High-Current Water-Enabled Electricity Generation in Mushrooms via Synergistic Ion Sieving and Adsorption.

Water-enabled electricity generation (WEG), which harvests energy from the natural water cycle, is a novel strategy for producing green electricity. Taking advantage of the ion sieving effect based on evaporation-induced water flows in charged nanopores, various WEG devices have been developed. Here, we report that a carbonized mushroom produces a record-high current output of up to 96.7 µA, which is attributed to a unique ion adsorption effect combined with an ion sieving effect. Specifically, the natural gradient potential from root to cap in a mushroom caused by tissue differentiation adsorbs different ions, enhancing the traditional ion sieving current. In synergy with the two effects, the mushroom can operate under a broad range of concentrations (0 to 0.6 mol L-1) and represents significant improvements in current, duration, and total charge transfer. These findings reveal the hidden talent of mushrooms as natural materials for WEG, providing inspiration for the development of high-performance WEG devices.

Spinal cord electrical stimulation for severe disturbance of consciousness after traumatic brain injury: A case report.

Background: Currently, the use of spinal cord electrical stimulations for patients with severe disorders of consciousness after traumatic brain injury remains limited, and long-term follow-up studies are even scarcer. To date, there have been few reports using near-infrared spectroscopy to evaluate the clinical effects and optimal parameters of spinal cord electrical stimulation for severe consciousness disorders. This report describes a case of a patient with severe disturbance of consciousness after traumatic brain injury who underwent spinal cord electrical stimulation implantation. Advanced near-infrared spectroscopy was employed to monitor and evaluate postoperative efficacy. The findings of this case report will provide a reference for the clinical treatment of severe consciousness disturbances. Methods: A patient diagnosed with a severe disturbance of consciousness following traumatic brain injury presented symptoms of coma and lack of voluntary activity. The treatment regimen included conventional approaches (medication combined with rehabilitation training) and adjustments to the spinal cord electrical stimulation parameters. Advanced functional near-infrared spectroscopy (fNIRS) was used to explore changes in brain functional connectivity strength and assess clinical efficacy. Results: The integration of conventional treatment and continuous modification of spinal cord electrical stimulation parameters, combined with fNIRS monitoring, demonstrated that conventional treatment and spinal cord electrical stimulation displayed a positive effect on increasing brain functional strength connection. The Glasgow Coma Scale(GCS) score significantly improved from the baseline. Optimal results were observed with spinal cord stimulation settings at 4.5 V amplitude, 210 µs pulse width, and 70 Hz frequency, operating from 8:00-20:00 in a cycling mode of 15 min on and 15 min off, where improvements in consciousness were markedly evident. Conclusions: Patients with severe disturbances of consciousness after traumatic brain injury recover slowly. Conventional treatment combined with spinal cord electrical stimulation can improve the degree of disturbance of consciousness and promote recovery from the condition.

Network pharmacology analysis and molecular docking using the Chinese herbal agent WYHX formula (according to Yan Dexin): Management of coronary artery disease.

BACKGROUND: The therapeutic impact of the Wenyang Huoxue (WYXH) formula on coronary atherosclerotic heart disease (CHD) is well established, yet the precise mechanisms are currently not fully understood. This study provides preliminary insights into the potential mechanisms underlying the therapeutic effects of the formula on CHD by utilizing network pharmacology and molecular docking technology. MATERIALS AND METHODS: The primary active constituents and their corresponding action targets for the formula were retrieved from the TCMSP database. Utilizing Cytoscape 3.9.1 software, a network linking the components of the formula to their respective targets was constructed. Information was collected from Genecards, OMIM, TTD, and DrugBank databases to identify targets related to CHD. The common targets shared by the formula and CHD were then imported into the STRING database to create a protein-protein interaction (PPI) network. Following this, enrichment analyses were performed on the shared targets using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Finally, molecular docking was conducted on the primary active compounds and the core targets. RESULTS: The network encompassing the components and targets of the formula comprises a total of 311 nodes and 895 edges. Compounds exhibiting higher degree centrality consist of quercetin, ß-sitosterol, and kaempferol. In the PPI network, proteins with elevated degree centrality are protein kinase B (AKT1), epidermal growth factor receptor (EGFR), and mitogen-activated protein kinase 3 (MAPK3). The results of GO and KEGG enrichment analyses reveal that the biological processes associated with the efficacy of the formula in treating CHD primarily involve positive regulation of gene expression, hypoxia response, and lipopolysaccharide response, among others. The signaling pathways primarily involved include phosphatidylinositol 3-kinase and protein kinase B (PI3K-AKT), MAPK3, tumor necrosis factor (TNF), and so on. Molecular docking results demonstrate a strong affinity between quercetin, ß-sitosterol, and kaempferol with AKT1, EGFR, and MAPK3. CONCLUSION: We showed for the first time that AKT1, EGFR, and MAPK3 are potential targets influenced by the WYHX formula in CHD treatment. The therapeutic effects could possibly involve signaling pathways such as the PI3K-AKT, MAPK, TNF, and AGE-RAGE pathways.

