Akkermansia muciniphila might improve anti-PD-1 therapy against HCC by changing host bile acid metabolism.

PD-1 monoclonal antibodies (mAb) have demonstrated remarkable efficacy in a variety of cancers, including Hepatocellular carcinoma (HCC). However, the patient response rates remain suboptimal, and a significant proportion of initial responders may develop resistance to this therapeutic approach. Akkermansia muciniphila (AKK), a microorganism implicated in multiple human diseases, has been reported to be more abundant in patients who exhibit favorable responses to PD-1mAb. However, the underlying mechanism has yet to be elucidated. In our study, we found that AKK could enhance the efficacy of PD-1mAb against HCC in a tumor-bearing mouse model. It promotes HCC tumor cells apoptosis and raise the CD8+ T proportion in the tumor microenvironment. Additionally, AKK downregulates PD-L1 expression in tumor cells. Furthermore, the analysis of metabonomics demonstrates that AKK induces alterations in the host's bile acid metabolism, leading to a significant increase in serum TUDCA levels. Considering the immunosuppresive roles of TUDCA in HCC development, it is plausible to speculate that AKK may reinforce the immunotherapy of PD-1mAb against HCC through its impact on bile acid metabolism.

Integrative analysis of histomorphology, transcriptome and whole genome resequencing identified DIO2 gene as a crucial gene for the protuberant knob located on forehead in geese.

BACKGROUND: During domestication, remarkable changes in behavior, morphology, physiology and production performance have taken place in farm animals. As one of the most economically important poultry, goose owns a unique appearance characteristic called knob, which is located at the base of the upper bill. However, neither the histomorphology nor the genetic mechanism of the knob phenotype has been revealed in geese. RESULTS: In the present study, integrated radiographic, histological, transcriptomic and genomic analyses revealed the histomorphological characteristics and genetic mechanism of goose knob. The knob skin was developed, and radiographic results demonstrated that the knob bone was obviously protuberant and pneumatized. Histologically, there were major differences in structures in both the knob skin and bone between geese owing knob (namely knob-geese) and those devoid of knob (namely non-knob geese). Through transcriptome analysis, 592 and 952 genes differentially expressed in knob skin and bone, and significantly enriched in PPAR and Calcium pathways in knob skin and bone, respectively, which revealed the molecular mechanisms of histomorphological differences of the knob between knob- and non-knob geese. Furthermore, integrated transcriptomic and genomic analysis contributed to the identification of 17 and 21 candidate genes associated with the knob formation in the skin and bone, respectively. Of them, DIO2 gene could play a pivotal role in determining the knob phenotype in geese. Because a non-synonymous mutation (c.642,923 G > A, P265L) changed DIO2 protein secondary structure in knob geese, and Sanger sequencing further showed that the AA genotype was identified in the population of knob geese, and was prevalent in a crossing population which was artificially selected for 10 generations. CONCLUSIONS: This study was the first to uncover the knob histomorphological characteristics and genetic mechanism in geese, and DIO2 was identified as the crucial gene associated with the knob phenotype. These data not only expand and enrich our knowledge on the molecular mechanisms underlying the formation of head appendages in both mammalian and avian species, but also have important theoretical and practical significance for goose breeding.

Impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain.

OBJECTIVE: To investigate the impacts of anti-nerve growth factor antibody on pain-related behaviors and expressions of µ-opioid receptor in spinal dorsal horn and dorsal root ganglia of rats with cancer-induced bone pain. METHODS: The rats were randomly grouped and then injected with 10 µl of phosphate buffer saline or Walker256 tumor cells into the upper segment of left tibia. Thirteen days after the injection, the intrathecal catheterization was performed, followed by the injection of saline, anti-nerve growth factor, nerve growth factor, and naloxone twice a day. The pain ethological changes were measured at the set time points; the expression changes of µ-opioid receptor protein and mRNA in spinal dorsal horn and dorsal root ganglia were detected on the 18th day. RESULTS: After the tumor cells were injected into the tibia, hyperalgesia appeared and the expression of µ-opioid receptor protein and mRNA in spinal dorsal horn and dorsal root ganglia was increased, compared with the sham group; after intrathecally injected anti-nerve growth factor, the significant antinociceptive effects appeared, and the µ-opioid receptor expression was increased, compared with the cancer pain group; the µ-opioid receptor expressions in the other groups showed no statistical significance. The naloxone pretreatment could mostly inverse the antinociception effects of anti-nerve growth factor. CONCLUSIONS: Anti-nerve growth factor could reduce hyperalgesia in the cancer-induced bone pain rats, and the antinociceptive effects were related with the upregulation of µ-opioid receptor.

