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Injectable shear-thinning biomaterials (STBs) have attracted significant attention because of their efficient and localized delivery of cells as well as various molecules ranging from growth factors to drugs. Recently, electrostatic interaction-based STBs, including gelatin/LAPONITE® nanocomposites, have been developed through a simple assembly process and show outstanding shear-thinning properties and injectability. However, the ability of different compositions of gelatin and LAPONITE® to modulate doxorubicin (DOX) delivery at different pH values to enhance the effectiveness of topical skin cancer treatment is still unclear. Here, we fabricated injectable STBs using gelatin and LAPONITE® to investigate the influence of LAPONITE®/gelatin ratio on mechanical characteristics, capacity for DOX release in response to different pH values, and cytotoxicity toward malignant melanoma. The release profile analysis of various compositions of DOX-loaded STBs under different pH conditions revealed that lower amounts of LAPONITE® (6NC25) led to higher pH-responsiveness capable of achieving a localized, controlled, and sustained release of DOX in an acidic tumor microenvironment. Moreover, we showed that 6NC25 had a lower storage modulus and required lower injection forces compared to those with higher LAPONITE® ratios. Furthermore, DOX delivery analysis in vitro and in vivo demonstrated that DOX-loaded 6NC25 could efficiently target subcutaneous malignant tumors via DOX-induced cell death and growth restriction. This journal is

Here, the effect of high-pressure conditions (0.1-400 MPa) on the water-loss, texture, gel strength, color, dynamic rheological property, and water migration of pork batters containing 0.1% (W/W) Artemisia sphaerocephala krasch gum (PB-AG) is studied. Results indicated that the cooking yield, water-holding capacity, texture, gel strength, L* values, and G' values increased with the increase in pressure (0.1-300 MPa) (p

Objective: To screen for α-glucosidase inhibitor active compounds in the total saponins of Baibiandou (Lablab Semen Album) based on UHPLC-Q-Exactive Orbitrap MS technology and to evaluate its hypoglycemic activity in vivo. Methods: Acarbose was used as the positive control, and the median inhibitory concentration (IC50) was used as the evaluation index of α-glucosidase inhibitory activity to establish an in vitro α-glucosidase inhibition model. Further, UHPLC-Q-Exactive Orbitrap MS technology was used to screen and identify the active compounds of α-glucosidase inhibitors in the total saponins of Baibiandou (Lablab Semen Album) in order to further verify the activity of the main active monomer and to perform homologous modeling and molecular docking of yeast-derived α-glucosidase and human-derived α-glucosidase, while the hypoglycemic activity was evaluated in diabetic mice. Results: This study successfully identified 15 compounds with potential α-glucosidase inhibitory activity, including Chikusetsusaponin IVa, from the total saponins of Baibiandou (Lablab Semen Album). Simultaneously, we verified the activity of the main active monomer Chikusetsusaponin IVa, and showed that it has strong α-glucosidase inhibitory activity. The α-glucosidase inhibitory concentration IC50 was (565.2 ± 1.026) μg/mL, and the IC50 of acarbose, which was lower than the positive control, was (706.6 ± 1.058) μg/mL. The docking energies of Chikusetsusaponin IVa were – 6.1 and – 7.7 kcal/mol with yeast-derived α-glucosidase and human-derived α-glucosidase molecules, respectively. Both showed strong binding activity, and the levels of alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), UREA, Creatinine (CREA), and cholesterol (CHO) were significantly decreased by Chikusetsusaponin IVa (P < 0.05). In addition, it could repair damaged liver and pancreas cells of diabetic mice to some extent. Conclusion: This study provides a basis for screening α-glucosidase inhibitors and structural modifications of the total saponins of Baibiandou (Lablab Semen Album).

The unique properties of fluorine-containing organic compounds make fluorine substitution attractive for the development of pharmaceuticals and various specialty materials, which have inspired the evolution of diverse C-F bond activation techniques. Although many advances have been made in functionalizations of activated C-F bonds utilizing transition metal complexes, there are fewer approaches available for nonactivated C-F bonds due to the difficulty in oxidative addition of transition metals to the inert C-F bonds. In this regard, using Lewis acid to abstract the fluoride and light/radical initiator to generate the radical intermediate have emerged as powerful tools for activating those inert C-F bonds. Meanwhile, these transition-metal-free processes are greener, economical, and for the pharmaceutical industry, without heavy metal residues. This review provides an overview of recent C-F bond activations and functionalizations under transition-metal-free conditions. The key mechanisms involved are demonstrated and discussed in detail. Finally, a brief discussion on the existing limitations of this field and our perspective are presented.

