Reconstruction of gene regulatory networks for Caenorhabditis elegans using tree-shaped gene expression data.

Constructing gene regulatory networks is a widely adopted approach for investigating gene regulation, offering diverse applications in biology and medicine. A great deal of research focuses on using time series data or single-cell RNA-sequencing data to infer gene regulatory networks. However, such gene expression data lack either cellular or temporal information. Fortunately, the advent of time-lapse confocal laser microscopy enables biologists to obtain tree-shaped gene expression data of Caenorhabditis elegans, achieving both cellular and temporal resolution. Although such tree-shaped data provide abundant knowledge, they pose challenges like non-pairwise time series, laying the inaccuracy of downstream analysis. To address this issue, a comprehensive framework for data integration and a novel Bayesian approach based on Boolean network with time delay are proposed. The pre-screening process and Markov Chain Monte Carlo algorithm are applied to obtain the parameter estimates. Simulation studies show that our method outperforms existing Boolean network inference algorithms. Leveraging the proposed approach, gene regulatory networks for five subtrees are reconstructed based on the real tree-shaped datatsets of Caenorhabditis elegans, where some gene regulatory relationships confirmed in previous genetic studies are recovered. Also, heterogeneity of regulatory relationships in different cell lineage subtrees is detected. Furthermore, the exploration of potential gene regulatory relationships that bear importance in human diseases is undertaken. All source code is available at the GitHub repository https://github.com/edawu11/BBTD.git.

Biclustering analysis on tree-shaped time-series single cell gene expression data of Caenorhabditis elegans.

BACKGROUND: In recent years, gene clustering analysis has become a widely used tool for studying gene functions, efficiently categorizing genes with similar expression patterns to aid in identifying gene functions. Caenorhabditis elegans is commonly used in embryonic research due to its consistent cell lineage from fertilized egg to adulthood. Biologists use 4D confocal imaging to observe gene expression dynamics at the single-cell level. However, on one hand, the observed tree-shaped time-series datasets have characteristics such as non-pairwise data points between different individuals. On the other hand, the influence of cell type heterogeneity should also be considered during clustering, aiming to obtain more biologically significant clustering results. RESULTS: A biclustering model is proposed for tree-shaped single-cell gene expression data of Caenorhabditis elegans. Detailedly, a tree-shaped piecewise polynomial function is first employed to fit non-pairwise gene expression time series data. Then, four factors are considered in the objective function, including Pearson correlation coefficients capturing gene correlations, p-values from the Kolmogorov-Smirnov test measuring the similarity between cells, as well as gene expression size and bicluster overlapping size. After that, Genetic Algorithm is utilized to optimize the function. CONCLUSION: The results on the small-scale dataset analysis validate the feasibility and effectiveness of our model and are superior to existing classical biclustering models. Besides, gene enrichment analysis is employed to assess the results on the complete real dataset analysis, confirming that the discovered biclustering results hold significant biological relevance.

Conjugated Porous Organic Polymers Featuring Both Soft-Hard Combined Coordination Sites and Photoelectrochemical Properties for Palladium Capture and Subsequent Photocatalysis.

Palladium (Pd) capture from high-level liquid waste for subsequent photocatalytic applications is desirable for the development of nuclear energy and the reutilization of valuable resources. Herein, we approach our design with a unique porous organic polymer containing thiazolo[5,4-d]thiazole units (denoted as TzPOP-OH). It possesses two potential soft-hard (N-O and S-O) combined coordination sites for Pd(II) coordination and features strong donor-acceptor repeating units and high planarity of linkage enforced by hydrogen bonds for subsequent photocatalysis. Accordingly, TzPOP-OH with three hydroxyl groups on the linkage exhibits a high Pd(II) capacity of 369 mg g-1 at 3 M HNO3, considerably surpassing those of the controlled polymer TzPOP without hydroxyl groups and most other reported materials. Additionally, TzPOP-OH boasts other merits, including outstanding acid tolerance, extraordinary radiation stability, good reusability, and remarkable selectivity. After palladium adsorption, Pd@TzPOP-OH demonstrates impressive photodegradation efficiency to reduce the concentration of rhodamine B in contaminated urban water from 10 to less than 0.1 ppm. This work provides a feasible approach to designing materials with both suitable coordination microenvironments and semiconductor properties for metal separation and photocatalysis.

