Human-multimodal deep learning collaboration in 'precise' diagnosis of lupus erythematosus subtypes and similar skin diseases.

BACKGROUND: Lupus erythematosus (LE) is a spectrum of autoimmune diseases. Due to the complexity of cutaneous LE (CLE), clinical skin image-based artificial intelligence is still experiencing difficulties in distinguishing subtypes of LE. OBJECTIVES: We aim to develop a multimodal deep learning system (MMDLS) for human-AI collaboration in diagnosis of LE subtypes. METHODS: This is a multi-centre study based on 25 institutions across China to assist in diagnosis of LE subtypes, other eight similar skin diseases and healthy subjects. In total, 446 cases with 800 clinical skin images, 3786 multicolor-immunohistochemistry (multi-IHC) images and clinical data were collected, and EfficientNet-B3 and ResNet-18 were utilized in this study. RESULTS: In the multi-classification task, the overall performance of MMDLS on 13 skin conditions is much higher than single or dual modals (Sen = 0.8288, Spe = 0.9852, Pre = 0.8518, AUC = 0.9844). Further, the MMDLS-based diagnostic-support help improves the accuracy of dermatologists from 66.88% ± 6.94% to 81.25% ± 4.23% (p = 0.0004). CONCLUSIONS: These results highlight the benefit of human-MMDLS collaborated framework in telemedicine by assisting dermatologists and rheumatologists in the differential diagnosis of LE subtypes and similar skin diseases.

Personalizing age of gastric cancer screening based on comorbidity in China: Model estimates of benefits, affordability and cost-effectiveness optimization.

The benefits of gastric cancer screening are related to age and comorbidity status, but reliable estimates are lacking in China. This study aimed to estimate the benefits and affordability of the gastric cancer screening strategy by level of comorbidity to inform decisions to screening age. We assessed six current gastric cancer screening strategies in China using a microsimulation model with different starting and stopping ages and comorbidity profiles, for a total of 378 strategies. 1,000,000 individuals were simulated in the model and followed the alternative strategies. Primary outcomes included gastric cancer incidence, the number of endoscopy and complications, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios. Future costs and QALYs are discounted by 5% per year. Sensitivity analyses were used to evaluate model uncertainty. Strategies with longer screening durations were associated with higher benefits of life-year gained and gastric cancer deaths averted, but were also accompanied by a large number of endoscopy screening, and complication events. Using the threshold of US$18,575 per QALY gained, at the no, moderate, and severe comorbidity level, the leading cost-effectiveness strategies were the new gastric cancer screening scoring system strategy (NGCS) screening from age 40 years to 60 years (40-60), 40-55-NGCS, and 40-55-NGCS strategy, respectively. The results are robust in sensitivity analyses. Our study illustrates the importance of considering comorbidity conditions and age when determining the starting and stopping screening age for gastric cancer and informs the discussion on personalizing decisions. The trade-off between benefits and harms can also be referenced when necessary.

A Multilayered Magnetoelectric Transmitter with Suppressed Nonlinearity for Portable VLF Communication.

Acoustically actuated magnetoelectric (ME) antenna based on the efficient oscillation of magnetic dipoles has recently been considered as a promising solution for portable very-low-frequency communications. However, the severe nonlinear dynamic behavior in the case of strong-field excitation results in insufficient radiation capability and poor communication performance for a conventional ME antenna. In this work, we propose to suppress the nonlinearity of an ME antenna by neutralizing the spring-hardening effect in amorphous Metglas and the spring-softening effect in piezoelectric ceramics through an ME multilayered transmitter (ME-MLTx) design. With a driving voltage of 50 Vpp at the resonance frequency of 21.2 kHz, a magnetic flux density as high as 108 fT at a distance of 100 m is produced from a single ME-MLTx. In addition, ME-MLTx performs a decreased mechanical quality factor (Q m) less than 40.65, and, thus, a broadened bandwidth of 500 Hz is generated. Finally, a communication link transmitting binary American Standard Code for Information Interchange-coded message is built, which allows for an error-free communication with a distance of 18 m and a data rate of 300 bit/s in the presence of heavy environment noise. The communication distance can be further estimated over 100 m when using a femtotesla-class-inductive magnetic field receiver. The obtained results are believed to bring ME antennas one step closer to being applicable in very-low-frequency communications.

Estimated projection of incidence and mortality of alcohol-related liver disease in China from 2022 to 2040: a modeling study.