Vaccination induces broadly neutralizing antibody precursors to HIV gp41.

A key barrier to the development of vaccines that induce broadly neutralizing antibodies (bnAbs) against human immunodeficiency virus (HIV) and other viruses of high antigenic diversity is the design of priming immunogens that induce rare bnAb-precursor B cells. The high neutralization breadth of the HIV bnAb 10E8 makes elicitation of 10E8-class bnAbs desirable; however, the recessed epitope within gp41 makes envelope trimers poor priming immunogens and requires that 10E8-class bnAbs possess a long heavy chain complementarity determining region 3 (HCDR3) with a specific binding motif. We developed germline-targeting epitope scaffolds with affinity for 10E8-class precursors and engineered nanoparticles for multivalent display. Scaffolds exhibited epitope structural mimicry and bound bnAb-precursor human naive B cells in ex vivo screens, protein nanoparticles induced bnAb-precursor responses in stringent mouse models and rhesus macaques, and mRNA-encoded nanoparticles triggered similar responses in mice. Thus, germline-targeting epitope scaffold nanoparticles can elicit rare bnAb-precursor B cells with predefined binding specificities and HCDR3 features.

Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice.

A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01B was found to induce VRC01-class bnAb precursors in 97% of vaccine recipients in the IAVI G001 phase 1 clinical trial; however, heterologous boost immunizations with antigens more similar to the native glycoprotein will be required to induce bnAbs. Therefore, we designed core-g28v2 60mer, a nanoparticle immunogen to be used as a first boost after eOD-GT8 60mer priming. We found, using a humanized mouse model approximating human conditions of VRC01-class precursor B cell diversity, affinity, and frequency, that both protein- and mRNA-based heterologous prime-boost regimens induced VRC01-class antibodies that gained key mutations and bound to near-native HIV envelope trimers lacking the N276 glycan. We further showed that VRC01-class antibodies induced by mRNA-based regimens could neutralize pseudoviruses lacking the N276 glycan. These results demonstrated that heterologous boosting can drive maturation toward VRC01-class bnAb development and supported the initiation of the IAVI G002 phase 1 trial testing mRNA-encoded nanoparticle prime-boost regimens.

mRNA-LNP prime boost evolves precursors toward VRC01-like broadly neutralizing antibodies in preclinical humanized mouse models.

Germline-targeting (GT) protein immunogens to induce VRC01-class broadly neutralizing antibodies (bnAbs) to the CD4-binding site of the HIV envelope (Env) have shown promise in clinical trials. Here, we preclinically validated a lipid nanoparticle-encapsulated nucleoside mRNA (mRNA-LNP) encoding eOD-GT8 60mer as a soluble self-assembling nanoparticle in mouse models. In a model with three humanized B cell lineages bearing distinct VRC01-precursor B cell receptors (BCRs) with similar affinities for eOD-GT8, all lineages could be simultaneously primed and undergo diversification and affinity maturation without exclusionary competition. Boosts drove precursor B cell participation in germinal centers; the accumulation of somatic hypermutations, including in key VRC01-class positions; and affinity maturation to boost and native-like antigens in two of the three precursor lineages. We have preclinically validated a prime-boost regimen of soluble self-assembling nanoparticles encoded by mRNA-LNP, demonstrating that multiple lineages can be primed, boosted, and diversified along the bnAb pathway.