Ultrasound-aided diagnosis of preclinical phases of psoriatic arthritis in biologic-naïve psoriasis patients with or without arthralgia.

OBJECTIVES: The evolution of psoriasis (PsO) to psoriatic arthritis (PsA) has been proposed recently. There are three phases that occur in sequence prior to classifiable PsA: PsO patients, PsO patients with a positive imaging, and PsO patients with arthralgia not explained by other diagnosis. The purpose of this study was to compare the differences among preclinical phases using ultrasound and clinical assessment. METHODS: Patients with psoriasis were recruited. Patients who had been previously diagnosed with psoriatic arthritis or who had used biologics were excluded. A 52-joint ultrasound (52j US) assessment and clinical assessments including the swollen joint count, tender joint count, erythrocyte sediment rate, C-reactive protein, dactylitis score, enthesitis score, psoriasis severity, and nail psoriasis severity, were performed. RESULTS: A total of 188 eligible psoriasis patients were enrolled. Physical examination revealed 39 patients (20%) with at least one swollen joint. The 52j US assessment demonstrated 90 patients (47%) having at least one joint with grey-scale score 2-3. All patients were further stratified into PsO patients (n=58), PsO patients with a positive imaging, (n=59), PsO patients with arthralgia not explained by other diagnosis (n=27), and classifiable PsA (n=39). There were no differences in clinical characteristics other than tender joint count found among the three preclinical phases of PsA. Dactylitis score, swollen joint count and heatly assessment questionnaire score were significantly higher in classifiable PsA. CONCLUSIONS: Nearly half of the psoriasis patients without previously diagnosed psoriatic arthritis would be classified into the preclinical phases of psoriatic arthritis based on the 52j US and clinical assessments. Ultrasound assessment is helpful for identifying psoriasis patients who are in the preclinical phases of psoriatic arthritis, particularly for those without arthralgia.

Metal-Organic Framework Surface Functionalization Enhancing the Activity and Stability of Palladium Nanoparticles for Carbon-Halogen Bond Activation.

Supported metal nanocatalyst is one of the efficient tools for organic transformations. However, catalyst deactivation caused by the migration, aggregation, and leaching of active metal species in the reaction process remains challenging. Herein, a metal-organic framework (MOF), MIL-101, was employed to covalently graft the PPh3 ligand on its surface and then supported palladium nanoparticles (Pd NPs), affording Pd/MIL-101-PPh3. A variety of spectral characterizations and DFT calculation reveal that there is an electron-donating effect of the MOF surface PPh3 toward Pd NPs, which markedly boosts the activation of the carbon-halogen bond in aryl halides. Consequently, Pd/MIL-101-PPh3 exhibits excellent activity for the three-component reaction of 2-iodoaniline, CO2, and isocyanide, as well as Suzuki-Miyaura and Heck coupling reactions, far exceeding amino-functionalized Pd/MIL-101-NH2, naked Pd/MIL-101, and other commercial-supported Pd catalysts. Furthermore, Pd/MIL-101-PPh3 can also frustrate the migration, aggregation, and leaching of reactive Pd species in the reaction process due to the molecular fence effect generated by MOF surface functionalization.

Application of Different Animal Fats as Solvents to Extract Carotenoids and Capsaicinoids from Sichuan Chili.

Inspired by the proved dissolving power of vegetable oils for non-polar and low-polar natural compounds, animal fats with triglycerides as the major components were investigated as food-grade solvents in this study for the simultaneous extraction of carotenoids and capsaicinoids from Sichuan chili. The dissolving power of lard, beef tallow, chicken fat and basa fish oil in the extraction of er jing tiao chili was firstly compared, where animal oils with worse extraction ratios for carotenoids (0.79 mg/g in average) performed better for the extraction of capsaicinoids (0.65 mg/g in average). Furthermore, the solvent effect of animal fats on the oleo-extracts was evaluated in terms of fatty acid composition, oil quality indexes, crystal polymorphism, melting and crystallization behaviors, where no significant differences were observed between animal fats before and after extraction. The oxidative stability of animal fats could be 1.02- up to 2.73-fold enhanced after extraction and the pungency degree could reach the same spicy level as commercial hotpot oil. In addition, the Hansen solubility parameters of solvents and solutes were predicted for further theoretical miscibility study, which helps to make a better comprehension of the dissolving mechanism behind such oleo-extraction. Overall, animal fats demonstrated their considerable solvent power for extracting carotenoids and capsaicinoids simultaneously from Sichuan chili, which showed significant potential for developing a novel Sichuan spicy hotpot oil with enhanced flavor and stability.

