration through the colonic mucus barrier. The galactose end groups promoted endocytosis of the LNPs by macrophages via asialoglycoprotein receptor-mediated endocytosis, with a transfection efficiency of 2.2-fold higher than Lipofectamine 6000. The LNPs significantly decreased CD98 expression, down-regulated pro-inflammatory cytokines (TNF-α and IL-6), up-regulated anti-inflammatory factors (IL-10), and polarized macrophages to M2 phenotype. Oral administration of LNPs mitigated UC and CAC by alleviating inflammation, restoring the colonic barrier, and modulating intestinal microbiota. As the first oral CRISPR/Cas9 delivery LNP, this system offers a precise and efficient platform for the oral treatment of colon diseases.

Flat-Silk-Cocoon-Based Wearable Flexible Piezoresistive Sensor and Its Performance.

Flexible sensors are becoming the focus of research because they are very vital for intelligent products, real-time data monitoring, and recording. The flat silk cocoon (FSC), as a special form of cocoon, has all the advantages of silk, which is an excellent biomass carbon-based material and a good choice for preparing flexible sensors. In this work, a flexible piezoresistive sensor was successfully prepared by encapsulating carbonized flat silk cocoons (CFSCs) using an elastic matrix polydimethylsiloxane (PDMS). The sensing performance of the material is 0.01 kPa-1, and the monitoring range can reach 680.57 kPa. It is proved that the sensor can detect human motion and has excellent durability (>800 cycles). In addition, a sensor array for a keyboard based on CFSCs was explored. The sensor has a low production cost and a simple preparation process, and it is sustainable and environmentally friendly. Thus, it may have potential applications in wearable devices and human-computer interactions.

Cyclin B3 plays pleiotropic roles in female reproductive organogenesis and early embryogenesis in the silkworm, Bombyx mori.

BACKGROUND: The reproductive system plays a crucial role in insect survival, reproduction and species specificity. Understanding the molecular mechanisms underlying reproductive organogenesis contributes to improving the efficiency of sterile insect technique marked by an eco-friendly pest management strategy. Lepidoptera is one of the largest orders of insects, most of which are major pests in agriculture and forestry. Our study aimed to screen the genes responsible for reproductive organogenesis and unravel the mechanism underlying female reproductive organ defects. RESULTS: Morphological investigation of female reproductive organs showed a defective connection between oviductus geminus and oviductus communis on the second day of pupa (P2) in Speckled mutant silkworm. RNA_Seq identified a total of 18 049 transcripts that were expressed in the P2 female internal reproductive organs without ovary in Spc/+ compared to +Spc /+Spc . Differential expression analysis identified 312 up-regulated genes and 221 down-regulated genes in Spc/+. KEGG analysis identified 44 significantly enriched pathways. The results of qRT-PCR performed on 33 genes significantly matched the outcomes of the RNA_Seq. Dysfunction of Cyclin B3 resulted in a defective connection of the oviductus communis with the ovariole, dysfunction of oogenesis, and a petite body. Moreover, homozygous recessive lethality of Cyclin B3/Cyclin B3 occurred during early embryogenesis. CONCLUSION: Our results suggest that Cyclin B3 is a pleiotropic functional gene that regulates early embryogenesis, oogenesis, development, and female reproductive organogenesis. These results showed that Cyclin B3 has significant effects on lepidopteran mortality, growth, and reproductive physiology, which might be considered a novel and potentially eco-friendly target for lepidopteran pest management. © 2023 Society of Chemical Industry.

The Enhancement Mechanism of Different Single-Transition Metal Atomic Catalysts/Sulfur Cathode on High-Performance of Li-S Batteries.

