Chronic hepatitis B is caused by prolonged infection with the hepatitis B virus (HBV), which can substantially increase the risk of developing liver disease. Despite the development of preventive ...vaccines against HBV, a therapeutic vaccine inducing an effective antibody response still remains elusive. The preS1 domain of the large HBV surface protein is the major viral attachment site on hepatocytes and thus offers a therapeutic target; however, its poor immunogenicity limits clinical translation. Here, we design a ferritin nanoparticle vaccine that can deliver preS1 to specific myeloid cells, including SIGNR1
dendritic cells (which activate T follicular helper cells) and lymphatic sinus-associated SIGNR1
macrophages (which can activate B cells). This nanoparticle vaccine induces a high-level and persistent anti-preS1 response that results in efficient viral clearance and partial serological conversion in a chronic HBV mouse model, offering a promising translatable vaccination strategy for the functional cure of chronic hepatitis B.
As the newest two members of the carbon materials family, carbon dots (CDs) and graphene oxide (GO) possess many excellent optical properties resulting in a wide range of applications. In this work, ...we successfully synthesized CDs with a high-quantum-yield, and labeled them on oligodeoxyribonucleotide (ODN). The fluorescence of resultant CDs-labeled oligodeoxyribonucleotide (ODN–CDs) was quenched by GO via fluorescence resonance energy transfer. In the presence of Hg2+, the fluorescence was recovered by the release of ODN–CDs from GO due to the formation of T–Hg2+–T duplex. In the light of this theory, we designed a simple, highly sensitive and selective fluorometric Hg2+ sensor based on CDs-labeled oligodeoxyribonucleotide and GO without complicated, costly and time-consuming operations. Under the optimal conditions, a linear relationship was obtained between relative fluorescence intensity and the concentration of Hg2+ in the range of 5–200nM (R2=0.974). The present GO-based sensor system is highly selective toward Hg2+ over a wide range of metal ions and has a detection limit of 2.6nM. This method is reliable, and has been successfully applied for the detection of Hg2+ in practical samples.
•We synthesized carbon dots (CDs) with a quantum yield as high as ca. 75.0%.•CDs were firstly labeled on T-rich oligodeoxyribonucleotide to be probe of Hg2+.•The fluorescence of CDs-labeled ODN was quenched by GO and recovered by adding Hg2+.•We designed Hg2+ biosensor by combining FRET of GO and CDs with selectivity of ODN.•CDs showed potential in the fluorescent label technology.
We proposed a polarization-insensitive absorber based on strontium titanate (STO) and bulk Dirac semimetal (BDS) in the terahertz (THz) region. The center frequency of the absorption peak can be ...independently regulated by temperature or Fermi energy level of STO or BDS, respectively. The numerical simulation result reveals that the peak absorptivity reaches to 99.98% at 2.16 THz when the temperature and Fermi energy were set at 300 K and 20 meV, respectively. Interestingly, by adjusting the temperature of STO from 250 to 400 K, the simulation results indicate that the center frequency can be tuned from 1.94 to 2.53 THz, and peak absorptivity can be maintained above 99% at normal incident. As the Fermi energy EF of Dirac semimetal increases from 10 to 60 meV, the center frequency can be changed from 2.14 to 2.44 THz and the amplitude of absorption peaks can be tuned from 99.9% to 82.8%. Impedance matching theory was used to understand the tunable performance. Furthermore, interference theory was employed to further explain the absorption mechanism of the proposed absorber. The absorber achieves bi-controlled absorptance via two independently controllable methods, which may provide guidance to research tunable, smart and multifunctional terahertz devices.
In response to stressors, individuals adopt different behavioral styles, which are essential for survival and form the basis of differential susceptibility to stress-related disorders. ...Corticotropin-releasing factor (CRF) and the medial prefrontal cortex (mPFC) have predominantly been studied in behavioral response to stress, while the role of mPFC CRF neurons is poorly understood. Using morphology, electrophysiology, and calcium imaging approaches, we characterized mPFC CRF neurons as a unique subtype of GABAergic inhibitory interneurons that were directly engaged in the tail suspension challenge. Genetic ablation or chemogenetic inhibition of dorsal mPFC (dmPFC) CRF neurons increased immobility under the tail-suspension and forced-swimming challenges and induced social avoidance behavior, whereas activation had the opposite effect on the same measures. Furthermore, increasing CRF neuronal activity promoted durable resilience to repeated social defeat stress. These results uncover a critical role of mPFC CRF interneurons in bidirectionally controlling motivated behavioral style selection under stress.
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•Prefrontal CRF GABAergic interneurons are recruited during behavioral challenges•Manipulation of CRF neurons motivates selection of behavioral styles under challenges•Activation of CRF neurons promotes persistent stress-resistant behaviors
Chen et al. identify a population of mPFC CRF neurons that form monosynaptic GABAergic inhibitory connections with pyramidal cells and play a key role in controlling behavioral style selection in the face of various stressful challenges.
