Diabetic retinopathy (DR) is a chronic eye condition that is rapidly growing due to the prevalence of diabetes. There are challenges such as the dearth of ophthalmologists, healthcare resources, and facilities that are unable to provide patients with appropriate eye screening services. As a result, deep learning (DL) has the potential to play a critical role as a powerful automated diagnostic tool in the field of ophthalmology, particularly in the early detection of DR when compared to traditional detection techniques. The DL models are known as black boxes, despite the fact that they are widely adopted. They make no attempt to explain how the model learns representations or why it makes a particular prediction. Due to the black box design architecture, DL methods make it difficult for intended end-users like ophthalmologists to grasp how the models function, preventing model acceptance for clinical usage. Recently, several studies on the interpretability of DL methods used in DR-related tasks such as DR classification and segmentation have been published. The goal of this paper is to provide a detailed overview of interpretability strategies used in DR-related tasks. This paper also includes the authors' insights and future directions in the field of DR to help the research community overcome research problems.
In the study, we evaluated chemical composition and antimicrobial, antibiofilm, and antitumor activities of essential oils from dried leaf essential oil of leaf and flower of Agastache rugosa for the first time. Essential oil of leaf and flower was evaluated with GC and GC-MS methods, and the essential oil of flower revealed the presence of 21 components, whose major compounds were pulegone (34.1%), estragole (29.5%), and p-Menthan-3-one (19.2%). 26 components from essential oil of leaf were identified, the major compounds were p-Menthan-3-one (48.8%) and estragole (20.8%). At the same time, essential oil of leaf, there is a very effective antimicrobial activity with MIC ranging from 9.4 to 42 μg ml(-1) and potential antibiofilm, antitumor activities for essential oils of flower and leaf essential oil of leaf. The study highlighted the diversity in two different parts of A. rugosa grown in Xinjiang region and other places, which have different active constituents. Our results showed that this native plant may be a good candidate for further biological and pharmacological investigations.
DNA strand displacement technique is widely used in DNA programming, DNA biosensors, and gene analysis. In DNA strand displacement, leaky reactions can cause DNA signals decay and detecting DNA signals fails. The mostly used method to avoid leakage is cleaning up after upstream leaky reactions, and it remains a challenge to develop reliable DNA strand displacement technique with low leakage. In this work, we address the challenge by experimentally evaluating the basic factors, including reaction time, ratio of reactants, and ion concentration to the leakage in DNA strand displacement. Specifically, fluorescent probes and a hairpin structure reporting DNA strand are designed to detect the output of DNA strand displacement, and thus can evaluate the leakage of DNA strand displacement reactions with different reaction time, ratios of reactants, and ion concentrations. From the obtained data, mathematical models for evaluating leakage are achieved by curve derivation. As a result, it is obtained that long time incubation, high concentration of fuel strand, and inappropriate amount of ion concentration can weaken leaky reactions. This contributes to a method to set proper reaction conditions to reduce leakage in DNA strand displacement.
Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in breast cancer. The major snag faced by the human population is the development of chemoresistance to HER2 inhibitors by advanced stage breast cancer cells. Moreover, recent researchers focussed on fisetin as an antiproliferative and chemotherapeutic agent. Therefore, this study was intended to analyze the effects of fisetin on HER2/neu-overexpressing breast cancer cell lines. Our results depicted that fisetin induced apoptosis of these cells by various mechanisms, such as inactivation of the receptor, induction of proteasomal degradation, decreasing its half-life, decreasing enolase phosphorylation, and alteration of phosphatidylinositol 3-kinase/Akt signaling.
BACKGROUND: Allergy to latex-containing articles is becoming more and more important because it can result in unexpected life-threatening anaphylactic reactions in sensitized individuals.
METHODS: A protein of 58 kd with an isoelectric point of 8.45 was purified from raw latex and from latex gloves and identified as the major allergen, completely blocking specific IgE antibodies in the serum of latex-sensitized subjects. The allergen is a noncovalent homotetramer molecule, in which the 14.6 kd monomer was identified, by amino acid composition and sequence homologies of tryptic peptides, to be the rubber elongation factor found in natural latex of the Malaysian rubber tree.
