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This paper describes a three-dimensional and comprehensive method for completing the northern extension of the Maoshan fracture zone from deep to shallow. Gravity field data interpretation and geomagnetic survey were used to initially locate the rupture, followed by shallow seismic survey for precise positioning, and finally the upper rupture point was captured and its Quaternary activities were investigated according to the method of joint geologic profile exploration with small spaced drill holes across the rupture point. Research has found: ① The Maoshan fracture zone continues to extend northward into the urban area of Zhenjiang, and the northern extension of the Maoshan fracture zone cuts at least to the mid-crustal region. ② The shallow part of the northern extension of the Maoshan fracture zone shows normal faulting characteristics, with an inclination to the east and a strike to the north-east, an apparent dip of about 60°, and an apparent break distance of about 3～5 m. ③ The results of the joint geologic profile of the boreholes show that the bedrock surface on both sides of the fracture point has a small difference, and the overlying Quaternary strata do not have any large undulation and do not have any obvious signs of Quaternary activity, so it is comprehensively judged that the northern extension of the Maoshan fracture zone is a pre-Quaternary fracture. This study preliminarily suggests that the Maoshan fault may be geospatially linked to two significant seismic events in the history of the Jiangsu landmass. This finding provides a new perspective for further research on the seismogenic tectonic features and seismic activity patterns in the region, and may inspire future related studies.

The activation of complement receptor 3 (CR3) in microglia contributes to neurodegeneration in neurological disorders, including Parkinson's disease (PD). However, it remains unclear for mechanistic knowledge on how CR3 mediates neuronal damage. In this study, the expression of CR3 and its ligands iC3b and ICAM-1 was found to be up-regulated in the midbrain of rotenone PD mice, which was associated with elevation of iron content and disruption of balance of iron metabolism proteins. Interestingly, genetic deletion of CR3 blunted iron accumulation and recovered the expression of iron metabolism markers in response to rotenone. Furthermore, reduced lipid peroxidation, ferroptosis of dopaminergic neurons and neuroinflammation were detected in rotenone-lesioned CR3−/− mice compared with WT mice. The regulatory effect of CR3 on ferroptotic death of dopaminergic neurons was also mirrored in vitro. Mechanistic study revealed that iron accumulation in neuron but not the physiological contact between microglia and neurons was essential for microglial CR3-regulated neuronal ferroptosis. In a cell-culture system, microglial CR3 silence significantly dampened iron deposition in neuron in response to rotenone, which was accompanied by mitigated lipid peroxidation and neurodegeneration. Furthermore, ROS released from activated microglia via NOX2 was identified to couple microglial CR3-mediated iron accumulation and subsequent neuronal ferroptosis. Finally, supplementation with exogenous iron was found to recover the sensitivity of CR3−/− mice to rotenone-induced neuronal ferroptosis. Altogether, our findings suggested that microglial CR3 regulates neuron ferroptosis through NOX2 -mediated iron accumulation in experimental Parkinsonism, providing novel points of the immunopathogenesis of neurological disorders.

Abstract Objectives This study aims to enhance supervised human activity recognition based on spatiotemporal graph convolutional neural networks by addressing two key challenges: (1) extracting local spatial feature information from implicit joint connections that is unobtainable through standard graph convolutions on natural joint connections alone. (2) Capturing long-range temporal dependencies that extend beyond the limited temporal receptive fields of conventional temporal convolutions. Methods To achieve these objectives, we propose three novel modules integrated into the spatiotemporal graph convolutional framework: (1) a connectivity feature extraction module that employs attention to model implicit joint connections and extract their local spatial features. (2) A long-range frame difference feature extraction module that captures extensive temporal context by considering larger frame intervals. (3) A coordinate transformation module that enhances spatial representation by fusing Cartesian and spherical coordinate systems. Findings Evaluation across multiple datasets demonstrates that the proposed method achieves significant improvements over baseline networks, with the highest accuracy gains of 2.76 $$\%$$ % on the NTU-RGB+D 60 dataset (Cross-subject), 4.1 $$\%$$ % on NTU-RGB+D 120 (Cross-subject), and 4.3 $$\%$$ % on Kinetics (Top-1), outperforming current state-of-the-art algorithms. This paper delves into the realm of behavior recognition technology, a cornerstone of autonomous systems, and presents a novel approach that enhances the accuracy and precision of human activity recognition.

Within the Tan-Lu Fault Zone, the largest active tectonic belt in eastern China, the Anqiu-Juxian Fault exhibits the most recent activity period, evident surface traces, and highest seismic hazard, making it a Holocene active fault. This study utilized the vertical component continuous data observed by 100 short-period temporary stations from August 1–21, 2023, and extracted 1,944 Rayleigh wave group velocity dispersion curves within the period of 0.2–4 s. Using the direct surface wave tomography method, we calculated a high-resolution 3-D shear-wave velocity structure at depths of 0.2–1.25 km within the study area. Our results are summarized as follows: 1) The development of faults F1, F2, and F5 in the Tan-Lu Fault Zone highly correlated with the shear-wave velocity anomalies at depths >0.8 km. Specifically, fault F5 comprised two boundary faults, F5-1 and F5-2, which together controlled a Cenozoic depression covered by a thick, low-velocity sediment layer. 2) The complex velocity structure characteristics in the Suqian area revealed that the influence of faults on the sedimentary layers in the Suqian area was not expressed as an overall uplift or subsidence of the block but rather as differential subsidence. 3) Near Sankeshu, the F5 fault formed a small pull-apart basin. The latest activity in this pull-apart basin has shifted to the fault in the center of the basin, indicating that the pull-apart basin has entered the extinction stage.

The non-protein amino acid β-N-methylamino-L-alanine (BMAA), produced by cyanobacteria, has been recognized as a neurotoxin. L-serine as an antagonist of BMAA can effectively alleviate BMAA-induced neurotoxicity. Although BMAA has long been emphasized as a neurotoxin, with the emergence of BMAA detected in a variety of algae in freshwater around the world and its clear biological enrichment effect, it is particularly important to study the non-neurotoxic adverse effects of BMAA. However, there is only limited evidence to support the ability of BMAA to cause oxidative damage in the liver. The exact molecular mechanism of BMAA-induced liver injury is still unclear. The formation of neutrophil extracellular traps (NETs) is a ‘double-edged sword’ for the organism, excessive formation of NETs is associated with inflammatory diseases of the liver. Our results innovatively confirmed that BMAA was able to cause the formation of NETs in the liver during the liver injury. The possible mechanism may associated with the regulation of ERK/p38 and cGAS/STING signaling pathways. The massive formation of NETs was able to exacerbate the BMAA-induced oxidative stress and release of inflammatory factors in the mice liver. And the removal of NETs could alleviate this injury. This article will bring a new laboratory evidence for BMAA-induced non-neurotoxicity and immunotoxicity.