Cognitive deficits are the core feature of schizophrenia and effective treatment strategies are still missing. Previous studies have reported that fisetin promotes long-term potentiation (LTP) and cognitive function in normal rodents and other model animals of neurological diseases. The aim of the present study was to assess the effect of fisetin on synaptic plasticity and cognitive deficits caused by a brief disruption of N-methyl-D-aspartate receptors (NMDARs) with dizocilpine (MK-801) during early development in rats. The cognitive performance was examined by the Morris water maze task and a fear conditioning test. Hippocampal synaptic plasticity was investigated by field potential recording. The expression of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) and cognition-related proteins were measured by Western blotting. We found that intraperitoneal administration of fisetin rescued hippocampus-dependent spatial and contextual fear memory in MK-801 rats. In parallel with these behavioral results, fisetin treatment in MK-801 rats reversed the impairment of hippocampal LTP. At the molecular level, fisetin treatment selectively increased the phosphorylation and surface expression of AMPA receptor subunit 1 (GluA1) in MK-801-treated rats. Moreover, fisetin restored the phosphorylation levels of calcium-calmodulin-dependent kinaseII (CaMKII), cAMP response element-binding protein (CREB) and the extracellular signal-regulated kinase (ERK1/2) in MK-801-treated rats. Collectively, our findings demonstrate that fisetin treatment can reverse the deficits of hippocampal synaptic plasticity and memory in a male rat model of schizophrenia by restoring the phosphorylation and surface expression of AMPAR GluA1 subunit, suggesting fisetin as a promising therapeutic candidate for schizophrenia-associated cognitive deficits.

Vibration stress relief (VSR) and thermal stress relief (TSR) are important method to eliminate the residual stress of structural parts. The thermal vibratory stress relief (TVSR) is a new method to decrease and homogenize the residual stress. Based on the stress relaxation tests and the equivalent vibration equation of modal analysis, the creep constitutive model and the bilinear isotropic hardening plasticity material model (BISO) are combined to establish the numerical simulation model of TVSR of 7075 aluminum alloy ring part. The simulation results show that four different initial blank residual stress levels are obtained after quenching process, and the residual stress elimination and homogenization effect of TSR and TVSR is better than that of VSR. TVSR has a better effect on both residual stress elimination and homogenization, and the residual stress relief rate can reach more than 20%.

Thiocarbonylation of alkenes offers an ideal procedure for the synthesis of thioesters. However, thiocarbonylation of alkenes, especially styrenes, to produce valuable linear thioesters has remaine...

Objective To explore the pharmacological mechanism of active saponin compounds of Tuchao Baibiandouren (Lablab Semen Album fried with earth, TCBBDR) in treating type 2 diabetes (T2DM) using UHPLC-Q-Exactive Orbitrap MS and network pharmacology. Methods UHPLC-Q-Exactive Orbitrap MS was used for a qualitative analysis of saponin compounds in TCBBDR. PharmMapper and CTD were used to screen drug active compounds and disease targets, and an active compound-target network was constructed via Cytoscape 3.8.0. Molecular docking was applied with the drug active compounds and key targets using AutoDock Vina 1.1.2, and a trajectory for the molecular dynamics simulation was completed by GROMACS 2019-3. Results Sixteen saponin compounds were identified from TCBBDR, along with 292 saponin compoud targets and 792 T2DM targets. Through Venn analysis of target saponin constituents and T2DM related targets, a total of 91 intersection targets were screened out in the treatment of T2DM with saponin. The mean values of degree, betweenness centrality and closeness centrality were taken as the thresholds to screen out 22 key genes, among which 4 key proteins namely MAPK1, IGF1 EGFR, PIK3R1 were selected in the top 10 key genes. On this basis, the saponin active constituent-target-signaling pathway network was established. The Gene Ontology (GO) enrichment analysis showed that the related biological modules included activity of steroid hormone receptor, steroid binding, and insulin receptor binding, etc.; the related signaling pathways were EGFR, PI3K-Akt and MAPK, etc.; regulating signaling pathways like MAPK could induce the proliferation, inhibition and apoptosis of pancreatic β cells, increase the quantity of pancreatic β cells, improve the functions of pancreatic β cells and stimulate the insulin secretion. Docking experiment analysis showed that all selected saponin compounds could enter the active sites of targets and form 3 – 14 hydrogen bonds with residues of the active sites. Moreover, van der Waals forces were present between chemical compounds and active sites. By combining the docking binding energy, we determined that the chemical compounds showed strong binding energy to the targets. Conclusion TCBBDR exerts therapeutic effects on diabetes through multi-compound and multi-target collaboration. Specifically, saponin components mediate pathways including inflammatory reaction and signal transduction to treat T2DM by regulating several key proteins that interact with EGFR and a series of signaling pathways related to disease development.

Background Increasing antibiotic resistance continues to focus on research into the discovery of novel antimicrobial agents. Due to its antimicrobial and wound healing-promoting activity, metal nanoparticles have attracted attention for dermatological applications. This study is designed to investigate the scope and bactericidal potential of zinc ferrite nanoparticles (ZnFe2O4 NPs), and the mechanism of anti-bacterial action along with cytocompatibility, hemocompatibility, and wound healing properties. Results ZnFe2O4 NPs were synthesized via a modified co-precipitation method. Structure, size, morphology, and elemental compositions of ZnFe2O4 NPs were analyzed using X-ray diffraction pattern, Fourier transform infrared spectroscopy, and field emission scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy. In PrestoBlue and live/dead assays, ZnFe2O4 NPs exhibited dose-dependent cytotoxic effects on human dermal fibroblasts. In addition, the hemocompatibility assay revealed that the NPs do not significantly rupture red blood cells up to a dose of 1000 µg/mL. Bacterial live/dead imaging and zone of inhibition analysis demonstrated that ZnFe2O4 NPs showed dose-dependent bactericidal activities in various strains of Gram-negative and Gram-positive bacteria. Interestingly, NPs showed antimicrobial activity through multiple mechanisms, such as cell membrane damage, protein leakage, and reactive oxygen species generation, and were more effective against gram-positive bacteria. Furthermore, in vitro scratch assay revealed that ZnFe2O4 NPs improved cell migration and proliferation of cells, with noticeable shrinkage of the artificial wound model. Conclusions This study indicated that ZnFe2O4 NPs have the potential to be used as a future antimicrobial and wound healing drug.