RESULTS: Competitive immunoinhibition tests showed that the starch powder covering the finished gloves is the airborne carrier of the allergen, resulting in bronchial asthma on inhalation. The purified allergen can induce allergic reactions in the nanogram range.
CONCLUSION: The identification of the allergen (Hev b I) may help to eliminate it during the production of latex-based articles in the future.
The cladded conductor is broadly utilized in engineering fields, such as aerospace, energy, and petrochemical; however, it is vulnerable to thickness loss occurring in the clad layer and nonconductive protection coating due to abrasive and corrosive environments. Such a flaw severely undermines the integrity and safety of the mechanical structures. Therefore, evaluating the thickness loss hidden inside cladded conductors via reliable nondestructive evaluation techniques is imperative. This paper intensively investigates the pulse-modulation eddy current technique (PMEC) for the assessment of thickness loss in a cladded conductor. An analytical model of the ferrite-cored probe is established for analyzing PMEC signals and characteristics of lift-off intersection (LOI) in testing signals. Experiments are conducted for evaluation of the thickness loss in cladded conductors. An inverse scheme based on LOI for estimation of the thickness-loss depth is proposed and further verified. Through simulations and experiments, it is found that the influences of the thickness loss in the clad layer and protective coating on the PMEC signals can be decoupled in virtue of the LOI characteristics. Based on LOI, the hidden thickness loss can be efficiently evaluated without much of a reduction in accuracy by using the PMEC probe for dedicated inspection of the cladded conductor.
The tiger frog Hoplobatrachus rugulosus (Wiegmann 1834) is a large robust dicroglossid frog widely distributed in southern China, Malaysia, Myanmar, Vietnam and Thailand. The escaped bred tiger frog introduced from Thailand hybridized with Chinese native population may have affected the genetic diversity of local Chinese tiger frogs. However, previous microsatellite loci of this species do not offer enough information to construct the genetic map. Here, we reported 33 new microsatellite loci from transcriptome sequencing for H. rugulosus. Alleles ranged between 1 and 10 per locus and only one locus (HRT001) was monomorphic. The polymorphic information content, observed and expected heterozygosity were 0-0.794, 0-0.969 and 0-0.831, respectively. None of the loci was observed in linkage disequilibrium and two loci (HRT023 and HRT068) deviated from Hardy-Weinberg equilibrium after Bonferroni correction for multiple tests. These transcriptome-derived microsatellite markers will be usedto study the genetic divergence and construct the genetic map in H. rugulosus.
Inertial measurement unit (IMU)-based joint angle estimation is an increasingly mature technique that has a broad range of applications in clinics, biomechanics and robotics. However, the deviations of different IMUs' reference frames, referring to IMUs' individual orientations estimating errors, is still a challenge for improving the angle estimation accuracy due to conceptual confusion, relatively simple metrics and the lack of systematical investigation. In this paper, we clarify the determination of reference frame unification, experimentally study the time-varying characteristics of reference frames' deviations and accordingly propose a novel method with a comprehensive metric to unify reference frames. To be specific, we firstly define the reference frame unification (RFU) and distinguish it with drift correction that has always been confused with the term RFU. Secondly, we design a mechanical gimbal-based experiment to study the deviations, where sensor-to-body alignment and rotation-caused differences of orientations are excluded. Thirdly, based on the findings of the experiment, we propose a novel method to utilize the consistency of the joint axis under the hinge-joint constraint, gravity acceleration and local magnetic field to comprehensively unify reference frames, which meets the nonlinear time-varying characteristics of the deviations. The results on ten human subjects reveal the feasibility of our proposed method and the improvement from previous methods. This work contributes to a relatively new perspective of considering and improving the accuracy of IMU-based joint angle estimation.