Abstract Object detection holds a crucial role in medical diagnostics. Tasks like organ segmentation and malignancy diagnosis typically necessitate preliminary localization of corresponding anatomical structures. Precise positioning ensures that only pertinent regions require processing, leading to a potential reduction in computational and storage demands. Conventional image detection approaches necessitate numerous candidate boxes, resulting in redundant computations. Developing techniques capable of accurately detecting medical image objects without reliance on candidate boxes holds substantial practical significance. This paper introduces a 2D method for detecting medical image objects, which leverages multi-agent deep Q-network reinforcement learning and a multi-scale image representation. The method constructs a collaborative environment for multiple agents. These agents individually govern the upper-right corner and lower-left corner positions of the object detection frame, progressively converging toward the actual endpoint through iterative interactions. To expedite the detection process, a multi-scale image representation technique is employed. This method segments the process into three scales. Initially, within the coarse-scale space, the agent approximates the region containing the true endpoint, subsequently executing oscillatory movements. Progressively, it refines its approach within the fine-scale space, advancing toward the genuine endpoint with smaller iterative steps. The detection results demonstrate that collaborative detection among agents yields a 2.45 $$\%$$ % higher intersection over union compared to non-collaborative detection. Agents exhibit varying step sizes and fields of view in different scale spaces, leading to a reduction in detection time by 0.12 s compared to single-scale comparison. Experimental outcomes demonstrate the superiority of the medical image target detection method proposed in this study over prevailing mainstream detection algorithms.

B-box (BBX) proteins, a subfamily of zinc-finger transcription factors, are involved in various environmental signaling pathways. In this study, we conducted a comprehensive analysis of BBX family members in Brassica crops. The 482 BBX proteins were divided into five groups based on gene structure, conserved domains, and phylogenetic analysis. An analysis of nonsynonymous substitutions and (Ka)/synonymous substitutions (Ks) revealed that most BBX genes have undergone purifying selection during evolution. An analysis of transcriptome data from rapeseed (Brassica napus) organs suggested that BnaBBX3d might be involved in the development of floral tissue-specific RNA-seq expression. We identified numerous light-responsive elements in the promoter regions of BnaBBX genes, which were suggestive of participation in light signaling pathways. Transcriptomic analysis under shade treatment revealed 77 BnaBBX genes with significant changes in expression before and after shading treatment. Of these, BnaBBX22e showed distinct expression patterns in yellow- vs. black-seeded materials in response to shading. UPLC-HESI-MS/MS analysis revealed that shading influences the accumulation of 54 metabolites, with light response BnaBBX22f expression correlating with the accumulation of the flavonoid metabolites M46 and M51. Additionally, BnaBBX22e and BnaBBX22f interact with BnaA10.HY5. These results suggest that BnaBBXs might function in light-induced pigment accumulation. Overall, our findings elucidate the characteristics of BBX proteins in six Brassica species and reveal a possible connection between light and seed coat color, laying the foundation for further exploring the roles of BnaBBX genes in seed development.

A growing number of large data sets have created challenges for the oil and gas industry in predicting reservoir parameters and assessing well productivity through efficient and cost-effective techniques. The design of drilling plans for a high-pressure tight-sand reservoir requires accurate estimations of pore pressure (Pp) and reservoir parameters. The objective of this study is to predict and compare the Pp of Huizhou Sag, Pearl River Mouth Basin, China, using conventional techniques and machine learning (ML) algorithms. We investigated the characteristics of low-permeability reservoirs by observing well-logging data sets and cores and examining thin sections under a microscope. In the reservoir zone, the average hydrocarbon saturation is 55%, and the average effective porosity is 11%. The tight sandstone reservoirs consist of fine- to extremely fine-grained argillaceous feldspathic sandstone. The mean absolute error for reservoir property prediction is 1.3%, 2.2%, and 4.8%, respectively, for effective porosity, shale volume, and water saturation. Moreover, the ML algorithm was employed to cross-check the validity of the prediction of Pp. Combining conventional and ML techniques with the core data demonstrates a correlation coefficient (R2) of 0.9587, indicating that ML techniques are the most effective in testing well data. This study shows that ML can effectively predict Pp at subsequent depths in adjacent geologically similar locations. Compared to conventional methods, a substantial data set and ML algorithms improve the precision of Pp predictions.

Microglia-mediated chronic neuroinflammation has been associated with cognitive decline induced by rotenone, a well-known neurotoxic pesticide used in agriculture. However, the mechanisms remain unclear. This work aimed to elucidate the role of complement receptor 3 (CR3), a highly expressed receptor in microglia, in cognitive deficits induced by rotenone. Rotenone up-regulated the expression of CR3 in the hippocampus and cortex area of mice. CR3 deficiency markedly ameliorated rotenone-induced cognitive impairments, neurodegeneration and phosphorylation (Ser129) of α-synuclein in mice. CR3 deficiency also attenuated rotenone-stimulated microglial M1 activation. In microglial cells, siRNA-mediated knockdown of CR3 impeded, while CR3 activation induced by LL-37 exacerbated, rotenone-induced microglial M1 activation. Mechanistically, CR3 deficiency blocked rotenone-induced activation of nuclear factor κB (NF-κB), signal transducer and activator of transcription 1 (STAT1) and STAT3 signaling pathways. Pharmacological inhibition of NF-κB or STAT3 but not STAT1 was confirmed to suppress microglial M1 activation elicited by rotenone. Further study revealed that CR3 deficiency or knockdown also reduced rotenone-induced expression of C3, an A1 astrocyte marker, and production of microglial C1q, TNFα and IL-1α, a cocktail for activated microglia to induce neurotoxic A1 astrocytes, via NF-κB and STAT3 pathways. Finally, a small molecule modulator of CR3 efficiently mitigated rotenone-elicited cognitive deficits in mice even administered after the establishment of cognitive dysfunction. Taken together, our findings demonstrated that CR3 is a key factor in mediating neurotoxic glial activation and subsequent cognitive impairments in rotenone-treated mice, giving novel insights into the immunopathogenesis of cognitive impairments in pesticide-related Parkinsonism.

