In Situ Construction of LiF-Li3N-Rich Interface Contributed to Fast Ion Diffusion in All-Solid-State Lithium-Sulfur Batteries.

All-solid-state lithium-sulfur batteries (ASSLSBs) have attracted wide attention due to their ultrahigh theoretical energy density and the ability of completely avoiding the shuttle effect. However, the further development of ASSLSBs is limited by the poor kinetic properties of the solid electrode interface. It remains a great challenge to achieve good kinetic properties, by common strategies to substitute sulfur-transition metal and organosulfur composites for sulfur without reducing the specific capacity of ASSLSBs. In this study, a sulfur-(Ketjen Black)-(bistrifluoromethanesulfonimide lithium salt) (S-KB-LiTFSI) composite is constructed by introducing LiTFSI into the S-KB composite. The initial discharge capacity reaches up to 1483 mA h g-1, benefited from the improved ionic conductivity and diffusion kinetics of the S-KB-LiTFSI composite, where numerous LiF interphases with a Li3N component are in situ formed during cycling. Combined with DFT calculations, it is found that the migration barriers of LiF and Li3N are much smaller than that of the Li6PS5Cl solid electrolyte. The fast ionic conductors of LiF and Li3N not only enhance the Li+ transfer efficiency but also improve the interfacial stability. Therefore, the assembled ASSLSBs operate stably for 600 cycles at 200 mA g-1, and this study provides an effective strategy for the further development of ASSLSBs.

New Chemical Synthesis Strategy To Construct a Silicon/Carbon Nanotubes/Carbon-Integrated Composite with Outstanding Lithium Storage Capability.

The Si/C anode is one of the most promising candidate materials for the next-generation lithium-ion batteries (LIBs). Herein, a silicon/carbon nanotubes/carbon (Si/CNTs/C) composite is in situ synthesized by a one-step reaction of magnesium silicide, calcium carbonate, and ferrocene. Transmission electron microscopy reveals that the growth of CNTs is attributed to the catalysis of iron atoms derived from the decomposition of ferrocene. In comparison to a Si/C composite, the cycle stability of the Si/CNTs/C composite can obviously be improved as an anode for LIBs. The enhanced performance is mainly attributed to the following factors: (i) the perfect combination of Si nanoparticles and in situ grown CNTs achieves high mechanical integrity and good electrical contact; (ii) Si nanoparticles are entangled in the CNT cage, effectively reducing the volume expansion upon cycling; and (iii) in situ grown CNTs can improve the conductivity of composites and provide lithium ion transport channels. Moreover, the full cell constructed by a LiFePO4 cathode and Si/CNTs/C anode exhibits excellent cycling stability (137 mAh g-1 after 300 cycles at 0.5 C with a capacity retention rate of 91.2%). This work provides a new way for the synthesis of a Si/C anode for high-performance LIBs.

Punicalagin promotes autophagic degradation of human papillomavirus E6 and E7 proteins in cervical cancer through the ROS-JNK-BCL2 pathway.

Punicalagin, which is derived from pomegranate peel, is reported to exert growth-inhibitory effects against various cancers. However, the underlying mechanisms have not been elucidated. Human papillomavirus (HPV), a major oncovirus, utilizes the host autophagic machinery to support its replication. Here, punicalagin markedly downregulated the levels of the major HPV oncoproteins E6 and E7 in cervical cancer cells through the autophagy-lysosome system. Additionally, punicalagin activated the reactive oxygen species (ROS)-JNK pathway and promoted the phosphorylation of BCL2, which led to the dissociation of BCL2 from BECN1 and the induction of autophagy. Treatment with autophagy and JNK inhibitors or ROS scavengers mitigated the punicalagin-induced degradation of E6 and E7. Moreover, the knockout of ATG5 using the clustered regularly interspaced palindrome repeat/Cas 9 system mitigated the punicalagin-induced downregulation of E6/E7. This indicated that punicalagin-induced degradation of E6 and E7 was dependent on autophagy. The results of in vivo studies demonstrated that punicalagin efficiently inhibits cervical cancer growth. In conclusion, this study elucidated a mechanism of punicalagin-induced autophagic degradation of E6 and E7. It will enable the future applications of punicalagin as a therapeutic for HPV-induced cervical cancer.

Broadly Protective CD8+ T Cell Immunity to Highly Conserved Epitopes Elicited by Heat Shock Protein gp96-Adjuvanted Influenza Monovalent Split Vaccine.