This study aims to solve the overfitting problem caused by insufficient labeled images in the automatic image annotation field. We propose a transfer learning model called CNN-2L that incorporates the label localization strategy described in this study. The model consists of an InceptionV3 network pretrained on the ImageNet dataset and a label localization algorithm. First, the pretrained InceptionV3 network extracts features from the target dataset that are used to train a specific classifier and fine-tune the entire network to obtain an optimal model. Then, the obtained model is used to derive the probabilities of the predicted labels. For this purpose, we introduce a squeeze and excitation (SE) module into the network architecture that augments the useful feature information, inhibits useless feature information, and conducts feature reweighting. Next, we perform label localization to obtain the label probabilities and determine the final label set for each image. During this process, the number of labels must be determined. The optimal K value is obtained experimentally and used to determine the number of predicted labels, thereby solving the empty label set problem that occurs when the predicted label values of images are below a fixed threshold. Experiments on the Corel5k multilabel image dataset verify that CNN-2L improves the labeling precision by 18% and 15% compared with the traditional multiple-Bernoulli relevance model (MBRM) and joint equal contribution (JEC) algorithms, respectively, and it improves the recall by 6% compared with JEC. Additionally, it improves the precision by 20% and 11% compared with the deep learning methods Weight-KNN and adaptive hypergraph learning (AHL), respectively. Although CNN-2L fails to improve the recall compared with the semantic extension model (SEM), it improves the comprehensive index of the F1 value by 1%. The experimental results reveal that the proposed transfer learning model based on a label localization strategy is effective for automatic image annotation and substantially boosts the multilabel image annotation performance.
A nuclear export signal (NES) is a protein localization signal, which is involved in binding of cargo proteins to nuclear export receptor, thus contributes to regulate localization of cellular proteins. Consensus sequences of NES have been used to detect NES from protein sequences, but suffer from poor predictive power. Some recent peering works were proposed to use biochemical properties of experimental verified NES to refine NES candidates. Those methods can achieve high prediction rates, but their execution time will become unacceptable for large-scale NES searching if too much properties are involved. In this work, we developed a novel computational approach, named NES-REBS, to search NES from protein sequences, where biochemical properties of experimental verified NES, including secondary structure and surface accessibility, are utilized to refine NES candidates obtained by matching popular consensus sequences. We test our method by searching 262 experimental verified NES from 221 NES-containing protein sequences. It is obtained that NES-REBS runs in 2-3[Formula: see text]mins and performs well by achieving precision rate 47.2% and sensitivity 54.6%.
A caustic vector vortex optical field is experimentally generated and demonstrated by a caustic-based approach. The desired caustic with arbitrary acceleration trajectories, as well as the structured states of polarization (SoP) and vortex orders located in different positions in the field cross-section, is generated by imposing the corresponding spatial phase function in a vector vortex optical field. Our study reveals that different spin and orbital angular momentum flux distributions (including opposite directions) in different positions in the cross-section of a caustic vector vortex optical field can be dynamically managed during propagation by intentionally choosing the initial polarization and vortex topological charges, as a result of the modulation of the caustic phase. We find that the SoP in the field cross-section rotates during propagation due to the existence of the vortex. The unique structured feature of the caustic vector vortex optical field opens the possibility of multi-manipulation of optical angular momentum fluxes and SoP, leading to more complex manipulation of the optical field scenarios. Thus this approach further expands the functionality of an optical system.
Wilson's disease (WD), also known as hepatoleticular degeneration (HLD), is a rare autosomal recessive genetic disorder of copper metabolism, which causes copper to accumulate in body tissues. In this study, rats fed with copper-laden diet are used to render the clinical manifestations of WD, and their copper toxicity-induced organ lesions are studied. To investigate metabolic behaviors of 'decoppering' process, penicillamine (PA) was used for treating copper-laden rats as this chelating agent could eliminate excess copper through the urine. To date, there has been limited metabolomics study on WD, while metabolic impacts of copper accumulation and PA administration have yet to be established.
