Deciphering disulfidptosis: Uncovering a lncRNA-based signature for prognostic assessment, personalized immunotherapy, and therapeutic agent selection in lung adenocarcinoma patients.

BACKGROUND: Disulfidptosis, a recently identified type of regulated cell death, plays critical roles in various biological processes of cancer; however, whether they can impact the prognosis of lung adenocarcinoma (LUAD) remains to be fully elucidated. We aimed to adopt this concept to develop and validate a lncRNA signature for LUAD prognostic prediction. METHODS: For this study, the TCGA-LUAD dataset was used as the training cohort, and multiple datasets from the GEO database were pooled as the validation cohort. Disulfidptosis regulated genes were obtained from published studies, and various statistical methods, including Kaplan-Meier (KM), Cox, and LASSO, were used to train our gene signature DISULncSig. We utilized KM analysis, COX analysis, receiver operating characteristic analysis, time-dependent AUC analysis, principal component analysis, nomogram predictor analysis, and functional assays in our validation process. We also compared DISULncSig with previous studies. We performed analyses to evaluate DISULncSig's immunotherapeutic ability, focusing on eight immune algorithms, TMB, and TIDE. Additionally, we investigated potential drugs that could be effective in treating patients with high-risk scores. Additionally qRT-PCR examined the expression patterns of DISULncSig lncRNAs, and the ability of DISULncSig in pan-cancer was also assessed. RESULTS: DISULncSig containing twelve lncRNAs was trained and showed strong predictive ability in the validation cohort. Compared with previous similar studies, DISULncSig had more prognostic ability advantages. DISULncSig was closely related to the immune status of LUAD, and its tight relationship with checkpoints KIR2DL3, IL10, IL2, CD40LG, SELP, BTLA, and CD28 may be the key to its potential immunotherapeutic ability. For the high DISULncSig score population, we found ten drug candidates, among which epothilone-b may have the most potential. The pan-cancer analysis found that DISULncSig was a risk factor in multiple cancers. Additionally, we discovered that some of the DISULncSig lncRNAs could play crucial roles in specific cancer types. CONCLUSION: The current study established a powerful prognostic DISULncSig signature for LUAD that was also valid for most pan-cancers. This signature could serve as a potential target for immunotherapy and might help the more efficient application of drugs to specific populations.

Silky Liquid Metal Electrodes for On-Skin Health Monitoring.

Next generation on-skin electrodes will require soft, flexible, and gentle materials to provide both high-fidelity sensing and wearer comfort. However, many commercially available on-skin electrodes lack these key properties due to their use of rigid hardware, harsh adhesives, uncomfortable support structures, and poor breathability. To address these challenges, this work presents a new device paradigm by joining biocompatible electrospun spider silk with printable liquid metal to yield an incredibly soft and scalable on-skin electrode that is strain-tolerant, conformable, and gentle on-skin. These electrodes, termed silky liquid metal (SLiM) electrodes, are found to be over five times more breathable than commercial wet electrodes, while the silk's intrinsic adhesion mechanism allows SLiM electrodes to avoid the use of harsh artificial adhesives, potentially decreasing skin irritation and inflammation over long-term use. Finally, the SLiM electrodes provide comparable impedances to traditional wet and other liquid metal electrodes, offering a high-fidelity sensing alternative with increased wearer comfort. Human subject testing confirmed the SLiM electrodes ability to sense electrophysiological signals with high fidelity and minimal irritation to the skin. The unique properties of the reported SLiM electrodes offer a comfortable electrophysiological sensing solution especially for patients with pre-existing skin conditions or surface wounds.

Silk fibroin nanoparticles and ß-tricalcium phosphate loaded tissue engineered gelatin bone scaffolds: A Nature-based, low-cost solution.

Tissue engineering has recently attracted attention as an alternative to traditional treatment methods for tissue and organ damage. Since bone is one of the most important vital parts of the body, the treatment of bone damage is important. Silk fibroin is a natural polymer with properties such as biocompatibility and biodegradability, which attracts attention with its controlled release, especially in drug delivery systems. In this study, gelatin-based scaffolds loaded with silk fibroin nanoparticles and ß -tricalcium phosphate (ß -TCP) were developed to be used as a potential drug delivery system in bone tissue engineering. The chosen nanoparticle formulation has a 294 nm average diameter with a 0.380 polidispersity index (PDI). In vitro characterization of scaffolds was performed by mechanical, morphological characterization, swelling capacity, Differential Scanning Calorimetry (DSC), Fourier-Transform Infrared Spectroscopy (FT-IR) measurements, and biocompatibility was evaluated by cell culture studies. Swelling index, tensile strength, elongation at break, and Young modulus of the ß -TCP and silk nanoparticles loaded scaffold were found as 456%, 1.476 MPa, 6.75%, and 24 MPa, respectively. In vitro cell culture studies have shown that scaffolds prepared in the present study can accelerate osteoblast differentiation and increase the healing rate of bone tissues. In addition, they have the potential to be used as a drug delivery system in bone tissue engineering that needs to be evaluated with further studies.

