A general method for rapid synthesis of refractory carbides by low-pressure carbothermal shock reduction.

Refractory carbides are attractive candidates for support materials in heterogeneous catalysis because of their high thermal, chemical, and mechanical stability. However, the industrial applications of refractory carbides, especially silicon carbide (SiC), are greatly hampered by their low surface area and harsh synthetic conditions, typically have a very limited surface area (<200 m2 g-1), and are prepared in a high-temperature environment (>1,400 °C) that lasts for several or even tens of hours. Based on Le Chatelier's principle, we theoretically proposed and experimentally verified that a low-pressure carbothermal reduction (CR) strategy was capable of synthesizing high-surface area SiC (569.9 m2 g-1) at a lower temperature and a faster rate (∼1,300 °C, 50 Pa, 30 s). Such high-surface area SiC possesses excellent thermal stability and antioxidant capacity since it maintained stability under a water-saturated airflow at 650 °C for 100 h. Furthermore, we demonstrated the feasibility of our strategy for scale-up production of high-surface area SiC (460.6 m2 g-1), with a yield larger than 12 g in one experiment, by virtue of an industrial viable vacuum sintering furnace. Importantly, our strategy is  also applicable to the rapid synthesis of refractory metal carbides (NbC, Mo2C, TaC, WC) and even their emerging high-entropy carbides (VNbMoTaWC5, TiVNbTaWC5). Therefore, our low-pressure CR method provides an alternative strategy, not merely limited to temperature and time items, to regulate the synthesis and facilitate the upcoming industrial applications of carbide-based advanced functional materials.

Dignity in nursing: A bibliometric and visual analysis of scientific publications.

BACKGROUND: Dignity-conserved nursing has been widely studied by scholars all over the world; however, there is no clear direction in which this field is trending. AIM: To conduct a bibliometric analysis that systematically characterises publications on dignity research in the nursing field from 2011 to 2020. DESIGN: Bibliometric and visual analysis of retrieved articles. METHODS: The Web of Science Core Collection database was used to retrieve all articles which addressed dignity in nursing from 2011 to 2020. The WoSCC's own analysis tool, CiteSpace and VOSviewer, were used to obtain visual analysis results. Reporting follows the STROBE checklist. RESULTS: A total of 1429 papers on dignity care are included in this study. We found that the number of papers on this topic increased steadily, and the United States topped the list with 366 articles in total. The institute with the most publications was King's College London, and the most widely published journal was Nursing Ethics. We were able to identify four major research topics, namely dignity in: (a) palliative care, (b) dementia and the elderly, (c) health care and (d) nursing ethics. Terminally ill patient, home, value, rehabilitation and psychological distress were the five keywords with the highest burst strength. CONCLUSIONS: The interest in dignity care research has been steadily increasing from 2011 and is reflected in the number of published papers. The United States and Western Europe are leading in this field, both having a high number of cutting-edge researchers and high-level scientific research institutions. In the domain of dignity care, several stable and high-yield core author groups have been formed. While the existing research mainly focuses on four hot spots, psychological distress, advanced cancer, maternity care and content analysis may be the research frontiers.

Near-Infrared Light-Driven Photoredox Catalysis by Transition-Metal-Complex Nanodots.

Developing light-harvesting materials with broad spectral response is of fundamental importance in full-spectrum solar energy conversion. We found that, when a series of earth-abundant metal (Cu, Co, Ni and Fe) salts are dissolved in coordinating solvents uniformly dispersed nanodots (NDs) are formed rather than fully dissolving as molecular species. The previously unrecognized formation of this condensed state is ascribed to spontaneous aggregation of molecular transition-metal-complexes (TMCs) via weak intermolecular interactions, which results in redshifted and broadened absorption into the NIR region (200-1100 nm). Typical photoredox reactions, such as carbonylation and oxidative dehydrogenation, well demonstrate the feasibility of efficient utilization of NIR light (λ>780 nm) by TMCs NDs. Our finding provides a conceptually new strategy for extending the absorption towards low energy photons in solar energy harvesting and conversion via photoredox transformations.

The influence mechanism of household waste separation behavior among college students in the post COVID-19 pandemic period.