Ovarian cancer (OC) is the most lethal gynecologic tumor and is characterized by a high rate of metastasis. Challenges in accurately delineating the metastatic pattern have greatly restricted the ...improvement of treatment in OC patients. An increasing number of studies have leveraged mitochondrial DNA (mtDNA) mutations as efficient lineage-tracing markers of tumor clonality. We applied multiregional sampling and high-depth mtDNA sequencing to determine the metastatic patterns in advanced-stage OC patients. Somatic mtDNA mutations were profiled from a total of 195 primary and 200 metastatic tumor tissue samples from 35 OC patients. Our results revealed remarkable sample-level and patient-level heterogeneity. In addition, distinct mtDNA mutational patterns were observed between primary and metastatic OC tissues. Further analysis identified the different mutational spectra between shared and private mutations among primary and metastatic OC tissues. Analysis of the clonality index calculated based on mtDNA mutations supported a monoclonal tumor origin in 14 of 16 patients with bilateral ovarian cancers. Notably, mtDNA-based spatial phylogenetic analysis revealed distinct patterns of OC metastasis, in which a linear metastatic pattern exhibited a low degree of mtDNA mutation heterogeneity and a short evolutionary distance, whereas a parallel metastatic pattern showed the opposite trend. Moreover, a mtDNA-based tumor evolutionary score (MTEs) related to different metastatic patterns was defined. Our data showed that patients with different MTESs responded differently to combined debulking surgery and chemotherapy. Finally, we observed that tumor-derived mtDNA mutations were more likely to be detected in ascitic fluid than in plasma samples. Our study presents an explicit view of the OC metastatic pattern, which sheds light on efficient treatment for OC patients.
We report here that size- and shape-focusing can be achieved through the well-known Ostwald ripening process to produce high-quality metal nanocrystals (NCs). Using Pd as an example, we show that the ...addition of small NCs of appropriate sizes could help in modulating the growth of larger NCs and enable excellent control over both the size and shape uniformity of the products. A detailed mechanistic study showed that the self-focusing of Pd NCs relied on a dissolution and regrowth process induced by redox reaction of HCHO. With the assistance of HCHO, injection of small sacrificial nanocrystals (SNCs), with sizes below a critical value, into larger seeds results in the dissolution of the SNCs and subsequent deposition onto the larger ones, thus allowing the formation of monodisperse Pd NCs. We have identified the critical radius of the SNCs to be ∼5.7 nm for Pd, and verified that SNCs with sizes larger than that could not effectively support the growth of larger seeds. More interestingly, since Ostwald ripening involves matter relocation, this synthetic approach could even break the self-termination growth habits of metal NCs and produce nanocrystals with sizes that are not conveniently accessible by direct growth.
The roles and benefits of pumped storage are reflected in different stakeholders of the power system. The multi-dimensionality and non-linearity of pumped storage multi-stakeholder decision-making ...make pumped storage benefit realization a hot research topic with challenges. This paper takes pumped storage benefit sharing as the breakthrough. It adopts multiple regulation strategies and multi-level decision-making measures based on the multiple objectives of different stakeholders. A method and a framework for pumped storage benefit realization are proposed. This paper proposes the objective function system with the fairness objective at the leader level, the participation objective at the secondary leader level, and the efficiency objective at the follower level. It also constructs a three-level Leader-Follower objective model with multi-dimensional regulation and multiple values, and it develops the corresponding solution method based on Stackelberg dynamic game and interactive algorithms. The results reveal that the values of fairness, participation, and efficiency indicators of the pumped storage plant are 1.75%, 0.25%, and 9.75%, respectively, and all the indicators meet the requirements. The research results are conducive to promoting the realization of a win-win situation for different stakeholders of pumped storage, and they highlight how pumped storage plants can fulfill their functions in the power system as well as ensure its survival and development.
Background
The clinical diagnosis of neonatal sepsis remains difficult because of various challenges, such as culturing the bacteria and avoiding contamination. Therefore, this study aimed to ...identify bacterial pathogens in patients with clinically diagnosed neonatal sepsis by next-generation sequencing (NGS).
Methods
High-throughput NGS and traditional culture identification were performed by comparing samples from newborns with neonatal sepsis with healthy control infants. All blood samples were separately inoculated into anaerobic and aerobic bottles and incubated for 7 days at 37 °C, the positive specimens were then identified. Novel bacteria identified through high-throughput NGS were analysed using polymerase chain reaction (PCR), PCR products were verified by Sanger sequencing. Wilcoxon rank-sum and chi-square tests were performed to assess the significance of differences in species abundance between groups. Subjects were clinically diagnosed and hospitalized at the Pediatrics Department of Shenzhen Seventh People’s Hospital and Pediatrics Department of the Longhua Branch of Shenzhen People’s Hospital. Experiments were performed at the Shenzhen Seventh People’s Hospital. The experimental group comprised 45 newborns clinically diagnosed with neonatal sepsis (age: 0–28 days; 28 males, 17 females). Fifteen normal newborns aged 0–28 days (7 males, 8 females) were included as the control group.