Microstructure and Corrosion Behavior of Zinc/Hydroxyapatite Multi-Layer Coating Prepared by Combining Cold Spraying and High-Velocity Suspension Flame Spraying.

The study aims to enhance the corrosion resistance and bioactivity of Mg alloy substrates through the development of a zinc/hydroxyapatite multi-layer (Zn/HA-ML) coating. The Zn/HA-ML coating was prepared by depositing a cold-sprayed (CS) Zn underlayer and a high-velocity suspension flame sprayed (HVSFS) Zn/HA multi-layer and was compared with the CS Zn coating and the Zn/HA dual-layer (Zn/HA-DL) coating. Phase, microstructure, and bonding strength were examined, respectively, by X-ray diffraction, scanning electron microscopy, and tensile bonding testing. Corrosion behavior and bioactivity were investigated using potentiodynamic polarization, electrochemical impedance spectroscopy, and immersion testing. Results show that the HVSFS Zn/HA composite layers were mainly composed of Zn, HA, and ZnO and were well bonded to the substrate. The HVSFS HA upper layer on the CS Zn underlayer in the Zn/HA-DL coating exhibited microcracks due to their mismatched thermal expansion coefficient (CTE). The Zn/HA-ML coating exhibited good bonding within different layers and showed a higher bonding strength of 27.3 ± 2.3 MPa than the Zn/HA-DL coating of 20.4 ± 2.7 MPa. The CS Zn coating, Zn/HA-DL coating, and Zn/HA-ML coating decreased the corrosion current density of the Mg alloy substrate by around two-fourfold from 3.12 ± 0.75 mA/cm2 to 1.41 ± 0.82mA/cm2, 1.06 ± 0.31 mA/cm2, and 0.88 ± 0.27 mA/cm2, respectively. The Zn/HA-ML coating showed a sixfold decrease in the corrosion current density and more improvements in the corrosion resistance by twofold after an immersion time of 14 days, which was mainly attributed to newly formed apatite and corrosion by-products of Zn particles. The Zn/HA-ML coating effectively combined the advantages of the corrosion resistance of CS Zn underlayer and the bioactivity of HVSFS Zn/HA multi-layers, which proposed a low-temperature strategy for improving corrosion resistance and bioactivity for implant metals.

Association between post-stroke cognitive impairment and gut microbiota: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Accumulating evidence has indicated a possible connection between post-stroke cognitive impairment (PSCI) and gut microbiota imbalance. To further investigate this association, the present work was designed to systematically assess the dissimilarity of gut microbiota between PSCI and healthy individuals or stroke patients. METHODS: A meta-analysis and systematic review was conducted by searching various databases including PubMed, Web of Science, Embase, VIP, CNKI, and Wangfang for relevant studies. The pooled outcomes were used to estimate the combined dissimilarity of gut microbiota composition between PSCI and healthy individuals or patients with stroke. RESULTS: Nine eligible studies were included in this meta-analysis. The results showed that there were no significant changes in observed richness indexes (Chao1 and ACE) and Shannon index. Notably, a significant decrease in Simpson index was observed in PSCI patients in comparison to the healthy individuals (-0.31, 95% CI: -0.62 to -0.01, P = 0.04). Moreover, the microbiota composition at the phylum level (increased abundance of Proteobacteria), family level (increased abundance of Bacteroidaceae, Lachnospiraceae, and Veillonellaceae; decreased abundance of Enterobacteriaceae), and genus level (increased abundance of Bacteroides, Clostridium XIVa, and Parabacteroides; decreased abundance of Prevotella and Ruminococcus) was found to be significantly different between PSCI and controls. CONCLUSION: This meta-analysis suggests a significant shift of observed species and microbiota composition in PSCI compared to healthy individuals or patients with stroke.

