Tumor-Targeted Multimodal Optical Imaging with Versatile Cadmium-Free Quantum Dots.

The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium. Here, a versatile bioimaging probe is developed by using highly luminescent cadmium-free CuInSe2/ZnS core/shell quantum dots conjugated with CGKRK (Cys-Gly-Lys-Arg-Lys) tumor-targeting peptides. This probe exhibits excellent photostability, reasonably long circulation time, minimal toxicity, and strong tumor-specific homing property. The most important feature of this probe is that it shows distinctive versatility in tumor-targeted multimodal imaging including near-infrared, time-gated, and two-photon imaging in different tumor models. In a glioblastoma mouse model, the targeted probe clearly denotes tumor boundaries and positively labels a population of diffusely infiltrating tumor cells, suggesting its utility in precise tumor detection during surgery. This work lays a foundation for potential clinical translation of the probe.

The differentiation of amniotic fluid stem cells into sweat glandlike cells is enhanced by the presence of Sonic hedgehog in the conditioned medium.

After patients suffer severe full-thickness burn injuries, the current treatments cannot lead to the complete self-regeneration of the sweat gland structure and function. Therefore, it is important to identify new methods for acquiring sufficient functional sweat gland cells to restore skin function. In this study, we induced CD117+ human amniotic fluid stem (hAFS) cells to differentiate into sweat glandlike (hAFS-SG) cells based on the use of conditioned medium (CM) from the human sweat gland (hSG) cells. Real-time PCR and immunofluorescent staining were used to confirm the expression of the sweat gland-related genes Ectodysplasin-A (EDA), Ectodysplasin-A receptor (EDAR), keratin 8 (K8) and carcino-embryonic antigen (CEA). Transmission electron microscopy analysis shows that microvilli, the cellular structures that are typical for hSG cells, can also be observed on the membrane of the hAFS-SG cells. Our test for the calcium response to acetylcholine (Ach) proved that hAFS-SG cells have the potential to respond to Ach in a manner similar to normal sweat glands. A three-dimensional culture is an effective approach that stimulates the hAFS-SG cells to form tubular structures and drives hAFS-SG cells to mature into higher stage. We also found that epidermal growth factor enhances the efficiency of differentiation and that Sonic hedgehog is an important factor of the CM that influences sweat gland differentiation. Our study provides the basis for further investigations into novel methods of inducing stem cells to differentiate into sweat glandlike cells.

MiR-335 functions as a tumor suppressor in pancreatic cancer by targeting OCT4.

Octamer-binding transcription factor 4 (OCT4) was closely related to pancreatic cancer progression, but its regulation in pancreatic cancer by microRNA (miRNA) is not fully clear. OCT4-positive and OCT4-negative pancreatic cells were isolated by flow cytometry, and it was found that OCT4-positive cells are enriched in transplanted pancreatic cancer cells compared with the primary ones and showed increasing proliferation and sphere formation. The data of miRNA array assay showed that miR-335 in OCT4-positive pancreatic cancer cells was lower than that in the negative ones. The results were confirmed in pancreatic cancer tissue and cell lines. Through expression analysis, it was found that miR-335 was underexpressed in OCT4(+) pancreatic cancer cells purified from primary tumors. Enforced expression of miR-335 in OCT4(+) pancreatic cancer cells inhibited clonogenic expansion and tumor development. miR-335 re-expression in OCT4(+) pancreatic cancer cells was blocked. Systemically delivered miR-335 inhibited pancreatic cancer metastasis and extended animal survival. Of significance, OCT4 was identified and validated as a direct and functional target of miR-335. Taken together, our results provide evidence that miR-335 might inhibit progression and stem cell properties of pancreatic cancer targeting OCT4.

Rapid liquid phase-assisted ultrahigh-temperature sintering of high-entropy ceramic composites.

