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Amyloid protein cross-seeding is a peculiar phenomenon of cross-spreading among different diseases. Unlike traditional infectious ones, diseases caused by amyloid protein cross-seeding are spread by misfolded proteins instead of pathogens. As a consequence of the interactions among misfolded heterologous proteins or polypeptides, amyloid protein cross-seeding is considered to be the crucial cause of overlapping pathological transmission between various protein misfolding disorders (PMDs) in multiple tissues and cells. Here, we briefly review the phenomenon of cross-seeding among amyloid proteins. As an interesting example worth mentioning, the potential links between the novel coronavirus pneumonia (COVID-19) and some neurodegenerative diseases might be related to the amyloid protein cross-seeding, thus may cause an undesirable trend in the incidence of PMDs around the world. We then summarize the theoretical models as well as the experimental techniques for studying amyloid protein cross-seeding. Finally, we conclude with an outlook on the challenges and opportunities for basic research in this field. Cross-seeding of amyloid opens up a new perspective in our understanding of the process of amyloidogenesis, which is crucial for the development of new treatments for diseases. It is therefore valuable but still challenging to explore the cross-seeding system of amyloid protein as well as to reveal the structural basis and the intricate processes.

A versatile hydrophilic and antifouling coating was designed and prepared based on catechol-modified four-arm polyethylene glycol. The dopamine (DA) molecules were grafted onto the end of the four-arm polyethylene glycol carboxyl (4A-PEG-COOH) through the amidation reaction, which was proven by

Polymeric carriers for RNA therapy offer potential advantages in terms of low immunogenicity, promoting modifiability and accelerating intracellular transport. However, balancing high transfection efficacy with low toxicity remains challenging with polymer-based vehicles; indeed, polyethyleneimine (PEI) remains the "gold standard" polymer for this purpose despite its significant toxicity limitations. Herein, we demonstrate the potential of polyvinylamine (PVAm), a commodity high-charge cationic polymer used in the papermaking industry and has similar structure with PEI, as an alternative carrier for RNA delivery. High levels of transfection of normal, tumor, and stem cells with a variety of RNA cargoes including small interfering RNA (siRNA), microRNA (miRNA), and recombinant RNA can be achieved in vitro under the proper complex conditions. While, both the anti-tumor effect achieved in a xenograft osteosarcoma model and lipid-lowering activity observed in a hyperlipidemia mice indicate the potential for highly effective in vivo activity. Of note, both the transfection efficiency and the cytotoxicity of PVAm compare more favorably with those of PEI, with PVAm offering the additional advantages of simpler purification and significantly lower cost. In addition, the mechanism for the difference in transfection efficiency between PVAm and PEI is explored by molecular docking as well as analyzing the process of association and dissociation between polymers (PVAm and PEI) and nucleic acids. Our research provides a novel, non-toxic, and cost-effective carrier candidate for next generation RNA therapy, and elucidates the potential mechanism of PVAm for its efficient delivery of RNA.

Protein crystallization could be promoted with a low concentration of impurities and inhibited with a high concentration of impurities, and this inhibition can be weakened by an audible sound.

RNA interference is a promising way to treat cancer and the construction of a stable drug delivery system is critically important for its application. Gelatin nanospheres (GNs) comprise a biodegradable drug vehicle with excellent biocompatibility, but there are limited studies on its delivery and role in the stabilization of miRNA and siRNA. Breast cancer is the most diagnosed type of female cancer worldwide. Abnormal miRNA expression is closely related to the occurrence and progression of estrogen receptor-positive (ER+) breast cancer. In this study, miR-4458 was upregulated in ER+ breast cancer and could inhibit MCF-7 cell viability, colony formation, migration, and invasion. Collagen type XI alpha 1 (COL11A1) was identified as a directly interacting protein of miR-4458 and an important component of the extracellular matrix. High COL11A1 expression was positively correlated with poor prognosis, lower overall survival, disease-free survival, and a late tumor-node-metastasis stage. COL11A1 knockdown could inhibit MCF-7 cell migration and invasion. GNs were used to load a miR-4458 mimic or COL11A1 siRNA (si-COL11A1) to achieve sustained and controlled release in xenograft nude mice. Their tumor volume was decreased, tumor cell apoptosis was promoted, and hepatic metastasis was significantly inhibited. Moreover, the DDR2/SRC signaling pathway was inactivated after transfection with the miR-4458 mimic and si-COL11A1. In conclusion, GNs can be potentially used to deliver siRNA or miRNA, and miR-4458 and COL11A1 can be possible targets for ER+ breast cancer treatment.