Non-thermal plasma (NTP) is widely used in the disinfection and surface modification of biomaterials. NTP treatment can regenerate and improve skin function; however, its effectiveness on hair follicle (HF) growth and its underlying mechanisms need to be elucidated. Herein, we propose an air-based NTP treatment, which generates exogenous nitric oxide (eNO), as a therapeutic strategy for hair growth. The topical application of air-based NTP generates large amounts of eNO, which can be directly detected using a microelectrode NO sensor, in the dermis of mouse dorsal skin. Additionally, NTP-induced eNO has no cytotoxicity in normal human skin cells and promotes hair growth by increasing capillary tube formation, cellular proliferation, and hair/angiogenesis-related protein expression. Furthermore, NTP treatment promotes hair growth with adipogenesis and activation of CD34+CD44+ stem cells and improves the inter-follicular macroenvironment via increased perifollicular vascularity in the mouse hair regrowth model. Given the importance of the hair follicle (HF) cycle ratio (growth vs. regression vs. resting) in diagnosing alopecia, NTP treatment upregulates the stem cell activity of the HF to promote the anagen : catagen : telogen ratio, leading to improved hair growth. We confirmed the upregulation of increasing Wnt/β-catenin signaling and activation of perifollicular adipose tissue and angiogenesis in HF regeneration. In conclusion, these results show that the eNO from NTP enhances the cellular activities of human skin cells and endothelial cells in vitro and stem cells in vivo, thereby increasing angiogenesis, adipogenesis, and hair growth in the skin dermis. Furthermore, the results of this study suggest that NTP treatment may be a highly efficient alternative in regenerative medicine for achieving enhanced hair growth.

How to make a carbonylative coupling faster than the easier nucleophilic substitution? In this communication, a rhodium-catalyzed radical-based carbonylative coupling of alkyl halides with thiolphenols has been realized. Thioesters were isolated in good yields in general.

Cryogenic ion spectroscopy was used to characterize adenine complexes containing alkali metal cations (M+A, M = Cs, Rb, K, Na, and Li) produced by electrospray ionization. The ultraviolet (UV) photodissociation spectra of the complexes stored in a cryogenic ion trap exhibited well-resolved vibronic bands near their origin bands of the S0–S1 transition. The UV-UV hole-burning and infrared ion-dip spectra showed that all the M+A ions in the ion trap were single isomers of M+A7a, where the M+ ion was not bound to canonical 9H-adenine (A9) but bound to a rare tautomer, 7H-adenine (A7). Density functional theory calculations showed lower tautomerization barriers for M+A9 than for bare A9 in aqueous solution. We suggest that M+ ions not only play a catalytic role in the tautomerization of A9 to A7 but also increase the tautomerization yield by forming stable M+A7a isomers.

Fluorescent nanomaterials have been widely used in biological imaging due to their selectivity, sensitivity, and noninvasive nature. These characteristics make the materials suitable for real-time and in situ imaging. However, further development of highly biocompatible nanosystems with long-lasting fluorescent intensity and photostability is needed for advanced bioimaging. We have used electrospraying to generate gelatin methacryloyl (GelMA)-based fluorescent nanoparticles (NPs) with chemically conjugated rhodamine B (RB). The extent of conjugation can be controlled by varying the mass ratio of RB and GelMA precursors to obtain RB-conjugated GelMA (RB-GelMA) NPs with optimal fluorescent properties and particle size. These NPs exhibited superior biocompatibility when compared with pure RB in in vitro cell viability and proliferation assays using multiple cell types. Moreover, RB-GelMA NPs showed enhanced cell internalization and improved brightness compared with unconjugated RB. Our experiments demonstrate that engineered RB-GelMA NPs can be used as a biocompatible fluorescent label for bioimaging.

A rhodium-catalyzed carbonylative transformation of unactivated phenols to aryl salicylates is described. This protocol is characterized by utilizing 1,3-rhodium migration as the key step to provide direct access to synthesize

A rhodium-catalyzed carbonylative transformation of alkyl halides under low pressure of CO has been developed. This robust catalyst system allows using phenols as the carbonylative coupling partner...

Anaerobic-oxic (AO) systems have been extensively adopted for the biological treatment of wastewater from recycled paper mills, which is characterized by high chemical oxygen demand (COD) concentrations and contains hundreds of organic compounds. In this study, an up-flow anaerobic sludge blanket (UASB) served as the anaerobic treatment of recycled paper mill wastewater. Then, either a sequential batch reactor (SBR) or a sequential batch biofilm reactor (SBBR) were adopted as aerobic treatment to treat the UASB effluent respectively. Parameters such as COD, BOD5, and TSS were measured to compare the treatment performance of SBR and the SBBR. After 80 days’ operation, COD removal efficiency of SBR and SBBR were 21.79 ± 3.4% and 38.38 ± 2.69% respectively; TSS removal efficiencies were 20.84 ± 5.15% and 47.02 ± 5.84% respectively. The results indicated that SBR was effective for removing residual organic matter in UASB effluent. However, SBBR showed significant advantages for the removal of COD and total suspended solids (TSS), which are ascribed to the effective biomass retention and biofiltration of SBBR.

