A drug-mediated organic electrochemical transistor for robustly reusable biosensors.

Reusable point-of-care biosensors offer a cost-effective solution for serial biomarker monitoring, addressing the critical demand for tumour treatments and recurrence diagnosis. However, their realization has been limited by the contradictory requirements of robust reusability and high sensing capability to multiple interactions among transducer surface, sensing probes and target analytes. Here we propose a drug-mediated organic electrochemical transistor as a robust, reusable epidermal growth factor receptor sensor with striking sensitivity and selectivity. By electrostatically adsorbing protonated gefitinib onto poly(3,4-ethylenedioxythiophene):polystyrene sulfonate and leveraging its strong binding to the epidermal growth factor receptor target, the device operates with a unique refresh-in-sensing mechanism. It not only yields an ultralow limit-of-detection concentration down to 5.74 fg ml-1 for epidermal growth factor receptor but, more importantly, also produces an unprecedented regeneration cycle exceeding 200. We further validate the potential of our devices for easy-to-use biomedical applications by creating an 8 × 12 diagnostic drug-mediated organic electrochemical transistor array with excellent uniformity to clinical blood samples.

The critical role of SETDB1-mediated CCND1/PI3K/AKT pathway via p53-RS di-methylation at K370 in the proliferation of WRL68 cells induced by nicotine.

Constituents of cigarette smoke are known to be carcinogens. Additionally, there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Nicotine, the primary constituent of tobacco, plays a role in cancer progression. In our previous study, it was found that nicotine enhances the proliferation of a human normal fetal hepatic (WRL68) cell due to the activation of p53 mutation at Ser249 (p53-RS)/STAT1/CCND1 signaling pathway. Here, we further elucidated the mechanism of regulating this pathway. Firstly, dose-dependent increase of SETDB1 protein level in WRL68 cells upon exposure to nicotine (1.25, 2.5, and 5 µM), significantly enhanced cellular proliferation. In addition, the upregulation of SETDB1 protein was necessary for the nuclear translocation of p53-RS to establish a ternary complex with STAT1 and SETDB1, which facilitated p53-RS di-methylation at K370 (p53-RS/K370me2). After that, the activation of CCND1/PI3K/AKT pathway was initiated when STAT1 stability was enhanced by p53-RS/K370me2, ultimately resulting in cell proliferation. Altogether, the study revealed that the increase in SETDB1 expression could potentially have a significant impact on the activation of CCND1/PI3K/AKT pathway through p53-RS/K370me2, leading to the proliferation of WRL68 cells induced by nicotine, which could contribute to hepatocellular carcinoma for smokers. Besides, the results of this study provided a foundation for the development of anticancer therapies for cancers associated with tobacco use.

Large-scale analysis of protein crotonylation reveals its diverse functions in Pinellia ternata.

BACKGROUND: Pinellia ternata is an important traditional medicine in China, and its growth is regulated by the transcriptome or proteome. Lysine crotonylation, a newly identified and important type of posttranslational modification, plays a key role in many aspects of cell metabolism. However, little is known about its functions in Pinellia ternata. RESULTS: In this study, we generated a global crotonylome analysis of Pinellia ternata and examined its overlap with lysine succinylation. A total of 2106 crotonylated sites matched on 1006 proteins overlapping in three independent tests were identified, and we found three specific amino acids surrounding crotonylation sites in Pinellia ternata: KcrF, K***Y**Kcr and Kcr****R. Gene Ontology (GO) and KEGG pathway enrichment analyses showed that two crucial alkaloid biosynthesis-related enzymes and many stress-related proteins were also highly crotonylated. Furthermore, several enzymes participating in carbohydrate metabolism pathways were found to exhibit both lysine crotonylation and succinylation modifications. CONCLUSIONS: These results indicate that lysine crotonylation performs important functions in many biological processes in Pinellia ternata, especially in the biosynthesis of alkaloids, and some metabolic pathways are simultaneously regulated by lysine crotonylation and succinylation.

Murine diabetic models for dengue virus infection.