BACKGROUND: China has one of the highest numbers of liver disease cases in the world, including 6.4 million cirrhosis associated with alcohol-related liver disease (ALD) cases. However, there is still a lack of urgent awareness about the growth of alcohol consumption and the increased burden of ALD in China. Therefore, we aimed to project the potential impact of changes in alcohol consumption on the burden of ALD in China up to 2040 under different scenarios. METHODS: We developed a Markov model to simulate the natural history of ALD until 2040 in China. We estimated the incidence and mortality of alcohol-related cirrhosis and hepatocellular carcinoma between 2022 and 2040 under four projected scenarios: status quo scenario and scenarios with a 2%, 4%, and 8% annual decrease in excessive alcohol consumption, respectively. RESULTS: Under the status quo scenario, the cumulative new cases of cirrhosis from 2022 to 2040 was projected to be 3.61 million (95% UI 3.03-4.44 million), resulting in a cumulative 1.96 million (1.66-2.32 million) deaths from alcohol-related cirrhosis and hepatocellular carcinoma. However, a 2% annual reduction in excessive alcohol consumption was expected to avert 0.3 million deaths associated with ALD, and a 4% annual reduction was projected to prevent about 1.36 million new cases of cirrhosis and prevent 0.5 million ALD-related deaths. Moreover, an 8% annual reduction would prevent about 2 million new cases of cirrhosis and 0.82 million deaths. CONCLUSIONS: Without any substantial change in alcohol attitudes and policies to regulate excessive drinking, the disease burden of ALD in China will increase enormously. Strengthening the implementation of alcohol restriction interventions is critical and urgent to reduce the impact of ALD on the Chinese population.

Leptin deficiency in CD8+ T cells ameliorates non-segmental vitiligo by reducing interferon-γ and Granzyme B.

Background: Vitiligo is an autoimmune skin disease mainly mediated by CD8+ T cells, which affects about 0.1%-2% population of the world. Leptin plays a critical role in regulating the activation of CD8+ T cells. However, the effect of Leptin on vitiligo remains unclear. Objectives: To explore the effect of leptin on CD8+ T cells and its influence on vitiligo. Methods: RNA sequencing and Quantitative Real-time PCR (RT-qPCR) were used to explore the differentially expressed genes. Immunofluorescence staining was performed on skin lesions. Leptin in serum was detected by enzyme linked immunosorbent assay (ELISA). The peripheral blood mononuclear cells were detected by flow cytometry after leptin stimulation for 72 hours. A vitiligo model was established by monobenzone on Leptin KO mice. Results: 557 differentially expressed genes were found, including 154 up-regulated and 403 down-regulated genes. Lipid metabolism pathways showed a close relationship to the pathogenesis of vitiligo, especially the PPAR signaling pathway. RT-qPCR (p = 0.013) and immunofluorescence staining (p = 0.0053) verified that LEPR expressed significantly higher in vitiligo. The serum leptin level of vitiligo patients was significantly lower than that of healthy controls (p = 0.0245). The interferon-γ subset of CD8+LEPR+ T cells from vitiligo patients was significantly higher (p = 0.0189). The protein level of interferon-γ was significantly increased after leptin stimulation in vitro (p = 0.0217). In mice, Leptin deficiency resulted in less severe hair depigmentation. Leptin deficiency also resulted in significantly lower expressed vitiligo-related genes, such as Cxcl9 (p = 0.0497), Gzmb (p < 0.001), Ifng (p = 0.0159), and Mx1 (p < 0.001) after modeling. Conclusion: Leptin could promote the progression of vitiligo by enhancing the cytotoxic function of CD8+ T cells. Leptin may become a new target for vitiligo treatment.

Sex separation by body color via a W-chromosome-linked transgene.

Sex separation processes are important for commercial insect production and sterile insect techniques. Here, we describe the transgenic insertion of a DsRed expression cassette driven by the enhancer HR3 and strong promoter IE1 into the silkworm W chromosome as a dominant visible marker of sex separation. The obtained transgenic lines showed female-specific body color visible to the naked eye at the second- to fifth-instar larval, pupal and adult stages, and their performance traits were comparable to those of a nontransgenic practical silkworm variety. This strategy can greatly facilitate the sex separation of silkworms for male-only rearing and to obtain hybrids while avoiding sibling mating, and it can also be applied to the sex separation of other light-colored insects.

Trametinib for patients with recurrent low-grade serous ovarian cancer: A cost-effectiveness analysis.