Human papillomavirus 16 E6 contributes HIF-1α induced Warburg effect by attenuating the VHL-HIF-1α interaction.

Cervical cancer is still one of the leading causes of cancer deaths in women worldwide, especially in the developing countries. It is a major metabolic character of cancer cells to consume large quantities of glucose and derive more energy by glycolysis even in the presence of adequate oxygen, which is called Warburg effect that can be exaggerated by hypoxia. The high risk subtype HPV16 early oncoprotein E6 contributes host cell immortalization and transformation through interacting with a number of cellular factors. Hypoxia-inducible factor 1α (HIF-1α), a ubiquitously expressed transcriptional regulator involved in induction of numerous genes associated with angiogenesis and tumor growth, is highly increased by HPV E6. HIF-1α is a best-known target of the von Hippel-Lindau tumor suppressor (VHL) as an E3 ligase for degradation. In the present work, we found that HPV16 E6 promotes hypoxia induced Warburg effect through hindering the association of HIF-1α and VHL. This disassociation attenuates VHL-mediated HIF-1α ubiquitination and causes HIF-1α accumulation. These results suggest that oncoprotein E6 plays a major role in the regulation of Warburg effect and can be a valuable therapeutic target for HPV-related cancer.

Exploring viscosity influence mechanisms on coating removal: Insights from single cavitation bubble behaviours in low-frequency ultrasonic settings.

The role of acoustic cavitation in various surface cleaning disciplines is important. However, the physical mechanisms underlying acoustic cavitation-induced surface cleansing are poorly understood. This is due to the combination of microscopic and ultrashort timescales associated with the dynamics of acoustic cavitation bubbles. Here, we have precisely controlled single-bubble cavitation in both space and time. Ultrasonic excitation leads to the cavitation of generated single bubbles. A synchronous ultrafast photomicrographic system simultaneously records the dynamics of single acoustic cavitation bubbles (SACBs) and the cleaning process of the nearby surface in liquids with varying viscosities. Finally, we analysed the correlation between bubble dynamics and surface cleaning situations. The differences in the typical dynamic characteristics of the bubbles during collapse in liquids with varying viscosities reveal two main mechanisms underlying surface cleaning by acoustic cavitation, which are respective the Laplace pressure during the bubble's movement and liquid jets during bubble collapse. Our study provides a better physical understanding of the ultrasonic cleaning process based on acoustic cavitation, and will help to optimize and facilitate the applications of surface cleaning, especially for the cleaning of substrates with tightly attached dirt.

Understanding Wavelength-Dependent Synergies between Morphology and Photonic Design in TiO2-Based Solar Powered Redox Cells.