High-entropy ceramics and their composites display high mechanical strength and attractive high-temperature stabilities. However, properties like strong covalent bond character and low self-diffusion coefficients make them difficult to get sintered, limiting their mass popularity. Here, we present a rapid liquid phase-assisted ultrahigh-temperature sintering strategy and use high-entropy metal diboride/boron carbide composite as a proof of concept. We use a carbon-based heater to fast-heat the composite to around 3000 K, and a small fraction of eutectic liquid was formed at the interface between high-entropy metal diborides and boron carbide. A crystalline dodecaboride intergranular phase was generated upon cooling to ameliorate the adhesion between the components. The as-sintered composite presents a high hardness of 36.4 GPa at a load of 0.49 N and 24.4 GPa at a load of 9.8 N. This liquid phase-assisted rapid ultrahigh-temperature strategy can be widely applicable for other ultrahigh-temperature ceramics as well.

Amniotic fluid derived stem cells promote skin regeneration and alleviate scar formation through exosomal miRNA-146a-5p via targeting CXCR4.

BACKGROUND AND OBJECTIVES: Regenerative medicine is promising in wound healing. Exosomes derived from human amniotic fluid derived stem cells (hAFS) have become an important area of research for many diseases as a key paracrine factor, but its effects in wound healing remains unknown. In this study, we investigated the possible role and possible mechanisms of hAFS in skin wound healing. METHODS: hAFS were isolated from human amniotic fluid via routine amniocentesis. The mice were randomly divided into 2 groups: control group and hAFS group treated with 1.25 × 106  hAFS cells. Immunohistochemistry staining was performed for histological analysis and qRT-PCR for the assessment of gene levels. Luciferase Reporter Assay was performed for the verification of target gene. RESULTS: Our results demonstrated that hAFS accelerated wound closure. hAFS alleviated scar formation via promoting ECM remodeling, upregulating molecular of immune response, enhancing anti-fibrotic activity, and decreasing the secretion of inflammation-associated cytokines through exosomal miRNA-146a-5p via targeting CXCR4. CONCLUSIONS: Taken together, hAFS was a promising cell source for wound healing. The findings in this study provide vital references and pave the way for future research.

A novel transfection method for eukaryotic cells using polyethylenimine coated albumin microbubbles.

Albumin microbubbles have been intensively studied for their application in gene delivery. However, with negative surface potential, albumin microbubbles hardly bind plasmid DNA, which might contribute to their low transgene efficiency. In this study, we developed polyethylenimine (PEI) coated albumin microbubbles (PAMB) which were prepared by sonicating the mixture of human albumin, PEI, polyethylene glycol and glucose. CHO cells, COS cells and 293T cells were transfected with PEI, PEI+albumin, PAMB and Lipofectamine 2000, respectively. Our results showed that the surface potential was elevated and PAMB could bind plasmid DNA. The transgene efficiency of PAMB was higher than PEI and PEI+albumin (P<0.05), and PAMB performed the same transgene effect as Lipofectamine 2000 did but with lower cytotoxicity than Lipofectamine 2000. Albumin microbubbles modified by PEI has high transgene efficiency and low cytotoxicity even without ultrasound medication, making it a useful non-virus gene delivery method in vitro.

CircPTK2 Suppresses the Progression of Gastric Cancer by Targeting the MiR-196a-3p/AATK Axis.

BACKGROUND: Gastric cancer is a type of malignant tumor with high morbidity and mortality. It has been shown that circular RNAs (circRNAs) exert critical roles in gastric cancer progression via working as microRNA (miRNA) sponges to regulate gene expression. However, the role and potential molecular mechanism of circRNAs in gastric cancer remain largely unknown. METHODS: CircPTK2 (hsa_circ_0005273) was identified by bioinformatics analysis and validated by RT-qPCR assay. Bioinformatics prediction, dual-luciferase reporter, and RNA pull-down assays were used to determine the interaction between circPTK2, miR-196a-3p, and apoptosis-associated tyrosine kinase 1 (AATK). RESULTS: The level of circPTK2 was markedly downregulated in gastric cancer tissues and gastric cancer cells. Upregulation of circPTK2 significantly suppressed the proliferation, migration, and invasion of gastric cancer cells, while circPTK2 knockdown exhibited opposite effects. Mechanically, circPTK2 could competitively bind to miR-196a-3p and prevent miR-196a-3p to reduce the expression of AATK. In addition, overexpression of circPTK2 inhibited tumorigenesis in a xenograft mouse model of gastric cancer. CONCLUSION: Collectively, circPTK2 functions as a tumor suppressor to suppress gastric cancer cell proliferation, migration, and invasion through regulating the miR-196a-3p/AATK axis, suggesting that circPTK2 may serve as a novel therapeutic target for gastric cancer.