Dengue virus (DENV) is a critical public health concern in tropical and subtropical regions worldwide. Thus, immunocompetent murine models of DENV infection with robust viremia are required for vaccine studies. Diabetes is highly prevalent worldwide, making it frequent comorbidity in patients with dengue fever. Therefore, murine models are needed to understand viral pathogenesis and disease progression. Acquired-induced and inherently diabetic C57BL/6 and db/db mice were inoculated with DENV-3 via the tail vein. After infection, both the diabetic C57BL/6 and db/db mice showed obvious weight loss with clinical manifestations. Quantitative reverse-transcription polymerase chain reaction revealed robust and replicable viremia in the two types of diabetic mice. Immunohistochemical detection showed persistent DENV-3 infection in the liver. Enzyme-linked immunosorbent assay for cytokine detection revealed that diabetic mice showed more severe inflammatory responses than did nondiabetic mice, and significant histological alterations were observed in diabetic mice. Thus, the diabetic mice were more susceptible to DENV infection than the nondiabetic mice. Taken together, we established two types of immunocompetent diabetic mice for DENV infection, which can be used to further study the mechanisms of dengue pathogenesis in diabetes and to develop antiviral pharmaceuticals and treatments.

Curriculum setting and students' feedback of pre-clinical training in different dental schools in China-A national-wide survey.

INTRODUCTION: Adequate time and effective training facilities are essential for undergraduate dental students participating in pre-clinical dental practice to ensure them providing safe treatment for patients in the future. The study aimed to explore the current status of pre-clinical dental training in China in relation to the curriculum setting and students' feedback of pre-clinical training in different dental schools and thus provide information for further standardise curricula. MATERIALS AND METHOD: An online questionnaire was distributed electronically to undergraduates in 44 Chinese dental schools of different levels according to China Discipline Ranking (CDR). The questionnaire collected information in relation to the training hour and student to facility ratio of four main dental courses (cariology and endodontics, periodontology, prosthodontics and oral surgery), as well as the application and effect of virtual reality (VR) simulator in pre-clinical dental practice in different schools. Students' feedback was also collected. RESULTS: A total of 565 valid questionnaires were recruited. Results of this cross-sectional survey show that training hour of periodontology course was the lowest, and oral surgery course showed most prominent shortage of facilities. The application of VR simulator amongst schools is uneven. Students from A and A+ level schools showed higher satisfaction with their pre-clinical courses and reported a more positive attitude towards the use of VR simulator than other students. (p < .05). CONCLUSION: Pre-clinical dental training in China remained imperfect in insufficient training time, training facility and students did not have access to standard pre-clinical training and quality assurance. VR technique has potential values in pre-clinical dental practice in China.

Integration of metabolome and transcriptome analyses reveals the mechanism of anthocyanin accumulation in purple radish leaves.

Anthocyanins are natural pigments and play significant roles in multiple growth, development, and stress response processes in plants. The vegetables with high anthocyanin content have better colours, higher antioxidant activity than green vegetables and are potent antioxidants with health benefits. However, the mechanism of anthocyanin accumulation in purple and green leaves of Raphanus sativus (radish) is poorly understood and needs further investigation. In the present study, the pigment content in a green leaf cultivar "RA9" and a purple-leaf cultivar "MU17" was characterized and revealed that the MU17 had significantly increased accumulation of anthocyanins and reduced content of chlorophyll and carotenoid compared with that in RA9. Meanwhile, these two cultivars were subjected to a combination of metabolomic and transcriptome studies. A total of 52 massively content-changed metabolites and 3463 differentially expressed genes were discovered in MU17 compared with RA9. In addition, the content of significantly increased flavonoids (such as pelargonidin and cyanidin) was identified in MU17 compared to RA9 using an integrated analysis of metabolic and transcriptome data. Moreover, the quantitative real-time polymerase chain reaction results also confirmed the differences in the expression of genes related to pathways of flavonoids and anthocyanin metabolism in MU17 leaves. The present findings provide valuable information for anthocyanin metabolism and further genetic manipulation of anthocyanin biosynthesis in radish leaves. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01245-w.

Comparative analysis of adding cotton straw and corn stover to improve the combustion performance of municipal sludge.

To address issues of high water content and low calorific value during combustion of municipal sludge, we added water-absorbent, easy-to-burn agricultural waste to improve the overall combustion performance. Cotton straw or corn stover were added to the sludge and mixed at high-speed to compare their capacities for improving combustion performance. Scanning Electron Microscopy (SEM) revealed that cotton straw or corn stover attached to the surface of the municipal sludge particles after blending, while analysis of thermogravimetric curves and activation energies of the blends showed that combustion and exhaustion rates increased significantly when 40% cotton straw or corn stover were blended into the sludge. Using the quadrilateral cut-ring boiler as a prototype, the mix of sludge with cotton straw or corn stover was simulated, and FLUENT software was used to obtain the temperature and pollutant emissions of the boiler. Sludge blended with cotton straw or corn stover increased furnace temperature and reduced SO2 and NO emissions, while that with cotton straw burned at higher temperatures with lower SO2 and NO emissions. Overall, the CO content of sludge combustion was lower when blended with proportions of cotton straw or corn stover under 50%. The findings of this study lay a theoretical foundation for treatment of municipal sludge according to local conditions.