Solar powered redox cells (SPRCs) are promising for large-scale and long-term storage of solar-energy, particularly when coupled with redox flow batteries (RFBs). While efforts have primarily focused on heterostructure engineering, the potential of synergistic morphology and photonic design has not been carefully studied. Here, we investigate the wavelength-dependent effects of light-absorption and charge transfer characteristics on the performance of gold decorated TiO2-based SPRC photoanodes operating with RFB-compatible redox couples. Through an in-depth optical and photoelectrochemical characterization of three complementary TiO2 microstructures, namely nanotubes, honeycombs, and nanoparticles, we elucidate the combined effects of nanometer-scale semiconductor morphology and plasmonic design across the visible spectrum. In particular, thin-walled TiO2 nanotubes exhibit a ∼ 50% increase in solar-to-chemical efficiency (STC) compared to thick-walled TiO2 honeycombs thanks to improved charge transfer. Au nanoparticles both increase generation and interfacial charge transfer (above bandgap) and promote hot carrier injection (below bandgap) leading to a further 25% increase in STC. Overall, Au/TiO2 nanotubes achieve a high photocurrent at 0.098 mA/cm2 and an excellent STC of 0.06%, among the highest with respect to the theoretical limit. The incident photon to current efficiency and internal quantum efficiency are also superior to those of bare TiO2 showing maximum values of 54.7% and 67%, respectively. Overall, nanophotonic engineering that synergistically combines morphology optimization and plasmonic sensitization schemes offer new avenues for improving rechargeable solar-energy technologies such as solar redox flow batteries.

Comparative analysis of amino acid content and protein synthesis-related genes expression levels in breast muscle among different duck breeds/strains.

Evidences have found important effects of breeds/strains on the content of amino acids (AAs) which is an important substrate for protein synthesis and contributes greatly to meat quality. Therefore, the objective of the present study was to compare the AAs content and protein synthesis-related genes expression levels in breast muscle of native breed (Jianchang duck (J)), hybrid strains (BH1, BH2, and MC♂ × (BGF2♂ × GF2♀)♀ (MC)), and commercial breed (Cherry Verry duck). Results showed that a total of 17 AAs (TAAs) was detected from breast muscle among 5 duck breeds/strains including 11 essential AAs (EAAs). Among these AAs, the contents of Proline, Threonine, Glutamine, Serine, Methionine, Phenylalanine, Histidine, and Cysteine were significant difference among 5 duck breeds/strains. The contents of EAAs, TAAs, and flavor AAs were higher in breast muscle of J and BH2 than those in other duck breeds/strains, and the ratio of EAAs/TAAs was higher in breast muscle of BH2. Furthermore, the expression levels of eukaryotic translation initiation factor 4E-binding protein 1, mammalian target of rapamycin, and proton-coupled amino acid transporter 1 were the highest in breast muscle of BH2, and that of solute carrier family 38 member 2 was the highest in breast muscle of J. Meanwhile, principal component analysis results showed that principal component 1 of BH1, principal component 3 of BH2, and principal component 2 of MC were positively corelated with EAAs/TAAs, and principal component 1 was positively correlated with flavor AAs and EAAs. In conclusion, compared to BH1, MC, and Cherry Verry duck, AA content was higher in breast muscle of BH2 and J, which might be associated with the higher expression levels of mammalian target of rapamycin, eukaryotic translation initiation factor 4E-binding protein 1, and proton-coupled amino acid transporter 1 in breast muscle of BH2 and solute carrier family 38 member 2 in breast muscle of J. The comparative analysis of AA content in breast muscle among different duck breeds/strains could provide an important basis for improving the nutritional value of duck meat in the breeding process.

Sustained-release oxycodone tablets for moderate to severe painful diabetic peripheral neuropathy: a multicenter, open-labeled, postmarketing clinical observation.

OBJECTIVE: To evaluate the efficacy and safety of sustained-release (SR) oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy (DPN). Design. This was a multicenter, randomized, open-labeled study. SETTING: This study was completed in 12 hospitals in China. PATIENTS: A total of 80 Chinese patients undergoing moderate to severe painful DPN. INTERVENTIONS: An initial dose of 10mg is recommended to be taken orally every 12 hours. Dose titration was done appropriately according to pain intensity and adverse reactions. OUTCOME MEASURES: Data record included days, dosage, analgesic efficacy, quality of sleep, adverse events, and combination therapy when patients were treated with SR oxycodone tablets. The continuous observation period was 6 weeks. RESULTS: After medication for 1 week, pain was significantly (P<0.01) relieved from 6.8±1.4 to 2.8±1.6. Onset time was within 45 minutes in nearly 60% of the patients, and within 1 hour in nearly 95% of that ones. More than 90% of the patients achieved stable analgesic dose within 3 days. After using SR oxycodone tablets for 1 week, sleep quality was significantly (P<0.01) improved. In week 1, the average dose of SR oxycodone tablets was 16.63±7.79mg. The average daily dose of most patients was about 20mg after 2 weeks. In all the enrolled patients, 38 (47.5%) had adverse reactions. No serious adverse reactions took place. CONCLUSION: The results of this clinical observation further elaborated the efficacy and safety of SR oxycodone tablets in the treatment of moderate to severe painful diabetic peripheral neuropathy in China.