Abstract Ad‐/desorption and diffusion processes are the key factors controlling methane production from coal. The experiments used samples from methane‐producing coal seams with different contents of carbonate mineral and different ranks. Acid treatment using 1.0 mol/L acetic acid (CH3COOH) and oxidant treatment using 1.0 mol/L ammonium persulfate ((NH4)2S2O8) were conducted on these coal samples to observe the changes in surface functional groups that act as primary sorption sites and pore structure that determines diffusivity by Fourier transform infrared spectrometer, in situ scanning electron microscopy (SEM) imaging and energy dispersive spectroscopy. The results showed that the acidizing‐related mass loss of coal samples is in the range of 3.78%–7.57% due to the complete dissolution of pore‐ and fracture‐filling carbonate minerals. For the coal samples after oxidizing treatment, dissolution evidence can be observed in both carbonate minerals and organic matter, with a mass loss ranging from 2.01% to 3.0%. Acidizing or oxidizing induced dissolution can destroy aliphatic functional groups and the cross‐linked structure of coal, resulting in a decrease in methane adsorption capacity that is beneficial to methane desorption. More opened pores and interconnected fractures can be observed in SEM images due to the dissolution of carbonate minerals, suggesting an alteration of methane diffusion pathways in the coal matrix. Although only some of the carbonate minerals were dissolved following oxidant treatment, coal organic matter is partially oxidized and generates some dissolution pores, which provides more methane diffusion pathways in the coal matrix. Therefore, all the treated coal samples showed a reduction in methane adsorption capacity and an enhancement of desorption capacity and diffusivity. This result suggests that chemical treatment in coal seams using acetic acid or oxidant has the potential to improve coalbed methane extraction.

BackgroundThis study aims to evaluate the clinical efficacy and safety of rimegepant for the treatment of migraine in adult patients using a meta-analysis.MethodsThe PubMed, EMBASE, and Cochrane Library were searched up to March 2022. Only randomized controlled trials (RCTs) that evaluated migraine and other comparator treatments in adult patients were included. The clinical response at the post-treatment evaluation, including acute pain free and relief effect, whereas the secondary outcomes were the risk of adverse events (AEs).ResultsA total of 4 RCTs involving 4,230 patients with episodic migraine were included. Outcome indicators for the number of pain free and relief patients at 2 h, 2–24 h, 2–48 h post-dose showed that rimegepant had better effects relative to the placebo [free at 2 h: OR = 1.84, 95% CI (1.55, 2.18), P < 0.00001; relief at 2 h: OR = 1.80, 95% CI (1.59, 2.04), P < 0.00001]. And there was no significant difference between the occurrence of adverse events in the experimental and control groups [OR = 1.29, 95% CI (0.99, 1.67), P = 0.06].ConclusionRimegepant has better therapeutic effects compared to placebo and no significant difference in adverse events.

Abstract Background Plasmodium vivax reticulocyte binding protein 2b (PvRBP2b) plays a critical role in parasite invasion of reticulocytes by binding the transferrin receptor 1. PvRBP2b is a vaccine candidate based on the negative correlation between antibody titers against PvRBP2b recombinant proteins and parasitemia and risk of vivax malaria. The aim of this study was to analyze the genetic diversity of the PvRBP2b gene in the global P. vivax populations. Methods Near full-length PvRBP2b nucleotide sequences (190–8349 bp) were obtained from 88 P. vivax isolates collected from the China–Myanmar border (n = 44) and Thailand (n = 44). An additional 224 PvRBP2b sequences were retrieved from genome sequences from parasite populations worldwide. The genetic diversity, neutral selection, haplotype distribution and genetic differentiation of PvRBP2b were examined. Results The genetic diversity of PvRBP2b was distributed unevenly, with peak diversity found in the reticulocyte binding region in the N-terminus. Neutrality analysis suggested that this region is subjected to balancing selection or population bottlenecks. Several amino acid variants were found in all or nearly all P. vivax endemic regions. However, the critical residues responsible for reticulocyte binding were highly conserved. There was substantial population differentiation according to the geographical separation. The distribution of haplotypes in the reticulocyte binding region varied among regions; even the two major haplotypes Hap_6 and Hap_8 were found in only five populations. Conclusions Our data show considerable genetic variations of PvRBPb in global parasite populations. The geographic divergence may pose a challenge to PvRBP2b-based vaccine development. Graphical Abstract

In the realm of modern medicine, medical imaging stands as an irreplaceable pillar for accurate diagnostics. The significance of precise segmentation in medical images cannot be overstated, especially considering the variability introduced by different practitioners. With the escalating volume of medical imaging data, the demand for automated and efficient segmentation methods has become imperative. This study introduces an innovative approach to heart image segmentation, embedding a multi-scale feature and attention mechanism within an inverted pyramid framework. Recognizing the intricacies of extracting contextual information from low-resolution medical images, our method adopts an inverted pyramid architecture. Through training with multi-scale images and integrating prediction outcomes, we enhance the network’s contextual understanding. Acknowledging the consistent patterns in the relative positions of organs, we introduce an attention module enriched with positional encoding information. This module empowers the network to capture essential positional cues, thereby elevating segmentation accuracy. Our research resides at the intersection of medical imaging and sensor technology, emphasizing the foundational role of sensors in medical image analysis. The integration of sensor-generated data showcases the symbiotic relationship between sensor technology and advanced machine learning techniques. Evaluation on two heart datasets substantiates the superior performance of our approach. Metrics such as the Dice coefficient, Jaccard coefficient, recall, and F-measure demonstrate the method’s efficacy compared to state-of-the-art techniques. In conclusion, our proposed heart image segmentation method addresses the challenges posed by diverse medical images, offering a promising solution for efficiently processing 2D/3D sensor data in contemporary medical imaging.

In the era of artificial intelligence, the significance of images and videos as intuitive conveyors of information cannot be overstated. Computer vision techniques rooted in deep learning have revolutionized our ability to autonomously and accurately identify objects within visual media, making them a focal point of contemporary research. This study addresses the pivotal role of image object detection, particularly in the contexts of autonomous driving and security surveillance, by presenting an in-depth exploration of this field with a focus on enhancing the feature pyramid network. One of the key challenges in existing object detection methodologies lies in mitigating information loss caused by multi-scale feature fusion. To tackle this issue, we propose the enhanced feature pyramid, which adeptly amalgamates features extracted across different scales. This strategic enhancement effectively curbs information attrition across various layers, thereby strengthening the feature extraction capabilities of the foundational network. Furthermore, we confront the issue of excessive classification loss in image object detection tasks by introducing the gradient density loss function, designed to mitigate classification discrepancies. Empirical results unequivocally demonstrate the efficacy of our approach in enhancing the detection of multi-scale objects within images. When evaluated across benchmark datasets, including MS COCO 2017, MS COCO 2014, Pascal VOC 2007, and Pascal VOC 2012, our method achieves impressive average precision scores of 39.4%, 42.0%, 51.5%, and 49.9%, respectively. This performance clearly outperforms alternative state-of-the-art methods in the field. This research not only contributes to the evolving landscape of computer vision and object detection but also has practical implications for a wide range of applications, aligning with the transformative trends in the automotive industry and security technologies.