Silver nanoparticles (AgNPs) have several applications in nanomedicine where the use of bacterial proteins for synthesis and capping of nanoparticles remain unstudied. Therefore, an extracellular protein of Enterobacter cloacae (SMP1) with ∼15.6 kDa size was partially purified and utilized for the synthesis of AgNPs. Synthesized AgNPs were detected by UV–vis spectrophotometer and characterized by dynamic light scattering (DLS), atomic force microscopy (AFM), cryo-scanning transmission electron microscopy (Cryo-STEM), and high-resolution transmission electron microscopy (HR-TEM). These AgNPs were monodispersed, spherical/quasi-spherical with zeta potential (ZP) of -26.9 mV with an average size of 58.75 nm measured by DLS. The encapsulation of AgNPs with protein was confirmed by electron elemental mapping and the potential mechanism of the synthesis of protein encapsulated AgNPs is outlined. These AgNPs showed broad spectrum bactericidal activity to clinical antibiotic-resistant bacteria. This study revealed that the extracellular protein of bacteria play a vital role in the synthesis of protein-encapsulated bactericidal AgNPs.

The self-assembly of biomacromolecules is an extremely important process. It is potentially useful in the fields of life science and materials science. To carry out the study on the self-assembly of proteins, it is necessary to find out the suitable self-assembly conditions, which have always been a challenging task in practice. Inspired by the screening technique in the field of protein crystallization, we proposed using the same screening technique for seeking suitable protein self-assembly conditions. Based on this consideration, we selected 5 proteins (β-lactoglobulin, hemoglobin, pepsin, lysozyme, α-chymotrypsinogen (II) A) together with 5 screening kits (IndexTM, BML, Morpheus, JCSG, PEG/Ion ScreenTM) to investigate the performance of these crystallization screening techniques in order to discover new optimized conditions of protein self-assembly. The screens were all kept at 293 K for certain days, and were analyzed using optical microscope, scanning electron microscope, transmission electron microscope, atomic force microscope, fluorescence microscope, and atomic absorption spectroscope. The results demonstrated that the method of protein crystallization screening can be successfully applied in the screening of self-assembly conditions. This method is fast, high throughput, and easily implemented in an automated system, with a low protein consumption feature. These results suggested that such strategy can be applied to finding new conditions or forms in routine research of protein self-assembly. KEY POINTS: • Protein crystallization screening method is successfully applied in the screening of self-assembly conditions. • This screening method can be applied on various kinds of proteins and possess a feature of low protein consumption. • This screening method is fast, high throughput, and easily implemented in an automated system.

Peritendinous blood circulation improvement is a challenge to promote the healing of ruptured tendons in clinical treatment. Although electrospun membranes or scaffolds enable the reduction of complications such as adhesion, however, low efficiency, toxicity issues, the loss of biological activity, and complex electrospinning techniques are all bottlenecks of these systems. Improving the blood supply is crucial for their successful use, which involves promoting the metabolism and nutrient absorption in tendons. Here, a multifunctional, structurally simple strategy involving heparin-loaded sutures (PPH) that are clinically applicable is reported, in the form of electrospun core-shell nanofibers, with the ability to perform sustained release of anticoagulants heparin (verified in our previous publication) for the improvement of the healing of Achilles tendon. The morphology and diameter distribution of the collagen fiber in the PPH group are closely related to the health of the Achilles tendon than those of commercial sutures (CS). The in vivo results of the total collagen content and the expression of collagen type I in the PPH group are more than those of the CS group. After 6 weeks of culture, the tensile strength of the PPH group shows no significant difference compared to the healthy group. The data obtained in this study improves the current understanding on the regeneration of ruptured tendons and presents a promising strategy for clinical treatment.