Black phosphorus (BP) shows great potential in electronic and optoelectronic applications; however, maintaining the stable performance of BP devices over temperature is still challenging. Here, a novel BP field-effect transistor (FET) fabricated on the atomic layer deposited AlN/SiO2/Si substrate is demonstrated. Electrical measurement results show that BP FETs on the AlN substrate possess superior electrical performance compared with those fabricated on the conventional SiO2/Si substrate. It exhibits a large on-off current ratio of 5 × 108, a low subthreshold swing of 2 V−1 s−1 in the temperature range from 77 to 400 K. However, these stable electrical performances are not found in the BP FETs on SiO2/Si substrate when the temperature increases up to 400 K; instead, the electrical performance of BP FETs on the SiO2/Si substrate degrades drastically. Furthermore, to gain a physical understanding on the stable performance of BP FETs on the AlN substrate, low-frequency noise analysis was performed, and it revealed that the AlN film plays a significant role in suppressing the lattice scattering and charge trapping effects at high temperatures.

A biomass involved rhodium-catalyzed carbonylative synthesis of furfuryl esters and tertiary amides has been developed. 5-Hydroxymethylfurfural (HMF) was used as both substrate and CO surrogate for the first time in a carbonylation reaction, and both alkyl and aryl iodides were tolerated well to afford the desired furfuryl esters in moderate to good yields. In addition, furfural was also utilized as a CO source for the synthesis of tertiary amides. A variety of tertiary amides were obtained in moderate to excellent yields with good functional groups compatibility. Notably, tertiary amines were used as the amine source through a C N bond cleavage pathway in the absence of additional oxidant.

A new method of low-cost copper-catalyzed carbonylative cyclization for preparing pyrrolidine-containing amides from γ,δ-unsaturated aromatic oxime esters and amines has been described. A range of readily available amines were examined, including primary, secondary, and heterocycle amines, giving over 60 examples of targeted N-heterocycle substituted amides with broad functional group tolerance, good chemical selectivity and moderate to excellent yields.

A new beam scanning method of a Fabry–Perot cavity (FPC) antenna is proposed. To obtain high gain in a target direction with a reduced sidelobe level (SLL), we devised a tapered partially reflective surface (PRS) as a superstrate. Moreover, to attain various beam scanning directions, a phase-controllable artificial magnetic conductor (AMC) ground plane with a broad reflection phase range and high reflection magnitudes was introduced. In the proposed method, a new formula to satisfy an FP resonance condition in a cavity for a scanned beam is also suggested. According to the formula, the FPC antenna can precisely scan the main beam in designed target directions with well-maintained high gain, which has been hardly achievable. In addition, our method demonstrates the potential of electrical beam-scanning antennas by employing active RF chips on the AMC cells. To validate the method, we fabricated a prototype FPC antenna for a scanned beam at θ = 30°. Furthermore, we conducted an additional simulation for a different beam scanning angle as well. Good agreement between the expected and experimental results verifies our design approach.

We obtained ultraviolet photodissociation (UVPD) circular dichroism (CD) spectra of protonated L-phenylalanyl-L-alanine (L-H+PheAla) near the origin band of the S0–S1 transition using cryogenic ion spectroscopy. Infrared (IR) ion-dip, IR-UV hole burning (HB) and UV-UV HB spectra showed that L-H+PheAla existed as two different conformers in a cryogenic ion trap, and they had nearly identical peptide backbones but different conformations in the Phe side chain. The UVPD CD spectra revealed that the two conformers had opposite CD signs and significantly different CD magnitudes from each other. These results demonstrate that the CD value of L-H+PheAla near the origin band is strongly influenced by the conformation of the Phe side chain.

Made available in DSpace on 2021-06-25T10:22:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-01 The skin serves a substantial number of physiological purposes and is exposed to numerous biological and chemical agents owing to its large surface area and accessibility. Yet, current skin models are limited in emulating the multifaceted functions of skin tissues due to a lack of effort on the optimization of biomaterials and techniques at different skin layers for building skin frameworks. Here, we use biomaterial-based approaches and bioengineered techniques to develop a 3D skin model with layers of endothelial cell networks, dermal fibroblasts, and multilayered keratinocytes. Analysis of mechanical properties of gelatin methacryloyl (GelMA)-based bioinks mixed with different portions of alginate revealed bioprinted endothelium could be better modeled to optimize endothelial cell viability with a mixture of 7.5% GelMA and 2% alginate. Matrix stiffness plays a crucial role in modulating produced levels of Pro-Collagen I alpha-1 and matrix metalloproteinase-1 in human dermal fibroblasts and affecting their viability, proliferation, and spreading. Moreover, seeding human keratinocytes with gelatin-coating multiple times proved to be helpful in reducing culture time to create multiple layers of keratinocytes while maintaining their viability. The ability to fabricate selected biomaterials for each layer of skin tissues has implications in the biofabrication of skin systems for regenerative medicine and disease modeling. Center for Minimally Invasive Therapeutics (C-MIT) University of California-Los Angeles Bioprocess and Biotechnology Department Sãao Paulo State University (Unesp) School of Pharmaceutical Sciences, Km 01 Araraquara-Jau Road São Paulo State University (Unesp) Institute of Chemistry, 55 Prof. Francisco Degni Street Terasaki Institute for Biomedical Innovation Department of Bioengineering Henry Samueli School of Engineering and Applied Sciences University of California-Los Angeles Department of Electrical and Electronic Engineering The University of Hong Kong College of Pharmacy Kangwon National University U.S. Air Force Research Laboratory 711th Human Performance Wing Airman Systems Directorate Bioeffects Division Molecular Bioeffects Branch (USAFRL/711HPW/RHDJ) Department of Radiological Sciences University of California-Los Angeles Department of Biomedical Engineering Michigan State University Department of Chemical and Biomolecular Engineering Henry Samueli School of Engineering and Applied Sciences University of California-Los Angeles Jonsson Comprehensive Cancer Centre University of California Bioprocess and Biotechnology Department Sãao Paulo State University (Unesp) School of Pharmaceutical Sciences, Km 01 Araraquara-Jau Road São Paulo State University (Unesp) Institute of Chemistry, 55 Prof. Francisco Degni Street