Results
High-throughput NGS showed a positivity rate of 44% (20/45) for bacteria in patients clinically diagnosed with neonatal sepsis, whereas traditional bacterial culture identification showed a positivity rate of 0% (0/45). The four main bacterial species identified were
Anoxybacillus kestanbolensis
,
Geobacillus vulcani
,
Klebsiella oxytoca
, and
Acinetobacter guillouiae
.
Conclusions
A. kestanbolensis
,
G. vulcani
,
K. oxytoca
, and
A. guillouiae
, newly discovered bacteria in patients with neonatal sepsis, were identified with high-throughput NGS. Which may result from maternal intrauterine infection or birth-canal infection and have a high clinical-cure rate. Owing to a lack of methods to culture these bacteria, their role in neonatal sepsis remains unclear. A definite diagnosis cannot rely solely on bacterial culture identification for patients with a suspected diagnosis and clinical diagnosis of neonatal sepsis and should involve other effective diagnostic techniques.
Objectives
Anticitrullinated protein/peptide antibodies (ACPAs) have shown valuable effects in the diagnosis of rheumatoid arthritis (RA). Both fibrinogen and vimentin are significant antigens of ...ACPAs. This study evaluated the diagnostic performance of fibrinogen and vimentin peptides in RA.
Methods
We searched the PubMed, Embase, and Cochrane Library databases for studies published in English until January 2019 that evaluated the utility of the peptides of both vimentin and fibrinogen. The bivariate mixed-effects model and summary receiver operating characteristic (SROC) curve were used to estimate sensitivity and specificity across studies.
Results
Seven peptides from 19 studies were included. The pooled sensitivities of Fibα36–50, Fibα563–583, Fibα580–600, Fibα621–635, Fibβ36–52, Fibβ60–74, and Vim60–75 were 35%, 41%, 18%, 26%, 0.53%, 57%, and 44%, respectively. The pooled specificities of Fibα36–50, Fibα563–583, Fibα580–600, Fibα621–635, Fibβ36–52, Fibβ60–74, and Vim60–75 were 97%, 98%, 98%, 98%, 97%, 98%, and 98%, respectively. The SROC areas under the curve (AUCs) of Fibα36–50, Fibα563–583, Fibα580–600, Fibα621–635, Fibβ36–52, Fibβ60–74, and Vim60–75 were 0.92, 0.85, 0.64, 0.82, 0.91, 0.96, and 0.86, respectively.
Conclusion
Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA. The diagnostic accuracies of Fibβ60–74 and Fibβ36–52 were better than those of Vim60–75, Fibα36–50, and Fibα563–583, and all of them were better than that of Fibα621–635 and Fibα580–600.
Key Points
•
Our study summarized the diagnostic accuracy of peptides derived from fibrinogen and vimentin and evaluated the diagnostic value of different peptides for RA patients.
•
Both fibrinogen and vimentin peptides have a high specificity but a relatively low sensitivity in diagnosing RA.
Objective Follicular helper T cells (Tfh) drive proliferation and differentiation of B cells into plasma cells, leading to antibody production; however, their role in multiple myeloma (MM) is ...unknown. We aimed to determine the alteration of Tfh subsets and their clinical significance in patients with MM.
Method Forty-nine patients with MM were recruited in this study, including 12 newly diagnosed patients, 10 relapsed patients, and 8 patients who received autologous hematopoietic stem cell transplantation (ASCT) from Zhejiang Provincial People's Hospital. Total CD4
+
CXCR5
+
CD25
low
CD127
intermediate-high
Tfh cells, CXCR3
+
CCR6
−
Tfh1 cells, CXCR3
−
CCR6
−
Tfh2 cells, and CXCR3
−
CCR6
+
Tfh17 cells from the peripheral blood of these patients were analyzed by flow cytometry.
Result Although total Tfh cells were not significantly changed in patients with MM compared to that in healthy controls (HCs), the Tfh17/Tfh ratio was significantly elevated in patients with MM compared to that in HCs (P = 0.0001). Importantly, relapsed patients had higher Tfh17/Tfh ratio than the newly diagnosed patients (P = 0.0077). Moreover, the Tfh17/Tfh ratio was significantly decreased in patients with MM who received ASCT (post-ASCT) when compared to that in HCs and non-ASCT patients (P < 0.0001), but no change was observed between post-ASCT patients and HCs (P = 0.7498).
Conclusion The Tfh17/Tfh ratio was significantly elevated in patients with MM, especially in relapsed patients, indicating that Tfh17 cells may play a critical role in the clinical progression of MM.
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