Efficacy evaluation through human trials is crucial for advancing a vaccine candidate to clinics. Next-generation sequencing (NGS) can be used to quantify B cell repertoire response and trace ...antibody lineages during vaccination. Here, we demonstrate this application with a case study of Hecolin®, the licensed vaccine for hepatitis E virus (HEV). Four subjects are administered the vaccine following a standard three-dose schedule. Vaccine-induced antibodies exhibit a high degree of clonal diversity, recognize five conformational antigenic sites of the genotype 1 HEV p239 antigen, and cross-react with other genotypes. Unbiased repertoire sequencing is performed for seven time points over six months of vaccination, with maturation pathways characterize for a set of vaccine-induced antibodies. In addition to dynamic repertoire profiles, NGS analysis reveals differential patterns of HEV-specific antibody lineages and highlights the necessity of the long vaccine boost. Together, our study presents a quantitative strategy for vaccine evaluation in small-scale human studies.
Distributed data naturally arise in scenarios involving multiple sources of observations, each stored at a different location. Directly pooling all the data together is often prohibited due to ...limited bandwidth and storage, or due to privacy protocols. A new robust distributed algorithm is introduced for fitting linear regressions when data are subject to heavy-tailed and/or asymmetric errors with finite second moments. The algorithm only communicates gradient information at each iteration, and therefore is communication-efficient. To achieve the bias-robustness tradeoff, the key is a novel double-robustification approach that applies on both the local and global objective functions. Statistically, the resulting estimator achieves the centralized nonasymptotic error bound as if all the data were pooled together and came from a distribution with sub-Gaussian tails. Under a finite (2+δ)-th moment condition, a Berry-Esseen bound for the distributed estimator is established, based on which robust confidence intervals are constructed. In high dimensions, the proposed doubly-robustified loss function is complemented with ℓ1-penalization for fitting sparse linear models with distributed data. Numerical studies further confirm that compared with extant distributed methods, the proposed methods achieve near-optimal accuracy with low variability and better coverage with tighter confidence width.
Prior studies generally focus on software vulnerability detection and have demonstrated the effectiveness of Graph Neural Network (GNN)-based approaches for the task. Considering the various types of ...software vulnerabilities and the associated different degrees of severity, it is also beneficial to determine the type of each vulnerable code for developers. In this paper, we observe that the distribution of vulnerability type is long-tailed in practice, where a small portion of classes have massive samples (i.e., head classes) but the others contain only a few samples (i.e., tail classes). Directly adopting previous vulnerability detection approaches tends to result in poor detection performance, mainly due to two reasons. First, it is difficult to effectively learn the vulnerability representation due to the over-smoothing issue of GNNs. Second, vulnerability types in tails are hard to be predicted due to the extremely few associated samples. To alleviate these issues, we propose a L ong-ta I led software V ulner AB i L ity typ E classification approach, called LIVABLE . LIVABLE mainly consists of two modules, including (1) vulnerability representation learning module, which improves the propagation steps in GNN to distinguish node representations by a differentiated propagation method. A sequence-to-sequence model is also involved to enhance the vulnerability representations. (2) adaptive re-weighting module, which adjusts the learning weights for different types according to the training epochs and numbers of associated samples by a novel training loss. We verify the effectiveness of LIVABLE in both type classification and vulnerability detection tasks. For vulnerability type classification, the experiments on the Fan et al. dataset show that LIVABLE outperforms the state-of-the-art methods by 24.18% in terms of the accuracy metric, and also improves the performance in predicting tail classes by 7.7%. To evaluate the efficacy of the vulnerability representation learning module in LIVABLE, we further compare it with the recent vulnerability detection approaches on three benchmark datasets, which shows that the proposed representation learning module improves the best baselines by 4.03% on average in terms of accuracy.
The serum 1,3-beta-D-glucan (BG) assay aids in the early diagnosis of invasive fungal diseases (IFDs) and has been approved for their diagnosis. However, reports on the screening performance of BG ...are scarce. We performed a meta-analysis of data extracted from only prospective cohort studies to evaluate the screening performance of the BG assay in the diagnosis of IFDs. We specifically searched 4 databases (the PubMed, Web of Science, Elsevier, and Cochrane Collaboration databases) according to EORTC-MSG criteria. A total of 1068 patients in 11 studies were analyzed. Deeks' funnel plot asymmetry test suggested a low likelihood of publication bias for the included studies (p = 0.055). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the summary receiver operating characteristic curve, with 95% confidence intervals, were 0.75(0.63,0.84), 0.87(0.81,0.92), 5.85(3.96,8.63), 0.30(0.20,0.45), 19.53(11.16,34.18), and 0.89(0.86,0.91), respectively. The findings of this meta-analysis suggest that the BG assay is a useful screening tool with high sensitivity and specificity for discriminating between patients with and without IFDs. In clinical practice, BG assay results should be evaluated together with clinical and microbiological findings.
Bone marrow-derived mesenchymal stem cells (BMSCs) can differentiate into hepatocyte-like cells (HLCs) to alleviate acute liver injury (ALI). Herpetfluorenone (HPF), as an active ingredient in the ...dried, mature seeds
Wall, used in Tibetan medicine, has been proven to effectively alleviate ALI. Therefore, the purpose of this study was to determine whether HPF can promote the differentiation of BMSCs into HLCs and promote ALI recovery. Mouse BMSCs were isolated, and the BMSCs' differentiation into HLCs was induced by HPF and hepatocyte growth factor (HGF). Under the induction of HPF and HGF, the expression of hepatocellular specific markers and the accumulation of glycogen and lipids in the BMSCs increased, indicating that BMSCs successfully differentiated into HLCs. Then, the ALI mouse model was established, using carbon tetrachloride, followed by an intravenous injection of BMSCs. Then, only HPF was injected intraperitoneally, in order to verify the effect of HPF in vivo. In vivo imaging was used to detect the homing ability of HPF-BMSCs, and it was detected that HPF-BMSCs significantly increased the levels of serum AST, ALT and ALP in the liver of ALI mice, and alleviated liver cell necrosis, oxidative stress and liver pathology. In conclusion, HPF can promote the differentiation of BMSCs into HLCs and promote the recovery of ALI in mice.