Rhizosphere Soil Microbial Community Under Ice in a High-Latitude Wetland: Different Community Assembly Processes Shape Patterns of Rare and Abundant Microbes.

The rhizosphere soil microbial community under ice exhibits higher diversity and community turnover in the ice-covered stage. The mechanisms by which community assembly processes shape those patterns are poorly understood in high-latitude wetlands. Based on the 16S rRNA gene and ITS sequencing data, we determined the diversity patterns for the rhizosphere microbial community of two plant species in a seasonally ice-covered wetland, during the ice-covered and ice-free stages. The ecological processes of the community assembly were inferred using the null model at the phylogenetic bins (taxonomic groups divided according to phylogenetic relationships) level. Different effects of ecological processes on rare and abundant microbial sub-communities (defined by the relative abundance of bins) and bins were further analyzed. We found that bacterial and fungal communities had higher alpha and gamma diversity under the ice. During the ice-free stage, the dissimilarity of fungal communities decreased sharply, and the spatial variation disappeared. For the bacterial community, homogeneous selection, dispersal limitation, and ecological processes (undominated processes) were the main processes, and they remained relatively stable across all stages. For the fungal community, during the ice-covered stage, dispersal limitation was the dominant process. In contrast, during the ice-free stage, ecological drift processes were more important in the Scirpus rhizosphere, and ecological drift and homogeneous selection processes were more important in the Phragmites rhizosphere. Regarding the different effects of community assembly processes on abundant and rare microbes, abundant microbes were controlled more by homogeneous selection. In contrast, rare microbes were controlled more by ecological drift, dispersal limitation, and heterogeneous selection, especially bacteria. This is potentially caused by the low growth rates or the intermediate niche breadths of rare microbes under the ice. Our findings suggest the high diversity of microbial communities under the ice, which deepens our understanding of various ecological processes of community assembly across stages and reveals the distinct effects of community assembly processes on abundant and rare microbes at the bin level.

DNA-Based Biosensors for the Biochemical Analysis: A Review.

In recent years, DNA-based biosensors have shown great potential as the candidate of the next generation biomedical detection device due to their robust chemical properties and customizable biosensing functions. Compared with the conventional biosensors, the DNA-based biosensors have advantages such as wider detection targets, more durable lifetime, and lower production cost. Additionally, the ingenious DNA structures can control the signal conduction near the biosensor surface, which could significantly improve the performance of biosensors. In order to show a big picture of the DNA biosensor's advantages, this article reviews the background knowledge and recent advances of DNA-based biosensors, including the functional DNA strands-based biosensors, DNA hybridization-based biosensors, and DNA templated biosensors. Then, the challenges and future directions of DNA-based biosensors are discussed and proposed.

Evaluation of the spoilage heterogeneity of meat-borne Leuconostoc mesenteroides by metabonomics and in-situ analysis.

