QbD-Guided Traditional Chinese Medicine Manufacturing Process: Development and Optimization of Fluid-Bed Granulation and Drying Processes for Xiaochaihu Capsules.

Traditional methods of producing Xiaochaihu (XCH) capsules, a traditional Chinese medicine, are time-consuming, costly, and labor-intensive, which is not conductive to modernizing TCM. To address the challenges, new fluid-bed granulation and drying processes with water as the binder were developed and optimized guided by the principles of Quality by Design (QbD) in this study. Ishikawa diagram was applied to conduct a preliminary risk assessment, followed by 6-factor definitive screening design (DSD) serving as a QbD statistical tool to develop and optimize the new processes. Multiple potential factors and interactions were studied with a small number of experiments using the DSD. This study identified critical process parameters (CPPs), established quadratic regression models to reveal CPP-critical quality attributes (CQAs) connections within the DSD framework, and defined a dependable design space. Processes conducted by parameter combinations in the design space produced qualified granules with production yield and raw material utilization higher than 90% and moisture content lower than 4%. Furthermore, quantitative analysis of baicalin of all the granules ensured qualified contents of active pharmaceutical ingredient. The newly developed processes for XCH capsules, with advantages of shorter time, environmental friendliness, and decreased cost, exemplify the effective application of QbD and design of experiments (DoE) methodologies in the modernization of TCM manufacturing processes.

Enzyme-Mimetic Molecular Selective Catalysis via Single Zr Atom Catalysis in Chelated Cage Embedded in a Flexible Piezoelectrical Matrix.

The molecularly selective catalysis in enzyme is central to life. However, their functioning mechanism remains elusive. We propose here that the synergistic effects from (i) effective orbital hybridizing and energy gap decreasing via chelating on single Zr atom as the catalytic center, (ii) selective supramolecular encapsulation in the cage, and (iii) piezoelectrical field motivation are able to achieve the enzyme-mimetic molecular selective high performance catalysis. Metal-organic polyhedra (MOPs) are added into a piezoelectrical polymer matrix to achieve the composite structure where ultrasonic treatment motivates redox reactions in the MOP-guest complex. Encapsulated and chelated guest such as Rhodamine B (RhB) is effectively converted with ratios higher than 90 % after 100 min. In comparison, molecules inefficient in either cage encapsulation or chelating with the Zr center can not be converted. This study first proposes a synergistic plot for enzyme-mimetic catalyst realization and is expected to inspire new mentality in efficient catalyst designing.

Characterization of the transcriptional activation domains of human TEF3-1 (transcription enhancer factor 3 isoform 1).

TEF3-1 (transcription enhancer factor 3 isoform 1) is a human transcriptional factor, which has a N-terminal TEA/ATTS domain supposedly for DNA binding and C-terminal PRD and STY domains for transcriptional activation. Taking advantage of the efficient reporter design of yeast two-hybrid system, we characterized the TEF3-1 domains in activating gene expression. Previously study usually mentioned that the C-terminal domain of TEF3-1 has the transcriptional activity, however, our data shows that the peptides TEF3-11-66 and TEF3-1197-434 functioned as two independent activation domains, suggesting that N-terminal domain of TEF3-1 also has transcriptional activation capacity. Additionally, more deletions of amino acids 197-434 showed that only the peptides TEF3-1197-265 contained the minimum sequences for the C-terminal transcriptional activation domain. The protein structure is predicted to contain a helix-turn-helix structure in TEF3-11-66 and four ß sheets in TEF3-1197-265. Finally, after the truncated fragments of TEF3-1 were expressed in HUVEC cells, the whole TEF3-1 and the two activation domains could increase F-actin stress fiber, cell proliferation, migration and targeted gene expression. Further analysis and characterization of the activation domains in TEF3-1 may broaden our understanding of the gene involved in angiogenesis and other pathological processes.

Piezoionic High Performance Hydrogel Generator and Active Protein Absorber via Microscopic Porosity and Phase Blending.

Generating electricity in hydrogel is very important but remains difficult. Hydrogel with electricity generation capability is more capable in bio-relevant tasks such as tissue engineering, artificial skin, or medical treatment, because electricity is indispensable in regulating physiological activities. Here, a porous and phase blending hydrogel structure for effective piezoionic electricity generation is developed. Dynamic electric field is generated taking advantage of the difference in streaming speeds of sodium and chloride in the material. Microscopic porosity and hydrophilic-hydrophobic phase blending are the two key factors for prominent piezoionic performance. Voltages as high as 600 mV are first realized in hydrogels in response to medical ultrasound stimulation. The hydrogel structure is also subjective to effective substance exchange and can actively enrich proteins from surroundings under mechanical stimuli. Preliminary applications in neural stimulation, constructing complex spatial-temporal chemical and electric field distribution patterns, mimetic tactile sensor, sample pretreatment in fast detection, and enzyme immobilization are demonstrated.