Circular RNA hsa_circ_0072309 inhibits the proliferation, invasion and migration of gastric cancer cells via inhibition of PI3K/AKT signaling by activating PPARγ/PTEN signaling.

Gastric cancer (GC) is a common malignant tumor in the digestive system, which presents without specific symptoms. Circular RNAs (circRNAs) play important roles in tumor progression and cellular functions; however, the relationship between GC and hsa_circ_0072309 remains unclear. The aim of the present study was to investigate the molecular mechanisms of hsa_circ_0072309 and the role that hsa_circ_0072309 plays in proliferation, invasion and migration of GC cells. The expression of hsa_circ_0072309 was evaluated using reverse transcription­quantitative PCR. A series of functional experiments were performed to study the role that hsa_circ_0072309 has in survival and metastasis of GC cells. In the present study, hsa_circ_0072309 was downregulated in GC cell lines and its overexpression inhibited the proliferation, migration and invasion of GC cells. In addition, hsa_circ_0072309 overexpression induced activation of the peroxisome proliferator­activated receptor γ (PPARγ)/PTEN pathway and inhibition of PI3K/AKT signaling. Moreover, pioglitazone, a PPARγ agonist, strengthened the effects of abundant hsa_circ_0072309 on the proliferative, migratory and invasive capabilities of GC cells, while GW9662, a PPARγ antagonist, abolished the effects of hsa_circ_0072309 overexpression on cell proliferation, migration and invasion. The present findings suggested that hsa_circ_0072309 inhibited proliferation, invasion and migration of gastric cancer cells via the inhibition of PI3K/AKT signaling by activating the PPARγ/PTEN signaling pathway. Targeting hsa_circ_0072309 may be an innovative therapeutic strategy for the treatment of GC.

Exosomal circ_0088300 Derived From Cancer-Associated Fibroblasts Acts as a miR-1305 Sponge and Promotes Gastric Carcinoma Cell Tumorigenesis.

Cancer-associated fibroblast (CAF)-derived exosomes play a major role in gastric carcinoma (GC) tumorigenesis. However, the mechanism behind the activity of circular RNAs in CAF-derived exosomes in GC remains unclear. In the present study, we identified differentially expressed circ_0088300 in GC tissues and plasma exosomes. We found that CAFs delivered functional circ_0088300 to GC tumor cells via exosomes and promoted the proliferation, migration and invasion abilities of GC cells. Furthermore, we demonstrated that circ_0088300 packaging into exosomes was driven by KHDRBS3. In addition, we verified that circ_0088300 served as a sponge that directly targeted miR-1305 and promoted GC cell proliferation, migration and invasion. Finally, the JAK/STAT signaling pathway was found to be involved in the circ_0088300/miR-1305 axis, which accelerates GC tumorigenesis. In conclusion, our results indicated a previously unknown regulatory pathway in which exosomal circ_0088300 derived from CAFs acts as a sponge of miR-1305 and promotes GC cell proliferation, migration and invasion; these data identify a potential biomarker and novel therapeutic target for GC in the future.

Primary cilia-dependent signaling is involved in regulating mesenchymal stem cell proliferation and pluripotency maintenance.

Using a large-scale quantitative mesenchymal stem cells (MSCs) membrane proteomics analysis, we identified a large group of ciliary proteins in the MSCs membrane fraction, which prompted us to examine the cilia, intricate organelles that were originally discovered approximately 100 years ago. Here we characterize their primary structure and function in MSCs. We first characterized the primary cilia on undifferentiated human MSCs by immunostaining and verified these observation with scanning and 3D electronic microscopy. To investigate the function of the primary cilia of the MSCs we induced loss of function by means of siRNA knockdown (targeted to two known ciliary proteins: IFT172 and KIF3A). After either of these two proteins was knocked down by the respective siRNA, the MSCs showed fewer and shortened primary cilia. The MSCs proliferation assays showed increased cell proliferative activity under confluent conditions after the siRNA knockdown of IFT172 or KIF3A; among these MSCs, the proportion in S phase was increased in the IFT172 siRNA knockdown group. The expression of stem cell markers on the MSCs, namely, Oct4, Nanog and Sox2, were downregulated after the siRNA-induced knockdown of IFT172 or KIF3A, and the gene expression upregulation of ectoderm lineage markers was notable. Furthermore, manipulation of the primary cilia-dependent Shh pathway, using the Shh activator SAG (smoothened agonist), upregulated the gene expression of pluripotency markers, including Nanog and Oct4, and transcriptional target genes in the Shh pathway. This study confirms that MSCs have primary cilia and provides evidence that primary cilia-dependent signaling pathways play functional roles in MSCs proliferation and stemness maintenance.