OBJECTIVE: The GOG 281/LOGS trial found that trametinib prolonged progression-free survival (PFS) in patients with recurrent low-grade serous ovarian cancer (LGSOC), compared with standard of care (SOC). The current study aimed to evaluate the cost-effectiveness of trametinib versus standard of care for recurrent LGSOC from the US payer perspective. METHODS: A Markov model was adopted to compare the cost and effectiveness of trametinib and standard of care group in patients with recurrent LGSOC. Life years (LYs), quality-adjusted LYs (QALYs), lifetime costs, and incremental cost-effectiveness ratios (ICERs) were calculated. One-way, and probabilistic sensitivity analyses were performed to explore the model robustness. RESULT: Trametinib group provided an additional 0.58 QALYs (1.14 LYs) and an incremental cost of $248,214 compared with the SOC group. The incremental cost-effectiveness ratio was $424,097 per QALY. The results of one-way sensitivity analyses suggested that our model was sensitive to the hazard ratio of OS and PFS between trametinib and SOC group, utility of PFS and the cycle cost of trametinib. Probabilistic sensitivity analyses revealed that there was 6% probability of the trametinib group being cost-effective at a willingness-to-pay (WTP) threshold of $150,000 per QALY. CONCLUSIONS: From the US payer perspective, trametinib is not cost-effective for patients with recurrent LGSOC at the assumed WTP threshold of $150,000 per QALY. Based on the value standpoint, price reduction of trametinib is expected to improve the cost-effectiveness of trametinib in patients with recurrent LGSOC.

Benefit-to-harm ratio and cost-effectiveness of government-recommended gastric cancer screening in China: A modeling study.

Objective: Current guidelines recommend the gastric cancer risk score scale (GCRSS) for screening in gastric cancer (GC) high-risk populations in China. This study aimed to estimate the clinical benefits, harms, cost, and cost-effectiveness of the GCRSS screening strategy from a Chinese healthcare system perspective. Materials and methods: Using a microsimulation model, we evaluated 7 screening scenarios of the GCRSS with varying starting ages. We simulated 100,000 individuals from the age of 20 for each screening scenario. The main outcomes included GC incidence reduction, number of cause-specific deaths, costs, quality-adjusted life year (QALY), incremental cost-effectiveness ratio (ICER), and benefit-to-harm ratio. Deterministic and probabilistic sensitivity analyses were done to explore the robustness of model findings. Results: Screening with the GCRSS strategy at the age of 40 years (40-GCRSS) provided the greatest reduction of GC incidence by 70.6%, with 7,374 GC deaths averted per 100,000 individuals and the lowest benefit-to-harm ratio of 0.392. Compared with no screening or previous less costly strategy, at a willingness-to-pay (WTP) threshold of $37,655 per QALY, the 40-GCRSS strategy was cost-effective, with ICERs of $12,586 and $29,115 per QALY, respectively. Results were robust across univariate and probabilistic sensitivity analyses. The 40-GCRSS strategy showed a 0.856 probability of being cost-effective at a $37,655 per QALY WTP threshold. Conclusions: The findings suggest that the GCRSS strategy is effective and cost-effective in reducing the GC disease burden in China from a Chinese healthcare system perspective. Screening from the age of 40 would be the optimal strategy.

Cost-Effectiveness of Pembrolizumab Plus Chemotherapy as First-Line Therapy for Advanced Oesophageal Cancer.

Objective: Pembrolizumab plus chemotherapy is recommended as the first-line treatment for advanced oesophageal cancer. The objective of this study is to evaluate the cost-effectiveness of pembrolizumab plus chemotherapy as first-line therapy for advanced oesophageal cancer from the healthcare system perspective in China. Methods: Based on the KEYNOTE-590 trial, a Markov model was constructed to estimate the cost and effectiveness of pembrolizumab plus chemotherapy and placebo plus chemotherapy, respectively. Total costs, life years (LYs), quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. One-way, probabilistic sensitivity analyses (PSA), and subgroup analyses were adapted to test the model robustness. Result: Compared with the placebo group, pembrolizumab group obtained an additional 1.05 QALY, but the cost was also increased by $121,478.76. The ICER was $115,391.84 per QALY gained, which was higher than the willingness-to-pay (WTP) of $31,304.31. The results of One-way sensitivity analyses showed that the ICER was sensitive to the hazard ratio of PFS and per cycle cost of pembrolizumab. At a WTP threshold of $31,304.31, the probability of pembrolizumab plus chemotherapy being cost-effective was 0%. Conclusion: From the perspective of China healthcare system, pembrolizumab plus chemotherapy as first-line treatment is not cost-effective for patients with advanced oesophageal cancer compared with placebo plus chemotherapy.