Thiocarbonylation of alkynes offers an ideal procedure for the synthesis of unsaturated thioesters. A robust ligand-controlled regioselective thiocarbonylation of alkynes is developed. Utilizing boronic acid and 5-chlorosalicylic acid as the acid additive to in situ form 5-chloroborosalicylic acid (5-Cl-BSA), and bis(2-diphenylphosphinophenyl)ether (DPEphos) as the ligand, linear α,β-unsaturated thioesters were produced in a straightforward manner. Switching the ligand to tri(2-furyl)phosphine can turn the reaction selectivity to give branched products. Remarkably, this approach also represents the first example on thiocarbonylation of internal alkynes.

QD LED has an ideal light source for growing crops and can also be used to control plant pathogenic microorganisms. The mycelial growth inhibition effect of QD LED light on Rhizoctonia solani, Phytophthora drechsleri, Sclerotinia sclerotiorum, Sclerotinia minor, Botrytis cinerea, Fusarium oxysporum, Pectobacterium carotovorum, and Xanthomonas campestris were investigated. According to the results, BLUE (450 nm) light, suppressed S. sclerotiorum by 16.7% at 50 cm height from the light source, and 94.1% mycelial growth at 30 cm height. Mycelial growth of Sclerotinia minor was inhibited by 80.4% at 50 cm height and 36.3% at 50 cm height in B. cinerea. S. minor, and B. cinerea was inhibited by 100% mycelial growth at a height of 30 cm from the light source. At 15 cm height, all three pathogens (B. cinerea, S. minor, and S. sclerotiorum) was inhibited by 100%. QD RED (M1) and QD RED (M2) light suppressed mycelial growth of S. minor and B. cinerea by 100% at 30 cm and 15 cm height from the light source. For S. sclerotiorum, QD RED (M1) and QD RED (M2) showed 75.2% and 100% inhibition, respectively. Further experiment was conducted to know the suppression effect of lights after inoculating the fungal pathogens on lettuce crop. According to the results, QD RED (M2) suppressed the S. sclerotiorum by 59.9%. In addition, Blue (450 nm), QD RED (M1), and QD RED (M2) light reduce the infestation by 59.9%. In case of B. cinerea, disease reduction was found 84% by BLUE (450 nm) light. Results : suggest that the growth inhibition of mycelium increases by Quantum dot LED light.

Budding yeast generate heterogeneous cells that can be separated into two distinctive cell types: short-living low-density and long-living high-density (HD) cells by density gradient centrifugation. We found that ethanol and acetate induce formation of HD cells, and mitochondrial respiration is required. From their transcriptomes and metabolomes, we found upregulated differentially expressed genes in HD cells involved in the RGT2/RGT1 glucose sensing pathway and its downstream genes encoding hexose transporters. For HD cells, we determined an abundance of various carbon sources including glucose, lactate, pyruvate, trehalose, mannitol, mannose, and galactose. Other upregulated differentially expressed genes in HD cells were involved in the TORC1–SCH9 signaling pathway and its downstream genes involved in cytoplasmic translation. We also measured an abundance of free amino acids in HD cells including valine, proline, isoleucine, and glutamine. These characteristics of the HD cell transcriptome and metabolome may be important conditions for maintaining a long-living phenotype.

Organoid is a cell organization grown in a three-dimensional (3D) culture system which represents all characteristics of its origin. However, this organ-like structure requires supporting matrix to maintain its characteristics and functions. Matrigel, derived from mouse sarcoma, has often been used as the supporting matrix for organoids, but the result may not be desirable for clinical applications because of the unidentified components from the mouse sarcoma. On the other hand, natural characteristics of collagen emphasize toxic-free friendly niche to both organoid and normal tissue. Hence, this study attempts to develop a new, collagen-based matrix that may substitute Matrigel in organoid culture. Collagen-based matrix was made, using type 1 collagen, Ham’s F12 nutrient mixture, and bicarbonate. Then, characteristics of mouse colon organoids were analyzed by morphology and quantitative messenger RNA (mRNA) expression, revealing that the mouse colon organoids grown in the collagen-based matrix and in Matrigel had quite similar morphology, specific markers, and proliferative rates. Mouse small intestine–derived organoids, stomach-derived organoids, and human colon–derived organoids were also cultured, all of which were successfully grown in the collagen-based matrix and had similar properties compared to those cultured in Matrigel. Furthermore, possibility of organoid transplantation was observed. When mouse colon organoids were transplanted with collagen matrix into the EDTA-colitis mouse model, colon organoids were successfully engrafted in damaged tissue. For that reason, the use of collagen-based matrix in organoid culture will render organoid cultivation less expensive and clinically applicable.