Vaccination induces HIV broadly neutralizing antibody precursors in humans.

Broadly neutralizing antibodies (bnAbs) can protect against HIV infection but have not been induced by human vaccination. A key barrier to bnAb induction is vaccine priming of rare bnAb-precursor B cells. In a randomized, double-blind, placebo-controlled phase 1 clinical trial, the HIV vaccine-priming candidate eOD-GT8 60mer adjuvanted with AS01B had a favorable safety profile and induced VRC01-class bnAb precursors in 97% of vaccine recipients with median frequencies reaching 0.1% among immunoglobulin G B cells in blood. bnAb precursors shared properties with bnAbs and gained somatic hypermutation and affinity with the boost. The results establish clinical proof of concept for germline-targeting vaccine priming, support development of boosting regimens to induce bnAbs, and encourage application of the germline-targeting strategy to other targets in HIV and other pathogens.

Influence of Heat Treatment on Microstructure, Mechanical Property, and Corrosion Behavior of Cold-Sprayed Zn Coating on Mg Alloy Substrate.

The influence of post-process heat treatment on cold-sprayed Zn coatings on the Mg alloy substrate was investigated at different temperatures (150, 250, and 350 °C) and times (2, 8, and 16 h). Phase, microstructure, microhardness, and tensile strength of Zn coatings were analyzed before and after heat treatment. Corrosion properties of Zn coatings after heat treatment were investigated in simulated body fluid by using potentiodynamic polarization and immersion testing. Results show that although the heat treatment presented little effect on phase compositions of Zn coatings, the full width at half maxima of the Zn phase decreased with the heat temperature and time. Zn coatings presented comparable microstructures before and after heat treatment in addition to the inter-diffusion layers, and the inter-diffusion layer was dependent on the heat temperature and time. Both the thickness and the microhardness of inter-diffusion layers were increased with the heat temperature and time, with the largest thickness of 704.1 ± 32.4 µm and the largest microhardness of 323.7 ± 104.1 HV0.025 at 350 °C for 2 h. The microhardness of Zn coating was significantly decreased from 70.8 ± 5.6 HV0.025 to 43.9 ± 12.5 HV0.025, with the heat temperature from the ambient temperature to 350 °C, and was slightly decreased with the heat time at 250 °C. Although the tensile strength of Zn coating was slightly increased by heat treatment, with the highest value of 40.9 ± 3.9 MPa at 150 °C for 2 h, excessive heat temperature and time were detrimental to the tensile strength, with the lowest value of 6.6 ± 1.6 MPa at 350 °C for 2 h. The heat temperature and heat time presented limited effects on the corrosion current and corrosion ratio of the Zn coatings, and Zn coatings before and after heat treatment effectively hindered the simulated body fluid from penetrating into the substrate. The corrosion behavior of Zn coatings was discussed in terms of corrosion products and microstructures after immersion.

Human immunoglobulin repertoire analysis guides design of vaccine priming immunogens targeting HIV V2-apex broadly neutralizing antibody precursors.

Broadly neutralizing antibodies (bnAbs) to the HIV envelope (Env) V2-apex region are important leads for HIV vaccine design. Most V2-apex bnAbs engage Env with an uncommonly long heavy-chain complementarity-determining region 3 (HCDR3), suggesting that the rarity of bnAb precursors poses a challenge for vaccine priming. We created precursor sequence definitions for V2-apex HCDR3-dependent bnAbs and searched for related precursors in human antibody heavy-chain ultradeep sequencing data from 14 HIV-unexposed donors. We found potential precursors in a majority of donors for only two long-HCDR3 V2-apex bnAbs, PCT64 and PG9, identifying these bnAbs as priority vaccine targets. We then engineered ApexGT Env trimers that bound inferred germlines for PCT64 and PG9 and had higher affinities for bnAbs, determined cryo-EM structures of ApexGT trimers complexed with inferred-germline and bnAb forms of PCT64 and PG9, and developed an mRNA-encoded cell-surface ApexGT trimer. These methods and immunogens have promise to assist HIV vaccine development.