Leuconostoc mesenteroides are generally recognized as a group of specific spoilage organisms in meat and poultry products, which cause acidification and blown pack spoilage of meat. In this study, a total of 6 representative strains selected from 55 L. mesenteroides isolated from spoiled meat were tested to evaluate the spoilage ability by metabonomics and in-situ analysis. The intra-species spoilage heterogeneity was observed. The results showed that the acidifying and gas production capacity of L. mesenteroides was distinct between in broth and on meat. The pH of inoculated MRS broth was 1.38 to 1.49 units lower than that of the sterile broth and the height of gas column in Durham tube ranged from 8 mm to 11 mm at 72 h, all significantly different from the sterile group. Metabonomic analysis revealed that the main produced organic acids were myristic acid, butyric acid, lactic acid, valeric acid and enoic acid. It also illustrated that the UHPLC-MS/MS profiles of L4 and L5 was distinct from the other strains. In terms of meat inoculated with L. mesenteroides, most pH values did not show significant difference from that of the meat without inoculation, and vacuum packaging distension was not observed. Increase of TVB-N was very limited as well. The growth rate of L2, L4 and L5, as well as the pH changes of L3 and L6, varied wildly between different growth matrix. The differences between L5 and the other strains were the most obvious. The growth rate of L5 was the highest in vitro but the lowest in situ, and its acid- and gas-producing rate was relatively lower than that of the other groups. The results exhibited that it is limited to judge the bacteria-derived meat spoilage only by in-vitro growth. What should be focused on is the spoilage strengths in situ rather than the pure standard culture. In conclusion, the present study analyses profiles related to growth, acidification and gas production of L. mesenteroides in vitro and in situ, and provides references for emphasis on future research to reduce the loss of meat in consequence of spoilage.

Metabolic lactate production coordinates vasculature development and progenitor behavior in the developing mouse neocortex.

Proper neural progenitor behavior in conjunction with orderly vasculature formation is fundamental to the development of the neocortex. However, the mechanisms coordinating neural progenitor behavior and vessel growth remain largely elusive. Here we show that robust metabolic production of lactate by radial glial progenitors (RGPs) co-regulates vascular development and RGP division behavior in the developing mouse neocortex. RGPs undergo a highly organized lineage progression program to produce diverse neural progeny. Systematic single-cell metabolic state analysis revealed that RGPs and their progeny exhibit distinct metabolic features associated with specific cell types and lineage progression statuses. Symmetrically dividing, proliferative RGPs preferentially express a cohort of genes that support glucose uptake and anaerobic glycolysis. Consequently, they consume glucose in anaerobic metabolism and produce a high level of lactate, which promotes vessel growth. Moreover, lactate production enhances RGP proliferation by maintaining mitochondrial length. Together, these results suggest that specific metabolic states and metabolites coordinately regulate vasculature formation and progenitor behavior in neocortical development.

Effects of different breeds/strains on fatty acid composition and lipid metabolism-related genes expression in breast muscle of ducks.

Fatty acid composition contributes greatly to the nutritional value of meat, and breeds/strains are important factors affecting the composition of fatty acid. Recently, few studies have focused on the fatty acid composition in breast muscle of different duck breeds. Therefore, the objective of the present study was to compare the fatty acid composition and lipid metabolism-related genes expression in breast muscle of Jianchang duck (J), Cherry Verry duck (CV) and 3 crossbred strains (BH1, BH2 and MC♂ × (BGF2♂  × GF2♀)♀ (MBG)). Our results showed that the breast muscle of J had the highest contents of C22:1(n-9) but the lowest ratios of Æ©-omega 6 (Æ©n-6)/Æ©-omega 3 (Æ©n-3), Æ©-mono-unsaturated fatty acid (Æ©MUFA)/Æ©-saturated fatty acid (Æ©SFA) and Æ©-polyunsaturated fatty acid (Æ©PUFA)/Æ©SFA. The Æ©PUFA/Æ©SFA ratio was higher in breast muscle of MBG than in that of BH2 and CV, and the contents of C22:1(n-9), Æ©MUFA and Æ©PUFA were higher in BH1 than in BH2 and CV. Furthermore, the mRNA levels of SCD1, FADS2, ELOVL2, and ELOVL5 were significantly higher in MBG (P < 0.05), while those of FASD1 and ACACA were significantly higher in BH1 than in BH2 and CV (P < 0.05). Principal component analysis showed that fatty acids variation exhibited extensive positive loading on principal components (PCs). Correlation analysis showed that PC1 and PC3 of BH1, as well as PC1 of MBG were correlated with the mRNA levels of ACACA and FABP3, respectively. Thus, it could be concluded that the breast muscles of MBG and BH1 have better fatty acid composition, which was closely related to the increased expression levels of SCD1, FADS2, ELOVL2, and ELOVL5 genes in MBG but FADS1 and ACACA in BH1. Moreover, these results also showed that crossbreeding could optimize the composition of fatty acid in breast muscle of ducks.