Wolbachia pipientis is a diverse, ubiquitous and most prevalent intracellular bacterial group of alpha-Proteobacteria that is concerned with many biological processes in arthropods. The coconut hispine beetle (CHB), Brontispa longissima (Gestro) is an economically important pest of palm cultivation worldwide. In the present study, we comprehensively surveyed the Wolbachia-infection prevalence and mitochondrial DNA (mtDNA) polymorphism in CHB from five different geographical locations, including China's Mainland and Taiwan, Vietnam, Thailand, Malaysia and Indonesia. A total of 540 sequences were screened in this study through three different genes, i.e., cytochrome oxidase subunit I (COI), Wolbachia outer surface protein (wsp) and multilocus sequencing type (MLST) genes. The COI genetic divergence ranges from 0.08% to 0.67%, and likewise, a significant genetic diversity (π = 0.00082; P = 0.049) was noted within and between all analyzed samples. In the meantime, ten different haplotypes (H) were characterized (haplotype diversity = 0.4379) from 21 different locations, and among them, H6 (46 individuals) have shown a maximum number of population clusters than others. Subsequently, Wolbachia-prevalence results indicated that all tested specimens of CHB were found positive (100%), which suggested that CHB was naturally infected with Wolbachia. Wolbachia sequence results (wsp gene) revealed a high level of nucleotide diversity (π = 0.00047) under Tajima's D test (P = 0.049). Meanwhile, the same trend of nucleotide diversity (π = 0.00041) was observed in Wolbachia concatenated MLST locus. Furthermore, phylogenetic analysis (wsp and concatenated MLST genes) revealed that all collected samples of CHB attributed to same Wolbachia B-supergroup. Our results strongly suggest that Wolbachia bacteria and mtDNA were highly concordant with each other and Wolbachia can affect the genetic structure and diversity within the CHB populations.
Impacts of climate change on the hydrologic processes under future climate change conditions were assessed over Muda and Dungun watersheds of Peninsular Malaysia by means of a coupled regional climate and physically-based hydrology model utilizing an ensemble of future climate change projections. An ensemble of 15 different future climate realizations from coarse resolution global climate models' (GCMs) projections for the 21st century was dynamically downscaled to 6km resolution over Peninsular Malaysia by a regional climate model, which was then coupled with the watershed hydrology model WEHY through the atmospheric boundary layer over Muda and Dungun watersheds. Hydrologic simulations were carried out at hourly increments and at hillslope-scale in order to assess the impacts of climate change on the water balances and flooding conditions in the 21st century. The coupled regional climate and hydrology model was simulated for a duration of 90years for each of the 15 realizations. It is demonstrated that the increase in mean monthly flows due to the impact of expected climate change during 2040-2100 is statistically significant from April to May and from July to October at Muda watershed. Also, the increase in mean monthly flows is shown to be significant in November during 2030-2070 and from November to December during 2070-2100 at Dungun watershed. In other words, the impact of the expected climate change will be significant during the northeast and southwest monsoon seasons at Muda watershed and during the northeast monsoon season at Dungun watershed. Furthermore, the flood frequency analyses for both watersheds indicated an overall increasing trend in the second half of the 21st century.
BACKGROUND: Hepatic alveolar echinococcosis (HAE) is caused by the growth of Echinococcus multilocularis larvae in the liver. It is a chronic and potentially lethal parasitic disease. Early stage diagnosis for this disease is currently not available due to its long asymptomatic incubation period. In this study, a proton nuclear magnetic resonance (1H NMR)-based metabolomics approach was applied in conjunction with multivariate statistical analysis to investigate the altered metabolic profiles in blood serum and urine samples obtained from HAE patients. The aim of the study was to identify the metabolic signatures associated with HAE.