In recent years, with the rapidly increasing demand for pure protein products in various fields (biomedicines, biochemical reagents, food industries, etc.), the need for low-cost, high-quality prot...

A sample delivery system is one of the key parts of serial crystallography. It is the main limiting factor affecting the application of serial crystallography. At present, although a variety of useful sample delivery systems have been developed for serial crystallography, it still remains the focus of the field to further improve the performance and efficiency of sample delivery. In existing sample delivery technologies, samples are usually delivered in linear motion. Here we show that the samples can also be delivered using circular motion, which is a novel motion mode never tested before. In this paper, we report a microfluidic rotating-target sample delivery device, which is characterized by the circular motion of the samples, and verify the performance of the device at a synchrotron radiation facility. The microfluidic rotating-target sample delivery device consists of two parts: a microfluidic sample plate and a motion control system. Sample delivery is realized by rotating the microfluidic sample plate containing in situ grown crystals. This device offers significant advantages, including a very wide adjustable range of delivery speed, low background noise, and low sample consumption. Using the microfluidic rotating-target device, we carried out in situ serial crystallography experiments with lysozyme and proteinase K as model samples at the Shanghai Synchrotron Radiation Facility, and performed structural determination based on the serial crystallographic data. The results showed that the designed device is fully compatible with the synchrotron radiation facility, and the structure determination of proteins is successful using the serial crystallographic data obtained with the device.

Liquid-liquid phase separation (LLPS) is a ubiquitous process found in a variety of fields. It is of particular importance in biological sciences since it plays essential and vital roles in a number of physiological and pathological processes in biological systems. After LLPS, the dense droplets can grow in size via incorporating solutes from surrounding environment and in some cases coalescing with other droplets. Interestingly, the size of the dense droplets seems to have an upper limit but the mechanism remains to be explored. Since the droplet size can be essential for biological functioning, it is important to understand the size evolution of the phase separated droplets. Here we propose a physical mechanism with consideration of impurities on the surface of the dense liquid droplets. The theoretical predictions can be used to explain the observations on the size evolution. Based on the coalescence mechanism, we succeeded for the first time performing a challenging task, i.e., growing a single suspended protein crystal via merging phase-separated droplets in a fully non-contact manner. The mechanism observed may be considered as a basic model for researches in much broader fields involving phase separation, such as in biology, materials science, physics, chemistry, and meteorology.

C22H15N3O2, triclinic, P 1 ‾ $P‾{1}$ (no. 2), a = 5.7613(4) Å, b = 12.3545(7) Å, c = 13.3427(8) Å, α = 110.002(2)°, β = 98.837(2)°, γ = 94.263(2)°, V = 873.55(9) Å3, Z = 2, Rgt (F) = 0.0471, wRref (F 2) = 0.1376, T = 293 K.

Graphitic carbon nitride (g-C3N4) is a visible light-responsive photocatalytic material with important application prospects in many fields. However, the interaction between g-C3N4 monolayers makes it easy to aggregate and precipitate in aqueous solutions, and it is necessary to prepare stable g-C3N4 aqueous dispersions for their applications. Here we propose a facile, green, and low-cost method for the preparation of stable g-C3N4 dispersions by ultrasonicating g-C3N4 in lysozyme (LYZ) solution. The LYZ was adsorbed on the surface of g-C3N4 through non-covalent interactions such as electrostatic interaction, hydrogen bonding and π-cation interaction to prevent the aggregation of g-C3N4 nanolayers. The LYZ/g-C3N4 could quickly re-form a uniform aqueous dispersion solution after freeze-drying, and exhibit good stability. Further, the results of photocatalytic sterilization showed that the assisted dispersion of LYZ enhanced the bactericidal activity of g-C3N4 and exhibited promising application prospects in the field of biomedicine and water disinfection.