Topology of leaf veins: Experimental observation and computational morphogenesis.

The unique, hierarchical patterns of leaf veins have attracted extensive attention in recent years. However, it remains unclear how biological and mechanical factors influence the topology of leaf veins. In this paper, we investigate the optimization mechanisms of leaf veins through a combination of experimental measurements and numerical simulations. The topological details of three types of representative plant leaves are measured. The experimental results show that the vein patterns are insensitive to leaf shapes and curvature. The numbers of secondary veins are independent of the length of the main vein, and the total length of veins increases linearly with the leaf perimeter. By integrating biomechanical mechanisms into the topology optimization process, a transdisciplinary computational method is developed to optimize leaf structures. The numerical results show that improving the efficiency of nutrient transport plays a critical role in the morphogenesis of leaf veins. Contrary to the popular belief in the literature, this study shows that the structural performance is not a key factor in determining the venation patterns. The findings provide a deep understanding of the optimization mechanism of leaf veins, which is useful for the design of high-performance shell structures.

A D-shaped fiber SPR sensor with a composite nanostructure of MoS2-graphene for glucose detection.

Fiber-based techniques make it possible to implant a miniaturized and flexible surface plasmon resonance (SPR) sensor into the human body for glucose detection. However, the miniaturization of fiber SPR sensors results in low sensitivity compared with traditional prism-type SPR sensors due to limited sensing area. In this paper, we proposed a D-shaped fiber SPR sensor with a composite nanostructure of molybdenum disulfide (MoS2)-graphene to improve the sensor sensitivity. Compared with the traditional cylindrical fiber, the planar sensing area on the side-polished fiber makes it easier to modify two-dimensional materials. Chemical vapor deposition (CVD) graphene and CVD MoS2 were modified on the sensor surface to obtain the MoS2-graphene composite nanostructure. π-π stacking interactions were used to modify pyrene-1-boronic acid (PBA) on the graphene. The excellent photoelectric properties of the MoS2-graphene composite nanostructure and the ability of PBA to specifically bind glucose molecules improved the glucose detection performance of the SPR sensor. The results show that specific detection of glucose was realized and that the highest sensitivity was achieved with three-layer MoS2 and monolayer graphene.

All-optical and polarization-independent spatial filter based on a vertically-aligned polymer-stabilized liquid crystal film with a photoconductive layer.

An all-optical and polarization-independent spatial filter was developed in a vertically-aligned (VA) polymer-stabilized liquid crystal (PSLC) film with a photoconductive (PC) layer. This spatial filter is based on the effect of light on the conductivity of PC layer: high (low)-intensity light makes the conductivity of the PC layer high (low), resulting in a low (high) threshold voltage of the PC-coated VA PSLC cell. Experimental results indicate that this spatial filter is a high-pass filter with low optical-power consumption (about 1.11 mW/cm(2)) in an optical Fourier transform system. The high-pass characteristic was confirmed by simulation. Accordingly, the all-optical and polarization-independent spatial filter can be used to enhance the edges of images.

Interconnected Ultrasmall V2O3 and Li4Ti5O12 Particles Construct Robust Interfaces for Long-Cycling Anodes of Lithium-Ion Batteries.