Single-phase high-entropy intermetallic compounds (HEICs): bridging high-entropy alloys and ceramics.

High-entropy intermetallic compounds (HEICs) were fabricated by mechanical alloying and spark plasma sintering to fill a knowledge gap between the traditional high-entropy alloys (HEAs) and emerging high-entropy ceramics (HECs). Notably, several four- or five-component equimolar aluminides, such as the B2-phase (Fe1/5Co1/5Ni1/5Mn1/5Cu1/5)Al, have been made into single-phase HEICs for the first time. Thermodynamic modeling and a reversible, temperature-dependent, phase-stability experiment suggest that such B2-phase HEICs are entropy-stabilized phases. The structure of these HEICs resembles that of HECs with high-entropy mixing of four or five elements of nearly equal fractions in one and only one sublattice, but with significant (∼10%) anti-site defects (differing from typical HECs). A new phase stability rule for forming single B2-phase HEICs is proposed. Five additional HEICs of predominantly D022 phases have also been made. This study broadens the families of equimolar, single-phase, high-entropy materials that have been successfully fabricated.

A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548g in the cytoplasm and interacting with YBX1 in the nucleus.

In the present study, two circular RNA (circRNA) expression profiles in paired gastric cancer (GC) tissues from the GEO database were examined. We identified a novel circRNA, has_circ_0001461, which we termed circFAT1(e2). We verified that circFAT1(e2) was significantly downregulated in GC tissues and cell lines and was correlated with overall survival of GC patients. Fluorescence in situ hybridization (FISH) analysis showed that circFAT1(e2) was distributed in the cytoplasm of GC cells, as well as in the nucleus. Functional assays indicated that overexpression of circFAT1(e2) inhibited GC cell proliferation, migration and invasion. Then, we investigated whether circFAT1(e2) acts as a sponge of microRNA-549g(miR-548g) and regulates the expression of tumor suppressor RUNX1 in GC cells. Moreover, we found that nucleus-located circFAT1(e2) could directly interact with Y-box binding protein-1 (YBX1) and inhibit its function. In conclusion, circFAT1(e2) may play a role as a tumor suppressor in GC cells by regulating the miR-548g/RUNX1 axis in the cytoplasm and targeting YBX1 in the nucleus.

Adsorption behaviors of supercritical Lennard-Jones fluid in slit-like pores.

Understanding the adsorption behaviors of supercritical fluid in confined space is pivotal for coupling the supercritical technology and the membrane separation technology. Based on grand canonical Monte Carlo simulations, the adsorption behaviors of a Lennard-Jones (LJ) fluid in slit-like pores at reduced temperatures over the critical temperature, Tc* = 1.312, are investigated; and impacts of the wall-fluid interactions, the pore width, and the temperature are taken into account. It is found that even if under supercritical conditions, the LJ fluid can undergo a "vapor-liquid phase transition" in confined space, i.e., the adsorption density undergoes a sudden increase with the bulk density. A greater wall-fluid attractive potential, a smaller pore width, and a lower temperature will bring about a stronger confinement effect. Besides, the adsorption pressure reaches a local minimum when the bulk density equals to a certain value, independent of the wall-fluid potential or pore width. The insights in this work have both practical and theoretical significances.

Excellent Infrared Nonlinear Optical Crystals BaMO(IO3)5 (M = V, Ta) Predicted by First Principle Calculations.