College students are one of the most important groups of participants and promoters of household waste separation. Taking Ningbo as a case study, an online + offline questionnaire survey among more than 1700 students in 10 colleges is conducted to identify the main factors and pathways influencing waste separation behavior in the post COVID-19 pandemic period. The results show that the KMO statistic is 0.926, Bartlet test is p < 0.001, indicating that questionnaire sample data is suitable for factor analysis. The modified Structural Equation Model test indicates that waste separation behavior of college students mainly results from the combined effect of eight subjective intrinsic factors and seven external situational factors. Among them, the convenience of recycling facilities, the convenience of sorting facilities and the publicity and education of sorting knowledge are the top three factors with the most significant influence. The mean value of epidemic impact factors is 0.277, which is slightly lower than conventional influence factors (0.289). Environmental Norms and Constraints are an essential component in the analysis framework of college students' waste separation behavior. In the future, society and colleges should give full play to the positive influence of the epidemic factor on college students' waste separation behavior. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10163-022-01363-3.

Reprogramming of m6A epitranscriptome is crucial for shaping of transcriptome and proteome in response to hypoxia.

Hypoxia causes a series of responses supporting cells to survive in harsh environments. Substantial post-transcriptional and translational regulation during hypoxia has been observed. However, detailed regulatory mechanism in response to hypoxia is still far from complete. RNA m6A modification has been proven to govern the life cycle of RNAs. Here, we reported that total m6A level of mRNAs was decreased during hypoxia, which might be mediated by the induction of m6A eraser, ALKBH5. Meanwhile, expression levels of most YTH family members of m6A readers were systematically down-regulated. Transcriptome-wide analysis of m6A revealed a drastic reprogramming of m6A epitranscriptome during cellular hypoxia. Integration of m6A epitranscriptome with either RNA-seq based transcriptome analysis or mass spectrometry (LC-MS/MS) based proteome analysis of cells upon hypoxic stress revealed that reprogramming of m6A epitranscriptome reshaped the transcriptome and proteome, thereby supporting efficient generation of energy for adaption to hypoxia. Moreover, ATP production was blocked when silencing an m6A eraser, ALKBH5, under hypoxic condition, demonstrating that m6A pathway is an important regulator during hypoxic response. Collectively, our studies indicate that crosstalk between m6A and HIF1 pathway is essential for cellular response to hypoxia, providing insights into the underlying molecular mechanisms during hypoxia.

[Mechanism of puerarin reversing SH-SY5Y cell injury induced by Aß_(1-42) based on proteomics].

Puerarin has the anti-Alzheimer's disease (AD) activity,which can reverse nerve injury induced by Aßand inhibit neuronal apoptosis.However,its potential pharmacodynamic mechanism still needs to be further researched.The occurrence and development of AD is due to the change of multiple metabolic links in the body,which leads to the destruction of balance.Puerarin may act on multiple targets and multiple metabolic processes to achieve therapeutic purposes.Quantitative proteomic analysis provides a new choice to understand the mechanism as completely as possible.This research adopted SH-SY5Y cells induced by Aß_(1-42)to establish AD cell model,and Aßimmunofluorescence detection showed that Aßdecreased significantly after puerarin intervention.The mechanism of puerarin reversing SH-SY5Y cell injured by Aß_(1-42)was further explored by using label-free non-labeled quantitative technology and Western blot detection based on bioinformatics analysis result.The results showed that most of the differential proteins were related to biological processes such as cellular component organization or biogenesis,cellular component organization and cellular component biogenesis,and they mainly participated in the top ten pathways of P value such as pathogenic Escherichia coli infection,m TOR signaling pathway,regulation of autophagy,regulation of actin cytoskeleton,spliceosome,hepatocellular carcinoma,tight junction,non-small cell lung cancer,apoptosis and gap junction.Annexin V/PI flow cytometry and TUNEL were used to detect apoptosis,and the results showed that Aßdecreased significantly and the rate of apoptosis decreased significantly after puerarin intervention.Western blot analysis found that the protein expression level of autophagy related protein LC3Ⅱwas up-regulated after Aßinduction,and the degree of this up-regulation was further enhanced in puerarin intervention group.The trend of the ratio of LC3Ⅱ/LC3Ⅰamong groups was the same as the protein expression level of LC3Ⅱ，the protein expression level of p62 in the control group,AD model group and puerarin intervention group decreased successively.Protein interaction network analysis showed that CAP1 was correlated with TUBA1B,HSP90AB2P,DNM1L,TUBA1A and ERK1/2,and the correlation between CAP1 and ERK1/2 was the highest among them.Western blot showed that the expressions of p-ERK1/2,Bax and CAP1 were significantly down-regulated and the protein expression level of Bcl-2 was significantly up-regulated after puerarin intervention.Therefore,puerarin might improve the SH-SY5Y cells injured by Aß_(1-42)through the interaction of multiple biological processes and pathways in cells multiple locations,and CAP1 might play an important role among them.