Application of SERS in In-Vitro Biomedical Detection.

Surface-enhanced Raman scattering (SERS), as a rapid and nondestructive biological detection method, holds great promise for clinical on spot and early diagnosis. In order to address the challenging demands of on spot detection of biomedical samples, a variety of strategies has been developed. These strategies include substrate structural and component engineering, data processing techniques, as well as combination with other analytical methods. This report summarizes the recent SERS developments for biomedical detection, and their promising applications in cancer detection, virus or bacterial infection detection, miscarriage spotting, neurological disease screening et al. The first part discusses the frequently used SERS substrate component and structures, the second part reports on the detection strategies for nucleic acids, proteins, bacteria, and virus, the third part summarizes their promising applications in clinical detection in a variety of illnesses, and the forth part reports on recent development of SERS in combination with other analytical techniques. The special merits, challenges, and perspectives are discussed in both introduction and conclusion sections.

In-Line Detection of Bed Fluidity in Gas-Solid Fluidized Beds Using Near-Infrared Spectroscopy.

A novel approach was developed to detect bed fluidity in gas-solid fluidized beds using diffuse reflectance near-infrared (NIR) spectroscopy. Because the flow dynamics of gas and solid phases are closely associated with the fluidization state, the fluidization quality can be evaluated through hydrodynamic characterization. In this study, the baseline level of NIR spectra was used to quantify the voidage of the fluidized bed. Two indicators derived from the NIR baseline fluctuation profiles were investigated to characterize bed fluidity, named bubble proportion and skewness. To establish a robust fluidity evaluation method, the relationships between the indicators and bed fluidity were investigated under different conditions firstly, including static bed height and average particle size. Then, a generalized threshold was identified to distinguish poor and good bed fluidity, ensuring that the probability of the α- and ß-errors was less than 15% regardless of material conditions. The results show that both indicators were sensitive to changes in bed fluidity under the investigated conditions. The indicator of skewness was qualified to detect bed fluidity under varied conditions with a robust threshold of 1.20. Furthermore, the developed NIR method was successfully applied to monitor bed fluidity and for early warning of defluidization in a laboratory-scale fluidized bed granulation process.

Effective Scald Wound Functional Recovery Patch Achieved by Molecularly Intertwined Electrical and Chemical Message in Self-Adhesive Assemblies.

Bioactive materials that communicate with bio-tissues via simultaneous chemical and electrical information promise an advanced medical treatment strategy. Rational design of simultaneous chemically and electrically active materials is still challenging. In this study, we develop a bioactive wound healing patch that enables functional recovery of scald skin wounds by integrating electrically and chemically active units at the molecular level. The patch should be used with massages for 10 min daily during the recovery process. This healing patch consists of a closely intertwined piezoelectric poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF) film and a self-adhesive poly(N,N-dimethylacrylamide) (PDMAA) hydrogel layer, which permits itself to adhere on skin wounds reversibly. Frequency-dependent electrical and chemical dose delivery is achieved in response to mechanical stimuli via the electrical-chemical crosstalk within the healing patch. Animal scald experiments show that the patch can effectively guide the functional recovery of grade I and shallow grade II scald wounds, promoting proper collagen deposition and hair follicle, blood vessel, and gland regeneration. Integrating electrically and chemically active units at the molecular level in treatment devices provides a new design concept for tissue engineering and medical treatment materials.

A Shapable Alginate Hydrogel Resolving the Conflicts between Multifunctionality and Fabrication Simplicity.