Efficacy of Yangxin Recipe in Combination with Conventional Western Medicine in Treatment of Angina Pectoris of Coronary Heart Disease.

OBJECTIVE: To study the efficacy of Yangxin Recipe (YXR) in patients with stable angina pectoris of coronary heart disease and its impacts on coronary CT angiography. METHODS: A total of 78 patients with coronary heart disease and angina pectoris were randomly divided into a control group (n = 39) and a YXR group (n = 39). The control group adopted conventional Western medicine while the YXR group received conventional western medicine + oral administration of YXR. After six months of continuous treatment, the clinical efficacy, traditional Chinese medicine (TCM) syndrome scores, Pittsburgh Sleep Quality Index (PSQI), and the level of coronary CT vascular stenosis were observed. RESULTS: After treatment, the total effective rate of YXR was 92.31%, which was higher than (P < 0.01) that of the western medicine control group. The total score of TCM syndromes in the YXR group was (14.44 ± 9.87), which was significantly lower than (P < 0.001) that in the simple western medicine control group (22.44 ± 13.87). The degree of coronary stenosis in the YXR group decreased to (49.87 ± 7.82) %, which was significantly lower than (P < 0.001) that in the western medicine control group (57.05 ± 9.92) %. CONCLUSION: The efficacy of YXR + conventional western medicine in treating coronary heart disease and angina pectoris is significantly improved compared with the simple conventional western medicine.

Highly mutated antibodies capable of neutralizing N276 glycan-deficient HIV after a single immunization with an Env trimer.

Elicitation of HIV broadly neutralizing antibodies (bnAbs) is challenging because unmutated bnAb precursors are rare and seldom bind HIV envelope glycoprotein (Env) trimers. One strategy to initiate bnAb responses is to use germline-targeting (GT) immunogens with high affinity to bnAb-class precursor B cells and then shepherd affinity maturation with booster immunogens that successively look more like native Env. In a mouse model where the frequency of VRC01-precursor (VRC01gHL) B cells mimics that of humans, we show that following a GT HIV Env trimer protein prime, VRC01-class B cells in the germinal center (GC) acquire high-affinity VRC01-class B cell somatic hypermutations (SHMs). Many GC-derived VRC01gHL antibodies robustly bind N276 glycan-deficient Env trimers and neutralize several N276 glycan-deficient tier 2 HIV strains. These results are encouraging for GT Env trimer vaccine designs and demonstrate accumulation of substantial SHMs, including deletions, uncommon point mutations, and functional bnAb features, after a single immunization.

Direct authentication and composition quantitation of red wines based on Tri-step infrared spectroscopy and multivariate data fusion.

A robust data fusion strategy integrating Tri-step infrared spectroscopy (IR) with electronic nose (E-nose) was established for rapid qualitative authentication and quantitative evaluation of red wines using Cabernet Sauvignon as an example. The chemical fingerprints of four types of wines were thoroughly interpreted by Tri-step IR, and the defined spectral fingerprint region of alcohol and sugar was 1200-950 cm-1. The wine types were authenticated by IR-based principal component analysis (PCA). Furthermore, ten quantitative models by partial least squares (PLS) were built to evaluate alcohol and total sugar contents. In particular, the model based on the fusion datasets of spectral fingerprint region and E-nose was superior to the others, in which RMSEP reduced by 47.95% (alcohol) and 79.90% (total sugar), rp increased by 11.95% and 43.47%, and RPD >3.0. The developed methodology would be applicable for mass screening and rapid multi-chemical-component quantification of wines in a more comprehensive and efficient manner.

Eight Trigrams Boxing Combined with Wenyang Huoxue Recipe Improves Cardiopulmonary Motor Function and the Quality of Life of Patients with Coronary Heart Disease.