RESULTS: A total of 21 distinct metabolic differences between HAE patients and healthy individuals were identified, and they are associated with perturbations in amino acid metabolism, energy metabolism, glyoxylate and dicarboxylate metabolism. Furthermore, the present results showed that the Fischer ratio, which is the molar ratio of branched-chain amino acids to aromatic amino acids, was significantly lower (P
Phalaenopsis orchids, originally from tropical Asia, are mainly planted in Thailand, Singapore, Malaysia, the Philippines, and Taiwan and have gained popularity from consumers all over the world. The cultivation area of Phalaenopsis orchids has been rising and large-scale bases have been established in mainland China, especially South China because of suitable environmental conditions. In September 2011, a soft rot of Phalaenopsis aphrodita was found in a Phalaenopsis planting base in Guangzhou with an incidence of ~15%. Infected plants initially showed water-soaked, pale-to-dark brown pinpoint spots on leaves that were sometimes surrounded by a yellow halo. Spots expanded rapidly with rising humidity and temperatures, and in a few days, severely extended over the blade with a light tan color and darker brown border. Lesions decayed with odorous fumes and tissues collapsed with inclusions exuding. The bacterium advanced to the stem and pedicle. Finally, leaves became papery dry and the pedicles lodged. Six diseased samples were collected, and bacteria were isolated from the edge of symptomatic tissues after sterilization in 0.3% NaOCl for 10 min, rinsing in sterile water three times, and placing on nutrient agar for culture. Twelve representative isolates were selected for further characterization. All strains were gram negative, grew at 37°C, were positive for indole production, and utilized malonate, glucose, and sucrose but not glucopyranoside, trehalose, or palatinose. Biolog identification (version 4.20.05, Hayward, CA) was performed and Pectobacterium chrysanthemi (SIM 0.868) was confirmed for the tested isolates (transfer to genus Dickeya). PCR was used to amplify the 16S rDNAgene with primers 27f and 1492r, dnaX gene with primers dnaXf and dnaXr (3), and gyrB gene with primers gyrBf (5'-GAAGGYAAAVTKCATCGTCAGG-3') and gyrB-r1 (5'-TCARATATCRATATTCGCYGCTTTC-3') designed on the basis of the published gyrB gene sequences of genus Dickeya. BLASTn was performed online, and phylogeny trees (100% bootstrap values) were created by means of MEGA 5.05 for these gene sequences, respectively. Results commonly showed that the representative tested strain, PA1, was most homologous to Dickeya dieffenbachiae with 98% identity for 16S rDNA(JN940859), 97% for dnaX (JN989971), and 96% for gyrB (JN971031). Thus, we recommend calling this isolate D. dieffenbachiae PA1. Pathogenicity tests were conducted by injecting 10 P. aphrodita seedlings with 100 μl of the bacterial suspension (1 × 108 CFU/ml) and another 10 were injected with 100 μl of sterile water as controls. Plants were inoculated in a greenhouse at 28 to 32°C and 90% relative humidity. Soft rot symptoms were observed after 2 days on the inoculated plants, but not on the control ones. The bacterium was isolated from the lesions and demonstrated identity to the inoculated plant by the 16S rDNA sequence comparison. Previously, similar diseases of P. amabilis were reported in Tangshan, Jiangsu, Zhejiang, and Wuhan and causal agents were identified as Erwinia spp. (2), Pseudomonas grimontii (1), E. chrysanthemi, and E. carotovora subsp. carovora (4). To our knowledge, this is the first report of D. dieffenbachiae causing soft rot disease on P. aphrodita in China. References: (1) X. L. Chu and B. Yang. Acta Phytopathol. Sin. 40:90, 2010. (2) Y. M. Li et al. J. Beijing Agric. Coll. 19:41, 2004. (3) M. Sławiak et al. Eur. J. Plant Pathol. 125:245, 2009. (4) Z. Y. Wu et al. J. Zhejiang For. Coll. 27:635, 2010.
Hepatocellular carcinoma (HCC) is a leading cause of cancer death worldwide. Because of its high recurrence rate and heterogeneity, effective treatment for advanced stage of HCC is currently lacking. There are accumulating evidences showing the therapeutic potential of pharmacologic vitamin C (VC) on HCC. However, the metabolic basis underlying the anticancer property of VC remains to be elucidated. In this study, we used a high-resolution proton nuclear magnetic resonance-based metabolomics technique to assess the global metabolic changes in HCC cells following VC treatment. In addition, the HCC cells were also treated with oxaliplatin (OXA) to explore the potential synergistic effect induced by the combined VC and OXA treatment. The current metabolomics data suggested different mechanisms of OXA and VC in modulating cell growth and metabolism. In general, VC treatment led to inhibition of energy metabolism via NAD+ depletion and amino acid deprivation. On the other hand, OXA caused significant perturbation in phospholipid biosynthesis and phosphatidylcholine biosynthesis pathways. The current results highlighted glutathione metabolism, and pathways related to succinate and choline may play central roles in conferring the combined effect between OXA and VC. Taken together, this study provided metabolic evidence of VC and OXA in treating HCC and may contribute toward the potential application of combined VC and OXA as complementary HCC therapies.