Clinical Benefit and Cost Effectiveness of Risk-Stratified Gastric Cancer Screening Strategies in China: A Modeling Study.

BACKGROUND AND OBJECTIVE: A new gastric cancer screening scoring system (NGCS) strategy was recommended for the early gastric cancer (GC) screening process in China. The current study aimed to assess the clinical benefits and the cost effectiveness of the NGCS strategy in GC high-risk areas of China from a societal perspective. METHODS: A Markov microsimulation model was developed to evaluate 30 alternative screening strategies with varying initiation age, including the NGCS strategy, the modified NGCS strategy, and the endoscopic screening strategy with various screening intervals. The primary outcomes included GC mortality, number of endoscopies, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). Cost estimates were reported in 2021 USD (US$) and both costs and benefits were discounted at 5% annually. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty. RESULTS: Screening with the NGCS strategy from age 40 years (40-NGCS) reduced the GC incidence by 86.4%, which provided the greatest benefit across strategies. Compared with all strategies, at a willingness-to pay threshold of US$17,922 per QALY, the 40-NGCS strategy was a leading cost-effective strategy, with an ICER of US$15,668 per QALY. Results were robust in univariate and probabilistic sensitivity analyses. The probability of the 40-NGCS strategy being cost effective was 0.863. CONCLUSIONS: The 40-NGCS strategy was an effective and cost-effective strategy to reduce GC incidence and mortality in China. The findings provide important evidence for decision makers to formulate and optimize targeted approaches for GC prevention and control policies in China.

Mechanism of silk secretion revealed by proteomic analysis of silkworm cocoons with fibroin light chain mutations.

Silkworm is an economically important insect due to its efficient production of silk proteins. Silk itself and the silk trade have enriched human civilization through art and culture and contributed to early globalization in the Silk Road era for nearly two thousand years. Although a large number of studies on silk have been carried out, the mechanism of silk secretion in silkworms has not been thoroughly studied thus far. As the main component of fibroin, fibroin light chain (Fib-L) plays a key role in the secretion of silk. In this study, we constructed a homozygous Fib-L gene mutant population of a nonpractical variety using the CRISPR/Cas9 system. The homozygous mutants displayed a thin cocoon layer, but their viability was not affected by the Fib-L mutation. Furthermore, a comparative proteomic analysis of homozygous mutant cocoons and wild-type cocoons was performed. Strikingly, fibrohexamerin (P25) was secreted almost normally in the homozygous mutant. Further analysis of cocoon proteins revealed that the mutant responded to greater environmental stress caused by a dramatic decrease in fibroin by significantly increasing the secretion of protease inhibitors. These results will further help explain the silk secretion mechanism of silkworm. SIGNIFICANCE: This study generated a homozygous Fib-L gene mutant population of a nonpractical variety using the CRISPR/Cas9 system. The homozygous mutants displayed a thin cocoon layer, but their viability was not affected by the Fib-L mutation. Furthermore, a comparative proteomic analysis of homozygous mutant cocoons and wild-type cocoons was performed. The analysis of the abundance of silk proteins in the cocoons revealed that P25 could be secreted almost normally. The analysis of the abundance of cocoon proteins other than silk proteins showed that the homozygous mutants responded to greater environmental stress by increasing the secretion of defense-related proteins, such as protease inhibitors. These results will further help explain the silk secretion mechanism of silkworm.

Economic Evaluation of Dapagliflozin in the Treatment of Patients With Heart Failure: A Systematic Review.

Objective: The objective of this study is to systematically review the economic evaluations of dapagliflozin in the treatment of patients with heart failure (HF) and describe their general and methodological features. Methods: This systematic review followed the PRISMA guidelines. MEDLINE/PubMed, Website Of Science, Embase, The Cochrane Library, ScienceDirect, CNKI, and Wanfang databases were searched to collect relevant studies, and the retrieval time ended on 31 October 2021. Articles on the economic evaluation of dapagliflozin in the treatment of heart failure were included. Secondary studies, incomplete economic indicators, and non-English-language and non-Chinese-language studies were excluded. Standard drug treatment was selected as the comparison. Basic characteristics, methods, and main results were extracted and analyzed systematically. Result: A total of eight studies were identified, and the overall quality was accepted, which were performed in nine developed countries (Austria, United States, Korea, Japan, Singapore, Spanish, Germany, and United Kingdom) and three developing countries (the Philippines, Thailand, and China). With the exception of the Philippines, the remaining countries considered that dapagliflozin was cost effective. In the analyses of all included studies, the incremental cost-effectiveness ratios were most sensitive to the cost of dapagliflozin, cardiovascular mortality, the duration of dapagliflozin effectiveness, and the probability of HF hospitalization. Conclusion: Dapagliflozin in the treatment of patients with heart failure with reduced ejection fraction was considered cost effective. Further studies are needed to evaluate the comprehensive value of dapagliflozin on HF.