Carbon carrier-based rapid Joule heating technology: a review on the preparation and applications of functional nanomaterials.

Compared to conventional heating techniques, the carbon carrier-based rapid Joule heating (CJH) method is a new class of technologies that offer significantly higher heating rates and ultra-high temperatures. Over the past few decades, CJH technology has spawned several techniques with similar principles for different application scenarios, including ultra-fast high temperature sintering (UHS), carbon thermal shock (CTS), and flash Joule heating (FJH), which have been widely used in material preparation research studies. Functional nanomaterials are a popular direction of research today, mainly including nanometallic materials, nanosilica materials, nanoceramic materials and nanocarbon materials. These materials exhibit unique physical, chemical, and biological properties, including a high specific surface area, strength, thermal stability, and biocompatibility, making them ideal for diverse applications across various fields. The CJH method is a remarkable approach to producing functional nanomaterials that has attracted attention for its significant advantages. This paper aims to delve into the fundamental principles of CJH and elucidate the efficient preparation of functional nanomaterials with superior properties using this technique. The paper is organized into three sections, each dedicated to introducing the process and characteristics of CJH technology for the preparation of three distinct material types: carbon-based nanomaterials, inorganic non-metallic materials, and metallic materials. We discuss the distinctions and merits of the CJH method compared to alternative techniques in the preparation of these materials, along with a thorough examination of their properties. Furthermore, the potential applications of these materials are highlighted. In conclusion, this paper concludes with a discussion on the future research trends and development prospects of CJH technology.

A review on the effect of COX-2-mediated mechanisms on development and progression of gastric cancer induced by nicotine.

Smoking is a documented risk factor for cancer, e.g., gastric cancer. Nicotine, the principal tobacco alkaloid, would exert its role of contribution to gastric cancer development and progression through nicotinic acetylcholine receptors (nAChRs) and ß-adrenergic receptors (ß-ARs), which then promote cancer cell proliferation, migration and invasion. As a key isoenzyme in conversion of arachidonic acid to prostaglandins, cyclooxygenase-2 (COX-2) has been demonstrated to have a wide range of effects in carcinogenesis and tumor development. At present, many studies have reported the effect of nicotine on gastric cancer by binding to nAChR, as well as indirectly stimulating ß-AR to mediate COX-2-related pathways. This review summarizes these studies, and also proposes more potential COX-2-mediated mechanisms. These events might contribute to the growth and progression of gastric cancer exposed to nicotine through tobacco smoke or cigarette substitutes. Also, this review article has therefore the potential not only to make a significant contribution to the treatment and prognosis of gastric cancer for smokers but also to the clinical application of COX-2 antagonists. In addition, this work also discusses the considerable challenges of this field with special reference to the future perspective of COX-2-mediated mechanisms in development and progression of gastric cancer induced by nicotine.

A Community-Based Framework Integrates Interspecific Interactions into Forest Genetic Conservation.

Forest genetic conservation is typically species-specific and does not integrate interspecific interaction and community structure. It mainly focuses on the theories of population and quantitative genetics. This approach depicts the intraspecific patterns of population genetic structure derived from genetic markers and the genetic differentiation of adaptive quantitative traits in provenance trials. However, it neglects possible interspecific interaction in natural forests and overlooks natural hybridization or subspeciation. We propose that the genetic diversity of a given species in a forest community is shaped by both intraspecific population and interspecific community evolutionary processes, and expand the traditional forest genetic conservation concept under the community ecology framework. We show that a community-specific phylogeny derived from molecular markers would allow us to explore the genetic mechanisms of a tree species interacting with other resident species. It would also facilitate the exploration of a species' ecological role in forest community assembly and the taxonomic relationship of the species with other species specific to its resident forest community. Phylogenetic ß-diversity would assess the similarities and differences of a tree species across communities regarding ecological function, the strength of selection pressure, and the nature and extent of its interaction with other species. Our forest genetic conservation proposal that integrates intraspecific population and interspecific community genetic variations is suitable for conserving a taxonomic species complex and maintaining its evolutionary potential in natural forests. This provides complementary information to conventional population and quantitative genetics-based conservation strategies.