Abstract Dynamic regulation of nanoparticles in a controllable manner has great potential in various areas. Compared to the individual nanoparticles, the assembled nanoparticles exhibit superior properties and functions, which can be applied to achieve desirable performances. Here, a pH‐responsive i‐motif DNA‐mediated strategy to tailor the programmable behaviors of erbium‐based rare‐earth nanoparticles (ErNPs) decorated copper doped metal‐organic framework (CPM) nanohybrids (ECPM) under physiological conditions is reported. Within the acidic tumor microenvironment, the i‐motif DNA strands are able to form quadruplex structures, resulting in the assembly of nanohybrids and selective tumor accumulation, which further amplify the ErNPs downconversion emission (1550 nm) signal for imaging. Meanwhile, the ECPM matrix acts as a near‐infrared (NIR) photon‐activated reactive oxygen species (ROS) amplifier through the singlet oxygen generation of the matrix in combination with its ability of intracellular glutathione depletion upon irradiation. In short, this work displays a classical example of engineering of nanoparticles, which will manifest the importance of developing nanohybrids with structural programmability in biomedical applications.

Visual saliency refers to the human’s ability to quickly focus on important parts of their visual field, which is a crucial aspect of image processing, particularly in fields like medical imaging and robotics. Understanding and simulating this mechanism is crucial for solving complex visual problems. In this paper, we propose a salient object detection method based on boundary enhancement, which is applicable to both 2D and 3D sensors data. To address the problem of large-scale variation of salient objects, our method introduces a multi-level feature aggregation module that enhances the expressive ability of fixed-resolution features by utilizing adjacent features to complement each other. Additionally, we propose a multi-scale information extraction module to capture local contextual information at different scales for back-propagated level-by-level features, which allows for better measurement of the composition of the feature map after back-fusion. To tackle the low confidence issue of boundary pixels, we also introduce a boundary extraction module to extract the boundary information of salient regions. This information is then fused with salient target information to further refine the saliency prediction results. During the training process, our method uses a mixed loss function to constrain the model training from two levels: pixels and images. The experimental results demonstrate that our salient target detection method based on boundary enhancement shows good detection effects on targets of different scales, multi-targets, linear targets, and targets in complex scenes. We compare our method with the best method in four conventional datasets and achieve an average improvement of 6.2% on the mean absolute error (MAE) indicators. Overall, our approach shows promise for improving the accuracy and efficiency of salient object detection in a variety of settings, including those involving 2D/3D semantic analysis and reconstruction/inpainting of image/video/point cloud data.

Understanding and analyzing 2D/3D sensor data is crucial for a wide range of machine learning-based applications, including object detection, scene segmentation, and salient object detection. In this context, interactive object segmentation is a vital task in image editing and medical diagnosis, involving the accurate separation of the target object from its background based on user annotation information. However, existing interactive object segmentation methods struggle to effectively leverage such information to guide object-segmentation models. To address these challenges, this paper proposes an interactive image-segmentation technique for static images based on multi-level semantic fusion. Our method utilizes user-guidance information both inside and outside the target object to segment it from the static image, making it applicable to both 2D and 3D sensor data. The proposed method introduces a cross-stage feature aggregation module, enabling the effective propagation of multi-scale features from previous stages to the current stage. This mechanism prevents the loss of semantic information caused by multiple upsampling and downsampling of the network, allowing the current stage to make better use of semantic information from the previous stage. Additionally, we incorporate a feature channel attention mechanism to address the issue of rough network segmentation edges. This mechanism captures richer feature details from the feature channel level, leading to finer segmentation edges. In the experimental evaluation conducted on the PASCAL Visual Object Classes (VOC) 2012 dataset, our proposed interactive image segmentation method based on multi-level semantic fusion demonstrates an intersection over union (IOU) accuracy approximately 2.1% higher than the currently popular interactive image segmentation method in static images. The comparative analysis highlights the improved performance and effectiveness of our method. Furthermore, our method exhibits potential applications in various fields, including medical imaging and robotics. Its compatibility with other machine learning methods for visual semantic analysis allows for integration into existing workflows. These aspects emphasize the significance of our contributions in advancing interactive image-segmentation techniques and their practical utility in real-world applications.

Abstract Background Recent studies suggest that lncRNAs may play significant roles in the development of hepatitis B virus (HBV) infection. However, as a special stage of HBV infection, the lncRNA expression in occult HBV infection (OBI) remains unclear. Methods The plasma level of 15 HBV infection-related lncRNAs was initially detected using qRT-PCR in 10 OBI and 10 healthy controls (HCs) in discovery phase. Significantly dysregulated lncRNAs were subsequently validated in another 64 OBI, 20 HCs, 31 chronic hepatitis B (CHB) and 20 asymptomatic HBsAg carriers (ASC). Moreover, the AP000253 expression in liver tissues and its potential biological functions in HBV infection were further investigate with public transcriptomic data and HBV-expressing cell lines. Results Among candidate lncRNAs, the plasma level of AP000253 decreased significantly in OBI, ASC and CHB patients compared to HCs, while no difference was found among OBI, ASC and CHB patients. In liver tissues, similar AP000253 expression was also observed from the GSE83148 dataset, while that in HBV-expressing hepatoma cells was opposite. ROC curve analysis indicated that plasma AP000253 yielded an AUC of 0.73 with 60% sensitivity and 75% specificity when differentiating OBI from HCs, but it could not specifically separate the stage of chronic HBV infection. Furthermore, functional experiments suggested that AP000253 could promote HBV transcription and replication in hepatoma cell lines. Conclusions AP000253 might be involved in HBV replication, and be served as a potential biomarker for HBV infection. In the setting of blood donations, plasma AP000253 would be more useful to moderately distinguish OBI in HBsAg-negative donors. However, the AP000253 expression in liver tissues and associated molecular mechanism of HBV infection deserve further study in future.