Designing composite structures of active materials is critical for high-performance lithium-ion batteries, as it determines the reversibility of lithium-ion insertion and extraction of the electrodes. The V2O3 anode has a high specific capacity but presents poor cycling stability due to a large volume change. Herein, a novel C@V2O3-Li4Ti5O12 composite with ultrastable cycling stability is constructed. In this composite structure, the interconnected ultrasmall V2O3 and Li4Ti5O12 nanoparticles (5-10 nm) construct robust interfaces in the carbon matrix. The Li4Ti5O12 nanoparticles with excellent cycling stability and a minor volume change act as fixtures that effectively restrict the volume change of V2O3 nanoparticles and improve the cycling stability of the C@V2O3-Li4Ti5O12 composite. The C@V2O3-Li4Ti5O12 composite maintains no degradation during 500 cycles under a current density of 100 mA g-1. The results demonstrate that constructing a highly stable interface between the active nanoparticles with smaller and larger volume changes is of great significance to suppress their pulverization and achieve high reversibility. This work contributes to a new strategy to design the structure of long-cycling anode materials for highly stable lithium-ion batteries.

Capacity Loss Mechanism of the Li4Ti5O12 Microsphere Anode of Lithium-Ion Batteries at High Temperature and Rate Cycling Conditions.

Li4Ti5O12 (LTO) as the anode of lithium (Li) ion batteries has high interfacial side reactivity with the electrolyte, which leads to severe gassing behavior and poor cycling stability. Herein, the capacity loss mechanism of the high-tap density LTO microsphere anode under different temperatures (25, 45, and 60 °C) and charge/discharge rates (1 and 5 C) is systematically investigated. The capacity retentions of the LTO/Li cell after 500 cycles at 1 C are 95.6, 90.0, and 87.1% under three temperatures, which drop to 91.9, 58.3, and 20.9% when cycling at 5 C, respectively. Results show that the high temperature and rate almost do not damage the structure of LTO, but greatly affect the thickness and components of the solid electrolyte interface (SEI), and consequently reduce the performance of the LTO/Li cells. An SEI mainly consisting of inorganic species forms on LTO after 500 cycles at 1 C, while organic compounds are observed after 500 cycles at 5 C. The capacity of cycled LTO cannot recover again because of the thick SEI although using new Li metal anodes, separators, and electrolytes. This work demonstrates that it is of great significance for LTO to construct a stable SEI for achieving excellent cycling performance at a high rate and temperature.

Inhibition of enterovirus 71 replication by an α-hydroxy-nitrile derivative NK-1.9k.

Enterovirus 71 (EV71) is one of the major etiological agents of human hand-foot-and-mouth disease (HFMD) worldwide. EV71 infection in young children and people with immunodeficiency causes severe symptoms with a high fatality rates. However, there is still no approved drugs to treat such infections. Based on our previous report of a peptide-aldehyde anti-EV71 protease, we present here a highly specific α-hydroxy-nitrile derivative NK-1.9k, which inhibited the proliferation of multiple EV71 strains and coxsackievirus A16 (CVA16) in various cells with EC50 of 37.0 nM with low cytotoxicity (CC50 > 200 µM). The hydroxy-nitrile covalent warhead conferred NK-1.9k high potency and selectivity to interact with the cysteine residue of the active site of the viral protease. We also documented the resistance to NK-1.9k with a N69S mutation in EV71 3Cpro. The combination of NK-1.9k and EV71 polymerase or entry inhibitors produced strong synergistic antiviral effects. Collectively, our findings suggest our compounds can potentially be developed as drugs for the treatment of HFMD.

HPV16 E6 upregulates Aurora A expression.

Overexpression of Aurora A kinase occurs in certain types of cancer, and therefore results in chromosome instability and phosphorylation-mediated ubiquitylation and degradation of p53 for tumorigenesis. The high-risk subtype human papillomavirus (HPV)16 early oncoprotein E6 is a major contributor inducing host cell immortalization and transformation through interaction with a number of cellular factors. In the present study, co-immunoprecipitation, glutathione S-transferase pull-down and immunostaining were used to show that HPV16 E6 and Aurora A bind to each other in vivo and in vitro. Western blotting and reverse transcription-polymerase chain reaction were used to reveal that HPV16 E6 inhibited cell apoptosis by stabilizing Aurora A expression. The present study may report a new mechanism for the involvement of HPV16 E6 in carcinogenesis, as HPV16 E6 elevates Aurora A expression and the latter may be a common target for oncogenic viruses that result in cell carcinogenesis.