Currently, immunization with inactivated influenza virus vaccines is the most prevalent method to prevent infections. However, licensed influenza vaccines provide only strain-specific protection and need to be updated and administered yearly; thus, new vaccines that provide broad protection against multiple influenza virus subtypes are required. In this study, we demonstrated that intradermal immunization with gp96-adjuvanted seasonal influenza monovalent H1N1 split vaccine could induce cross-protection against both group 1 and group 2 influenza A viruses in BALB/c mouse models. Vaccination in the presence of gp96 induced an apparently stronger antigen-specific T cell response than split vaccine alone. Immunization with the gp96-adjuvanted vaccine also elicited an apparent cross-reactive CD8+ T cell response that targeted the conserved epitopes across different influenza virus strains. These cross-reactive CD8+ T cells might be recalled from a pool of memory cells established after vaccination and recruited from extrapulmonary sites to facilitate viral clearance. Of note, six highly conserved CD8+ T epitopes from the viral structural proteins hemagglutinin (HA), M1, nucleoprotein (NP), and PB1 were identified to play a synergistic role in gp96-mediated cross-protection. Comparative analysis showed that most of conservative epitope-specific cytotoxic T lymphocytes (CTLs) apparently induced by heterologous virus infection were also activated by gp96-adjuvanted vaccine, thus resulting in broader protective CD8+ T cell responses. Our results demonstrated the advantage of adding gp96 to an existing seasonal influenza vaccine to improve its ability to provide better cross-protection.IMPORTANCE Owing to continuous mutations in hemagglutinin (HA) or neuraminidase (NA) or recombination of the gene segments between different strains, influenza viruses can escape the immune responses developed by vaccination. Thus, new strategies aimed to efficiently activate immune response that targets to conserved regions among different influenza viruses are urgently needed in designing broad-spectrum influenza vaccine. Heat shock protein gp96 is currently the only natural T cell adjuvant with special ability to cross-present coupled antigen to major histocompatibility complex class I (MHC-I) molecule and activate the downstream antigen-specific CTL response. In this study, we demonstrated the advantages of adding gp96 to monovalent split influenza virus vaccine to improve its ability to provide cross-protection in the BALB/c mouse model and proved that a gp96-activated cross-reactive CTL response is indispensable in our vaccine strategy. Due to its unique adjuvant properties, gp96 might be a promising adjuvant for designing new broad-spectrum influenza vaccines.

MM Algorithms For Variance Components Models.

Variance components estimation and mixed model analysis are central themes in statistics with applications in numerous scientific disciplines. Despite the best efforts of generations of statisticians and numerical analysts, maximum likelihood estimation and restricted maximum likelihood estimation of variance component models remain numerically challenging. Building on the minorization-maximization (MM) principle, this paper presents a novel iterative algorithm for variance components estimation. Our MM algorithm is trivial to implement and competitive on large data problems. The algorithm readily extends to more complicated problems such as linear mixed models, multivariate response models possibly with missing data, maximum a posteriori estimation, and penalized estimation. We establish the global convergence of the MM algorithm to a Karush-Kuhn-Tucker (KKT) point and demonstrate, both numerically and theoretically, that it converges faster than the classical EM algorithm when the number of variance components is greater than two and all covariance matrices are positive definite.

MM ALGORITHMS FOR VARIANCE COMPONENT ESTIMATION AND SELECTION IN LOGISTIC LINEAR MIXED MODEL.

Logistic linear mixed models are widely used in experimental designs and genetic analyses of binary traits. Motivated by modern applications, we consider the case of many groups of random effects, where each group corresponds to a variance component. When the number of variance components is large, fitting a logistic linear mixed model is challenging. Thus, we develop two efficient and stable minorization-maximization (MM) algorithms for estimating variance components based on a Laplace approximation of the logistic model. One of these leads to a simple iterative soft-thresholding algorithm for variance component selection using the maximum penalized approximated likelihood. We demonstrate the variance component estimation and selection performance of our algorithms by means of simulation studies and an analysis of real data.

An ultrasensitive electrochemiluminescent immunosensor based on graphene oxide coupled graphite-like carbon nitride and multiwalled carbon nanotubes-gold for the detection of diclofenac.