Abstract Background Klebsiella pneumoniae is a bacterium that can be used as producer for numerous chemicals. Glycerol can be catabolised by K. pneumoniae and dihydroxyacetone is an intermediate of this catabolism pathway. Here dihydroxyacetone and glycerol were produced from glucose by this bacterium based a redirected glycerol catabolism pathway. Results tpiA, encoding triosephosphate isomerase, was knocked out to block the further catabolism of dihydroxyacetone phosphate in the glycolysis. After overexpression of a Corynebacterium glutamicum dihydroxyacetone phosphate dephosphorylase (hdpA), the engineered strain produced remarkable levels of dihydroxyacetone (7.0 g/L) and glycerol (2.5 g/L) from glucose. Further increase in product formation were obtained by knocking out gapA encoding an iosenzyme of glyceraldehyde 3-phosphate dehydrogenase. There are two dihydroxyacetone kinases in K. pneumoniae. They were both disrupted to prevent an inefficient reaction cycle between dihydroxyacetone phosphate and dihydroxyacetone, and the resulting strains had a distinct improvement in dihydroxyacetone and glycerol production. pH 6.0 and low air supplement were identified as the optimal conditions for dihydroxyacetone and glycerol production by K, pneumoniae ΔtpiA-ΔDHAK-hdpA. In fed batch fermentation 23.9 g/L of dihydroxyacetone and 10.8 g/L of glycerol were produced after 91 h of cultivation, with the total conversion ratio of 0.97 mol/mol glucose. Conclusions This study provides a novel and highly efficient way of dihydroxyacetone and glycerol production from glucose.

Abstract Background Chlorhexidine is a widely used disinfectant in clinical settings and a broad-spectrum antimicrobial agent effective against aerobic and anaerobic bacteria. However, disinfectant resistant or non-susceptible bacteria, including antibiotic-resistant Acinetobacter baumannii, have been found. This study aimed to develop a new technique to prevent and control A. baumannii infection in the hospital setting. Methods Chlorhexidine combined with minocycline, doxycycline, meropenem, imipenem, levofloxacin and ciprofloxacin were tested against the 30 multidrug-resistant and extremely drug-resistant A. baumannii clinical isolates. The checkerboard test was used to calculate the fractional inhibitory concentration index according to the minimum inhibitory concentration value for chlorhexidine combined with antibiotics. Results The combination of chlorhexidine with minocycline, doxycycline, meropenem, or ciprofloxacin showed synergistic responses in all clinical isolates, and more than 50% of isolates showed FICI ≤0.5. However, chlorhexidine together with imipenem or levofloxacin showed indifferent responses in 10% and 3.33% clinical isolates, respectively. In all tests, combinations of chlorhexidine with each of the above six antibiotics showed synergistic and additive effects, and inhibited the clinical isolates. Conclusions We concluded that, chlorhexidine combined with antibiotics could be used to control the risk of infection with A. baumannii.

Abstract Background In the Greater Mekong sub-region, Plasmodium vivax has become the predominant species and imposes a major challenge for regional malaria elimination. This study aimed to investigate the variations in genes potentially related to drug resistance in P. vivax populations from the China–Myanmar border area. In addition, this study also wanted to determine whether divergence existed between parasite populations associated with asymptomatic and acute infections. Methods A total of 66 P. vivax isolates were obtained from patients with acute malaria who attended clinics at the Laiza area, Kachin State, Myanmar in 2015. In addition, 102 P. vivax isolates associated with asymptomatic infections were identified by screening of volunteers without signs or symptoms from surrounding villages. Slide-positive samples were verified with nested PCR detecting the 18S rRNA gene. Multiclonal infections were further excluded by genotyping at msp-3α and msp-3β genes. Parasite DNA from 60 symptomatic cases and 81 asymptomatic infections was used to amplify and sequence genes potentially associated with drug resistance, including pvmdr1, pvcrt-o, pvdhfr, pvdhps, and pvk12. Results The pvmdr1 Y976F and F1076L mutations were present in 3/113 (2.7%) and 97/113 (85.5%) P. vivax isolates, respectively. The K10 insertion in pvcrt-o gene was found in 28.2% of the parasites. Four mutations in the two antifolate resistance genes reached relatively high levels of prevalence: pvdhfr S58R (53.4%), S117N/T (50.8%), pvdhps A383G (75.0%), and A553G (36.3%). Haplotypes with wild-type pvmdr1 (976Y/997K/1076F) and quadruple mutations in pvdhfr (13I/57L/58R/61M/99H/117T/173I) were significantly more prevalent in symptomatic than asymptomatic infections, whereas the pvmdr1 mutant haplotype 976Y/997K/1076L was significantly more prevalent in asymptomatic than symptomatic infections. In addition, quadruple mutations at codons 57, 58, 61 and 117 of pvdhfr and double mutations at codons 383 and 553 of pvdhps were found both in asymptomatic and symptomatic infections with similar frequencies. No mutations were found in the pvk12 gene. Conclusions Mutations in pvdhfr and pvdhps were prevalent in both symptomatic and asymptomatic P. vivax infections, suggestive of resistance to antifolate drugs. Asymptomatic carriers may act as a silent reservoir sustaining drug-resistant parasite transmission necessitating a rational strategy for malaria elimination in this region.

Abstract Background Countries within the Greater Mekong Sub-region (GMS) of Southeast Asia have committed to eliminating malaria by 2030. Although the malaria situation has greatly improved, malaria transmission remains at international border regions. In some areas, Plasmodium vivax has become the predominant parasite. To gain a better understanding of transmission dynamics, knowledge on the changes of P. vivax populations after the scale-up of control interventions will guide more effective targeted control efforts. Methods This study investigated genetic diversity and population structures in 206 P. vivax clinical samples collected at two time points in two international border areas: the China-Myanmar border (CMB) (n = 50 in 2004 and n = 52 in 2016) and Thailand-Myanmar border (TMB) (n = 50 in 2012 and n = 54 in 2015). Parasites were genotyped using 10 microsatellite markers. Results Despite intensified control efforts, genetic diversity remained high (H E = 0.66–0.86) and was not significantly different among the four populations (P > 0.05). Specifically, H E slightly decreased from 0.76 in 2004 to 0.66 in 2016 at the CMB and increased from 0.80 in 2012 to 0.86 in 2015 at the TMB. The proportions of polyclonal infections varied significantly among the four populations (P

Abstract Background Intensive malaria transmission along international borders is a significant impediment to malaria elimination in the Greater Mekong Subregion (GMS) of Southeast Asia. Passive case detection (PCD) was used to study the dynamics and trends of malaria transmission at the China–Myanmar border to provide epidemiologic information for improved malaria control. Methods PCD was conducted in one hospital and 12 clinics near the Laiza town in northeast Myanmar from 2011 to 2016. Clinical malaria was diagnosed by microscopy and demographic information was captured using a structured questionnaire at the time of the patient’s presentation for care. Results Over the study period, 6175 (19.7%) malaria cases were confirmed by microscopy from 31,326 suspected cases. The four human malaria parasite species were all identified, with Plasmodium vivax and Plasmodium falciparum accounting for 5607 (90.8%) and 481 (7.8%) of the confirmed cases, respectively. In contrast to the steady decline of malaria in the general GMS, the study site had an upward trend of malaria incidence with vivax malaria outbreaks in 2013 and 2016. Adult males, children under the age of 15, and those with occupations such as farming, being a soldier or student, had significantly higher risks of clinical malaria compared to having fevers from other aetiologies. A self-reported history of clinical malaria was also associated with a higher risk of confirmed malaria. Conclusions The China–Myanmar border area has experienced an overall upward trend of malaria incidence in recent years with P. vivax becoming the predominant species. Evidence-based control strategies need to focus on high-risk populations.