Two nonlinear optical crystals, BaVO(IO3)5 and BaTaO(IO3)5, are designed by substituting Nb with V and Ta, respectively, in BaNbO(IO3)5, which is itself a recently synthesized infrared nonlinear optical (NLO) material. The designs of BaVO(IO3)5 and BaTaO(IO3)5 from BaNbO(IO3)5 are based on the following motivation: BaVO(IO3)5 should have a larger second-harmonic generation (SHG) coefficient than BaNbO(IO3)5, as V will result in a stronger second-order Jahn-Teller effect than Nb due to its smaller ion radius; at the same time, BaTaO(IO3)5 should have a larger laser-damage threshold, due to the fact that Ta has a smaller electronegativity leading to a greater band-gap. Established on reliable first-principle calculations, it is demonstrated that BaVO(IO3)5 has a much larger SHG coefficient than BaNbO(IO3)5 (23.42 × 10-9 vs. 18.66 × 10-9 esu); and BaTaO(IO3)5 has a significantly greater band-gap than BaNbO(IO3)5 (4.20 vs. 3.55 eV). Meanwhile, the absorption spectra and birefringences of both BaVO(IO3)5 and BaTaO(IO3)5 are acceptable for practice, suggesting that these two crystals can both be expected to be excellent infrared NLO materials.

Quercetin and doxorubicin co-delivery using mesoporous silica nanoparticles enhance the efficacy of gastric carcinoma chemotherapy.

BACKGROUND: Effective gastric carcinoma (GC) chemotherapy is subject to many in vitro and in vivo barriers, such as tumor microenvironment and multidrug resistance. MATERIALS AND METHODS: Herein, we developed a hyaluronic acid (HA)-modified silica nanoparticle (HA-SiLN/QD) co-delivering quercetin and doxorubicin (DOX) to enhance the efficacy of GC therapy (HA-SiLN/QD). The HA modification was done to recognize overexpressed CD44 receptors on GC cells and mediate selective tumor targeting. In parallel, quercetin delivery decreased the expression of Wnt16 and P-glycoprotein, thus remodeling the tumor microenvironment and reversed multidrug resistance to facilitate DOX activity. RESULTS: Experimental results demonstrated that HA-SiLN/QD was nanoscaled particles with preferable stability and sustained release property. In vitro cell experiments on SGC7901/ADR cells showed selective uptake and increased DOX retention as compared to the DOX mono-delivery system (HA-SiLN/D). CONCLUSION: In vivo anticancer assays on the SGC7901/ADR tumor-bearing mice model also revealed significantly enhanced efficacy of HA-SiLN/QD than mono-delivery systems (HA-SiLN/Q and HA-SiLN/D).

In vivo cation exchange in quantum dots for tumor-specific imaging.

In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor. The etchant rapidly quenches the quantum dots through cation exchange (ionic etching), and facilitates renal clearance of metal ions released from the quantum dots. The quantum dots are intravenously delivered into orthotopic breast and pancreas tumors in mice by using the tumor-penetrating iRGD peptide. Subsequent etching quenches excess quantum dots, leaving a highly tumor-specific signal provided by the intact quantum dots remaining in the extravascular tumor cells and fibroblasts. No toxicity is noted. The system also facilitates the detection of peritoneal tumors with high specificity upon intraperitoneal tumor targeting and selective etching of excess untargeted quantum dots. In vivo cation exchange may be a promising strategy to enhance specificity of tumor imaging.The imaging of tumors in vivo using nanoprobes has been challenging due to the lack of sufficient tumor specificity. Here, the authors develop a tumor-specific quantum dot system that permits in vivo cation exchange to achieve selective background quenching and high tumor-specific imaging.

Upregulation of microRNA-524-5p enhances the cisplatin sensitivity of gastric cancer cells by modulating proliferation and metastasis via targeting SOX9.

Cisplatin-based chemotherapy is the most commonly used treatment regimen for gastric cancer (GC), however, the resistance to cisplatin represents the key limitation for the therapeutic efficacy. Aberrant expression of MiR-524-5p appears to be involves in tumorigenesis and chemoresistance. However, the mechanism by which miR-524-5p mediates effects of cisplatin treatment in GC remains poorly understood. Expressions of MiR-524-5p was detected in GC tissues and cell lines by qRT-PCR. Cell proliferation was observed by MTT assay; Cell migration was detected by transwell migration and invasion assay. The targeting protein of miR-524-5p was identified by luciferase reporter assay and western blot. We found that downregulation of miR-524-5p in GC tissues and cell lines. SC-M1 and AZ521 cells resistant to cisplatin expressed low levels of miR-524-5p in comparison to the sensitive parental cells. Overexpression of miR-524-5p expression in SC-M1 and AZ521 cells inhibited cell proliferation, migration, and invasion, and conferred sensitivity to cisplatin-resistant GC cells. Subsequently, we identified SOX9 as a functional target protein of miR-524-5p and found that SOX9 overexpression could counteracts the chemosensitizing effects of miR-524-5p. These results provide novel insight into the regulation of GC tumorigenesis and progression by miRNAs. Restoration of miR-524-5p may have therapeutic potential against GC.