Investigation of the quality of Lu'an Guapian tea during Grain Rain period by sensory evaluation, objective quantitative indexes and metabolomics.

The harvest date is a crucial factor in determining tea quality. For Lu'an Guapian (LAGP) tea, Grain Rain period (GRP) represents a pivotal phase in the transformation of tea quality. The sensory evaluation, computer vision and E-tongue revealed that the liquor color score, B and G values of tea infusion were increased during GRP, while the astringency, bitterness intensities and the R value of the tea infusion were decreased. Consequently, the tea infusion exhibited a greener hue and the taste became appropriate during GRP. Non-targeted metabolomics revealed that the majority of amino acids and derivatives was reduced during GRP. Furthermore, flavonoids, in particular flavonol glycosides, exhibited considerable variation during GRP. Finally, nine metabolites were identified as markers for quality transformation during GRP by PLS and Random Forest. This study investigated the quality of LAGP teas during GRP and filled the gap in the variation of LAGP tea quality during GRP.

Exploring microbial and moist-heat effects on Pu-erh tea volatiles and understanding the methoxybenzene formation mechanism using molecular sensory science.

Piling fermentation (PF) is crucial for Pu-erh tea aroma, yet its microbial and moist-heat impact on aroma quality is poorly understood. Solid-phase microextraction, solvent-assisted flavor evaporation, and gas chromatography-mass spectrometry were used to detected and analyses the samples of sun-green green tea, sterile PF and spontaneous PF. Microbiological action promotes the formation of stale aromas. Moist-heat action promotes the formation of plum-fragrance and sweet aroma. 20 microbial markers and 28 moist-heat markers were screened from 184 volatile components. Combining odor activity values and gas chromatography-olfactometry, 22 aroma-active compounds were screened (1,2,3-trimethoxybenzene, linalool, 1,2,4-trimethoxybenzene …), and analyzed during PF processing. Aroma omission and addition experiments verified its importance. Gallic acid addition experiments successfully verified that microorganisms are the main contributors to the synthesis of methoxybenzenes. Finally, Blastobotrys, Rasamsonia, and Thermomyces showed positive correlation with the synthesis of 1-ethyl-4-methoxybenzene, 1,2,4-trimethoxybenzene, 1,2,3-trimethoxybenzene, and 1,2-dimethoxybenzene. The formation mechanism of Pu-erh tea's aroma was clarified. Exploring microbial and moist-heat effects on Pu-erh tea volatiles and understanding the methoxybenzene formation mechanism using molecular sensory science.

Fatty acid degradation driven by heat during ripening contributes to the formation of the "Keemun aroma".

Ripening refers to the process of chemical change during the refinement of Keemun black tea (KBT) and is crucial in the formation of Keemun Congou black tea's quality. In this study, the aroma composition of KBT during the ripening was analyzed. Sensomics indicated that ripening strengthened the coconut and fatty aroma of KBT and contributed to the decrease of green aroma substances, resulting in a shift of the overall aroma type of KBT to an integrated aroma profile, which was consistent with sensory evaluation. Changes in fatty acid content and the results of in vitro addition simulation tests confirmed that heat causes highly degradation of fatty acids into fatty aroma volatiles, which is a key driver of the formation of "Keemun aroma" quality. This study revealed the mechanism behind the formation of KBT's integrated "Keemun aroma" quality and the mode of thermal degradation of major fatty acids.

Multi-Chemical Omics Analysis of the Symbiodiniaceae Durusdinium trenchii under Heat Stress.