Proteins are like miracle machines, playing important roles in living organisms. They perform vital biofunctions by further combining together and/or with other biomacromolecules to form assemblies or condensates such as membraneless organelles. Therefore, studying the self-assembly of biomacromolecules is of fundamental importance. In addition to their biological activities, protein assemblies also exhibit extra properties that enable them to achieve applications beyond their original functions. Herein, this study showed that in the presence of monosaccharides, ethylene glycols, and amino acids, β-lactoglobulin (β-LG) can form assemblies with specific structures, which were highly reproducible. The mechanism of the assembly process was studied through multi-scale observations and theoretical analysis, and it was found that the assembling all started from the formation of solute-rich liquid droplets via liquid-liquid phase separation (LLPS). These droplets then combined together to form condensates with elaborate structures, and the condensates finally evolved to form assemblies with various morphologies. Such a mechanism of the assembly is valuable for studying the assembly processes that frequently occur in living organisms. Detailed studies concerning the properties and applications of the obtained β-LG assemblies showed that the assemblies exhibited significantly better performances than the protein itself in terms of autofluorescence, antioxidant activity, and metal ion absorption, which indicates broad applications of these assemblies in bioimaging, biodetection, biodiagnosis, health maintenance, and pollution treatment. This study revealed that biomacromolecules, especially proteins, can be assembled via LLPS, and some unexpected application potentials could be found beyond their original biological functions.

The problem of global water pollution is becoming more and more severe, among which organic dyes and heavy metal ions are two typical types of the most common pollutants. The adsorption method for water purification and wastewater treatment is widely studied and applied. Hydrogel has unique advantages in the field of adsorption due to its three-dimensional porous structure. In this paper, a new type of self-healing hydrogels based on reversible covalent bond were prepared by mixing poly(vinyl alcohol) (PVA) and 2-aminophenylboronic acid modified polyacrylic acid (PAA-2APBA). In addition, the introduction of laponite nanoparticles into the hydrogel can increase both the mechanical strength and adsorption efficiency. This low-cost PAA-2APBA/PVA/laponite nano-composite hydrogel could efficiently remove the organic dyes and heavy metal ions in model waste water through simple immersion, which makes it have application prospects in the fields of both biomedical and environmental engineering.

Muscle atrophy usually occurs under mechanical unloading, which increases the risk of injury to reduce the functionality of the moving system, while there is still no effective therapy until now. It was found that miR-194 was significantly downregulated in a muscle atrophy model, and its target protein was the myocyte enhancer factor 2C (MEF2C). miR-194 could promote muscle differentiation and also inhibit ubiquitin ligases, thus miR-194 could be used as a nucleic acid drug to treat muscle atrophy, whereas miRNA was unstable in vivo, limiting its application as a therapeutic drug. A gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA here. Exogenous miR-194 was loaded in GNs and injected into the muscle atrophy model. It demonstrated that the muscle fiber cross-sectional area, in situ muscle contractile properties, and myogenic markers were increased significantly after treatment. It proposed miR-194 loaded in GNs as an effective treatment for muscle atrophy by promoting muscle differentiation and inhibiting ubiquitin ligase activity. Moreover, the developed miRNA delivery system, taking advantage of its tunable composition, degradation rate, and capacity to load various drug molecules with high dosage, is considered a promising platform to achieve precise treatment of muscle atrophy-related diseases.

C15H11N3O2, triclinic, P1̄ (no. 2), a = 8.4680(5) Å, b = 9.7578(5) Å, c = 10.2101(6) Å, α = 104.578(5)°, β = 111.882(6)°, γ = 106.589(5)°, V = 686.77(8) Å3, Z = 2, R gt(F) = 0.0394, wR ref(F 2) = 0.1261, T = 250(2) K.

