Characterizing the dynamics of BCR repertoire from repeated influenza vaccination.

Yearly epidemics of seasonal influenza cause an enormous disease burden around the globe. An understanding of the rules behind the immune response with repeated vaccination still presents a significant challenge, which would be helpful for optimizing the vaccination strategy. In this study, 34 healthy volunteers with 16 vaccinated were recruited, and the dynamics of the BCR repertoire for consecutive vaccinations in two seasons were tracked. In terms of diversity, length, network, V and J gene segments usage, somatic hypermutation (SHM) rate and isotype, it was found that the overall changes were stronger in the acute phase of the first vaccination than the second vaccination. However, the V gene segments of IGHV4-39, IGHV3-9, IGHV3-7 and IGHV1-69 were amplified in the acute phase of the first vaccination, with IGHV3-7 dominant. On the other hand, for the second vaccination, the changes were dominated by IGHV1-69, with potential for coding broad neutralizing antibody. Additional analysis indicates that the application of V gene segment for IGHV3-7 in the acute phase of the first vaccination was due to the elevated usage of isotypes IgM and IgG3. While for IGHV1-69 in the second vaccination, it was contributed by isotypes IgG1 and IgG2. Finally, 41 public BCR clusters were identified in the vaccine group, with both IGHV3-7 and IGHV1-69 were involved and representative complementarity determining region 3 (CDR3) motifs were characterized. This study provides insights into the immune response dynamics following repeated influenza vaccination in humans and can inform universal vaccine design and vaccine strategies in the future.

Reinforced, Incremental and Cross-Lingual Event Detection From Social Messages.

Detecting hot social events (e.g., political scandal, momentous meetings, natural hazards, etc.) from social messages is crucial as it highlights significant happenings to help people understand the real world. On account of the streaming nature of social messages, incremental social event detection models in acquiring, preserving, and updating messages over time have attracted great attention. However, the challenge is that the existing event detection methods towards streaming social messages are generally confronted with ambiguous events features, dispersive text contents, and multiple languages, and hence result in low accuracy and generalization ability. In this paper, we present a novel reinForced, incremental and cross-lingual social Event detection architecture, namely FinEvent, from streaming social messages. Concretely, we first model social messages into heterogeneous graphs integrating both rich meta-semantics and diverse meta-relations, and convert them to weighted multi-relational message graphs. Second, we propose a new reinforced weighted multi-relational graph neural network framework by using a Multi-agent Reinforcement Learning algorithm to select optimal aggregation thresholds across different relations/edges to learn social message embeddings. To solve the long-tail problem in social event detection, a balanced sampling strategy guided Contrastive Learning mechanism is designed for incremental social message representation learning. Third, a new Deep Reinforcement Learning guided density-based spatial clustering model is designed to select the optimal minimum number of samples required to form a cluster and optimal minimum distance between two clusters in social event detection tasks. Finally, we implement incremental social message representation learning based on knowledge preservation on the graph neural network and achieve the transferring cross-lingual social event detection. We conduct extensive experiments to evaluate the FinEvent on Twitter streams, demonstrating a significant and consistent improvement in model quality with 14%-118%, 8%-170%, and 2%-21% increases in performance on offline, online, and cross-lingual social event detection tasks.

Electroactive Hydroxyapatite/Carbon Nanofiber Scaffolds for Osteogenic Differentiation of Human Adipose-Derived Stem Cells.

Traditional bone defect treatments are limited by an insufficient supply of autologous bone, the immune rejection of allogeneic bone grafts, and high medical costs. To address this medical need, bone tissue engineering has emerged as a promising option. Among the existing tissue engineering materials, the use of electroactive scaffolds has become a common strategy in bone repair. However, single-function electroactive scaffolds are not sufficient for scientific research or clinical application. On the other hand, multifunctional electroactive scaffolds are often complicated and expensive to prepare. Therefore, we propose a new tissue engineering strategy that optimizes the electrical properties and biocompatibility of carbon-based materials. Here, a hydroxyapatite/carbon nanofiber (HAp/CNF) scaffold with optimal electrical activity was prepared by electrospinning HAp nanoparticle-incorporated polyvinylidene fluoride (PVDF) and then carbonizing the fibers. Biochemical assessments of the markers of osteogenesis in human adipose-derived stem cells (h-ADSCs) cultured on HAp/CNF scaffolds demonstrate that the material promoted the osteogenic differentiation of h-ADSCs in the absence of an osteogenic factor. The results of this study show that electroactive carbon materials with a fibrous structure can promote the osteogenic differentiation of h-ADSCs, providing a new strategy for the preparation and application of carbon-based materials in bone tissue engineering.

Topographical regulation of stem cell differentiation by plant-derived micro/nanostructures.

This study examines the osteogenic differentiation promotion effect of micro/nanostructures of raffia on human adipose-derived stem cells to confirm the potential application of plant-derived micro/nanotopographies in tissue regeneration. The results confirm that the nanorod array on the front surface and the honeycomb-like microstructure on the back surface of raffia can not only regulate the adhesion, spreading, and migration of stem cells but also promote the osteogenic differentiation of the stem cells at a subsequent stage of cell culture. The osteocalcin expressions by the 21-day cultured cells on the front and back surfaces of raffia were 55-fold and 36-fold higher compared to the expression on a tissue culture plate. This indicates that plant-derived micro/nanotopographies can significantly promote stem cell differentiation. Furthermore, a general strategy for the application of plant-derived materials to stem-cell differentiation and bone-tissue engineering is suggested.