The urgency of responding to climate change for corals necessitates the exploration of innovative methods to swiftly enhance our understanding of crucial processes. In this study, we employ an integrated chemical omics approach, combining elementomics, metabolomics, and volatilomics methodologies to unravel the biochemical pathways associated with the thermal response of the coral symbiont, Symbiodiniaceae Durusdinium trenchii. We outline the complimentary sampling approaches and discuss the standardised data corrections used to allow data integration and comparability. Our findings highlight the efficacy of individual methods in discerning differences in the biochemical response of D. trenchii under both control and stress-inducing temperatures. However, a deeper insight emerges when these methods are integrated, offering a more comprehensive understanding, particularly regarding oxidative stress pathways. Employing correlation network analysis enhanced the interpretation of volatile data, shedding light on the potential metabolic origins of volatiles with undescribed functions and presenting promising candidates for further exploration. Elementomics proves to be less straightforward to integrate, likely due to no net change in elements but rather elements being repurposed across compounds. The independent and integrated data from this study informs future omic profiling studies and recommends candidates for targeted research beyond Symbiodiniaceae biology. This study highlights the pivotal role of omic integration in advancing our knowledge, addressing critical gaps, and guiding future research directions in the context of climate change and coral reef preservation.

The enhancement of flowery-like aroma in green tea under optimized processing conditions by sensory-directed flavor analysis.

Flowery-like aroma are positive contributors to green tea. Here, the optimal processing conditions for green tea with flowery-like aroma were designed using spreading time, fixation time and drying temperature as three factors designed by response surface methodology (RSM), and the response value of aroma sensory evaluation score. The volatiles in batches of tea samples were analyzed by GC-MS. The optimal quality was obtained with a flowery-like aroma by RSM under a spreading time of 8.97 h, fixation time of 162.3 s, and drying temperature of 103.32 °C. GC-O and odor activity values further revealed floral-like volatiles, including decanal, linalool oxide, ß-lonone, geraniol, (Z)-jasmone, linalool, nonanal, and benzeneacetaldehyde. The recombination of these floral volatiles confirmed the consistency with the floral green tea. Furthermore, the extending spreading duration (8-10 h), reducing fixation duration (160-190 s), and increasing drying temperature (100-115 °C) promote their accumulation in green tea. This study provides new perspectives for the precise enhancement of floral odorants for green tea.

Investigation of the aroma profile and blending strategy of Lu'an Guapian teas during grain rain period by sensory evaluation combined with SBSE-GC-MS, GC-O and OAV.

Grain Rain Period (GRP), one of the 24 solar terms in China, signifies a crucial phase for the transformation of tea quality, especially for Lu'an Guapian (LAGP) tea. During GRP, LAGP teas showed 3 distinct aroma profiles, each spanning 3-4 days. Specifically, the sensory evaluation result revealed that LAGP tea exhibited stronger flowery and fresh aromas in the early phase, with the soybean-like aroma significantly intensifying as the harvest period progressed during GRP. Furthermore, the key contributors to the aroma profile and its variation during GRP were identified as indole, δ-decalactone, geraniol, linalool, decanal, jasmone, (E)-ß-ionone, benzeneacetaldehyde, dihydroactinolide, nonanal, octanal, (E)-isoeugenol, (E,E)-2,4-nonadienal, 4-ketoisophorone, (E,Z)-2,6-nonadienal, and 1-octen-3-one. Additionally, we proposed a binary blending strategy using sensory evaluation with the methods of triangle test and normal distribution fitting to predict the blending threshold accurately. This study elucidated the dynamics of LAGP tea aroma during GRP and offered insights for tea blending optimization.

Contribution of tea stems to large-leaf yellow tea aroma.

Large-leaf yellow tea (LYT) is processed from both leaves and stems, resulting in a distinctive rice crust-like aroma. Tea stems may contribute differently to the aroma of LYT than leaves. This study aimed to clarify the specific contribution of stems to LYT. The volatile compounds in different components of LYT were extracted and analyzed using a combination of headspace solid-phase microextraction and stir bar sorptive extraction coupled with gas chromatography-olfactory-mass spectrometry. The results revealed high concentrations of compounds with roasty attributes in stems such as 2-ethyl-3,5-dimethylpyrazine (OAV 153-208) and 2-ethyl-3,6-dimethylpyrazine (OAV 111-140). Aroma recombination and addition experiments confirmed that the roasty aroma provided by stems plays a pivotal role in the formation of the distinctive flavor of LYT. This study offers novel insights into the contribution of stems to the aroma of LYT, which can be used for processing and quality enhancement of roasted tea.