Introduction: Vascular calcification (VC) is a complex, regulated process involved in many disease entities. So far, there are no treatments to reverse it. Exploring novel strategies to prevent VC is important and necessary for VC-related disease intervention. Objective: In this study, we evaluated whether MOTS-c, a novel mitochondria-related 16-aa peptide, can reduce vitamin D3 and nicotine-induced VC in rats. Methods: Vitamin D3 plus nicotine-treated rats were injected with MOTS-c at a dose of 5 mg/kg once a day for 4 weeks. Blood pressure, heart rate, and body weight were measured, and echocardiography was performed. The expression of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and the angiotensin II type 1 (AT-1) and endothelin B (ET-B) receptors was determined by Western blot analysis. Results: Our results showed that MOTS-c treatment significantly attenuated VC. Furthermore, we found that the level of phosphorylated AMPK was increased and the expression levels of the AT-1 and ET-B receptors were decreased after MOTS-c treatment. Conclusions: Our findings provide evidence that MOTS-c may act as an inhibitor of VC by activating the AMPK signaling pathway and suppressing the expression of the AT-1 and ET-B receptors.

Crystallography has made a notable contribution to our knowledge of structural biology. For traditional crystallography experiments, the growth of crystals with large size and high quality is crucial, and it remains one of the bottlenecks. In recent years, the successful application of serial femtosecond crystallography (SFX) provides a new choice when only numerous microcrystals can be obtained. The intense pulsed radiation of X-ray free-electron lasers (XFELs) enables the data collection of small-sized crystals, making the size of crystals no longer a limiting factor. The ultrafast pulses of XFELs can achieve 'diffraction before destruction', which effectively avoids radiation damage and realizes diffraction near physiological temperatures. More recently, the SFX has been expanded to serial crystallography (SX) that can additionally employ synchrotron radiation as the light source. In addition to the traditional ones, these techniques provide complementary opportunities for structural determination. The development of SX experiments strongly relies on the advancement of hardware including the sample delivery system, the X-ray source, and the X-ray detector. Here, in this review, we categorize the existing sample delivery systems, summarize their progress, and propose their future prospectives.

Obtaining good quality protein crystals is still desirable for high resolution structural determination of the proteins using crystallography. The crystal quality is affected by the growth environment and growth methods. As frequently used methods in practical protein crystallization, sitting and hanging-drop methods are seldom compared in terms of crystal quality in the literatures. We performed a systematic comparison on the quality of the protein crystals grown in sitting and hanging-drop methods using different crystallization plates: cross-diffusion microbatch plate (CDM SD: CDM plate, sitting drop method; CDM HD: CDM plate, hanging drop method), traditional sitting and hanging-drop vapor diffusion plates (T SD: traditional plate, sitting drop method; and T HD: traditional plate, hanging drop method). Five different proteins, proteinase K (prk), lysozyme (lys), concanavalin A VI (con), catalase (cat) and α-Chymotrypsinogen A II (chy), were used. The crystal quality was compared in terms of the resolution limit, mosaicity and Wilson plot B factor. It was found that the crystals grown in CDM plate using the hanging drop method (CDM HD) exhibited the best morphology and the best crystal quality. X-ray diffraction tests showed that the CDM plate using hanging drop method is indeed a practical and useful method for obtaining high-quality protein crystals.

Synthesis of silver nanoparticles (AgNPs) with desired physicochemical properties using a cost-effective, energy, and time efficient way is vital. In this study, we have optimized the synthesis of ...

Microbially synthesized iron oxide nanoparticles (FeONPs) hold great potential for biomedical, clinical, and environmental applications owing to their several unique features. Biomineralization, a process that exists in almost every living organism playing a significant role in the fabrication of FeONPs through the involvement of 5-100 nm sized protein compartments such as dodecameric (Dps), ferritin, and encapsulin with their diameters 9, 12, and ∼32 nm, respectively. This contribution provides a detailed overview of the green synthesis of FeONPs by microbes and their applications in biomedical and environmental fields. The first part describes our understanding in the biological fabrication of zero-valent FeONPs with special emphasis on ferroxidase (FO) mediated series of steps involving in the translocation, oxidation, nucleation, and storage of iron in Dps, ferritin, and encapsulin protein nano-compartments. Secondly, this review elaborates the significance of biologically synthesized FeONPs in biomedical science for the detection, treatment, and prevention of various diseases. Thirdly, we tried to provide the recent advances of using FeONPs in the environmental process, e.g. detection, degradation, remediation and treatment of toxic pesticides, dyes, metals, and wastewater.