Enhanced Antibacterial Photocatalytic Activity of Porous Few-Layer C3N4.

Nowadays, antibacterial photocatalytic activity of semiconductors has attracted great attention due to its excellent stability, good biocompatibility and no disinfection byproducts. Herein, a porous few-layer C3N4 was successfully fabricated via a simple and low-cost bottom-up method. The asprepared porous few-layer C3N4 exhibits large specific surface areas, which is about 4.8 times than bulk C3N4. Under the light (<430 nm) irradiation, reactive oxygen species (ROS) (singlet oxygen (1O2), hydroxyl radicals (·OH), and superoxide (O·-2)) can be generated. The porous few-layer C3N4 was used as an antibacterial agent to kill gram-positive bacterium S. Aureus with an anibacterial efficiency up to 99.7%. The log removal rate of the porous few-layer C3N4 is more than 50 times than the bulk C3N4. The material shows a potential application in water purification and antibacterial photocatalytic therapy.

Evaluation of safety of iridoids rich fraction from Valeriana jatamansi Jones: Acute and sub-chronic toxicity study in mice and rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Valeriana jatamansi Jones named Zhizhuxiang in China is one of the most popular traditional medicine for varied ailments related to malaise, abdominal distention, insomnia, and rheumatism. AIM OF THE STUDY: Evaluate the safety of iridoids rich fraction from V. jatamansi Jones (IRFV) and to provide data for clinical application. MATERIALS AND METHODS: The acute and sub-chronic toxicity of IRFV were investigated by employing established methods. The acute toxicity study was conducted through oral administration of a single dose (3,200 mg/kg body weight) of IRFV to adult mice. The vehicle used for dilution of the IRFV was a mixture of 0.5% CMC-Na and 99.5% water. The weight, diet, toxic reaction, and death after 14 days were observed. In the sub-chronic toxicity study, low doses (240 mg/kg bw), middle doses (960 mg/kg bw), and high doses (1,200 mg/kg bw) of IRFV were administered daily to adult rats for 6 days a week (except Sunday) for 3 months. The general behavior of the rats was observed and recorded daily. The weight and food consumption of rats were tested weekly. The effect on organs, the hematological and blood biochemical parameters, and the histopathology were assessed after 1.5 months (five males and five females) and after 3 months (10 males and 10 females).The remaining 10 rats (five males and five females) in each group were fed for 2 weeks to observe reversible and delayed toxicity after the medicine was administered. RESULTS: In the acute toxicity study, no significant difference was found in the body weight of the mice in the control group and those in the drug group (p>0.05). The maximum tolerated dose of IRFV on mice was 3,200 mg/kg, which is 2666 times of the clinical adult daily dose. In the sub-chronic toxicity study on rats, the daily single oral doses of the IRFV did not result in death nor affected the general behavior, including appearance, activities, discharge, and waste at all tested doses. Moreover, no significant difference was found (p>0.05) between the body weights of the rats from the drug groups and those from the control group. Food consumption was significantly affected (p<0.05) only in the first 3 weeks. No statistically significant differences (p>0.05) were observed in the hematological and blood biochemical parameters, and no abnormality of other organs were noted in both gross and histopathological examinations, except several animal transients (p<0.05) or spontaneous lesions (abnormality). CONCLUSION: IRFV is extremely safe in the usual clinical dose, and may not have any single dose toxicity. The lethal dose with 50% mortality rate (LD50) on mice is over 2,000 mg/kg bw. The no-observed adverse effects level is 1,200 mg/kg/day for rats. No direct correlation was found between the hematology, blood biochemical indexes, and organ coefficient of tested rats and the toxicity of IRFV.

[Effect of pricking blood at Neiyingxiang (EX-HN 9) on the intraocular pressure of patients with primary open angle glaucoma].

OBJECTIVE: To observe the effect of pricking blood at Neiyingxiang (EX-HN 9) on the intraocular pressure of patients of primary open angle glaucoma (POAG). METHODS: Ninty-six cases (166 eyes) were randomly divided into an observation group (44 cases) and a control group (52 cases). The observation group was treated with pricking blood at Neiyingxiang (EX-HN 9), and the control group was treated with 0.5% Timolol Maleate drops in eyes. The changes of patients' intraocular pressure in both groups were observed before and after treatment. RESULTS: The intraocular pressure were (29.81 +/- 3.49) mmHg and (23.18 +/- 3.61) mmHg before and after treatment in the observation group, and (29.94 +/- 3.64) mmHg and (23.88 +/- 3.96) mmHg in the control group respectively, there were significant differences after treatment in the two groups (both P<0.01), while there was no significant difference in decreasing the intraocular pressure between the two groups (P>0.05). CONCLUSION: Pricking blood at Neiyingxiang (EX-HN 9) can effectively decrease the intraocular pressure and the effect is equivalent to Timolol Maleate drops.