The role of ultrasound synovitis scores for patients who are at risk of rheumatoid arthritis.

OBJECTIVES: The development of rheumatoid arthritis (RA) has been classified into 6 phases A-F according to the present risk factors in sequence of genes, environments, autoimmunity, arthralgia and joint swelling. To clarify the ultrasound synovitis scores in at-risk patients (phases C-E) and RA (phase F). METHODS: Patients who had been experiencing hand joint symptoms for at least 6 weeks and asymptomatic patients with positive rheumatoid factor and/or anti-cyclic citrullinated peptide antibodies were enrolled. A 40-joint ultrasonography with semiquantitative synovitis scoring for gray scale (GS) and power Doppler (PD) images was performed. RESULTS: A total of 139 patients were enrolled and classified into non-RA, phase C, phase D, phase E and phase F. Total GS scores in phases C (17.4 ± 7.0), D (16.0 ± 5.4), E (18.5 ± 7.7) and F (21.8 ± 9.1) were higher than those in non-RA (9.8 ± 4.0, P < 0.001). The total PD score in phase F (3.1 ± 4.6) was higher than that in phases C (0.2 ± 0.5), D (0.1 ± 0.4), and E (0.1 ± 0.3), as well as in non-RA (0.0 ± 0.0, P < 0.01). A total GS score ≥14 differentiated patients at risk for RA from patients with non-RA (area under curve [AUC] 0.82), while a total PD score ≥2 differentiated patients with RA from patients at risk for RA (AUC 0.71). CONCLUSION: Total GS score may differentiate patients at risk for RA from non-RA patients, while total PD score may differentiate patients with RA from those who are at risk for RA.

The electronic medical record management systems may improve monitoring and control of disease activity in patients with ankylosing spondylitis.

To investigate the impact of an electronic medical record management system (EMRMS) on disease activity and the frequency of outpatient visits among patients with ankylosing spondylitis (AS). We identified 652 patients with AS who were followed up for at least 1 year before and after the first Ankylosing Spondylitis Disease Activity Score (ASDAS) assessment and compared the number of outpatient visits and average visit time within 1 year before and after the initial ASDAS assessment. Finally, we analyzed 201 patients with AS who had complete data and received ≥ 3 continuous ASDAS assessments at an interval of 3 months, and we compared the results of the second and third ASDAS assessments with those of the first. The number of annual outpatient visits increased after ASDAS assessment (4.0 (4.0, 7.0) vs. 4.0 (4.0, 8.0), p < 0.001), particularly among those with a high initial disease activity. The average visit time was reduced within 1 year after ASDAS assessment (6.4 (8.5, 11.2) vs. 6.3 (8.3, 10.8) min, p = 0.073), especially among patients whose with an inactive disease activity was < 1.3 (ASDAS C-reactive protein (CRP) 6.7 (8.8, 11.1) vs. 6.1 (8.0, 10.3) min, p = 0.033; ASDAS erythrocyte sedimentation rate (ESR) 6.4 (8.7, 11.1) vs. 6.1 (8.1, 10.0) min, p = 0.027). Among patients who received at least three ASDAS assessments, the third ASDAS-CRP tended to be lower than the first (1.5 (0.9, 2.1) vs. 1.4 (0.8, 1.9), p = 0.058). The use of an EMRMS increased the frequency of ambulatory visits among AS patients with high and very high disease activity and reduced the visit time among those with an inactive disease. Continual ASDAS assessments may help control the disease activity of patients with AS.

Mechanisms of Tumor Necrosis Factor-Alpha Inhibitor-Induced Systemic Lupus Erythematosus.

Systemic lupus erythematosus induced by biologics mainly results from tumor necrosis factor-alpha remains unclear. The objectives of the study were to investigate the mechanisms of tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus. Peripheral blood mononuclear cells obtained from thirteen psoriasis patients were cultured and treated with the following: untreated control, Streptococcus pyogenes with or without different biologics. The supernatants were collected for cytokines assay. Analysis of cytokine expression revealed that IL-2 and IL-10 levels decreased only in the TNF-α inhibitor-treated groups but not in the groups treated with biologics involving IL-17, IL-12/IL-23 or IL-23 inhibitor mechanisms (p < 0.001, p < 0.05). The IFN-γ/IL-13 ratio increased significantly in patients with SLE inducing biologics to S. pyogenes induction only compared with non-SLE inducing biologics to S. pyogenes induction only (p = 0.001). IL-2 and IL-10 depletion and a shift to the Th-1 pathway in the innate response are the correlated mechanism for tumor necrosis factor-alpha inhibitor-induced systemic lupus erythematosus.