As a kind of physical environment, magnetic fields are widely used in many different fields, ranging from scientific research to industrial production. With the rapid development of magnetic technology, the importance of magnetic fields in scientific research and practical applications has become increasingly prominent. One notable research field is the application of magnetic fields in the research of biological macromolecules. In this research field, gradient magnetic fields, as one kind of magnetic fields, have attracted much attention and have been widely used in various research fields because they can induce effects caused not only by a magnetic field but also by a magnetic field gradient. This feature makes magnetic fields applicable in many research areas, except for those directly related to the magnetic field itself. So far, the application-based research of gradient magnetic fields involving biological macromolecules has mainly focused on the crystallization, separation and purification as well as the self-assembly of biological macromolecules. Since biological macromolecules usually need to complete various processes in their solution state, the influence of gradient magnetic fields on biological macromolecules is mainly realized through their influence on the solution system. It has been found that a gradient magnetic field can affect convection in biological macromolecular solutions through Lorentz forces and magnetization forces; in practice, partial or even complete suppression of convection can often be observed. In addition, other conditions or parameters of solutions are significantly affected by the gradient magnetic field. For example, in a gradient magnetic field, the following phenomena may occur: (1) superparamagnetic particles in the solution are strongly attracted by the magnetization force, and quick clustering of these particles can happen; (2) the solution itself may have some kind of solution structure; (3) the aggregation of biological macromolecules may show a preferred orientation in the magnetic field direction; (4) the diffusion coefficient of biological macromolecules in the solution will decrease; (5) the solutions viscosity will increase, and so on. As a result of these effects, the following phenomena can be observed: during the crystallization of biological macromolecules, a preferred orientation of the crystals and crystal quality improvement of the biological macromolecules can happen; in the process of separation and purification of biological macromolecules, high-purity and highly bioactive macromolecules can be obtained rapidly and efficiently; and, in the process of the self-assembly of biological macromolecules, abnormal behaviours can occur. Based on these specific effects, the utilization of gradient magnetic fields can be further explored in more professional applications. Currently, the most common applications include the utilization of gradient magnetic fields for obtaining high- quality protein crystals and the achievement of highly efficient and low-cost separation and purification of biological macromolecules. It is obvious that gradient magnetic fields have very important application value in biological macromolecular structure analysis technology, biological drug preparation and preservation technology, theoretical studies involving biomolecular phase separation and nucleation processes, and many other directions. In this paper, the fundamental effects of the gradient magnetic field on the solution of biological macromolecules are reviewed, the applications based on the effects are discussed, and the future prospects in this field are anticipated.

Metallic nanoparticles (MNPs) with their diverse physical and chemical properties have been applied in various biomedical domains. The increasing demand for MNPs has attracted researchers to develop straightforward, inexpensive, simple, and eco-friendly processes for the enhanced production of MNPs. To discover new biomedical applications first requires knowledge of the interactions of MNPs with target cells. This review focuses on plant and microbial synthesis of biological MNPs, their cellular uptake, biocompatibility, any biological consequences such as cytotoxicity, and biomedical applications. We highlighted the involvement of biomolecules in capping and stabilization of MNPs and the effect of physicochemical parameters particularly the pH on the synthesis of MNPs. Recently achieved milestones to understand the role of synthetic biology (SynBiol) in the synthesis of tailored MNPs are also discussed.