The need for continuous size downscaling of silicon transistors is driving the industrial development of strategies to enable further footprint reduction1,2. The atomic thickness of two-dimensional materials allows the potential realization of high-area-efficiency transistor architectures. However, until now, the design of devices composed of two-dimensional materials has mimicked the basic architecture of silicon circuits3-6. Here, we report a transistor based on a two-dimensional material that can realize photoswitching logic (OR, AND) computing in a single cell. Unlike the conventional transistor working mechanism, the two-dimensional material logic transistor has two surface channels. Furthermore, the material thickness can change the logic behaviour-the architecture can be flexibly expanded to achieve in situ memory such as logic computing and data storage convergence in the same device. These devices are potentially promising candidates for the construction of new chips that can perform computing and storage with high area-efficiency and unique functions.

Delivery of synovium-resident mesenchymal stem cells (synMSCs) to cartilage defect site might provide a novel therapeutic modality for treatment of articular cartilage diseases. However, low isolation efficiency of synMSCs limits their therapeutic application. Niche-preserving non-enzymatic isolation of synMSCs was firstly attempted by employing micro-organ culture system based on recapitulating tissue-specific homeostasis ex vivo. The isolated synMSCs retained superior long-term growth competency, proliferation and chondrogenic potential to bone marrow-derived MSCs (BMSCs). It was noted that synMSCs demonstrated 9-fold increase in cartilaginous micro-tissue formation and 13-fold increase in sulfated proteoglycans deposition compared to BMSCs. For delivery of synMSCs, fibrous PLGA scaffolds were specifically designed for full-thickness osteochondral defects in rabbits. The scaffolds provided effective micro-environment for growth and host-integration of synMSCs. Combined delivery of synMSCs with bone morphogenetic proteins-7 (BMP-7) was designed to achieve synergistic therapeutic efficacy. BMP-7-loaded PLGA nanoparticles electrosprayed onto the scaffolds released BMP-7 over 2 weeks to conform with its aimed role in stimulating early stage endochondral ossification. Scaffold-supported combined administration of synMSCs with BMP-7 resulted in high proteoglycan and collagen type II induction and thick hyaline cartilage formation. Intra-articular co-delivery of synMSCs with BMP-7 via fibrous PLGA scaffolds may be a promising therapeutic modality for articular cartilage repair.

In this work we studied front electrodes of nickel/silver (Ni/Ag) deposited on Gr/Si solar cell structure using field induced plating. These electrodes also be used as a front electrode on 2D graphene-based devices at very low cost and temperature (

Contamination in coastal aquifer plains is of great concern in many countries given that non-aqueous phase liquids (NAPLs) have polluted numerous sites through accidental oil spills or improper disposal. We have developed a method to remove pollutants such as NAPLs from sandy sediment samples collected from the Mandol area of Gomso Bay in western South Korea. The sediments were collected from around the diffuser in a two-dimensional (2D) acrylic reaction apparatus, and these contained a total petroleum hydrocarbon (TPH) concentration of 89.3 ppm (mg/kg media). The maximum perchloroethylene (PCE) concentration was 398.51 ppm in the unsaturated zone and 0.77 ppm in the saturated zone. Volatile organic compounds (VOCs) were detected between 20 and 44 hour. However, non-volatile contaminants remained in the sediments after treatment. In situ air sparging (IAS) combined with soil vapor extraction (SVE), transformation from sorbed and nonaqueous phases to the vapor phase, is incomplete when treatment is performed using a pervasive air flow for sediments such as the sand of Mandol. During air transformation, the groundwater flow conditions increased the rate of contaminant removal. Although pilot-scale testing in the field site was fluctuated due to the heterogeneous of sediments condition, this 2D study found that the proposed method can alter the measurable geophysical properties of NAPLs. These findings demonstrate that IAS combined with SVE in the saturated zone is an effective technology for aquifer remediation high applicability of sandy coastal sediments contaminated by NAPLs.

Surface modified poly l -lactic acid (PLLA) samples with hydroxyapatite (HA), heparin and bone morphogenetic protein-2 (BMP-2) mediated by polydopamine (pDA) coating (PLLA/pDA/HA/Hep/BMP-2) were prepared, and their effects on the enhancements of bone formation and osseointegration were evaluated in vitro and in vivo as compared to PLLA, PLLA/pDA/HA, and PLLA/pDA/Hep/BMP-2. The changes in surface chemical compositions, morphologies and wettabilities were observed by X-ray photoelectron spectroscopy (XPS), field-emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM) and water contact angle measurements. Pre-coating of HA particles with pDA provided uniform and homogeneous anchoring of particles to PLLA surface. In addition, the strong ionic interaction between heparin and pDA led PLLA surface readily heparinized for loading of BMP-2. In vitro experiments revealed that the levels of alkaline phosphatase (ALP) activity, calcium deposition, and osteocalcin (OCN) gene expression were higher in MG-63 human osteosarcoma cell lines grown on PLLA/pDA/HA/Hep/BMP-2 than on control PLLA, PLLA/pDA/HA, and PLLA/pDA/Hep/BMP-2. In vivo studies using micro-computed tomography (micro-CT) also showed that PLLA/pDA/HA/Hep/BMP-2 screw exhibited greatest value of bone volume (BV) and bone volume/tissue volume (BV/TV) among samples. Histological evaluations with H&E and Von Kossa staining demonstrated that a combination of HA and BMP-2 contributed to the strong osseointegration.