Systemic lupus erythematosus patients contain B-cell receptor repertoires sensitive to immunosuppressive drugs.

Immune repertoire (IR) during treatment may be a surrogate biomarker for disease response. Changes of the IR in systemic lupus erythematosus patients in response to immunosuppressive drugs were identified in ten SLE patients. Patients provided peripheral blood mononuclear cells at two time points for sequencing. They were divided into sensitive and nonsensitive groups by their clinical responses to immunosuppressive drugs. After treatment, the BCR expression significantly decreased in patients from the sensitive group while there was no change in patients from the nonsensitive group. IgM comprised a dominant portion of the BCR repertoire and increased slightly in all patients in the sensitive group but decreased in the nonsensitive group. IgA also exhibited opposing changes between the two groups. Shorter CDR3 of TRB and TRG chains occurred in the sensitive group. CDR3 length of IGK decreased significantly in the sensitive group. CDR3 of TCR δ/γ changed distinctly between time points in the sensitive group. Six immune-related genes showed differential expression levels in sensitive and nonsensitive groups. Our study shows that it is BCR repertoire sensitivity to immunosuppressive drugs in SLE patients and sheds light on personalized therapy for SLE.

The Bio-Persistence of Reversible Inflammatory, Histological Changes and Metabolic Profile Alterations in Rat Livers after Silver/Gold Nanorod Administration.

As a widely applied nanomaterial, silver nanomaterials (AgNMs) have increased public concern about their potential adverse biological effects. However, there are few related researches on the long-term toxicity, especially on the reversibility of AgNMs in vivo. In the current study, this issue was tackled by exploring liver damage after an intravenous injection of silver nanorods with golden cores (Au@AgNRs) and its potential recovery in a relatively long term (8 w). After the administration of Au@AgNRs into rats, Ag was found to be rapidly cleared from blood within 10 min and mainly accumulated in liver as well as spleen until 8 w. All detected parameters almost displayed a two-stage response to Au@AgNRs administration, including biological markers, histological changes and metabolic variations. For the short-term (2 w) responses, some toxicological parameters (hematological changes, cytokines, liver damages etc.) significantly changed compared to control and AuNRs group. However, after a 6-week recovery, all abovementioned changes mostly returned to the normal levels in the Au@AgNRs group. These indicated that after a lengthy period, acute bioeffects elicited by AgNMs could be followed by the adaptive recovery, which will provide a novel and valuable toxicity mechanism of AgNMs for potential biomedical applications of AgNMs.

High mechanical property silk produced by transgenic silkworms expressing the spidroins PySp1 and ASG1.

Spider silk is one of the best natural fibers with excellent mechanical properties; however, due to the visual awareness, biting behavior and territory consciousness of spiders, we cannot obtain spider silk by large-scale breeding. Silkworms have a spinning system similar to that of spiders, and the use of transgenic technology in Bombyx mori, which is an ideal reactor for producing spider silk, is routine. In this study, the piggyBac transposon technique was used to achieve specific expression of two putative spider silk genes in the posterior silk glands of silkworms: aggregate spider glue 1 (ASG1) of Trichonephila clavipes (approximately 1.2 kb) and two repetitive units of pyriform spidroin 1 (PySp1) of Argiope argentata (approximately 1.4 kb). Then, two reconstituted spider silk-producing strains, the AG and PA strains, were obtained. Finally, the toughness of the silk fiber was increased by up to 91.5% and the maximum stress was enhanced by 36.9% in PA, and the respective properties in AG were increased by 21.0% and 34.2%. In summary, these two spider genes significantly enhanced the mechanical properties of silk fiber, which can provide a basis for spidroin silk production.

Mechanism of the growth and development of the posterior silk gland and silk secretion revealed by mutation of the fibroin light chain in silkworm.