Abstract Background The malaria burden of Myanmar still remains high within the Greater Mekong Subregion of Southeast Asia. An important indicator of progress towards malaria elimination is the prevalence of parasite infections in endemic populations. Information about malaria epidemiology is mostly derived from reports of confirmed acute malaria cases through passive case detection, whereas the prevalence of baseline subclinical malaria infections is much less known. Methods In this study, cross-sectional surveys were conducted during the rainy season of 2017 in four townships (Bilin, Thabeikkyin, Banmauk and Paletwa) of Myanmar with divergent annual malaria incidences. A total of 1991 volunteers were recruited from local villages and Plasmodium subclinical infections were estimated by light microscopy (LM), rapid diagnostic tests (RDTs) and nested PCR. The nested PCR analysis was performed with a modified pooling strategy that was optimized based on an initial estimate the infection prevalence. Results The overall malaria infection prevalence based on all methods was 13.9% (277/1991) and it differed drastically among the townships, with Paletwa in the western border having the highest infection rate (22.9%) and Thabeikkyin in central Myanmar having the lowest (3.9%). As expected, nested PCR was the most sensitive and identified 226 (11.4%) individuals with parasite infections. Among the parasite species, Plasmodium vivax was the most prevalent in all locations, while Plasmodium falciparum also accounted for 32% of infections in the western township Paletwa. Two RDTs based on the detection of the hrp2 antigen detected a total of 103 P. falciparum infections, and the ultrasensitive RDT detected 20% more P. falciparum infections than the conventional RDT. In contrast, LM missed the majority of the subclinical infections and only identified 14 Plasmodium infections. Conclusions Cross-sectional surveys identified considerable levels of asymptomatic Plasmodium infections in endemic populations of Myanmar with P. vivax becoming the predominant parasite species. Geographical heterogeneity of subclinical infections calls for active surveillance of parasite infections in endemic areas. The pooling scheme designed for nested PCR analysis offers a more practical strategy for large-scale epidemiological studies of parasite prevalence. Such information is important for decision-makers to put forward a more realistic action plan for malaria elimination.

Abstract Background The management of pancreatic cancer (PanCa) is exceptionally difficult due to poor response to available therapeutic modalities. Tubulins play a major role in cell dynamics, thus are important molecular targets for cancer therapy. Among various tubulins, βIII and βIV-tubulin isoforms have been primarily implicated in PanCa progression, metastasis and chemo-resistance. However, specific inhibitors of these isoforms that have potent anti-cancer activity with low toxicity are not readily available. Methods We determined anti-cancer molecular mechanisms and therapeutic efficacy of a novel small molecule inhibitor (VERU-111) using in vitro (MTS, wound healing, Boyden chamber and real-time xCELLigence assays) and in vivo (xenograft studies) models of PanCa. The effects of VERU-111 treatment on the expression of β-tubulin isoforms, apoptosis, cancer markers and microRNAs were determined by Western blot, immunohistochemistry (IHC), confocal microscopy, qRT-PCR and in situ hybridization (ISH) analyses. Results We have identified a novel small molecule inhibitor (VERU-111), which preferentially represses clinically important, βIII and βIV tubulin isoforms via restoring the expression of miR-200c. As a result, VERU-111 efficiently inhibited tumorigenic and metastatic characteristics of PanCa cells. VERU-111 arrested the cell cycle in the G2/M phase and induced apoptosis in PanCa cell lines via modulation of cell cycle regulatory (Cdc2, Cdc25c, and Cyclin B1) and apoptosis - associated (Bax, Bad, Bcl-2, and Bcl-xl) proteins. VERU-111 treatment also inhibited tumor growth (P

Melanoma is one of the deadliest skin cancers having a five-year survival rate around 15–20%. An overactivated MAPK/AKT pathway is well-established in BRAF mutant melanoma. Vemurafenib (Vem) was the first FDA-approved BRAF inhibitor and gained great clinical success in treating late-stage melanoma. However, most patients develop acquired resistance to Vem within 6–9 months. Therefore, developing a new treatment strategy to overcome Vem-resistance is highly significant. Our previous study reported that the combination of a tubulin inhibitor ABI-274 with Vem showed a significant synergistic effect to sensitize Vem-resistant melanoma both in vitro and in vivo. In the present study, we unveiled that VERU-111, an orally bioavailable inhibitor of α and β tubulin that is under clinical development, is highly potent against Vem-resistant melanoma cells. The combination of Vem and VERU-111 resulted in a dramatically enhanced inhibitory effect on cancer cells in vitro and Vem-resistant melanoma tumor growth in vivo compared with single-agent treatment. Further molecular signaling analyses demonstrated that in addition to ERK/AKT pathway, Skp2 E3 ligase also plays a critical role in Vem-resistant mechanisms. Knockout of Skp2 diminished oncogene AKT expression and contributed to the synergistic inhibitory effect of Vem and VERU-111. Our results indicate a treatment combination of VERU-111 and Vem holds a great promise to overcome Vem-resistance for melanoma patients harboring BRAF (V600E) mutation.

The existing cholesterols (Chols) in animal cell membranes play key roles in many fundamental cellular processes, which also promise the possibility to modulate the bioactivity of various membrane-active biomacromolecules. Here, combining dynamic giant unilamellar vesicle leakage experiments and molecular dynamics simulations, the inhibitory effect of Chols on the membrane poration activity of melittin (Mel), a typical natural antimicrobial peptide, is demonstrated. Molecular details of the Mel-Chol interactions in membrane show that, for a Chol-contained lipid membrane, Mel exposure would perturb the symmetric bilayer structure of the membrane and specifically influence the location and orientation distributions of Chol molecules to an asymmetric state between the two leaflets; moreover, the Mel-Chol interactions are significantly influenced by the membrane environment such as unsaturation degree of the lipid components. Such inhibitory effect is normally ascribed to an accumulation of Chol molecules around the membrane-bound peptide chains and formation of Chol-Mel complexes in the membrane, which hinder the further insertion of peptides into the membrane. This work clarifies the molecular interactions between membrane-active peptides and Chol-contained membranes, and suggest the possibility to develop targeted drugs due to the membrane component specificity between bacterial and animal cells.