A magnetic field has been proved useful in protein crystallization in that it can help to improve the crystal quality, which is essential for high-resolution diffraction using crystallography. However, it is not widely utilized as a high-field magnet usually provides limited space which is usually too small for commercially available crystallization plates, so that the crystallization screening and optimization in such a magnet become a challenging task. Here we show that a specially designed flexible capillary array containing 96 conditions can be easily crimped into a small curl so that it can be accommodated into the bore of a large gradient superconducting magnet. Using the capillary array, we conducted a systematic investigation on the crystallization screening and crystal quality of lysozyme under different simulated gravities (μg, 1g, and 2g) in a large-gradient magnetic field and normal gravity outside the magnet. This is the first statistical study of the crystallization screening of protein in such a high-field magnet. The results showed that both the simulated gravity and the magnetic field affect the crystallization of lysozyme. The simulated microgravity can significantly improve the crystal quality, and the simulated hypergravity is helpful to increase the chance for obtaining crystallization conditions. Moreover, the method exhibits more potential features, such as the capability of in situ diffraction and the applicability for space experiments.

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. Some microRNAs (miRNAs) were abnormally expressed in TNBC, and they are closely related to the occurrence and progression of TNBC. Here, we found that miR-506 was significantly downregulated in TNBC and relatively lower miR-506 expression predicted a poorer prognosis. Moreover, we found that miR-506 could inhibit MDA-MB-231 cell viability, colony formation, migration, and invasion, and suppress the ERK/Fos oncogenic signaling pathway through upregulating its direct target protein proenkephalin (PENK). Therefore, miR-506 was proposed as a nucleic acid drug for TNBC therapy. However, miRNA is unstable in vivo, which limiting its application as a therapeutic drug via conventional oral or injected therapies. Here, a gelatin nanosphere (GN) delivery system was applied for the first time to load exogenous miRNA. Exogenous miR-506 mimic was loaded on GNs and injected into the in situ TNBC animal model, and the miR-506 could achieve sustained and controlled release. The results confirmed that overexpression of miR-506 and PENK in vivo through loading on GNs inhibited in situ triple-negative breast tumor growth and metastasis significantly in the xenograft model. Moreover, we indicated that the ERK/Fos signaling pathway was intensively inactivated after overexpression of miR-506 and PENK both in vitro and in vivo, which was further validated by the ERK1/2-specific inhibitor SCH772984. In conclusion, this study demonstrates that miR-506-loaded GNs have great potential in anti-TNBC aggressiveness therapy.

Non-coding RNAs (ncRNAs) include miRNA, lncRNA, and circRNA. NcRNAs are involved in multiple biological processes, including chromatin remodeling, signal transduction, post-transcriptional modification, cell autophagy, carbohydrate metabolism, and cell cycle regulation. Triple negative breast cancer (TNBC) is notorious for high invasiveness and metastasis, poor prognosis, and high mortality, and it is the most malignant breast cancer, while the effective targets for TNBC treatment are still lacking. NcRNAs act as oncogenes or suppressor genes, as well as promote or inhibit the occurrence and development of TNBC. Here, we reviewed some important miRNAs, lncRNAs, circRNAs, their target(s) and molecular mechanisms in TNBC. It is benefited to understand the occurrence and development of TNBC, further some ncRNAs might be potential targets for TNBC treatment.

Membrane proteins are crucial for biological processes, and many of them are important to drug targets. Understanding the three-dimensional structures of membrane proteins are essential to evaluate their bio-function and drug design. High-purity membrane proteins are important for structural determination. Membrane proteins have low yields and are difficult to purify because they tend to aggregate. We summarized membrane protein expression systems, vectors, tags, and detergents, which have deposited in the Protein Data Bank (PDB) in recent four-and-a-half years. Escherichia coli is the most expression system for membrane proteins, and HEK293 cells are the most commonly cell lines for human membrane protein expression. The most frequently vectors are pFastBac1 for alpha-helical membrane proteins, pET28a for beta-barrel membrane proteins, and pTRC99a for monotopic membrane proteins. The most used tag for membrane proteins is the 6×His-tag. FLAG commonly used for alpha-helical membrane proteins, Strep and GST for beta- barrel and monotopic membrane proteins, respectively. The detergents and their concentrations used for alpha-helical, beta-barrel, and monotopic membrane proteins are different, and DDM is commonly used for membrane protein purification. It can guide the expression and purification of membrane proteins, thus contributing to their structure and bio function studying.