In this study, a novel competition-type electrochemiluminescent (ECL) immunosensor for detecting diclofenac (DCF) was fabricated with graphene oxide coupled graphite-like carbon nitride (GO-g-C3N4) as signal probe for the first time. The ECL intensity of carboxylated g-C3N4 was significantly enhanced after being combined with graphene oxide (GO) which exhibited excellent charge-transport property. The sensing platform was constructed by multiwalled carbon nanotubes and gold nanoparticles (MWCNTs-AuNPs), which not only provided an effective matrix for immobilizing a large amount of coating antigen but also facilitated the electronic transmission rate to enhance the ECL intensity. Based on the synergistic effect of GO-g-C3N4 and MWCNTs-AuNPs composite, the proposed sensor showed high sensitivity, good stability, and wide linearity for the detection of DCF in the range of 0.005-1000ngmL-1 with a detection limit of 1.7pgmL-1. Furthermore, the developed immunoassay has been applied to real samples with satisfactory results. Therefore, this work provided a promising method for the detection of DCF and other small molecular compounds in the future.

Multiple signal amplified electrochemiluminescent immunoassay for brombuterol detection using gold nanoparticles and polyamidoamine dendrimers-silver nanoribbon.

Electrochemiluminescent (ECL) immunosensor with multiple signal amplification was designed based on gold nanoparticles (AuNPs), polyamidoamine dendrimers (PAMAM) and silver-cysteine hybrid nanoribbon (SNR). Low toxic l-cysteine capped CdSe QDs was chosen as the ECL signal probe. To verify the proposed ultrasensitive ECL immunosensor for ß-adrenergic agonists (ß-AA), we detected Brombuterol (Brom) as a proof-of-principle analyte. Therein, AuNPs as the substrate can simplify the experiment process, accelerate the electron transfer rate, and carry more coating antigen (Ag-OVA) to enlarge ECL signal. On one hand, SNR on the surface of electrode can avoid the aggregation of AuNPs, and SNR-PAMAM-AuNPs also can be acted as a good accelerator for electron transfer. On the other hand, PAMAM (16 -NH2) functionalized SNR (SNR-PAMAM) with numerous amino groups could be employed to bond abundant actived QDs to further amplify ECL signal. The new immunosensor can offer a simple, reliable, rapid, and selective detection for Brom, which have a dynamic range of 0.005-700 ng mL-1 with a low detection limit at 1.5 pg mL-1. The proposed biosensor will extend the application of nanomaterials in ECL immunoassays and open a new road for the detection of Brom and other ß-AA in the future.

Heal rate of metatarsal fractures: A propensity-matching study of patients treated with low-intensity pulsed ultrasound (LIPUS) vs. surgical and other treatments.

INTRODUCTION: Whether to treat metatarsal fractures conservatively or surgically is controversial. We test a hypothesis that metatarsal fractures treated conservatively with non-invasive low-intensity pulsed ultrasound (LIPUS) obtain heal rates comparable to current surgical techniques. PATIENTS AND METHODS: This is a retrospective observational cohort study, using patient outcomes from a prospectively-collected LIPUS registry required by the U.S. Food & Drug Administration. Registry data were collected over a 5-year period and were reviewed and validated by a registered nurse. Data required for analysis were days-to-treatment (DTT) with LIPUS and a dichotomous outcome of healed versus failed, as assessed by clinical and radiographic criteria. Registry patients (DTT<365days) were propensity-matched to metatarsal fracture patients from a health claims database that includes medical and drug expenses for ∼90.1 million patients. The propensity match was based on patient demographic data (age, gender, body weight, fracture severity, and smoking status). RESULTS: A total of 594 metatarsal fractures were treated with LIPUS, including 161 Jones fractures. Compared to patients in the claims database, LIPUS-treated patients were more likely to: be overweight or obese; be male; have open fracture; and smoke (all, P<0.0001), suggesting that these variables were perceived as nonunion risk factors by prescribing physicians. After propensity-matching, none of these differences between the registry and the health claims database remained significant. The heal rate with LIPUS treatment was 97.3%, comparable to the heal rate of 95.3% among claims patients in 2011 who did not receive LIPUS (P=0.0654). When fresh fractures (0-90days) and delayed unions (91-365days) were analyzed separately, the LIPUS fresh fracture heal rate was superior to claims patients (P=0.0381), and the delayed union heal rate was comparable. After exclusion of registry patients who received surgery, heal rate with LIPUS alone (97.4%) was significantly better (P<0.0097) than the heal rate for matched patients in 2011 (94.2%). CONCLUSIONS: LIPUS significantly improved the heal rate of metatarsal fractures <1year old without surgery (P=0.0097). Metatarsal fractures treated with LIPUS alone have a heal rate comparable to fractures treated by surgical intervention.