Large-scale and cost-effective production of recombinant human serum albumin (rHSA) in transgenic Bombyx mori cocoons.

HSA is considered a versatile natural cargo carrier with multiple bio-functions and applications. However, insufficient supply of HSA has limited widespread use. Although various recombinant expression systems had been applied to produce the rHSA to overcome the limited resource, cost-effective and large scale production of rHSA remains a challenge. Herein, we provide a strategy for the large-scale and cost-effective production of rHSA in cocoons of transgenic silkworms, achieving a final 13.54 ± 1.34 g/kg of rHSA yield in cocoons. rHSA was efficiently synthesized and stable over the long-term in the cocoons at room temperature. Artificial control of silk crystal structure during silk spinning significantly facilitated rHSA extraction and purification, with 99.69 ± 0.33 % purity and a productivity of 8.06 ± 0.17 g rHSA from 1 kg cocoons. The rHSA had the same secondary structure to natural HSA, along with effective drug binding capacity, biocompatibility, and bio-safe. The rHSA was successfully evaluated as a potential substitute in serum-free cell culture. These findings suggest the silkworm bioreactor is promising for large-scale and cost-effective production of high quality rHSA to meet the increased worldwide demand.

Eco-geological consequences of textile processing wastes: Risk assessment, elemental dissolution kinetics, and health hazard potential.

Although substantial quantities of toxic wastes are generated from textile industries, the characteristics of textile processing wastes (TPWs) have yet scantily been investigated from ecological and agricultural perspectives. Here, the eco-geological consequences of TPWs are evaluated by considering three types of sludges (i.e., silk fibre sludge (SFS), dye mixed silk processing sludge (DSPS), and cotton processing wastewater sludge (CPWS)). The predominance of certain components between different wastes (e.g., fibrous substances in silk industry wastes (i.e., SFS and DSPS) and amorphous materials in cotton processing wastes (i.e., CPWS)) is accounted for by the use of different raw materials in different industries. According to the FTIR and other characterization analyses, all three types of TPWs were rich in carbonaceous compounds and nutrients (e.g., CNPK) because of their biological origin. Further, high accumulation of toxic metals (e.g., Cd, Cr, Cu, Zn, Pb, and Mn) was apparent with chemical-processing routes. The principal component analysis indicated strong relationships between certain environmental variables (e.g., moisture content and bulk density) and bioavailability of several metals (e.g., Cd, Zn, Cu, and Mn), while C levels in TPWs were tightly associated with Cr levels. According to the Visual MINTEQ model, the dissolution-precipitation dynamics of potentially toxic elements (e.g., Pb, Cr, and Zn) in TPWs are predicted to be controlled by the levels of phosphates/chlorides/sulphates in line with the textile processing steps employed in different factories. The great toxicity potential of CPWS (e.g., relative to SFS and DSPS) is recognized to pose significant metal-induced hazards to ecosystems and human health over time. Among the three TPWs, SFS could be prescribed for agricultural application after proper treatment (e.g., via valorization techniques) with the aid of its benign nature and high nutrient (Total N: 3.83%; available P: 118.6 mg kg-1) value.

Exchanges of economic plants along the land silk road.

BACKGROUD: The greatest contribution of the Silk Road is to communicate among different countries and nationalities, and promote two-way cultural exchanges between the East and the West. We now have clearer understanding about how material civilization and religious culture of Central Asia and West Asia spread eastward along the Land Silk Road. However, there is controversial about how crops migrate along the Land Silk Road. RESULTS: We summarize archaeology, genetics, and genomics data to explore crop migration patterns. Of the 207 crops that were domesticated along the Land Silk Road, 19 for which genomic evidence was available were selected for discussion. CONCLUSIONS: There were conflicting lines of evidence for the domestication of Tibetan barley, mustard, lettuce, buckwheat, and chickpea. The main reasons for the conflicting results may include incomplete early knowledge, record differences in different period, sample sizes, and data analysis techniques. There was strong evidence that Tibetan barley, barley, wheat, and jujube were introduced into China before the existence of the Land Silk Road; and mustard, lettuce, buckwheat, chickpea, alfalfa, walnut, cauliflower, grape, spinach, apple, cucumber, mulberry, and pea spread to China via trade and human migration along the Land Silk Road.