For the reduction of optical loss and contact material cost in silicon heterojunction (SHJ) solar cells, copper plating has been considered as a suitable metallization technique. Usually, a metal seed layer is deposited on an indium tin oxide (ITO) prior to copper plating for adhesive contact between copper and ITO. As a requirement of suitable seed layer material, contact resistivity (ρc) between the seed and the ITO is also important, as well as the adhesion, because high series resistance results in fill factor loss. In this study, we applied alloy seed layers which were deposited by co-evaporating copper with other metals (Cu-X). Contact resistivity values of the samples were extracted by using transfer length method (TLM). Also, tape tests were carried out to simply confirm the adhesion of contacts with different seed layers. Among the Cu-X alloy seed materials, the Cu-Ni alloy film resulted in good adhesion to the ITO as well as low average contact resistivity under 1 mΩ cm2.

Background Alzheimer's disease is a neurodegenerative disease. Previous study has reported that caspase-1/IL-1β is closely associated with Alzheimer's disease. However, the biological role of caspase-1/IL-1β in Alzheimer's disease has not been fully elucidated. This study aimed to explore the mechanism of action of caspase-1/IL-1β in Alzheimer's disease. Methods Mouse hippocampal neurones were treated with Aβ1-42 to induce Alzheimer's disease cell model. APP/PS1 mice and Aβ1-42-induced hippocampal neurones were treated with AC-YVAD-CMK (caspase-1 inhibitor). Spatial learning and memory ability of mice were detected by morris water maze. Flow cytometry, TUNEL staining, Thioflavin S staining and immunohistochemistry were performed to examine apoptosis and senile plaque deposition. Enzyme linked immunosorbent assay and western blot were performed to assess the levels of protein or cytokines. Co-Immunoprecipitation was performed to verify the interaction between Stargazin and GluA1. Results AC-YVAD-CMK treatment improved spatial learning and memory ability and reduced senile plaque deposition of APP/PS1 mice. Moreover, AC-YVAD-CMK promoted membrane transport of GluA1 in APP/PS1 mice. In vitro, Aβ1-42-induced hippocampal neurones exhibited an increase in apoptosis and a decrease in the membrane transport of GluA1, which was abolished by AC-YVAD-CMK treatment. In addition, Stargazin interacted with GluA1, which was repressed by caspase-1. Caspase-1/IL-1β inhibited membrane transport of GluA1 by inhibiting the interaction between Stargazin and GluA1. Conclusions Our data demonstrate that caspase-1/IL-1β represses membrane transport of GluA1 by inhibiting the interaction between Stargazin in Alzheimer's disease. Thus, caspase-1/IL-1β may be a target for Alzheimer's disease treatment.

Elaborately and serially pH-modulated hydrogels possessing optimized viscoelastic natures for short gelation time and single syringe injection were designed for peritumoral injection of an anticancer agent. Boronate ester bonds between phenylboronic acid (PBA) (installed in HA-PBA (HP)) and dopamine (included in HA-dopamine (HD)) along with self-polymerization of dopamine (via interactions between HD conjugates) were introduced as the main cross-linking strategies of a hyaluronic acid (HA) hydrogel. Considering pKa values (8.0-9.5) of PBA and dopamine, the pH of each polymer dispersion was controlled elaborately for injection through a single syringe, and the final pH was tuned nearby the physiological pH (pH 7.8). The shear-thinning behavior, self-healing property, and single syringe injectability of a designed hydrogel cross-linked nearby physiological pH may provide its convenient application to peritumoral injection and prolonged retention in local cancer therapy. Erlotinib (ERT) was encapsulated in a microsphere (MS), and it was further embedded in an HP/HD-based hydrogel for sustained and locoregional delivery. A rheologically tuned hydrogel containing an ERT MS exhibited superior tumor-suppressive efficiencies compared to the other groups in A549 tumor-bearing mice. A designed injectable hydrogel through a single syringe system may be efficiently applied to local cancer therapy with lower toxicities to healthy organs.

Endovascular embolization is performed to treat various vascular diseases including hemorrhage, aneurysms, and vascular malformations. In article number 2003327, Rahmi Oklu, Ali Khademhosseini, and co‐workers report a tantalum microparticle‐loaded shear‐thinning gel embolic material (Ta‐GEM) that can be rapidly delivered into diseased arteries using clinical catheters to achieve rapid hemostasis. The cover image shows the swine pelvic vasculature, with both iliac arteries demonstrating vascular hemorrhage. The left side is successfully occluded using the gel embolic material (GEM), whereas the right side received coil embolization (the standard treatment today) where blood continues to bleed through the coils. [Image: see text]