Fluxes and composition dynamics of atmospheric nitrogen deposition play key roles in better balancing economic development and ecological environment. However, there are some knowledge gaps and difficulties in urban ecosystems, especially for small and medium-sized cities. In this study, both flux and composition (ratio of NH4+-N to NO3--N, RN) of wet-deposited dissolved inorganic nitrogen (DIN, sum of NO3--N and NH4+-N) were estimated and sources were identified at a long-term urban observation station in Tongling, a typical medium-sized city in eastern China during 2010-2016, respectively. Results showed that wet-deposited DIN fluxes were 33.20 and 28.15 kgN ha-1 yr-1 in Tongling city during 2010-2011 and 2015-2016, respectively. Compared to these two periods, both DIN and NO3--N fluxes decreased by 15.2% and 31.8% for a series of NOx abatement measures applied effectively, respectively. At the same time, the NH4+-N flux remained stable and ranged from 19.53 to 20.62 kgN ha-1 yr-1, and the RN increased from 1.7 to 2.2. Seasonally, winds from the southwest and west-southwest with higher frequencies and speeds in spring and summer brought more NH4+-N and DIN wet deposition from an ammonia plant, which could threaten the safety of regional hydrosphere ecosystems. On the whole, the wet-deposited NH4+-N was threatening regional ecosystems of both the hydrosphere and forest. The wet-deposited DIN including NH4+-N in Tongling city stemmed mainly from a combined source of coal combustion and dust from Cu extraction and smelting, ammonia production, and roads. Therefore, production lines should be updated for Cu extraction and smelting industries, thermal power generations and the ammonia plant, old vehicles should be eliminated, and the use of new energy vehicles should be promoted for regional sustainable development and human health in the medium-sized city.
Real-time and visual monitoring of pollutants in the air is of great importance since they are usually cannot be seen, smelled, or touched. Lanthanide nano-cluster is a kind of luminescent sensor for various species. However, controlling synthesis of lanthanide nano-cluster remains experimentally challenging. In this work, four series of lanthanide-barium (Ln-Ba) nano-clusters of Dy2Ba (1), Tb2Ba2 (2), Ln4Ba3 (Ln = Tb, 3a; Eu, 3b), Tb4Ba4 (4) were assembled through precisely controlling the pH of the reactant solutions. The work features the first example that the number of cluster's nuclei changes regularly with the pH. Moreover, investigation reveals that nano-cluster 3a is a highly selective and sensitive sensor towards acetylacetone (acac) and aniline. Interestingly, easy-to-use sensing devices of test paper, agarose gel, and five kinds of film on CaCO3, polyfoam, coin, mask, and wall that based on 3a were fabricated by facile methods. The seven sensing devices showed remarkable ability to sense aniline and acac vapors with visibility to the naked eyes. This is the first work on multiple real-time and visual sensing devices based on the lanthanide nano-cluster.
In this study, three soil amendments (inorganic, liming, or organic-inorganic materials) were used in a Cd-contaminated purple field soil to investigate their impacts on soil Cd availability, enzyme (urease, catalase, sucrase, and acid phosphatase) activities, microbial biomass (carbon/nitrogen) and type (bacteria, fungi, and actinomycetes) in mustard and corn trials. Results showed that soil amendments generally decreased soil exchangeable Cd, fungi and bacterial populations while increasing the activities of all the four soil enzymes tested, microbial biomass carbon and populations of actinomycetes (p 0.05) whereas stronger effects appeared in soil organic matter and available nutrients (nitrogen, phosphorous and potassium; p