OBJECTIVE: To investigate the therapeutic effects of Eight Trigrams Boxing combined with a Wenyang Huoxue recipe on the cardiopulmonary motor function and quality of life in patients with coronary heart disease after an interventional operation (percutaneous coronary intervention [PCI]); further, to provide new clinical evidence and ideas for integrated traditional Chinese and Western medicine in cardiac rehabilitation. METHODS: Sixty patients were selected and successfully underwent PCI in designated hospitals after four weeks, from June 2018 to September 2020. The patients were randomly divided into a treatment group and control group, and both groups were given standard pharmaceuticals after PCI and the Wenyang Huoxue recipe. The treatment group was additionally treated with the Eight Trigrams Boxing Method. The control group was provided with aerobic rehabilitation exercise. The maximum oxygen uptake (VO2max), metabolic equivalent (MET), the results of a 6-min walking test, the Seattle Angina Questionnaire (SAQ) score, SF-36 score, and other indicators were evaluated before and after treatment. The therapeutic effect was evaluated by comparison between the groups and within the groups. RESULTS: The VO2max, MET, 6-min walking distance, SAQ score, and SF-36 score in both groups improved after treatment compared with before treatment. There was no difference between the two groups before treatment. However, after treatment, the VO2max, MET, 6 min walking distance, SAQ score, and SF-36 score in the treatment group were higher compared with the control group. CONCLUSION: A traditional Chinese medicine cardiac rehabilitation program of Eight Trigrams Boxing combined with a Wenyang Huoxue recipe can improve the cardiopulmonary function and quality of life of patients. The therapeutic effect was clear and is worthy of further investigation.

Effect of Prescription Tongxin on Endothelial Progenitor Cells in Peripheral Blood.

CONTEXT: Coronary heart disease (CHD) refers to a disease where coronary atherosclerosis induces stenosis or obstruction of the blood vessels. Endothelial progenitor cells (EPCs) function to protect and repair the vascular endothelium, and their functional activity state reflects the ability of the body to repair vascular damage. In the peripheral blood of patients with CHD, the density of EPCs decreases, and the function of EPCs is low. OBJECTIVE: This study aimed to investigate the effects of a China Food and Drug Administration (CFDA)-approved prescription medicine, Tongxin, on the density and function of endothelial progenitor cells (EPCs) in peripheral blood. DESIGN: In this study, a randomized, single blind, parallel controlled clinical trial was used. The single blind subjects were subjects. SETTING: The study took place in the Cardiology and Emergency Departments at Shanghai Municipal Hospital of Traditional Chinese Medicine in Shanghai, China. PARTICIPANTS: Participants were 48 patients with coronary heart disease at the hospital. INTERVENTION: Participants were randomly divided into 2 groups (n = 24 each): a control group and an intervention group. Both groups received routine drug treatments, such as platelet inhibitors, nitrates, ß-receptor blockers, statins, angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor antagonists (ARBs), and calcium blockers. The control group was treated with the Shexiang Baoxin Pill, while the intervention group was treated with prescription Tongxin. The course of treatment was 3 months for both groups. OUTCOME MEASURES: Changes in the density and function of EPCs in the peripheral blood of the 2 groups were measured at baseline and postintervention, and the clinical efficacy of the 2 treatments was statistically analyzed. RESULTS: The density of EPCs was significantly higher in both groups after 3 months of treatment, compared to the densities at baseline (P < .05). The change in density between baseline and postintervention was significantly greater for the intervention group than for the control group (P < .05). For the control group, the proliferative vitality [optical density (OD)] value of the EPCs was significantly higher than that at baseline from the fourth day of treatment (P < .05). In the intervention group, the OD value was significantly higher than that at baseline from the first day of treatment (P < .05). Furthermore, the intervention group's cells began to enter the logarithmic growth phase of increase from the fifth day of treatment, and the group's increase as significantly higher than the control group's from the fifth to the seventh dayof treatment (P < .05 for all 3 days). Moreover, the total effective rate was higher in the intervention group than in the control group (P < .05). CONCLUSIONS: Prescription Tongxin can stimulate the release of EPCs from the bone marrow to the peripheral blood of patients with CHD, can significantly increase the proliferation of EPCs in the peripheral blood, and can improve the clinical symptoms of patients. Its curative effect was greater than that of the control treatment.