Polypseudorotaxane structure and polydopamine bond-based crosslinked hyaluronic acid (HA) hydrogels including donepezil-loaded microspheres were developed for subcutaneous injection. Both dopamine and polyethylene glycol (PEG) were covalently bonded to the HA polymer for catechol polymerization and inclusion complexation with alpha-cyclodextrin (α-CD), respectively. A PEG chain of HA-dopamine-PEG (HD-PEG) conjugate was threaded with α-CD to make a polypseudorotaxane structure and its pH was adjusted to 8.5 for dopamine polymerization. Poly(lactic-co-glycolic acid) (PLGA)/donepezil microsphere (PDM) was embedded into the HD-PEG network for its sustained release. The HD-PEG/α-CD/PDM 8.5 hydrogel system exhibited an immediate gelation pattern, injectability through single syringe, self-healing ability, and shear-thinning behavior. Donepezil was released from the HD-PEG/α-CD/PDM 8.5 hydrogel in a sustained pattern. Following subcutaneous injection, the weight of excised HD-PEG/α-CD/PDM 8.5 hydrogel was higher than the other groups on day 14. These findings support the clinical feasibility of the HD-PEG/α-CD/PDM 8.5 hydrogel for subcutaneous injection.

Keratin is known to be a major protein in hair, but the biological function of keratin in hair growth is unknown, which led us to conduct a pilot study to elucidate biological function of keratin in hair growth via cellular interactions with hair forming cells. Here, we show hair growth is stimulated by intradermal injection of keratin into mice, and show that outer root sheath cells undergo transforming growth factor-β2-induced apoptosis, resulting in keratin exposure. Keratin exposure appears to be critical for dermal papilla cell condensation and hair germ formation as immunodepletion and silencing keratin prevent dermal papilla cell condensation and hair germ formation. Furthermore, silencing keratin in mice resulted in a marked suppression of anagen follicle formation and hair growth. Our study imply a new finding of how to initiate hair regeneration and suggests the potent application of keratin biomaterial for the treatment of hair loss.

BackgroundAlthough the clinical effect of stir-fried Dolichos lablab L. kernel has been approved in modern traditional Chinese medicine, existing associated studies mainly focus on its clinical studies and chemical ingredients. However, there are few studies on pharmacodynamics material basis and molecular mechanism of stirfried Dolichos lablab L. kernel in treatment of type-2 diabetes(T2DM), thus restricting the further development and utilization of stir-fried Dolichos lablab L. kernel.MethodsA qualitative analysis on saponin chemical ingredients of stir-fried Dolichos lablab L. kernel was performed using UHPLC-Q-Exactive Orbitrap MS. A total of 10 saponin ingredients were selected. Moreover, target screening, biological process and metabolism pathway analysis were accomplished by network pharmacology. Four key proteins(EGFR, IGF1, MAPK1 and PIK3R1) of type-2 diabetes were selected for molecular docking verification with saponin ingredients. Specifically, molecular dynamics simulation of ingredients which have strong bindings with proteins was conducted. ResultsIn this study, 16 saponin ingredients were identified from stir-fried Dolichos lablab L. kernel. There were 91 intersection targets and the KEGG pathway enrichment involved 20 relevant pathways. According to the molecular docking verification, saponin ingredients of stir-fried Dolichos lablab L. kernel can form stable binding with key protein targets. The molecular dynamics simulation further verifies stability and reasonability of the docking results. ConclusionsThis study provides references to identification of efficient ingredients of stir-fried Dolichos lablab L. kernel, screening of quality markers and explanation of relevant action mechanism by combining UHPLC-Q-Exactive Orbitrap MS and network pharmacology.

The effects of different homogenization pressure levels on the solubility, particle size, surface hydrophobicity, free sulfhydryl content, surface tension, water distribution and mobility, rheological, foaming and gel properties of soy 11S globulin were investigated in this study. High-pressure homogenization treatment (50–150 MPa) significantly increased the magnitude of protein zeta potential, solubility, while reduced the particle size, which increased surface hydrophobicity, and exposure to free sulfhydryl and disulfide bonds, as well as surface tension, foaming capacity and stability, elasticity index, macroviscosity index, initial apparent viscosity and shear stress. On the other hand, excessive pressure treatment at 150 MPa caused solubility, surface hydrophobicity, exposure to free sulfhydryl, the elasticity index, macroviscosity index, initial apparent viscosity and shear stress to decrease. The gel strength and water immobilization also increased, whereas the mobility of the water was low. Overall, our results show that high-pressure homogenization improves the physicochemical, foaming and gel properties of 11S globulin.

Nanofiltration (NF) as a promising candidate is widely used in charge-based separation of ampholytic biomolecules. Construction of strongly charged permeation channel of NF membrane is one of the key factors for this process. In this work, random amphiphilic copolymer (RACP) nanoparticles were first packed to prepare nanoscale permeation channel. The RACP emulsion was firstly prepared by soap-free emulsion polymerization between [2-(methacryloyloxy) ethyl] trimethyl ammonium chloride (DMC) and methyl methacrylate (MMA), and then directly depositing onto porous substrate to form nanochannel selective layer of NF membrane. The optimal NF membrane shows a relatively large pore structure (i.e., cut-off pore size is 1.43 nm) and high pure water permeance (PWP) of 13.3 L·m−2·h−1·bar−1. Moreover, it shows a desirable rejection of basic amino acids and biopeptides (i.e., ∼95%) and allows neutral or acidic ones with similar molecule weight to permeate through. This work provides an innovative and facile method directly from RACP emulsion to construct NF membrane via nanoparticle packing, which greatly simplifies the preparation procedure for NF membrane. In addition, this novel NF membrane also demonstrates great potential in charge-based separation of biomolecules.