Bone morphogenetic protein 9 (BMP‐9) is a member of the transforming growth factor (TGF)‐β/BMP superfamily, and we have demonstrated that it is one of the most potent BMPs to induce osteoblast ...differentiation of mesenchymal stem cells (MSCs). Here, we sought to investigate if canonical Wnt/β‐catenin signalling plays an important role in BMP‐9‐induced osteogenic differentiation of MSCs. Wnt3A and BMP‐9 enhanced each other’s ability to induce alkaline phosphatase (ALP) in MSCs and mouse embryonic fibroblasts (MEFs). Wnt antagonist FrzB was shown to inhibit BMP‐9‐induced ALP activity more effectively than Dkk1, whereas a secreted form of LPR‐5 or low‐density lipoprotein receptor‐related protein (LRP)‐6 exerted no inhibitory effect on BMP‐9‐induced ALP activity. β‐Catenin knockdown in MSCs and MEFs diminished BMP‐9‐induced ALP activity, and led to a decrease in BMP‐9‐induced osteocalcin reporter activity and BMP‐9‐induced expression of late osteogenic markers. Furthermore, β‐catenin knockdown or FrzB overexpression inhibited BMP‐9‐induced mineralization in vitro and ectopic bone formation in vivo, resulting in immature osteogenesis and the formation of chondrogenic matrix. Chromatin immunoprecipitation (ChIP) analysis indicated that BMP‐9 induced recruitment of both Runx2 and β‐catenin to the osteocalcin promoter. Thus, we have demonstrated that canonical Wnt signalling, possibly through interactions between β‐catenin and Runx2, plays an important role in BMP‐9‐induced osteogenic differentiation of MSCs.
Recombinant adenoviruses provide a versatile system for gene expression studies and therapeutic applications. We have developed an approach that simplifies the generation and production of such ...viruses called the AdEasy system. A recombinant adenoviral plasmid is generated with a minimum of enzymatic manipulations, employing homologous recombination in bacteria rather than in eukaryotic cells. After transfection of such plasmids into a mammalian packaging cell line, viral production is conveniently followed with the aid of GFP encoded by a gene incorporated into the viral backbone. This system has expedited the process of generating and testing recombinant adenoviruses for a variety of purposes. In this protocol, we describe the practical aspects of using the AdEasy system for generating recombinant adenoviruses. The full protocol usually takes 4-5 weeks to complete.
Soluble starch synthases (SSs) play important roles in the synthesis of cassava starch. However, the expression characteristics of the cassava SSs genes have not been elucidated. In this study, the
...gene and its promoter, from SC8 cassava cultivars, were respectively isolated by PCR amplification. MeSSIII-1 protein was localized to the chloroplasts. qRT-PCR analysis revealed that the
gene was expressed in almost all tissues tested, and the expression in mature leaves was 18.9 times more than that in tuber roots.
expression was induced by methyljasmonate (MeJA), abscisic acid (ABA), and ethylene (ET) hormones in cassava.
expression patterns were further confirmed in
transgenic cassava. The promoter deletion analysis showed that the -264 bp to -1 bp
promoter has basal activity. The range from -1228 bp to -987 bp and -488 bp to -264 bp significantly enhance promoter activity. The regions from -987 bp to -747 bp and -747 bp to -488 bp have repressive activity. These findings will provide an important reference for research on the potential function and transcriptional regulation mechanisms of the
gene and for further in-depth exploration of the regulatory network of its internal functional elements.
•The 3D PdIr uniform alloy with KI showed enhanced MOR activity and stability, confirmed with the theoretical calculation.•The KI can be used to regulate the structure and surface composition of PdIr ...catalysts.•The 3D structure, bifunctional mechanism, synergistic catalytic and electronic structure of Ir are the main reasons for the enhanced MOR performance.
Pure iridium (Ir) is easy to produce OH adsorbent species and has a wide range of applications in electrocatalysis. The structure–activity relationship between controlled synthesis and surface regulation of Ir-based alloys and their properties needs further study.When P123(poly (ethylene oxide)-poly (ethylene oxide)-poly (ethylene oxide)(PEO20-PPO70-PEO20) is used as reducing agent and protective agent, the ir-rich core–shell structure PdIr@Ir catalyst can be obtained by the solution thermal method without adding KI, and the PdIr alloy can be obtained after the addition of KI. The complexation ability of KI can change the reduction rate of the precursor and regulate the surface composition of the catalyst.After optimizing the dose of KI, the PdIr-4 shows the highest methanol oxidation reaction (MOR) activity and anti-CO toxicity.The PdIr-2 catalysts with rich Ir on the surface showed high stability, possibly due to the gradual activation of Ir on the surface by PdIr inside. The results of experimental characterization and theoretical calculations show that the main reasons for the performance improvement of PdIr series catalysts are the special three-dimensional structure of PdIr, the bifunctional mechanism between Pd and Ir, especially the synergistic catalytic action of Ir and the effect of regulating the electron structure.The experimental results of this paper are expected to provide some ideas and guidance for Ir-based catalysts with high activity and high stability.
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