LncRNA ADAMTS9-AS1 Restrains the Aggressive Traits of Breast Carcinoma Cells via Sponging miR-513a-5p.

PURPOSE: Long noncoding RNAs (lncRNAs) exert important functions in the progression of cancers. Currently, we aim to investigate the potential roles of lncRNA ADAM Metallopeptidase with Thrombospondin Type 1 Motif 9 Antisense RNA 1 (ADAMTS9-AS1) in breast carcinoma. MATERIALS AND METHODS: The expressions of ADAMTS9-AS1 and miR-513a-5p in breast carcinoma tissues and cell lines were detected using qRT-PCR. Cell Counting Kit-8 (CCK-8) and transwell assays were used to assess the viability and invasive ability of breast cancer cells. The direct interaction between ADAMTS9-AS1 and miR-513a-5p was predicted using bioinformatics tools. The target of miR-513a-5p, ZFP36 Ring Finger Protein (ZFP36) was validated by luciferase assay. The expression of ZFP36 was measured using Western blot assay. Breast cancer MDA-MB-231 cells growth in vivo was evaluated using xenograft tumor assay. RESULTS: ADAMTS9-AS1 was downregulated in breast cancer tissues as well as cell lines. Upregulation of ADAMTS9-AS1 suppressed the growth and invasiveness of breast carcinoma cells in vitro as well as inhibiting cellgrowth in vivo. Furthermore, ZFP36 was manifested as the target gene of miR-513a-5p and negatively modulated by ADAMTS9-AS1. In addition, overexpression of ADAMTS9-AS1 neutralized the promoting impact of miR-513a-5p on the aggressiveness of breast cancer cells. CONCLUSION: In conclusion, lncRNA ADAMTS9-AS1 inhibited the aggressive phenotypes of breast carcinoma cells via sponging miR-513a-5p and regulating ZFP36.

A Comparative Study of Pressureless Sintered Nanostructured Hydroxyapatite/TiO2 Composites Prepared by Different TiO2 Addition Methods.

Two methods of TiO2 addition were applied to prepare hydroxyapatite/TiO2 (HA/TiO2) composite, i.e., in-situ hydrolysis TiO2 in HA powders (N-HA/TiO2) and mixing commercial nano-sized HA and TiO2 powder (C-HA/TiO2). Effects of TiO2 addition methods and sintering temperatures on phase, microstructure and microhardness were investigated for pressureless sintered HA/TiO2 composites, and pure HA was investigated for comparison. Results show that TiO2 from both in-situ hydrolysis and mixing commercial powder presented similar effects on phase structures and composition, and trended to chemically react with HA in the HA/TiO2 composites at high sintering temperature. Weight loss for different composites was investigated by thermal analysis. Sintering behavior for two different composite was also discussed. The TiO2 from in-situ hydrolysis can effectively enhance the TiO2 distribution and densification for the N-HA/TiO2 composites. Both two different composites showed typical grain growth and pore formation with the increase of sintering temperature. The N-HA/TiO2 composite had a lower porosity, higher shrinkage and microhardness than that of C-HA/TiO2 composite at sintering temperature from 700 °C to 1100 °C.

A generalized HIV vaccine design strategy for priming of broadly neutralizing antibody responses.

Vaccine induction of broadly neutralizing antibodies (bnAbs) to HIV remains a major challenge. Germline-targeting immunogens hold promise for initiating the induction of certain bnAb classes; yet for most bnAbs, a strong dependence on antibody heavy chain complementarity-determining region 3 (HCDR3) is a major barrier. Exploiting ultradeep human antibody sequencing data, we identified a diverse set of potential antibody precursors for a bnAb with dominant HCDR3 contacts. We then developed HIV envelope trimer-based immunogens that primed responses from rare bnAb-precursor B cells in a mouse model and bound a range of potential bnAb-precursor human naïve B cells in ex vivo screens. Our repertoire-guided germline-targeting approach provides a framework for priming the induction of many HIV bnAbs and could be applied to most HCDR3-dominant antibodies from other pathogens.