Origami-Enhanced Mechanical Properties for Worm-Like Robot.

In recent years, the exploration of worm-like robots has garnered much attention for their adaptability in confined environments. However, current designs face challenges in fully utilizing the mechanical properties of structures/materials to replicate the superior performance of real worms. In this article, we propose an approach to address this limitation based on the stacked Miura origami structure, achieving the seamless integration of structural design, mechanical properties, and robotic functionalities, that is, the mechanical properties originate from the geometric design of the origami structure and at the same time serve the locomotion capability of the robot. Three major advantages of our design are: the implementation of origami technology facilitates a more accessible and convenient fabrication process for segmented robotic skin with periodicity and flexibility, as well as robotic bristles with anchoring effect; the utilization of the Poisson's ratio effect for deformation amplification; and the incorporation of localized folding motion for continuous peristaltic locomotion. Utilizing the high geometric designability inherent in origami, our robot demonstrates customizable morphing and quantifiable mechanical properties. Based on the origami worm-like robot prototype, we experimentally verified the effectiveness of the proposed design in realizing the deformation amplification effect and localized folding motion. By comparing this to a conventional worm-like robot with discontinuous deformation, we highlight the merits of these mechanical properties in enhancing the robot's mobility. To sum up, this article showcases a bottom-up approach to robot development, including geometric design, mechanical characterization, and functionality realization, presenting a unique perspective for advancing the development of bioinspired soft robots.

Sponge iron enriches autotrophic/aerobic denitrifying bacteria to enhance denitrification in sequencing batch reactor.

Sponge iron (SFe) coupled with a sludge system has great potential for improving biological denitrification; however, the underlying mechanism is not yet fully understood. In this study, the denitrification performance and microbial characteristics of ordinary sludge and SFe-sludge systems were investigated. Overall, the SFe-sludge reactor had faster ammonium degradation rate (94.0 %) and less nitrate accumulation (1.5-53.3 times lower) than ordinary reactor during the complete operation cycle of sequencing batch reactors. The addition of SFe increased the activities of nitrate and nitrite reductases. The total relative abundance of autotrophic denitrifying bacteria (Acidovorax, Arenimonas, etc.) in the SFe-sludge system after 38 days of operation was found to be 10.6 % higher than that in the ordinary sludge reactor. The aerobic denitrifying bacteria (Dokdonella, Phaeodactylibacter, etc.) was 5.3 % higher than ordinary sludge. The SFe-sludge system improved denitrification by enriching autotrophic/aerobic denitrifying bacteria in low carbon-to-nitrogen ratio wastewater treatment.

The role of α7-nAChR-mediated PI3K/AKT pathway in lung cancer induced by nicotine.

Nicotine enters the environment mainly through human activity, as well as natural sources. This review article examines the increasing evidence implicating nicotine in the initiation and progression of lung cancer. Moreover, it primarily focuses on elucidating the activation mechanism of phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, regulated by α7 subtype nicotinic acetylcholine receptor (α7-nAChR), in relation to the proliferation, invasion, and metastasis of lung cancer cells induced by nicotine, as well as nicotine-mediated anti-apoptotic effects. This process involves PI3K/AKT phosphorylated-B-cell lymphoma-2 (Bcl-2) family proteins, PI3K/AKT/mammalian target of rapamycin (mTOR), PI3K/AKT/nuclear factor-κB (NF-κB), hepatocyte growth factor (HGF)/cellular-mesenchymal epithelial transition factor (c-Met)-induced PI3K/AKT and PI3K/AKT activated-hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) pathways. In addition, we also deliberated on the related challenges and upcoming prospects within this field. These lay the foundation for further study on nicotine, lung tumorigenesis, and PI3K/AKT related molecular mechanisms. This work has the potential to significantly contribute to the treatment and prognosis of gastric cancer in smokers. Besides, the crucial significance of PI3K/AKT signaling pathway in multiple molecular pathways also suggests that its target antagonists may inhibit the development and progression of lung cancer, providing a possible new perspective for solving the problem of nicotine-promoted lung cancer. The emerging knowledge about the carcinogenic mechanisms of nicotine action should be considered during the environmental assessment of tobacco and other nicotine-containing products.

Population Structure and Genetic Diversity of the Toona ciliata (Meliaceae) Complex Assayed with Chloroplast DNA Markers.