Atomevo: a web server combining protein modelling, docking, molecular dynamic simulation and MMPBSA analysis of Candida antarctica lipase B (CalB) fusion protein.

Although current computational biology software is available and has prompted the development of enzyme-substrates simulation, they are difficult to install and inconvenient to use. This makes the time-consuming and error-prone process. By far there is still a lack of a complete tool which can provide a one-stop service for the enzyme-substrates simulation process. Hence, in this study, several computational biology software was extended development and integrated as a website toolbox named Atomevo. The Atomevo is a free web server providing a user-friendly interface for enzyme-substrates simulation: (1) protein homologous modeling; (2) parallel docking module of Autodock Vina 1.2; (3) automatic modeling builder for Gromacs molecular dynamics simulation package; and (4) Molecular Mechanics/Poisson-Boltzmann Surface Area (MMPBSA) analysis module for receptor-ligand binding affinity analysis. We officially launched the web server and provided instructions through a case for the design and simulation of Candida antarctica lipase B (CalB) fusion protein called Maltose Binding Protein-Thioredoxin A-Candida antarctica lipase B (MBP-TrxA-CalB).

The BASDAI Cut-Off for Disease Activity Corresponding to the ASDAS Scores in a Taiwanese Cohort of Ankylosing Spondylitis.

Objectives: The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) has been widely utilized to evaluate disease activity in patients with ankylosing spondylitis (AS) by an arbitrary cut-off of ≥4 to indicate high disease activity and initiate biological therapy. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is a new composite index to assess AS disease activity states that have been defined and validated. ASDAS ≥2.1 was selected as a criterion to start biological therapy. The purpose of this study was to estimate the corresponding BASDAI and ASDAS cut-off in a Taiwanese AS cohort. Methods: From November 2016 to October 2018, we assessed the ASDAS and the BASDAI regularly and recorded demographic data for 489 AS patients in Taichung Veterans General hospital (TCVGH) using an electronic patient-reported data system linked to electronic medical records. We used receiver operating characteristic curves with Youden's J statistic to determine the BASDAI values that correspond to ASDAS disease activity cut-offs (i.e., 1.3, 2.1, and 3.5). Results: In our population, the best trade-off BASDAI values corresponding to ASDAS -C-reactive protein (CRP) 1.3, 2.1, and 3.5 were 2.1, 3.1, and 3.7, respectively. The optimal BASDAI values corresponding to ASDAS-erythrocyte sedimentation rates 1.3, 2.1, and 3.5 were 2.0, 2.6, and 4.8, respectively. Conclusion: We propose a revised BASDAI cut-off based on our data, as BASDAI scores are commonly used globally. A more reasonable, lower BASDAI cut-off to initiate or change biological therapy will bring us closer to better decisions to treat AS patients.

An Ultra-Low Power Surface EMG Sensor for Wearable Biometric and Medical Applications.

In recent years, the surface electromyography (EMG) signal has received a lot of attention. EMG signals are used to analyze muscle activity or to evaluate a patient's muscle status. However, commercial surface EMG systems are expensive and have high power consumption. Therefore, the purpose of this paper is to implement a surface EMG acquisition system that supports high sampling and ultra-low power consumption measurement. This work analyzes and optimizes each part of the EMG acquisition circuit and combines an MCU with BLE. Regarding the MCU power saving method, the system uses two different frequency MCU clock sources and we proposed a ping-pong buffer as the memory architecture to achieve the best power saving effect. The measured surface EMG signal samples can be forwarded immediately to the host for further processing and additional application. The results show that the average current of the proposed architecture can be reduced by 92.72% compared with commercial devices, and the battery life is 9.057 times longer. In addition, the correlation coefficients were up to 99.5%, which represents a high relative agreement between the commercial and the proposed system.