Serum is an indispensable factor in the maintenance of the biological characteristics of sweat gland cells.

The tolerance of sweat gland cells for in vitro amplification and subcultivation is low as they are somatic cells. The present study aimed to formulate an optimal medium for the culture of human eccrine sweat gland cells (HESGCs) and to establish a method for induction of HESGCs proliferation, whilst maintaining the characteristics of sweat gland cells. HESGCs cultured in sweat gland (SG):keratinocyte growth medium­2 (KGM­2) (1:1) medium had a higher proliferation rate and a stable morphology compared with cells cultured in SG and KGM­2 medium only. Reverse transcription­quantitative polymerase chain reaction indicated that cells cultured in the SG:KGM­2 (1:1) medium exhibited higher expression levels of α­smooth muscle actin, keratin (K)77, carcinoembryonic antigen, K8, K18, ectodysplasin A receptor, c­Myc, Kruppel­like factor 4 and octamer­binding transcription factor 4 compared with cells cultured in SG only or KGM­2 only medium. Three­dimensional culture analysis revealed that HESGCs cultured in SG:KGM­2 1:1 medium differentiated into sweat gland­like structures, whereas cells cultured in KGM­2 only medium underwent cornification. The present study also determined that the maintenance of the biological characteristics of HESGCs occurred due to the presence of fetal bovine serum (FBS). Cells cultured in medium without FBS differentiated into keratinocytes. Therefore, the SG:KGM­2 (1:1) medium may be a suitable culture medium for HESGCs. In conclusion, this mixed medium is a valuable compound and should be considered to be a potential supplemental medium for HESGCs.

Direct Reprogramming of Human Amniotic Fluid Stem Cells by OCT4 and Application in Repairing of Cerebral Ischemia Damage.

Amniotic fluid stem cells (AFSCs) are a type of fetal stem cell whose stemness encompasses both embryonic and adult stem cells, suggesting that they may be easily and efficiently reprogrammed into induced pluripotent stem cells (iPSCs). To further simplify the reprogramming process, the creation of AFSC-derived iPSCs using a single factor is desirable. Here we report the generation of one-factor human AFSC-iPSCs (AiPSCs) from human AFSCs by ectopic expression of the transcription factor OCT4. Just like human embryonic stem cells, AiPSCs exhibited similar epigenetic status, global gene expression profiles, teratoma formation and in vitro & in vivo pluripotency. Our results indicate that the OCT4 is necessary and sufficient to directly reprogram human AFSCs into pluripotent AiPSCs. Moreover, reflecting the similar memory characteristics of AFSCs and neural stem cells, we show that AiPSC membrane-derived vesicles (MVs) repair cerebral ischemia damage. We anticipate that the successful generation of one-factor AiPSCs will facilitate the creation of patient-specific pluripotent stem cells without the need for transgenic expression of oncogenes. Moreover, MVs from tissue-specific AiPSCs have potential in tissue repair, representing a novel application of iPSCs.

Regeneration of high-quality silk fibroin fiber by wet spinning from CaCl2-formic acid solvent.

Silks spun by silkworms and spiders feature outstanding mechanical properties despite being spun under benign conditions. The superior physical properties of silk are closely related to its complicated hierarchical structures constructed from nanoscale building blocks, such as nanocrystals and nanofibrils. Here, we report a novel silk dissolution behavior, which preserved nanofibrils in CaCl2-formic acid solution, that enables spinning of high-quality fibers with a hierarchical structure. This process is characterized by simplicity, high efficiency, low cost, environmental compatibility and large-scale industrialization potential, as well as having utility and potential for the recycling of silk waste and the production of silk-based functional materials.