Chondroitin sulfate hydrogels based on electrostatic interactions with enhanced adhesive properties: exploring the bulk and interfacial contributions.

Adhesive polysaccharide gels have highlighted their potential in biomedicine, tissue engineering, and wearable/implantable devices due to their tissue adhesive nature and excellent biocompatibility. However, the weak adhesive strength caused by the unclear relationship between the structure and the adhesive properties seriously hinders their further practical application. Here, a facile one-step synthesis method for adhesive and self-healing hydrogels with chondroitin sulfate (CS) and poly (methyl chloride quarternized N,N-dimethylamino ethylacrylate) (PDMAEA-Q) by ultraviolet light irradiation has been presented. We investigate the mechanism of the adhesion enhancement including improving the mechanical strength of gels (cohesion) and gel/substrate interfacial interactions (interfacial adhesion) by tailoring the compliance and cohesive energy density of the gel. The resultant soft and viscoelastic hydrogels displayed favorable adhesion ability on various substrates, and the adhesive strength to the iron substrate and porcine skin can reach 49.4 kPa and 15.4 kPa, respectively. Additionally, the gels also exhibited rapid self-healing properties and good cytocompatibility. We believe that the adhesive PDMAEA-Q/CS gel would be an ideal candidate for hydrogel glues for human-machine interfaces and biological tissues, and this design idea can open a new path for the preparation of adhesive polysaccharide hydrogels.

CIRDES: an efficient genome-wide method for in vivo RNA-RNA interactome analysis.

Complex RNA-RNA interactions underlie fundamental biological processes. However, a large number of RNA-RNA interactions remain unknown. Most existing methods used to map RNA-RNA interactions are based on proximity ligation, but these strategies also capture a huge amount of intramolecular RNA secondary structures, making it almost impossible to detect most RNA-RNA interactions. To overcome this limitation, we developed an efficient, genome-wide method, Capture Interacting RNA and Deep Sequencing (CIRDES) for in vivo capturing of the RNA interactome. We designed multiple 20-nt CIRDES probes tiling the whole RNA sequence of interest. This strategy obtained high selectivity and low background noise proved by qRT-PCR data. CIRDES enriched target RNA and its interacting RNAs from cells crosslinked by formaldehyde in high efficiency. After hybridization and purification, the captured RNAs were converted to the cDNA library after a highly efficient ligation to a 3' end infrared-dye-conjugated RNA adapter based on adapter ligation library construction. Using CIRDES, we detected highly abundant known interacting RNA, as well as a large number of novel targets of U6 snRNA. The enrichment of U4 snRNA, which interacts with U6, confirmed the robustness of the identification of the RNA-RNA interaction by CIRDES. These results suggest that the CIRDES is an efficient strategy for genome-wide RNA-RNA interactome analysis.

Chemical Insights into Antibacterial N-Halamines.

Microbial contamination arising from pathogens poses serious threats to human health and in recent decades has presented an unprecedented challenge to antibacterial research. Of the various antibacterial agents that effectively kill pathogens, halogen-based antibacterial compounds have been successful in eliminating harmful pathogen-associated diseases and are becoming the most popular disinfectants. As a significant subcategory of halogen antibacterial agents, N-halamines have drawn increasing research interest into their chemistry and practical applications. N-Halamines have many advantages over other antibacterial agents, including effectiveness against a broad spectrum of microorganisms, long-term physicochemical stability, high structural durability, and the regenerability of their functional groups, with corresponding renewal of their antibacterial properties. This review examines recent progress and research trends in both theoretical and experimental studies of N-halamines, with the aim of providing a systematic and comprehensive survey and assessment of the significant advances in our understanding of antibacterial N-halamines. This review serves as a practical guide to developing N-halamines through both broad and in-depth basic research and offers suggestions for their potential future applications.

Deep sequencing reveals a global reprogramming of lncRNA transcriptome during EMT.