Geo-Economic Linkages between China and the Countries along the 21st-Century Maritime Silk Road and Their Types.

With the advances of the Belt and Road Initiative (BRI), the geo-economic interactions between China and countries along the 21st-Century Maritime Silk Road counties (MSRCs) continue to increase, and analyzing the geo-economic relations between China and the MSRCs is extremely important for a scientific understanding of bilateral geo-economic cooperation. Differently from the traditional logic of geo-economic competition and cooperation, we constructed a new framework based on the dominant factors of geo-economic relations and used an extreme random forest regression model to classify the geo-economic relation types between China and MSRCs from 2006 to 2017. The results show that the unbalanced development of investment and trade between China and MSRCs hindered the enhancement of the intensity of bilateral geo-economic linkage from 2006 to 2017. The "Matthew effect" of China's geo-economic flow linkage with MSRCs is significant. There are obvious differences in the dominant factors affecting the types of geo-economic relations between China and MSRCs, and the distribution of the importance of the indices of the types of geo-economic relations in each country is disordered. Geopolitics, markets, and resources have played important roles in the geo-economic linkages between China and MSRCs. There are five types of geo-economic relations between China and the MSRCs: market-oriented type, resource-oriented type, market-resource-oriented type, market-geopolitics-oriented type, and resource-geopolitics-oriented type, of which the market-oriented type is the most important type of geo-economic relations. In the future, China should focus on regional powers along the Maritime Silk Road for bilateral geo-economic cooperation, actively promote the balanced development of bilateral geo-economic elements flows, strengthen geopolitical cooperation with MSRCs, and formulate cooperation plans according to the types of geo-economic relations.

The Multiple Cooperative Mechanism and Globalization Path of Small Inland Cities in China: A Showcase Study of Dunhuang, China.

Currently, urbanization driven by global capital flows entails a main trend in many large cites in China, while global capital investment in small inland cities especially in western China is extremely scarce, where their globalization characters the powerful nationalization power and market activation. Dunhuang, a small inland city in western China, has transformed successfully from an agricultural county to an international tourist city, a platform for worldwide cultural communication, and a node city in the Belt and Road region because of its unique and brilliant resources: Mogao Grottoes and Dunhuangology. Therefore, this paper develops a conceptual framework of the multiple cooperative mechanisms and globalization path (MCMGP) of Dunhuang, elaborating the process of industrial transformation, urban globalization, and multiple cooperative mechanisms between government and market actors based on interviewing records and statistics. Findings show that the MCMGP features government-led intervention, resource orientation, and centralization that embodies the driver of state-owned enterprises (SOEs). Also, the MCM in Dunhuang's globalization contains the mechanism of enrolment, mobilization and action, governance and global marketing, distributed in the two phases. Equally important, in response to the Belt and Road Initiative (BRI) and Silk Road (Dunhuang) International Cultural Expo (SRDICE) from the state, the city government has significantly reinvested and refined cultural tourism via governance mechanisms, carving out a key node city in the Silk Road and elevating an international tourist city. Environmentally, Dunhuang's tourism internationalization enhances the process of the development of a sustainable shared mobility industry. Furthermore, its tourism development and social-ecology system maintain the synergistic relationships which international tourism promotes such as urban ecosystem and public welfare and in turn, social-ecological enhancement serve Dunhuang's international tourism well. Practical implications of how Dunhuang's experience may have lessons for others are discussed in China's peculiar socialist market economy discourse.

Towards a green world: the impact of the Belt and Road Initiative on the carbon intensity reduction of countries along the route.