Toona ciliata is a deciduous or semi-deciduous tree species and belongs to the Toona genus of the Meliaceae family. Owing to low natural regeneration and over-exploitation, the species is listed as an endangered species at level II in China and its conservation has received increasing concern. Here, we sampled 447 individuals from 29 populations across the range-wide distribution of the T. ciliata complex in China and assessed their genetic variation using two chloroplast DNA markers. The results showed that the overall haplotype diversity and nucleotide diversity per site were high at h = 0.9767 and π = 0.0303 for the psbA-trnH fragment and h= 0.8999 and π = 0.0189 for the trnL-trnL fragment. Phylogenetic analysis supported the division of the natural distribution of T. ciliata complex into western and eastern regions. The genetic diversity was higher in the western region than in the eastern region, showing significant phylogeographic structure. Genetic differentiation among populations was moderate (Φst=42.87%), and the effects of isolation by distance (IBD) were significant. A neutrality test and mismatch distribution analysis indicated that the distribution of the T. ciliata complex generally did not expand, although a few local populations could likely expand after bottleneck effects. The overall results were complementary to and consolidated previous studies using mitochondrial and nuclear DNA markers. We finally discussed strategies for the genetic conservation of the T. ciliata complex.

The role of ß2-AR/PI3K/AKT pathway in the proliferation, migration and invasion of THLE-2 cells induced by nicotine.

Nicotine, the primary constituent of tobacco, is one of the important factors that induce the occurrence of hepatocellular carcinoma (HCC). The ß2-adrenergic receptor (ß2-AR) is implicated in the growth and advancement of tumors. However, the role of ß2-AR and its mediated cascades in nicotine-induced HCC remains unclear. This present study aims to observe the effects of nicotine on the proliferation, migration, and invasion of immortalized human liver epithelial (THLE-2) cells, as well as to explore the underlying mechanisms of action. The results of cell counting kit-8 (CCK-8) assay showed that 0.3125 µM nicotine had the ability to promote the proliferation of THLE-2 cells with a significant time-dependent manner. Therefore, THLE-2 cells were mainly selected for chronic treatment with 0.3125 µM nicotine in the later stage to cause transformation. After 30 passages of THLE-2 cells with 0.3125 µM nicotine treatment, chronic exposure to nicotine significantly enhanced the proliferation, metastasis, and invasion of cells. Besides, it also upregulated the intracellular levels of ß2-AR, phosphoinositide 3-kinase (PI3K), AKT, matrix metalloproteinase-2 (MMP-2) and Cyclin D1, as well as downregulated the expression of p53. More importantly, the ß2-AR/PI3K/AKT pathway was found to mediate the expression of MMP-2, Cyclin D1, and p53 in THLE-2 cells, playing a crucial role in their proliferation, migration, and invasion after continuous exposure to nicotine. Simply put, it demonstrated the role of ß2-AR/PI3K/AKT pathway in the transformation of THLE-2 cells induced by nicotine. This study could provide valuable insights into the relationship between nicotine and HCC. Additionally, it lays the groundwork for investigating potential anticancer treatments for liver cancer linked to tobacco consumption.

Structural properties, bioactivities, structure-activity relationships and bio-applications of polysaccharides from Auricularia auricula: A review.

Auricularia auricula (A. auricula), is a medicinal and edible fungus in China for thousands of years with rich nutrition and delicious taste. The main active ingredient of A. auricula is polysaccharide, which has antitumor, hypoglycemic, antioxidant, and immune regulation bioactivities. It is widely recognized that the biological activity of polysaccharides is closely related to the chemical structure and advanced structure. In terms of polysaccharides extracted from A. auricula (AAPs), there were distinguished structures reported due to the different original resources and extraction methods, leading to various bioactivities. However, the structure-activity relationship of AAPs has scarcely been reviewed till now. In addition, polysaccharides were found to have specific self-assembly properties recently, together with their bioactivities, endowing them with unique physicochemical properties. Nowadays, an increasing number of polysaccharides, such as cellulose, chitin, and pectin, have been used to construct various functional materials in the fields of food, cosmetics, and biomedical materials. Therefore, the construction of functional materials by AAPs is of great research significance. This article aims to provide a systematic review of the structure-activity relationship of AAPs and summarize the functional materials constructed based on AAPs to provide theoretical references for further research and application of AAPs.