Several studies have shown that long non-coding RNAs (lncRNAs) may play an essential role in Epithelial-Mesenchymal Transition (EMT), which is an important step in tumor metastasis; however, little is known about the global change of lncRNA transcriptome during EMT. To investigate how lncRNA transcriptome alterations contribute to EMT progression regulation, we deep-sequenced the whole-transcriptome of MCF10A as the cells underwent TGF-ß-induced EMT. RESULTS: Deep-sequencing results showed that the long RNA transcriptome of MCF10A had undergone global changes as early as 8h after treatment with TGF-ß. The expression of 3403 known and novel lncRNAs, and 570 known and novel circRNAs were altered during EMT. To identify the key lncRNA-regulator, we constructed the co-expression network and found all junction nodes in the network are lncRNAs. One junction node, RP6-65G23.5, was further verified as a key regulator of EMT. Intriguingly, we identified 216 clusters containing lncRNAs which were located in "gene desert" regions. The expressions of all lncRNAs in these clusters changed concurrently during EMT, strongly suggesting that these clusters might play important roles in EMT. Our study reveals a global reprogramming of lncRNAs transcriptome during EMT and provides clues for the future study of the molecular mechanism of EMT.

Percutaneous ablation of the tumor feeding artery for hypervascular hepatocellular carcinoma before tumor ablation.

OBJECTIVE: To evaluate the efficiency and safety of percutaneous ablation of the tumor feeding artery (PAA) before radiofrequency ablation (RFA) for hypervascular hepatocellular carcinoma (HCC) under ultrasound guidance. PATIENTS AND METHODS: In total, 94 patients with hypervascular HCC and tumor feeding artery visible by contrast-enhanced ultrasound were prospectively randomized to receive either PAA combined with RFA (RFA + PAA) or RFA alone. This study was registered at the clinical trials registry website (No. NCT03143140). The mean tumor size was 3.2 ± 0.9 cm (2.0-5.0 cm). The mean follow-up was 23.7 ± 9.7 months (4-44 months). The technical success, local tumor progression and intrahepatic distant recurrence rates were compared. Survival analysis was performed using the Kaplan-Meier method and compared with the log-rank test. RESULTS: The local tumor progression rate was lower for the PAA + RFA group than for the RFA group (8.5% vs 21.3%, p < .082). No significant differences in the technical success and intrahepatic distant recurrence rates were observed between the two groups (97.9% vs 91.5%, p = .203 and 40.4% vs 42.6%, p = .834). The 1- and 3-year local tumor progression-free survival rates were 91.5% and 69.9% vs 68.1% and 52.1% for the PAA + RFA vs RFA groups, respectively (p = .052). The 1- and 3-year overall survival rates were 95.7% and 69.1% vs 89.4% and 66.6% in the PAA + RFA vs RFA groups, respectively (p = .744). The major complication rate was 4.3% in both groups. CONCLUSIONS: PAA appears to be an effective and safe technique for the treatment of hypervascular HCC, with a lower local tumor progression rate than that of conventional RFA.

Long-term outcome of percutaneous radiofrequency ablation in recurrent hepatocellular carcinoma after liver transplantation.

PURPOSE: To investigate the long-term outcome and prognostic factors of radiofrequency ablation (RFA) in recurrent hepatocellular carcinoma (HCC) after liver transplantation (LT). METHODS: From 2004 to 2014, 15 patients with 23 hepatic recurrent HCCs after LT underwent ultrasound-guided percutaneous RFA. There were 14 males and 1 female aged 54.3 ± 9.5 years old (37-78 years old). The average tumour size was 3.3 ± 1.2 cm (1.7-6.0 cm). Seven patients had a single HCC and eight had 2-4 HCCs. Regular follow-up after RFA was performed to assess local response rates and long-term survival rates. Survival results were generated using Kaplan-Meier estimates, and a multivariate analysis was performed using the Cox regression model. RESULTS: The technical success rate was 95.7% (22/23 tumours). The minor complication rate was 7.7% (2/26 sessions), and there were no major complications. The follow-up period was 27.4 ± 18.9 months (12-116 months). The local progression rate and intrahepatic new lesion rate were 13.0% (3/23 tumours) and 53.3% (8/15 patients), respectively. Extrahepatic metastasis was found in four patients (26.7%). The 1-, 3- and 5-year estimated overall survival rates were 71.8%, 35.9% and 26.9%, respectively. Additionally, the multivariate analysis revealed that serum α-fetoprotein (AFP) before RFA, tumour number and extrahepatic metastasis were significantly related to overall survival after RFA. CONCLUSION: Ultrasound-guided percutaneous RFA of recurrent HCC after LT had a high technical success rate and local control. However, RFA cannot decrease the frequency of new tumours or extrahepatic metastasis. The AFP level and tumour number before RFA should be considered to predict the outcome.