The Belt and Road Initiative (BRI) has attracted widespread attention since its implementation, especially the ecological effect. However, the net environmental impact of the BRI on countries along the route has rarely been directly assessed, though nearly 8 years after the BRI was proposed. This study quantitatively estimates the net effect, impact mechanism, and impact heterogeneity of the BRI on the carbon intensity reduction of countries along the route by adopting the difference-in-differences estimator based on propensity score matching, which enables a more convincing causal relationship between the BRI and the countries' ecological improvement. Research indicates that the BRI has significantly promoted the carbon intensity reduction of countries along the route, which is mainly achieved by boosting the growth of green economy (scale effect), the progress of green technology (technique effect), and the upgrading of industrial structure (composition effect). Moreover, the impact reveals obvious heterogeneity, manifested as the BRI has significantly promoted the carbon intensity reduction of countries with high institutional quality, high-income countries, and countries along the Silk Road Economic Belt, while its impacts on countries with low institutional quality, low-income countries, and countries along the 21st Century Maritime Silk Road are not significant. A series of validity tests further demonstrate the robustness of the estimation.

Economies of scale shape energetics of solitary and group-living spiders and their webs.

Metabolic scaling, whereby larger individuals use less energy per unit mass than smaller ones, may apply to the combined metabolic rate of group-living organisms as group size increases. Spiders that form groups in high disturbance environments can serve to test the hypothesis that economies of scale benefit social groups. Using solitary and group-living spiders, we tested the hypothesis that spiders exhibit negative allometry between body or colony mass and the standing mass of their webs and whether, and how, such a relationship may contribute to group-living benefits in a cooperative spider. Given the diverse architecture of spider webs-orb, tangle and sheet-and-tangle, and associated differences in silk content, we first assessed how standing web mass scales with spider mass as a function of web architecture and whether investment in silk differs among web types. As group-living spiders are predominantly found in clades that build the presumably costlier sheet-and-tangle webs, we then asked whether cost-sharing through cooperative web maintenance contributes to a positive energy budget in a social species. We found that larger spiders had a relatively smaller investment in silk per unit mass than smaller ones, but more complex sheet-and-tangle webs contained orders of magnitude more silk than simpler orb or tangle ones. In the group-living species, standing web mass per unit spider mass continued to decline as colony size increased with a similar slope as for unitary spiders. When web maintenance activities were considered, colonies also experienced reduced mass-specific energy expenditure with increasing colony size. Activity savings contributed to a net positive energy balance for medium and large colonies after inputs from the cooperative capture of large prey were accounted for. Economies of scale have been previously demonstrated in animal societies characterized by reproductive and worker castes, but not in relatively egalitarian societies as those of social spiders. Our findings illustrate the universality of scaling laws and how economies of scale may transcend hunting strategies and levels of organization.

Morus alba: Host reaction for Meloidogyne javanica, biological nematicides assessment and study of these relationships with yield and quality of leaves, cocoon and health of the silkworm.

Root-knot nematodes cause damage to several crops and the importance of each species can vary according with the crop and the agricultural region. In Brazil, Meloidogyne javanica is one of the most important nematode species parasitizing mulberry. To define management strategies, it is important to know if the crop species is damaged by the parasitism of the nematode and the best choices for control, as the use of nematicides. Biological nematicides have been extensively used in Brazil, but no information regarding its efficiency to control M. javanica in mulberry is available. Besides, it is not known if biological nematicides could improve the quality of leaves or if they alter the nutrient composition of leaves, which could interfere in the development of the silkworms that are feed with these leaves or in the quality of the silk produced. With the aim to address these questions, we propose a study that will start in the phenotyping of the main Brazilian mulberry cultivars to Meloidogyne species, passing through the test of efficiency of biological nematicides in the control of M. javanica in mulberry cultivar Miura, evaluation of the amount and quality of leaves produced and, using these leaves to feed silkworms, in the analyzes of the impact of these diet in the health of silkworms, and in the production and quality of the silk.

Comparative assessment between bio-adhesive material and silk suture in regard to healing, clinical attachment level and width of keratinized gingiva in gingival recession defects cases.

The objective of this study was to compare the silk suture with a cyanoacrylate adhesive to stabilize the free gingival graft in conjunction with Er: YAG laser-assisted recipient site preparation to augment the keratinized tissue in gingival recession cases. This randomized trial comprised of 300 recession defects patients. All the included patients were diagnosed using Miller class I and II gingival recession defects classification. Group I sites were treated with a free gingival graft (FGG) harvested using an Er: YAG laser and further sutured with silk. Group II sites were stabilized with isoamyl 2 cyanoacrylate bio-adhesive material. Clinical parameters, such as gingival recession depth, clinical attachment level, gain in gingival tissue thickness, and width of keratinized gingiva were recorded at baseline, and at third month, sixth month, and 12th month postoperatively. The mean changes in gingival recession from months 3 to 6 and months and 6 to 12 were significant (p < 0.05) in both groups. However, the improvement in recession depth was better in group II than in group I. The mean change in clinical attachment level did not differ significantly between the groups at the different time intervals. However, values tended to be higher in group II than in group I. The width of the keratinized gingiva tended to be higher from baseline to 3 months, baseline to 6 months, baseline to 12 months, 3 to 6 months, and from 6 to 12 months in group II as compared with group I (p > 0.05). Cyanoacrylate could be used as a substitute to silk sutures to stabilize FGGs. Cyanoacrylate was easy to apply, consumed less operating time, and was considered equally efficacious for stabilizing FGGs.