The ß-glucan nanotube carrier achieves detoxification and efficacy enhancement of celastrol in intrahepatic cholangiocarcinoma therapy by increasing targeted controlled release and macrophage polarization.

Celastrol (Cel) is a monomer from a famous traditional Chinese medicine named Tripterygium wilfordii Hook. f. Cel has shown great potential in treating intrahepatic cholangiocarcinoma (ICC) but still faces problems, including poor water solubility, high toxicity, and lack of targeting ability. Thus, the present work constructed a drug-delivery system using black fungus polysaccharide self-assembled -nanotubes (BFP). Cel-loaded nanotubes (BFP-Cel) were confirmed to have a high loading content of Cel (38 %), liver targeting, and enzyme-controlled release abilities. Moreover, BFP carriers could significantly increase the uptake efficiency of Cel by tumor cells. In vivo experiments showed that BFP-Cel could effectively inhibit tumor growth and reduce the physiological toxicity of Cel. Furthermore, BFP, as a carrier, could regulate the immune microenvironment in the liver through the activation of macrophages and play an immunomodulatory role. In summary, the BFP nanotube carrier could achieve detoxification and efficacy enhancement of Cel in treating ICC by increasing the targetability, controlled release ability, cell-uptake effect, and regulation of the immune microenvironment.

Intestinal newborn regulatory B cell antibodies modulate microbiota communities.

The role of immunoglobulins produced by IL-10-producing regulatory B cells remains unknown. We found that a particular newborn regulatory B cell population (nBreg) negatively regulates the production of immunoglobulin M (IgM) via IL-10 in an autocrine manner, limiting the intensity of the polyreactive antibody response following innate activation. Based on nBreg scRNA-seq signature, we identify these cells and their repertoire in fetal and neonatal intestinal tissues. By characterizing 205 monoclonal antibodies cloned from intestinal nBreg, we show that newborn germline-encoded antibodies display reactivity against bacteria representing six different phyla of the early microbiota. nBreg-derived antibodies can influence the diversity and the cooperation between members of early microbial communities, at least in part by modulating energy metabolism. These results collectively suggest that nBreg populations help facilitate early-life microbiome establishment and shed light on the paradoxical activities of regulatory B cells in early life.

Nanoscale doping of polymeric semiconductors with confined electrochemical ion implantation.

Nanoresolved doping of polymeric semiconductors can overcome scaling limitations to create highly integrated flexible electronics, but remains a fundamental challenge due to isotropic diffusion of the dopants. Here we report a general methodology for achieving nanoscale ion-implantation-like electrochemical doping of polymeric semiconductors. This approach involves confining counterion electromigration within a glassy electrolyte composed of room-temperature ionic liquids and high-glass-transition-temperature insulating polymers. By precisely adjusting the electrolyte glass transition temperature (Tg) and the operating temperature (T), we create a highly localized electric field distribution and achieve anisotropic ion migration that is nearly vertical to the nanotip electrodes. The confined doping produces an excellent resolution of 56 nm with a lateral-extended doping length down to as little as 9.3 nm. We reveal a universal exponential dependence of the doping resolution on the temperature difference (Tg - T) that can be used to depict the doping resolution for almost infinite polymeric semiconductors. Moreover, we demonstrate its implications in a range of polymer electronic devices, including a 200% performance-enhanced organic transistor and a lateral p-n diode with seamless junction widths of <100 nm. Combined with a further demonstration in the scalability of the nanoscale doping, this concept may open up new opportunities for polymer-based nanoelectronics.

The architecture of silk-secreting organs during the final larval stage of silkworms revealed by single-nucleus and spatial transcriptomics.

Natural silks are renewable proteins with impressive mechanical properties and biocompatibility that are useful in various fields. However, the cellular and spatial organization of silk-secreting organs remains unclear. Here, we combined single-nucleus and spatially resolved transcriptomics to systematically map the cellular and spatial composition of the silk glands (SGs) of mulberry silkworms late in larval development. This approach allowed us to profile SG cell types and cell state dynamics and identify regulatory networks and cell-cell communication related to efficient silk protein synthesis; key markers were validated via transgenic approaches. Notably, we demonstrated the indispensable role of the ecdysone receptor (ultraspiracle) in regulating endoreplication in SG cells. Our atlas presents the results of spatiotemporal analysis of silk-secreting organ architecture late in larval development; this atlas provides a valuable reference for elucidating the mechanism of efficient silk protein synthesis and developing sustainable products made from natural silk.