Biomass-derived nanostructured carbons and their composites as anode materials for lithium ion batteries.

Since ever-increasing energy demands stimulated intensive research activities on lithium-ion batteries (LIBs), biomass as an earth-abundant renewable energy source has played an intriguing and promising role in developing sustainable biomass-derived carbons and their composite materials for high-performance LIB anodes. Different from other materials (e.g., silicon, tin, metal oxides, etc.), biomass-derived carbons and their composite materials have been applied more and more to LIBs due to their advantages such as low cost, green and eco-friendly synthesis, easy accessibility, sustainable strategy, and improved battery performance, including capacity, cycling property, and stability/durability. This tutorial review focusing on biomass-derived carbons and their composites in the application of LIB anodes will act as a strategic guide to build a close connection between renewable materials and electrochemical energy storage devices. Also, this review provides a critical analysis and comparison of biomass-derived carbons and their composites for LIB anodes, coupled with an important insight into the remaining challenges and future directions in the field.

Inhibition of Endoplasmic Reticulum Stress Apoptosis by Estrogen Protects Human Umbilical Vein Endothelial Cells Through the PI3 Kinase-Akt Signaling Pathway.

We aimed to investigate whether the cardioprotective effect of estrogen is mediated by inhibiting the apoptosis induced by endoplasmic reticulum stress (ERS) and to explore the underlying signaling pathway responsible for this effect. The effect of estrogen on ERS apoptosis, the mechanism responsible for that effect, and the ERS signaling pathways were examined in human umbilical vein endothelial cells (HUVECs) and measured using Western blot, Hoechst stains and caspase-3 activity assay. In vitro, 10-8 mol/l estrogen directly inhibited the up-regulation of the ERS marker glucose-regulated protein 78 (GRP78) and ERS apoptosis marker C/EBP homologous protein (CHOP). ERS was induced using the ERS inducer tunicamycin (TM, 10 µmol/l) or dithiothreitol (DTT, 2 mmol/l) in HUVECs. Estrogen can also decrease the apoptosis cells mediated by ERS, based on the results of Hoechst stains. Protein expression in the three main ERS signaling pathways was upregulated in TM- or DTT-induced HUVEC ERS. Increases in p-PERK/PERK were the most obvious, and estrogen significantly inhibited the upregulation of p-PERK/PERK, p-IRE1/IRE1, and ATF6. These inhibitory effects were abolished by specific estrogen receptor antagonists (ICI182, 780, and G15) and inhibitors of the E2 post-receptor signaling pathway, including phosphoinositide 3-kinase (PI3K) inhibitor LY294002, p38-mitogen activated protein kinase (p38-MAPK) inhibitor SB203580, c-Jun N-terminal kinase (JNK) inhibitor SP600125 and extracellular signal-regulated kinases1/2 (ERK1/2) inhibitor U0126; of these inhibitors, LY294002 was the most effective. Further experiments showed that when the PI3K pathway was blocked, the inhibitory effect of estrogen on ERS apoptosis was reduced. Estrogen can prevent HUVEC apoptosis by inhibiting the ERS apoptosis triggered by the PERK pathway, which may protect vascular endothelial cells and the cardiovascular system. The main mechanism responsible for ERS inhibition is the activation of the PI3K-Akt pathway for the activated estrogen receptor. J. Cell. Biochem. 118: 4568-4574, 2017. © 2017 Wiley Periodicals, Inc.

[Effects of Modified Ruji Recipe in Preventing Relapse and Metastasis of Breast Cancer Patients with Negative Hormone Receptor].