Safety Assessment of Silk Protein Ingredients as Used in Cosmetics.

The Expert Panel for Cosmetic Ingredient Safety (Panel) reviewed the safety of Hydrolyzed Silk and 9 other silk protein ingredients, which function primarily as skin and hair conditioning agents and bulking agents in cosmetic products. The Panel reviewed relevant data relating to the safety of these ingredients and concluded that 8 ingredients are safe in the present practices of use and concentration in cosmetics, as described in this safety assessment, but that the available data are insufficient for determining the safety of 2 silk protein ingredients in cosmetic products, MEA-Hydrolyzed Silk and Silkworm Cocoon Extract.

Transcriptomics and proteomics-based analysis of heterosis on main economic traits of silkworm, Bombyx mori.

The application of silkworm hybrids have promoted the innovation and development of agricultural technology, but the mechanism of heterosis in silkworm has not been explained clearly. In this study, the heterosis of silkworm in the aspects of body weight, silk gland and cocoon weight was investigated by means of silkworm hybridization and multi-omics approaches, including transcriptome and proteome. The results showed that heterosis of silkworm body weight, silk gland and cocoon weight was overdominant, but only part of genes and proteins were overdominant, and most of genes and proteins were non-additive. Combined analysis obtained six up-regulated genes and four down-regulated genes that were consistent both in transcriptome and proteome. Gene functional enrichment analysis indicated that most up-regulated genes and proteins were mostly related to metabolism, which led to accelerated metabolism and protein synthesis and contributing to improved heterosis. The up-regulation of 6-phosphate glucose dehydrogenase (G6PDH), phosphatidylethanolamine-binding protein (PEBP) and sHSP20.4, which are involved in metabolism, might be related to silk gland heterosis. SIGNIFICANCE: A combination of transcriptomic and proteomic analysis was used to understand the molecular mechanism of silkworm heterosis. We found that the phenotypic traits of silkworm are overdominant, while the analysis of transcriptome and proteome showed that only part of genes and proteins were overdominant, and most of genes and proteins were non-additive. Some of the genes had unique expression in F1, which was speculated that genes under heterozygous condition may result in rearrangement and cause metabolic changes in the hybrids. Those both up-regulated in transcriptomic and proteomic analysis were found to be involved in various metabolic processes, so as to accelerate metabolism and protein synthesis, thus exhibiting heterosis.

Development of the PVA/CS nanofibers containing silk protein sericin as a wound dressing: In vitro and in vivo assessment.

Skin and soft tissue infections are major concerns with respect to wound repair. Recently, anti-bacterial wound dressings have been emerging as promising candidates to reduce infection, thus accelerating the wound healing process. This paper presents our work to develop and characterize poly(vinyl alcohol) (PVA)/chitosan (CS)/silk sericin (SS)/tetracycline (TCN) porous nanofibers, with diameters varying from 305 to 425 nm, both in vitro and in vivo for potential applications as wound dressings. The fabricated nanofibers possess a considerable capacity to take up water through swelling (~325-650%). Sericin addition leads to increased hydrophilicity and elongation at break while decreasing fiber diameter and mechanical strength. Moreover, fibroblasts (L929) cultured on the nanofibers with low sericin content (PVA/CS/1-2SS) displayed greater proliferation compared to those on nanofibers without sericin (PVA/CS). Nanofibers loaded with high sericin and tetracycline content significantly inhibited the growth of Escherichia coli and Staphylococcus aureus. In vivo examination revealed that PVA/CS/2SS-TCN nanofibers enhance wound healing, re-epithelialization, and collagen deposition compared to traditional gauze and nanofibers without sericin. The results of this study demonstrate that the PVA/CS/2SS-TCN nanofiber creates a promising alternative to traditional wound dressing materials.