Materials with various single-transition metal atoms dispersed in nitrogenated carbons (M─N─C, M = Fe, Co, and Ni) are synthesized as cathodes to investigate the electrocatalytic behaviors focusing on their enhancement mechanism for performance of Li-S batteries. Results indicate that the order of both electrocatalytic activity and rate capacity for the M─N─C catalysts is Co > Ni > Fe, and the Co─N─C delivers the highest capacity of 1100 mAh g-1 at 1 C and longtime stability at a decay rate of 0.05% per cycle for 1000 cycles, demonstrating excellent battery performance. Theoretical calculations for the first time reveal that M─N─N─C catalysts enable direct conversion of Li2 S6 to Li2 S rather than Li2 S4 to Li2 S by stronger adsorption with Li2 S6 , which also has an order of Co > Ni > Fe. And Co─N─C has the strongest adsorption energy, not only rendering the highest electrocatalytic activity, but also depressing the polysulfides' dissolution into electrolyte for the longest cycle life. This work offers an avenue to design the next generation of highly efficient sulfur cathodes for high-performance Li-S batteries, while shedding light on the fundamental insight of single metal atomic catalytic effects on Li-S batteries.

Salidroside promotes healthy longevity by interfering with HSP90 activity.

Aging is a risk factor for human health and quality of life. Screening and development of novel supplements and medications to combat aging and delay the incidence of age-related diseases are of great significance. In this study, salidroside (SA), a primary natural small molecule from Rhodiola rosea, was investigated regarding its effects on life and healthspan and the underlying molecular mechanism(s) of anti-aging and antioxidation. Our results showed that SA effectively prolonged lifespan and exhibited anti-aging and antioxidative properties. Computer-assisted methods, label-free interaction analysis, and in vitro assays showed that SA directly bound heat shock protein 90 (HSP90). Furthermore, SA significantly inhibited the ATPase activity of HSP90, affecting the interaction between HSP90 and its interacting proteins and the expression of downstream genes to regulate lifespan and the oxidative stress response. Our findings provided new insights into the pharmacological properties of SA across multiple species and its potential as an anti-aging drug.

Super silkworm cocoons constructed by multi-silkworm larvae: Promising composites with dense structures and excellent mechanical properties.

A normal silkworm cocoon (NSC) with a unique nonwoven structure is usually spun by a single silkworm larva. Notably, there is a special Bombyx mori genetic resource that many (three or more) mature larvae tend to collectively spin into one cocoon, which was named "multi-silkworm cocoon" ("MSC"). However, the MSCs display loose structure and poor mechanical properties which limits their further application. In this study, a series of hybrid silkworm cocoons (HMSCs) are obtained by hybridizing "MSC" with a selected commercial silkworm strain successfully. The morphology, microstructures, and mechanical properties of cocoons constructed by one to three silkworm larvae were characterized and compared. The results indicated that about 48.3 % of silkworm larvae could create double and triple cocoons in the F1 generation of the silkworm hybrid, displaying robust fiber networks and dense structures. The mechanical characteristics of the HMSCs, including the tensile, peeling, compression, and needle penetration resistance properties, exceeded those of MSCs, showing significant application potential for high-performance bio-composites. This study provides a practical approach for obtaining silkworm cocoons with controllable structures and mechanical properties to develop and fabricate natural composite and biomimetic materials.

SilkMeta: a comprehensive platform for sharing and exploiting pan-genomic and multi-omic silkworm data.

The silkworm Bombyx mori is a domesticated insect that serves as an animal model for research and agriculture. The silkworm super-pan-genome dataset, which we published last year, is a unique resource for the study of global genomic diversity and phenotype-genotype association. Here we present SilkMeta (http://silkmeta.org.cn), a comprehensive database covering the available silkworm pan-genome and multi-omics data. The database contains 1082 short-read genomes, 546 long-read assembled genomes, 1168 transcriptomes, 294 phenotype characterizations (phenome), tens of millions of variations (variome), 7253 long non-coding RNAs (lncRNAs), 18 717 full length transcripts and a set of population statistics. We have compiled publications on functional genomics research and genetic stock deciphering (mutant map). A range of bioinformatics tools is also provided for data visualization and retrieval. The large batch of omics data and tools were integrated in twelve functional modules that provide useful strategies and data for comparative and functional genomics research. The interactive bioinformatics platform SilkMeta will benefit not only the silkworm but also the insect biology communities.