Rural settlements serve as an important part of the rural landscape, and environmental conditions influence their spatial distribution. We hypothesize that there are variations in the spatial patterns of settlements across different farming–pastoral ecotones that exist in accordance with different human activities and environmental conditions. We used remote sensing imagery, digital elevation model, and GIS technology to analyze and compare the spatial patterns of settlements and factors influencing these patterns across pastoral, agricultural, and ecotone areas in Inner Mongolia, China. A Voronoi model, adjacency analysis, landscape metrics, and quantitative analysis were conducted. The results indicated that (1) the settlements in the three areas tended to have a random spatial distribution, and although there were no significant differences between the settlement types, agricultural settlements tended to be clustered and pastoral settlements tended to be evenly distributed; (2) the pastoral area had only a few large and sparsely fragmented patches; (3) the factors influencing settlement distribution mainly differed with respect to the NDVI, distance to roads and rivers, and elevation across three areas, but the slope degree was similar. These results indicated there are no significant differences between the spatial patterns of settlements along the agricultural to pastoral gradient, although environmental conditions differ. Consequently, we can optimize the spatial pattern of settlements and achieve sustainable development within farming–pastoral ecotones.

In the field of oil and gas exploration, drilling fluid is regarded as the essential “blood” for drilling, which mainly helps to control the formation pressure and remove cuttings from the well. During the drilling fluid cycle, the drilling fluid penetrates into the pores of the formation rock, thus blocking the rock pores and resulting in a decline in oil and gas recovery efficiency. Therefore, it is very important to understand the microscopic mechanism of formation damage caused by drilling fluid. However, as an important component of formation damage, the microscopic mechanism of fluid damage has not yet been clearly revealed. In this study, a new microetching model (MEM), along with displacement equipment, was designed. The pore network of rock samples was extracted from thin-section images and etched to a thin aluminum sheet by laser. Oil-based drilling fluid was used to displace the stratum water in the MEM. The displacement process was recorded by a camera and analyzed. A core flooding experiment, permeability measurement, and SEM observations were performed. The results show that, for low-porosity and low-permeability sandstone, the main forms of formation damage by drilling fluid include solid damage and liquid damage. Solid damage is mainly caused by the blockage of small pores and narrow throats with solid particles of the size 0.1~30.0 μm in drilling fluid, while liquid damage is mainly caused by the water lock and hydrocarbon lock effects formed by the oil–water two-phase interface, gas–water two-phase interface, or the oil–gas–water three-phase interface.

Abstract Background Border malaria, a shared phenomenon in the Greater Mekong Sub-region of Southeast Asia, is a major obstacle for regional malaria elimination. Along the China–Myanmar border, an additional problem arose as a result of the settlement of internally displaced people (IDP) in the border region. Since asymptomatic malaria significantly impacts transmission dynamics, assessment of the prevalence, dynamics and risk factors of asymptomatic malaria infections is necessary. Methods Cross-sectional surveys were carried out in 3 seasons (March and April, July and November) and 2 sites (villages and IDP camps) in 2015. A total of 1680 finger-prick blood samples were collected and used for parasite detection by microscopy and nested RT-PCR (nRT-PCR). Logistic regression models were used to explore the risk factors associated with asymptomatic malaria at individual and household levels. Results The prevalence of asymptomatic Plasmodium infections was 23.3% by nRT-PCR, significantly higher than that detected by microscopy (1.5%). The proportions of Plasmodium vivax, Plasmodium falciparum and mixed-species infections were 89.6, 8.1 and 2.3%, respectively. Asymptomatic infections showed obvious seasonality with higher prevalence in the rainy season. Logistic regression analysis identified males and school children (≤ 15 years) as the high-risk populations. Vector-based interventions, including bed net and indoor residual spray, were found to have significant impacts on asymptomatic Plasmodium infections, with non-users of these measures carrying much higher risks of infection. In addition, individuals living in poorly constructed households or farther away from clinics were more prone to asymptomatic infections. Conclusions Sub-microscopic Plasmodium infections were highly prevalent in the border human populations from IDP camps and surrounding villages. Both individual- and household-level risk factors were identified, which provides useful information for identifying the high-priority populations to implement targeted malaria control.

Abstract Background Sensitive methods for detecting asymptomatic malaria infections are essential for identifying potential transmission reservoirs and obtaining an accurate assessment of malaria epidemiology in low-endemicity areas aiming to eliminate malaria. PCR techniques to detect parasite nucleic acids (DNA or RNA) are among the most commonly used molecular methods. However, most of these methods are of low throughput and cannot be used for large-scale molecular epidemiological studies. A recently developed capture and ligation probe-PCR (CLIP-PCR) is claimed to have the sensitivity of molecular techniques and the high throughput capacity needed for screening purposes. This study aimed to compare several molecular methods for detecting asymptomatic and submicroscopic Plasmodium infections in healthy residents of a malaria-hypoendemic region in Southeast Asia, where malaria elimination is in sight. Method This study compared three molecular detection methods side-by-side, namely nested PCR targeting the rRNA genes, nested RT-PCR to detect parasite rRNA, and CLIP-PCR to detect parasite rRNA in 1005 healthy individuals in northeastern Myanmar. For nested PCR and RT-PCR, parasite DNA and total RNA were extracted from ~100 µL of blood, whereas RNA used for CLIP-PCR was from a 3 mm disk of dried blood filter paper. The sensitivity and specificity of these methods were compared with those of conventional light microscopy. In addition, RT-PCR and quantitative RT-PCR (qRT-PCR) targeting the Pvs25 gene in Plasmodium vivax were used to assess gametocyte prevalence in the samples. Results Light microscopy detected Plasmodium infections in only 1.19% of the residents harbouring the parasites. CLIP-PCR had slightly better performance and detected Plasmodium infections in 1.89% of the population. Further improvement was achieved by nested PCR to detect parasite DNA, which detected P. vivax and Plasmodium falciparum infections in 2.39% of the residents. The nested RT-PCR targeting rRNA, however, detected as many as 187 (18.61%) individuals having Plasmodium infections with P. vivax being the predominant species (176 P. vivax, 5 P. falciparum and 6 P. falciparum/P. vivax mixed infections). Of the 210 Plasmodium-positive samples detected by all molecular methods, 115 were Pvs25-positive by qRT-PCR, indicating that a large proportion of asymptomatic individuals were gametocyte carriers. Conclusion Nested RT-PCR based on the detection of asexual-stage parasite rRNA was the most sensitive, with a more than sixfold higher sensitivity than the other two molecular methods of parasite detection. CLIP-PCR has an increased throughput, but its sensitivity in this study was much lower than those of other molecular methods, which may be partially due to the smaller amount of RNA input used.