Silkworm, as a model organism, has very high economic value due to its silk secretion ability. Although a large number of studies have attempted to elucidate the mechanism of silk secretion, it remains unclear. In this study, the fibroin light chain (Fib-L) gene of silkworm was subjected to CRISPR/Cas9 editing, which yielded premature termination of translation at 135 aa. Compared with those of the wild type, the posterior silk glands (PSGs) of the homozygous mutants on the third day of the fifth instar showed obvious premature degeneration. Comparative transcriptome and proteomic analyses of the PSGs of wild-type individuals, heterozygous mutants and homozygous mutants were performed on the fourth day of the fifth instar. A GO enrichment analysis showed that the differentially expressed genes (DEGs) between homozygous mutants and wild-type individuals were enriched in cytoskeleton-related terms, and a KEGG enrichment analysis showed that the upregulated DEGs between homozygous mutants and wild-type individuals were enriched in the phagosome and apoptosis pathways. These results indicated that apoptosis was activated prematurely in the PSGs of homozygous mutants. Furthermore, autophagy and heat shock response were activated in the PSGs of homozygous mutants, as demonstrated by an analysis of the DEGs related to autophagy and heat shock. A comparative proteomic analysis further confirmed that autophagy, apoptosis and the heat shock response were activated in the PSGs of homozygous mutants, which led to premature degradation of the PSGs. These results provide insights for obtaining a more in-depth understanding of the mechanism of silk secretion in silkworms.

Role of sericin 1 in the immune system of silkworms revealed by transcriptomic and proteomic analyses after gene knockout.

The domestic silkworm is a type of lepidopteran insect that feeds on mulberry leaves and has high economic value because of its ability to spin cocoons. Sericin 1 is an important component of silkworm cocoons, accounting for approximately 25% of the material. In this study, CRISPR/Cas9-mediated gene editing was successfully used to destroy the sericin 1 gene, and homozygous mutants were obtained after continuous screening. Homozygous mutation resulted in premature termination of the translation of sericin 1 protein at 323 amino acids. Comparative transcriptomic and proteomic analyses of middle silk gland cells from wild-type individuals and mutants were performed on the fourth day of the fifth instar, and the results suggest that sericin 1 plays an important role in the cellular immune system. In addition, the results suggest that sericin 1 has a synergistic effect with some protease inhibitors and that the secretion of these proteins is strictly regulated. These results will provide new insights into the function and expression pattern of sericin 1 and the mechanism of silk secretion.

P25 Gene Knockout Contributes to Human Epidermal Growth Factor Production in Transgenic Silkworms.

Transgenic silkworm expression systems have been applied for producing various recombinant proteins. Knocking out or downregulating an endogenous silk protein is considered a viable strategy for improving the ability of transgenic expression systems to produce exogenous proteins. Here, we report the expression of human epidermal growth factor (hEGF) in a P25 gene knockout silkworm. The hEGF gene regulated by the P25 gene promoter was integrated into a silkworm's genome. Five transgenic positive silkworm lineages were generated with different insertion sites on silkworm chromosomes and the ability to synthesize and secrete proteins into cocoons. Then, a cross-strategy was used to produce transgenic silkworms with a P25 gene knockout background. The results of the protein analysis showed that the loss of an endogenous P25 protein can increase the hEGF production to about 2.2-fold more than normal silkworms. Compared to those of transgenic silkworms with wild type (non-knockout) background, the morphology and secondary structure of cocoon silks were barely changed in transgenic silkworms with a P25 gene knockout background, indicating their similar physical properties of cocoon silks. In conclusion, P25 gene knockout silkworms may become an efficient bioreactor for the production of exogenous proteins and a promising tool for producing various protein-containing silk biomaterials.

Human epidermal growth factor-functionalized cocoon silk with improved cell proliferation activity for the fabrication of wound dressings.

Human epidermal growth factor (hEGF) is a key factor involved in wound healing owing to its powerful ability to stimulate cell proliferation. In this study, we used piggyBac transposon technology to produce transgenic silkworms expressing the hEGF protein fused to truncated heavy chain (FibH-hEGF). The FibH-hEGF fusion protein was successfully expressed and secreted into silkworm cocoons. Compared to wild-type silk, the transgenic silkworm silk had the similar morphology about silks fiber surface and cocoon nets, while the secondary structure between the transgenic silk and wild-type silk was different. Most importantly, transgenic silkworm cocoon silk powder extract significantly increased human fibroblast FIB cell proliferation for a long duration with no apparent cytotoxicity. Our study provides a promising method for obtaining cost-effective and functional biomaterials for the fabrication of wound dressings.