Integrated Analysis of Machine Learning and Deep Learning in Silkworm Pupae (Bombyx mori) Species and Sex Identification.

Hybrid pairing of the corresponding silkworm species is a pivotal link in sericulture, ensuring egg quality and directly influencing silk quantity and quality. Considering the potential of image recognition and the impact of varying pupal postures, this study used machine learning and deep learning for global modeling to identify pupae species and sex separately or simultaneously. The performance of traditional feature-based approaches, deep learning feature-based approaches, and their fusion approaches were compared. First, 3600 images of the back, abdomen, and side postures of 5 species of male and female pupae were captured. Next, six traditional descriptors, including the histogram of oriented gradients (HOG), and six deep learning descriptors, including ConvNeXt-S, were utilized to extract significant species and sex features. Finally, classification models were constructed using the multilayer perceptron (MLP), support vector machine, and random forest. The results indicate that the {HOG + ConvNeXt-S + MLP} model excelled, achieving 99.09% accuracy for separate species and sex recognition and 98.40% for simultaneous recognition, with precision-recall and receiver operating characteristic curves ranging from 0.984 to 1.0 and 0.996 to 1.0, respectively. In conclusion, it can capture subtle distinctions between pupal species and sexes and shows promise for extensive application in sericulture.

Novel Bioinspired Nerve Scaffold with High Synchrony between Biodegradation and Nerve Regeneration for Repair of Peripheral Nerve Injury.

The morphological structure reconstruction and functional recovery of long-distance peripheral nerve injury (PNI) are global medical challenges. Biodegradable nerve scaffolds that provide mechanical support for the growth and extension of neurites are a desired way to repair long-distance PNI. However, the synchrony of scaffold degradation and nerve regeneration is still challenging. Here, a novel bioinspired multichannel nerve guide conduit (MNGC) with topographical cues based on silk fibroin and ε-polylysine modification was constructed. This conduit (SF(A) + PLL MNGC) exhibited sufficient mechanical strength, excellent degradability, and favorable promotion of cell growth. Peripheral nerve repairing was evaluated by an in vivo 10 mm rat sciatic model. In vivo evidence demonstrated that SF(A) + PLL MNGC was completely biodegraded in the body within 4 weeks after providing sufficient physical support and guide for neurite extension, and a 10 mm sciatic nerve defect was effectively repaired without scar formation, indicating a high synchronous effect of scaffold biodegradation and nerve regeneration. More importantly, the regenerated nerve of the SF(A) + PLL MNGC group showed comparable morphological reconstruction and functional recovery to that of autologous nerve transplantation. This work proved that the designed SF(A) + PLL MNGC has potential for application in long-distance PNI repair in the clinic.

A tool to automatically design multiplex PCR primer pairs for specific targets using diverse templates.

Multiplex PCR is an increasingly popular method for identifying species, investigating environmental diversity, and conducting phylogenetic analysis. The complexity and increasing availability of diverse templates necessitate a highly automated approach to design degenerate primer pairs for specific targets with multiple sequences. Existing tools for degenerate primer design suffer from poor maintenance, semi-automation, low adaptability, and low tolerance for gaps. We developed PMPrimer, a Python-based tool for automated design and evaluation of multiplex PCR primer pairs for specific targets using diverse templates. PMPrimer automatically designs optimal multiplex PCR primer pairs using a statistical-based template filter; performs multiple sequence alignment, conserved region identification, and primer design; and evaluates the primers based on template coverage, taxon specificity, and target specificity. PMPrimer identifies conserved regions using Shannon's entropy method, tolerates gaps using a haplotype-based method, and evaluates multiplex PCR primer pairs based on template coverage and taxon specificity. We tested PMPrimer using datasets with diverse levels of conservation, sizes, and applications, including tuf genes of Staphylococci, hsp65 genes of Mycobacteriaceae, and 16S ribosomal RNA genes of Archaea. PMPrimer showed outstanding performance compared with existing tools and experimental validated primers. PMPrimer is available as a Python package at https://github.com/AGIScuipeng/PMPrimer .