Alginate is a naturally derived biocompatible polymer widely used as a drug or food adjuvant. However, its usage as a biofunctional material has been confounded by the lack of shapable strategies. In this study, we report an easily applied ionic cross-linking strategy for fabricating shapable multifunctional SA-Ca(II) hydrogels employing the process of regulated diffusion. The fabrication proceeds in neutral solutions under ambient conditions. The obtained SA-Ca(II) hydrogel presents tunable moduli ranging from 4 to 30 kPa, resembling a series of human tissues. The tunable mechanical strength provides differentiation signals for stem cell polarization. The hydrogel film can lift a weight of 10 kg. The hydrogel can be prepared into various shapes and remains stable over one year upon rinsing in deionized water, but rapidly degrades in alginate lyase solutions. Subcutaneously embedded SA-Ca(II) hydrogels in mice show high biocompatibility and degrade over 4 weeks accompanied by hair follicle regeneration. Wearable protections as well as stimuli-responsive electronic circuits are then achieved, which not only protect the model body against high-temperature environments but also show warning signals when the protection loses effectiveness because of high temperatures. Overall, these results demonstrate that our SA-Ca(II) hydrogel offers appealing comprehensive functionalities from multifaceted perspectives, including mechanical strength, economic and environmental considerations, transparency, forming capability, biocompatibility, and conductivity.

Recent Development of Alginate-Based Materials and Their Versatile Functions in Biomedicine, Flexible Electronics, and Environmental Uses.

Alginate is a natural polysaccharide that is easily chemically modified or compounded with other components for various types of functionalities. The alginate derivatives are appealing not only because they are biocompatible so that they can be used in biomedicine or tissue engineering but also because of the prospering bioelectronics that require various biomaterials to interface between human tissues and electronics or to serve as electronic components themselves. The study of alginate-based materials, especially hydrogels, have repeatedly found new frontiers over recent years. In this Review, we document the basic properties of alginate, their chemical modification strategies, and the recent development of alginate-based functional composite materials. The newly thrived functions such as ionically conductive hydrogel or 3D or 4D cell culturing matrix are emphasized among other appealing potential applications. We expect that the documentation of relevant information will stimulate scientific efforts to further develop biocompatible electronics or smart materials and to help the research domain better address the medicine, energy, and environmental challenges faced by human societies.

Nuclear localization of TEF3-1 promotes cell cycle progression and angiogenesis in cancer.

TEF3-1 (transcriptional enhancer factor 3 isoform 1), also known as TEAD4 (TEA domain family member 4), was recently revealed as an oncogenic character in cancer development. However, the underlying molecular pathogenic mechanisms remain undefined. In this paper, we investigated nuclear TEF3-1 could promote G1/S transition in HUVECs, and the expression levels of cyclins and CDKs were upregulated. Additionally, if TEF3-1 was knocked down, the expression of cyclins and CDKs was downregulated while the expression of P21, a negative regulator of the cell cycle, was upregulated. A microarray analysis also confirmed that TEF3-1 overexpression upregulates genes that are related to cell cycle progression and the promotion of angiogenesis. Moreover, we observed that nuclear TEF3-1 was highly expressed during the formation of vascular structures in gastric cancer (GC). Finally, tumor xenograft experiments indicated that, when TEF3-1 was knocked down, tumor growth and angiogenesis were also suppressed. Taken together, these results demonstrate for the first time that TEF3-1 localization to the nucleus stimulates the cell cycle progression in HUVECs and specifically contributes to tumor angiogenesis. Nuclear TEF3-1 in HUVECs may serve as an oncogenic biomarker, and the suppression of TEF3-1 may be a potential target in anti-tumor therapy.

rBmαTX14 Increases the Life Span and Promotes the Locomotion of Caenorhabditis Elegans.

The scorpion has been extensively used in various pharmacological profiles or as food supplies. The exploration of scorpion venom has been reported due to the presence of recombinant peptides. rBmαTX14 is an α-neurotoxin extracted from the venom gland of the East Asian scorpion Buthus martensii Karsch and can affect ion channel conductance. Here, we investigated the functions of rBmαTX14 using the Caenorhabditis elegans model. Using western blot analysis, rBmαTX14 was shown to be expressed both in the cytoplasm and inclusion bodies in the E.coli Rosetta (DE3) strain. Circular dichroism spectroscopy analysis demonstrated that purified rBmαTX14 retained its biological structures. Next, feeding nematodes with E.coli Rosetta (DE3) expressing rBmαTX14 caused extension of the life span and promoted the locomotion of the nematodes. In addition, we identified several genes that play various roles in the life span and locomotion of C. elegans through microarray analysis and quantitative real-time PCR. Furthermore, if the amino acid site H15 of rBmαTX14 was mutated, rBmαTX14 no longer promoted the C. elegans life span. In conclusion, the results not only demonstrated the functions and mechanism of rBmαTX14 in C. elegans, but also provided the new sight in the utility of recombinant peptides from scorpion venom.