Objective To observe the effect of Ruji Recipe (RR) (treated by syndrome typing) in preventing the relapse and metastasis of invasive ductal breast cancer patients with negative hormone receptor (HR) after surgery and chemotherapy. Methods Using a prospective, cohort method, 136 pa- tients with stage I - III C HR negative invasive ductal breast cancer were equally assigned to the treat- ment group (treated by RR in syndrome typing way) and the control group (routine follow-ups). Disease free survival (DFS) , overall survival (OS) , relapse and metastasis were observed in the two groups. Re- sults All patients were followed-up for 15 to 57 months, with the median follow-up of 44 months. The median DFS and OS had not reached. The 1. 0, 1. 5, 2. -0, and 3. 0 years DFS were 94.1 % (64/68) , 86. 4 % (51/59), 81. 8% (45/55), and 72. 0% (36/50) in the treatment group. They were 77. 9% (53/68), 67.2% (45)67), 60. 6% (40)66), and 54. 5% (36/66) in the control group. Significant difference existed in 1. 0, 1. 5, and 2. 0 years DFS between the two groups (X² = 7.403, 6.426, 6.459; P =0. 012, 0.013, 0. 016). No statistical difference existed in 1. 0, 1. 5, 2. 0, and 3. 0 years OS between the two groups (P >0. 05). Among triple negative breast cancer (TNBC) patients, 1. 0, 1. 5, 2. 0, and 3. 0 years DFS were 97. 0% (32/33), 92. 9% (26/28), 92.6% (2527), and 84. 6% (22/26) in the treatment group, 81. 5% (2227), 66. 7% (1827), 61. 5% (16/26), and 57. 7% (15/26) in the control group. Of them, significant difference existed in 1. 5, 2. 0, and 3. 0 years DFS between the two groups (X² =5. 893, 7. 293, 4. 591 ; P = 0. 015, 0. 007, 0. 032). At the end of follow-ups, relapse and metastasis occurred in 15 patients, local recur- rence in 2 patients, single organ metastasis in 6 patients, and multiple organs metastasis in 7 patients of the treatment group. The relapse and metastasis occurred in 30 patients , local recurrence in 2 patients , single organ metastasis in 12 patients, and multiple organs metastasis in 16 patients of the treatment group. Conclusions RR ( by syndrome typing) could improve DFS and delay progression of invasive ductal breast cancer patients with negative HR in the first 2 years after surgery. It also had certain value for relapse and metastasis of TNBC patients within 2 years.

Photocatalytic Reduction of CO2 over Heterostructure Semiconductors into Value-Added Chemicals.

Photoreduction of CO2 , which utilizes solar energy to convert CO2 into hydrocarbons, can be an effective means to overcome the increasing energy crisis and mitigate the rising emissions of greenhouse gas. This article covers recent advances in the CO2 photoreduction over heterostructure-based photocatalysts. The fundamentals of CO2 photoreduction and classification of the heterostructured photocatalysts are discussed first, followed by the latest work on the CO2 photoreduction over heterostructured photocatalysts in terms of the classification of the coupling semiconductors. Finally, a brief summary and a perspective on the challenges in this area are presented.

Dual Function of Glucosamine in Gelatin/Hyaluronic Acid Cryogel to Modulate Scaffold Mechanical Properties and to Maintain Chondrogenic Phenotype for Cartilage Tissue Engineering.

Glucosamine (GlcN) fulfills many of the requirements as an ideal component in scaffolds used in cartilage tissue engineering. The incorporation of GlcN in a gelatin/hyaluronic acid (GH) cryogel scaffold could provide biological cues in maintaining the phenotype of chondrocytes. Nonetheless, substituting gelatin with GlcN may also decrease the crosslinking density and modulate the mechanical properties of the cryogel scaffold, which may be beneficial as physical cues for chondrocytes in the scaffold. Thus, we prepared cryogel scaffolds containing 9% GlcN (GH-GlcN9) and 16% GlcN (GH-GlcN16) by carbodiimide-mediated crosslinking reactions at -16 °C. The crosslinking density and the mechanical properties of the cryogel matrix could be tuned by adjusting the content of GlcN used during cryogel preparation. In general, incorporation of GlcN did not influence scaffold pore size and ultimate compressive strain but increased porosity. The GH-GlcN16 cryogel showed the highest swelling ratio and degradation rate in hyaluronidase and collagenase solutions. On the contrary, the Young's modulus, storage modulus, ultimate compressive stress, energy dissipation level, and rate of stress relaxation decreased by increasing the GlcN content in the cryogel. The release of GlcN from the scaffolds in the culture medium of chondrocytes could be sustained for 21 days for GH-GlcN16 in contrast to only 7 days for GH-GlcN9. In vitro cell culture experiments using rabbit articular chondrocytes revealed that GlcN incorporation affected cell proliferation, morphology, and maintenance of chondrogenic phenotype. Overall, GH-GlcN16 showed the best performance in maintaining chondrogenic phenotype with reduced cell proliferation rate but enhanced glycosaminoglycans (GAGs) and type II collagen (COL II) secretion. Quantitative real-time polymerase chain reaction also showed time-dependent up-regulation of cartilage-specific marker genes (COL II, aggrecan and Sox9) for GH-GlcN16. Implantation of chondrocytes/GH-GlcN16 constructs into full-thickness articular cartilage defects of rabbits could regenerate neocartilage with positive staining for GAGs and COL II. The GH-GlcN16 cryogel will be suitable as a scaffold for the treatment of articular cartilage defects.