Emerging studies have reported circRNAs were dysregulated in HCC. However, the clinical value of these circRNAs remains to be clarified. Herein, we aimed to comprehensively explore their association with the diagnosis, prognosis, and clinicopathological characteristics of HCC. PubMed, EMBASE, Web of Science, and Cochrane Library databases were comprehensively searched for eligible studies up to October 30, 2018. The diagnostic effect was evaluated by the pooled sensitivity, specificity, and other indexes. The pooled hazard ratio (HR) for overall survival (OS) and recurrence free survival (RFS) was calculated to assess the prognostic value. Ten studies on diagnosis, 12 on prognosis, and 23 on clinicopathology were identified from the databases. A total of 11 upregulated and 11 downregulated circRNAs showed an association with clinicopathological features of HCC. For the diagnosis analyses, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) of circRNAs for HCC were 0.74 (95%CI: 0.65-0.82) and 0.76 (95%CI: 0.70-0.81), 3.1 (95%CI: 2.5-3.8), 0.34 (95%CI: 0.25-0.47), and 9 (95%CI: 6-14), respectively. The area under SROC curve (AUC) was 0.81 (95% CI: 0.78–0.84), indicating moderate diagnostic accuracy. In stratified analyses, the diagnostic performance of circRNAs varied based on the source of control and specimen type. For the prognosis analyses, increased expression of upregulated circRNAs was associated with worse OS (HR: 3.67, 95%: 2.07-6.48), while high expression of downregulated circRNAs was associated with better OS (HR: 0.38, 95%: 0.30-0.48). In conclusion, this study reveals that circRNAs may serve as promising diagnostic and prognostic biomarkers for HCC. However, further investigations are still required to explore the clinical value of circRNAs.

A skeleton-based fiber tracing algorithm is described and applied on a specific fibrous material, porous metal fiber sintered sheet (PMFSS), featuring high porosity and curved fibers. The skeleton segments are firstly categorized according to the connectivity of the skeleton paths. Spurious segments like fiber bonds are detected making extensive use of the distance transform (DT) values. Single fibers are then traced and reconstructed by consecutively choosing the connecting skeleton segment pairs that show the most similar orientations and radius. Moreover, to reduce the misconnection due to the tracing orders, a multilevel tracing strategy is proposed. The fibrous network is finally reconstructed by dilating single fibers according to the DT values. Based on the traced single fibers, various morphology information regarding fiber length, radius, orientation, and tortuosity are quantitatively analyzed and compared with our previous results (Wang et al., 2013). Moreover, the number of bonds per fibers are firstly accessed. The methodology described in this paper can be expanded to other fibrous materials with adapted parameters. Keywords: Fiber tracing, Skeleton, Morphology analysis

Objective. Critical limb ischemia (CLI) is the most dangerous stage of peripheral artery disease (PAD). Many basic researches and clinical treatment had been focused on stem cell transplantation for CLI. This systematic review was performed to review evidence for safety and efficacy of autologous stem cell therapy in CLI. Methods. A systematic literature search was performed in the SinoMed, PubMed, Embase, ClinicalTrials.gov, and Cochrane Controlled Trials Register databases from building database to January 2018. Results. Meta-analysis showed that cell therapy significantly increased the probability of ulcer healing (RR = 1.73, 95% CI = 1.45–2.06), angiogenesis (RR = 5.91, 95% CI = 2.49–14.02), and reduced the amputation rates (RR = 0.59, 95% CI = 0.46–0.76). Ankle-brachial index (ABI) (MD = 0.13, 95% CI = 0.11–0.15), TcO2 (MD = 12.22, 95% CI = 5.03–19.41), and pain-free walking distance (MD = 144.84, 95% CI = 53.03–236.66) were significantly better in the cell therapy group than in the control group (P

Understanding naturally acquired immunity to infections caused by Plasmodia in different malaria endemicity settings is needed for better vaccine designs and for exploring antibody responses as a proxy marker of malaria transmission intensity. This study investigated the sero-epidemiology of malaria along the international border between China and Myanmar, where malaria elimination action plans are in place. This study recruited 233 P. vivax and 156 P. falciparum infected subjects with acute malaria at the malaria clinics and hospitals. In addition, 93 and 67 healthy individuals from the same endemic region or from non-endemic region, respectively, were used as controls. Acute malaria infections were identified by microscopy. Anti-recombinant PfMSP119 and PvMSP119 antibody levels were measured by ELISA. Antibody responses to respective MSP119 were detected in 50.9% and 78.2% patients with acute P. vivax and P. falciparum infections, respectively. There were cross-reacting antibodies in Plasmodium patients against these two recombinant proteins, though we could not exclude the possibility of submicroscopic mixed-species infections. IgG1, IgG3 and IgG4 were the major subclasses. Interestingly, 43.2% of the healthy endemic population also had antibodies against PfMSP119, whereas only 3.9% of this population had antibodies against PvMSP119. Higher antibody levels were correlated with age and parasite density, but not with season, gender or malaria history. Both total IgG and individual IgG subclasses underwent substantial declines during the convalescent period in three months. This study demonstrated that individuals in a hypoendemic area with coexistence of P. vivax and P. falciparum can mount rapid antibody responses against both PfMSP119 and PvMSP119. The significantly higher proportion of responders to PfMSP119 in the healthy endemic population indicates higher prevalence of P. falciparum in the recent past. Specific antibodies against PvMSP119 could serve as a marker of recent exposure to P. vivax in epidemiological studies.

A dual-motor coupling-propulsion electric bus (DMCPEB) is modeled, and its optimal control strategy is studied in this paper. The necessary dynamic features of energy loss for subsystems is modeled. Dynamic programming (DP) technique is applied to find the optimal control strategy including upshift threshold, downshift threshold, and power split ratio between the main motor and auxiliary motor. Improved control rules are extracted from the DP-based control solution, forming near-optimal control strategies. Simulation results demonstrate that a significant improvement in reducing energy loss due to the dual-motor coupling-propulsion system (DMCPS) running is realized without increasing the frequency of the mode switch.