A sample delivery system is one of the key parts of serial crystallography. It is the main limiting factor affecting the application of serial crystallography. At present, although a variety of useful sample delivery systems have been developed for serial crystallography, it still remains the focus of the field to further improve the performance and efficiency of sample delivery. In existing sample delivery technologies, samples are usually delivered in linear motion. Here we show that the samples can also be delivered using circular motion, which is a novel motion mode never tested before. In this paper, we report a microfluidic rotating-target sample delivery device, which is characterized by the circular motion of the samples, and verify the performance of the device at a synchrotron radiation facility. The microfluidic rotating-target sample delivery device consists of two parts: a microfluidic sample plate and a motion control system. Sample delivery is realized by rotating the microfluidic sample plate containing in situ grown crystals. This device offers significant advantages, including a very wide adjustable range of delivery speed, low background noise, and low sample consumption. Using the microfluidic rotating-target device, we carried out in situ serial crystallography experiments with lysozyme and proteinase K as model samples at the Shanghai Synchrotron Radiation Facility, and performed structural determination based on the serial crystallographic data. The results showed that the designed device is fully compatible with the synchrotron radiation facility, and the structure determination of proteins is successful using the serial crystallographic data obtained with the device.

Relative stability of mineral elements in tissues is necessary for health. High static magnetic fields (HiSMFs) have been widely used in biomedical research and industry. However, the bioeffect of HiSMFs on animals is still unclear. In this study, we investigated the effects of HiSMF exposure on the levels of Mg, Fe, Zn, Ca, and Cu in the main organs of mice. The 8-week male C57BL/6 mice were treated by 2–4 T, 6–8 T, 10–12 T HiSMFs for 28 days. The mass fractions of Mg, Fe, Zn, Ca, and Cu in the liver, brain, kidney, and heart in mice were respectively measured by atomic absorption spectroscopy, and used to evaluate mineral element content in tissues. The 2–4 T HiSMF exposure has increased the Mg, Fe, and Ca content in the kidney, as well as the Zn content in the brain. The 6–8 T HiSMF exposure has increased the Zn level in the liver; Mg, Fe, and Ca levels in the kidney; and Fe level in the heart, while the Zn in the kidney, and Zn and Ca in the heart was decreased by 6–8 T HiSMF exposure. For the 10–12 T HiSMF exposure, the Mg in the kidney, the Fe in the liver and kidney, and Cu in the brain have been increased significantly. However, the Zn in the kidney and the Ca in the brain and the heart were reduced by 10–12 T HiSMF exposure. The HiSMF exposure for 28 days can alter the Mg, Fe, Zn, Ca, and Cu content in mice, and change with the different magnetic flux density of HiSMFs (2–4 T, 6–8 T, 10–12 T), elements, and organ types.

Zinc is a biodegradable metal, which exhibits more moderate biodegradability than magnesium and iron, so that it has great application potential in the field of biomedical materials. Alloying of zinc and iron may lead to producing a new type of implant material Zn—Fe alloy, which might be able to meet the requirements for a moderate degradation rate. However, due to the huge difference in the melting point between zinc and iron, the preparation of Zn—Fe alloy is quite challenging and hence rarely reported. In this study, we show that Zn—Fe alloys can be successfully prepared by electrodeposition technology. The microstructures, composition, degradation properties and biocompatibility of the Zn—Fe alloys were systematically studied. The results showed that the content of iron in the alloys ranged from 0 to 8 wt%, depending on the concentration of Fe ions and the current density. In the alloys, the major's phases were η, δ and Г1, and they were mainly affected by the ion concentration in the electrolyte. In the in vitro immersion tests, the Zn—Fe alloy ZF2–1 showed the highest immersion corrosion rate, while ZF3–1 showed the highest electrochemical corrosion rate. Moreover, we found that the corrosion rates of the alloys were significantly higher than that of the pure Fe. In the in vivo experiments, we confirmed that the Zn—Fe alloy possessed good biocompatibility. These results demonstrate that the electrodeposition technology is a good method to prepare Zn—Fe alloys, and the Zn—Fe alloys prepared by this method are potentially promising materials for biomedical applications.