Prohibitin is involved in the activated internalization and degradation of protease-activated receptor 1.

The protease-activated receptor 1 (PAR1) is a G-protein-coupled receptor that is irreversibly activated by either thrombin or metalloprotease 1. Due this irrevocable activation, activated internalization and degradation are critical for PAR1 signaling termination. Prohibitin (PHB) is an evolutionarily conserved, ubiquitously expressed, pleiotropic protein and belongs to the stomatin/prohibitin/flotillin/HflK/C (SPFH) domain family. In a previous study, we found that PHB localized on the platelet membrane and participated in PAR1-mediated human platelet aggregation, suggesting that PHB likely regulates the signaling of PAR1. Unfortunately, PHB's exact function in PAR1 internalization and degradation is unclear. In the current study, flow cytometry revealed that PHB expressed on the surface of endothelial cells (HUVECs) but not cancer cells (MDA-MB-231). Further confocal microscopy revealed that PHB dynamically associates with PAR1 in a time-dependent manner following induction with PAR1-activated peptide (PAR1-AP), though differently between HUVECs and MDA-MB-231 cells. Depletion of PHB by RNA interference significantly inhibited PAR1 activated internalization and led to sustained Erk1/2 phosphorylation in the HUVECs; however, a similar effect was not observed in MDA-MB-231 cells. For both the endothelial and cancel cells, PHB repressed PAR1 degradation, while knockdown of PHB led to increased PAR1 degradation, and PHB overexpression inhibited PAR1 degradation. These results suggest that persistent PAR1 signaling due to the absence of membrane PHB and decreased PAR1 degradation caused by the upregulation of intracellular PHB in cancer cells (such as MDA-MB-231 cells) may render cells highly invasive. As such, PHB may be a novel target in future anti-cancer therapeutics, or in more refined cancer malignancy diagnostics.

Therapeutic potential of the antimicrobial peptide OH-CATH30 for antibiotic-resistant Pseudomonas aeruginosa keratitis.

The therapeutic potential of antimicrobial peptides (AMPs) has been evaluated in many infectious diseases. However, the topical application of AMPs for ocular bacterial infection has not been well investigated. The AMP OH-CATH30, which was identified in the king cobra, exhibits potent antimicrobial activity. In this study, we investigated the therapeutic potential of OH-CATH30 for Pseudomonas aeruginosa keratitis. Ten isolates of P. aeruginosa from individuals with keratitis were susceptible to OH-CATH30 but not to cefoperazone, ciprofloxacin, gentamicin, and levofloxacin. The microdilution checkerboard assay showed that OH-CATH30 exhibited synergistic activity with ciprofloxacin and levofloxacin against antibiotic-resistant P. aeruginosa. Meanwhile, P. aeruginosa did not develop resistance to OH-CATH30, even after exposure at 0.5× the MIC for up to 25 subcultures. Furthermore, treatment with OH-CATH30, alone or in combination with levofloxacin, significantly improved the clinical outcomes of rabbit keratitis induced by antibiotic-resistant P. aeruginosa. Taken together, our data indicate that the topical application of OH-CATH30 is efficacious against drug-resistant P. aeruginosa keratitis. In addition, our study highlights the potential application of AMPs in treating ocular bacterial infections.

Alkaline polymer electrolyte membranes for fuel cell applications.

In this review, we examine the most recent progress and research trends in the area of alkaline polymer electrolyte membrane (PEM) development in terms of material selection, synthesis, characterization, and theoretical approach, as well as their fabrication into alkaline PEM-based membrane electrode assemblies (MEAs) and the corresponding performance/durability in alkaline polymer electrolyte membrane fuel cells (PEMFCs). Respective advantages and challenges are also reviewed. To overcome challenges hindering alkaline PEM technology advancement and commercialization, several research directions are then proposed.