A simple and novel technique for training in microvascular suturing in a rat model.

BACKGROUND: Though microvascular clamps are widely used for anastomosis training, there still have several shortcomings, including the bulging, expensiveness and unavailability due to sterilization. The aim of this study is to introduce a simple and novel microvascular training model without use of microvascular clamps. METHODS: Femoral vessels of Sprague Dawley rats training model were used to evaluate the usefulness of 4-0 silk as a slipknot for performing arterio-arterial and veno-venous microvascular anastomoses. A total of 12 Sprague Dawley rats were randomly assigned to either slipknot group or vascular clamp group. We also assess other endpoints, including ischemic time, patency rate, and clinical features. An additional histological study was performed to compare their immediate traumatic effects on vessel wall. RESULTS: There was no ischemic change or congestive sign in the lower limb after microvascular anastomosis. The total warm ischemic time for the vascular anastomosis was not significantly different. We performed the patency test immediately after microvascular anastomosis and one week after surgery. No intraoperative vascular bleeding was found during these procedures and no thrombosis occurred postoperatively. The histologic damages to occluded area were not significantly different in both groups. CONCLUSION: We demonstrate a microsurgical suture technique performed without any vascular clamp on a rat model. This rat model was designed for training in the technique of microvascular anastomosis. Compared with microvascular clamps, silk slipknot is a cheap, easily available, less space-occupying technique while performing microvascular anastomoses training. This preliminary study provides a simple and effective alternative method for microvascular anastomosis training.

Preclinical assessment of resorbable silk splints for the treatment of pediatric tracheomalacia.

OBJECTIVE: Tracheomalacia is characterized by weakness of the tracheal wall resulting in dynamic airway collapse during respiration; severe cases often require surgical intervention. Off-label external splinting with degradable implants has been reported in humans; however, there remains a need to develop splints with tunable mechanical properties and degradation profiles for the pediatric population. The objective of this pilot study is to assess the safety and efficacy of silk fibroin-based splints in a clinically relevant preclinical model of tracheomalacia. METHODS: Silk splints were evaluated in a surgically induced model of severe tracheomalacia in N = 3 New Zealand white rabbits for 17, 24, and 31 days. An image-based assay was developed to quantify the dynamic change in airway area during spontaneous respiration, and histopathology was used to study the surrounding tissue response. RESULTS: The average change in area in the native trachea was 23% during spontaneous respiration; surgically induced tracheomalacia resulted in a significant increase to 86% (P < 0.001). The average change in airway area after splint placement was reduced at all terminal time points (17, 24, and 31 days postimplantation), indicating a clinical improvement, and was not statistically different than the native trachea. Histopathology showed a localized inflammatory reaction characterized by neutrophils, eosinophils, and mononuclear cells, with early signs suggestive of fibrosis at the splint and tissue interface. CONCLUSION: This pilot study indicates that silk fibroin splints are well tolerated and efficacious in a rabbit model of severe tracheomalacia, with marked reduction in airway collapse following implantation and good tolerability over the studied time course. LEVEL OF EVIDENCE: NA Laryngoscope, 129:2189-2194, 2019.

[Construction of a Platform for the Development of Pharmaceutical and Medical Applications Using Transgenic Silkworms].

　We have been constructing a platform for the development of pharmaceutical and medical applications using the domesticated silkworm, Bombyx mori, as a new animal model for drug development and evaluation. Because silkworm larvae originally have the capacity to synthesize up to 0.5 g of silk proteins, genetically modified silkworms (transgenic silkworms) are expected to have high potential in the production of recombinant silks/proteins. An innovative method for generating transgenic silkworms was established in 2000, and ever since this epoch-defining technological development, longstanding efforts have succeeded in developing novel silks that enable the manufacture of new textile materials for regenerative medical uses. Furthermore, we have succeeded in developing a new system of recombinant protein production. This recombinant protein production system is currently capable of producing a maximum of approximately 15 mg recombinant protein per silkworm larva. Transgenic silkworms have also been shown to produce a wide variety of useful proteins, including antibodies and membrane proteins. Some of these recombinant proteins have been in commercial use since 2011. In addition, we have been developing transgenic silkworms as a novel animal model for testing medicines based on metabolic similarities between silkworms and mammals. These applications show the suitability and potential of transgenic silkworms for medical use. Here, we will describe the challenges faced in creating a transgenic silkworm-based platform for pharmaceutical and medical applications.