Optimising microplastics analysis for quantifying and identifying microplastic fibres in laundry wastewater.

Current methods for measuring microplastic fibres (MPF) are cumbersome, time consuming and unscalable for routine high throughput analysis. This study reports a method for rapidly extracting, quantifying and analysing MPFs in laundry wastewater with several key improvements which vastly enhance overall efficiency and scalability of analysis. FT-IR surveying is employed as a preliminary step in analysis to quickly determine what polymers are present in a sample prior to fluorescence treatment. Using random quadrating, whole 25 mm filter membranes were surveyed in <30 min with high recovery rates. In industrial laundry wastewater samples, polyester was the most common MPF, however acrylic, nylon, cotton and rayon were all ubiquitous. The study also demonstrates that an excitation wavelength of 365 nm was optimal for fluorescing PET fibres like polyester which were stained with Nile Red, but not 495 nm, which is commonly used in microplastic analysis. Finally, a custom ImageJ macro was written to automatically enumerate and describe MPFs on filter membranes using just a single stitched fluorescence image. In just a few seconds, concentrations of up to 40,000 fibres/L were analysed in industrial laundry wastewater samples with a lower particle size limit of 20 µm. This study highlights the need for more optimised and scalable analysis workflows which maintain high levels of reliability and accuracy.

Determination of toxicological relevant arsenic species in urine by hydride generation microwave-induced plasma optical emission spectrometry.

An analytical method for the determination of toxicological relevant species of arsenic in urine was developed and validated using hydride generation microwave-induced emission spectrometry (HG-MP-AES). This strategy can be used as an alternative to HG-HPLC-ICP-MS considered as a reference technique for arsenic speciation. This procedure is notably less expensive than other techniques and sample preparation and requires only a few steps.•Hydride generation with MP-AES detection has proven to be an effective technique for measuring arsenic metabolites in urine, which is relevant for occupational monitoring and health risk assessment purposes.•This method offers simplicity and cost-effectiveness, serving as an alternative to classical analytical procedures typically used for arsenic analysis in urine.•The methodology has been successfully applied for the purpose of workers' health surveillance.

Massive chylous pleural effusion and protein­losing enteropathy caused by mesenteric panniculitis: A case report.

Mesenteric panniculitis (MP), also known as sclerosing mesenteritis, is a rare idiopathic condition characterised by chronic inflammation and fibrosis in the mesentery. While small amounts of chylous ascites due to lymph drainage obstruction are not rare in patients with MP, massive ascites is a rare complication. Moreover, protein-losing enteropathy (PLE), a rare intestinal condition of uncompensated plasma protein loss, can occur in patients with MP. To the best of our knowledge, the present study is the first to report MP with massive chylous pleural effusion and PLE in a 56-year-old male presenting with dyspnoea at Osaka Medical and Pharmaceutical University Hospital (Osaka, Japan) in March 2023. Approximately 5 years prior, the patient noticed systemic oedema, transient abdominal pain and fever and weight loss, and was diagnosed with chylous ascites and PLE by abdominal paracentesis and endoscopic examination of the small intestine. Although initial prednisolone (20 mg/day) administration improved the oedema gradual and uncontrolled fluid buildup was observed. Computed tomography revealed pneumothorax, bilateral massive pleural effusion, and pneumonia. Despite extensive antibiotic therapy [voriconazole (300 mg, twice/day), Ampicillin/Sulbactam (3 g x 4/day), and Vancomycin (1,000 mg x 2/day)], the patient succumbed to respiratory failure 1 month later. Autopsy revealed massive chylous ascites, pleural effusion and the presence of thickened and calcified nodules in the mesentery. Histopathological examination showed diffuse fat necrosis with fibrosclerosis, calcification and lymphocytic infiltration within the mesentery. Therefore, a definitive diagnosis of MP was made. The present case highlighted the importance of considering MP as a differential diagnosis in cases of concurrent chylous ascites, pleural effusion and PLE in patients with abdominal pain, fever and weight loss.

Drug development in LMICs: could the emerging Indian model usher the southeast Asian region?

Low-income and middle-income countries (LMICs) of southeast Asia are passing through a similar phase as India in their tryst with the development of novel drugs. They are beginning to break away from their dependency on the institutions of our developed world. Over the past few years, Tata Memorial Centre-India's premier cancer centre-has shown the tenacity to develop drugs within the national frontiers. By collaborating with the domestic pharmaceutical industries, it has been able to have a steady pipeline of drugs under development, with two of them receiving marketing authorization recently. Lately, Indonesia and Vietnam have also shown an inclination towards public-private partnerships for similar motives. However, due to prolonged innovative stagnation, the entire drug development machinery faces challenges stretching all the way from arranging funds to persuading regulatory bodies. In this Viewpoint, we have tried to address a few of those issues and their potential solutions, with the intention to share our own experience which might be useful to other LMICs in connecting some adamant dots.

Macrogenomes reveal microbial-mediated microplastic degradation pathways in the porcine gut: a hope for solving the environmental challenges of microplastics.

It is increasingly recognized that microplastics (MPs) are being transmitted through the food chain system, but little is known about the microorganisms involved in MP degradation, functional biodegradation genes, and metabolic pathways of degradation in the intestinal tract of foodborne animals. In this study, we explored the potential flora mainly involved in MP degradation in the intestinal tracts of Taoyuan, Duroc, and Xiangcun pigs by macrogenomics, screened relevant MP degradation genes, and identified key enzymes and their mechanisms. The pig colon was enriched with abundant MP degradation-related genes, and gut microorganisms were their main hosts. The fiber diet did not significantly affect the abundance of MP degradation-related genes but significantly reduced their diversity. We identified a total of 94 functional genes for MP degradation and classified them into 27 categories by substrate type, with polystyrene (PS), polyethylene terephthalate (PET), and di(2-ethylhexyl) phthalate (DEHP) were the most predominant degradation types. The MP degradation functional genes were widely distributed in a variety of bacteria, mainly in the phylum Firmicutes and Bacteroidetes. Based on the identified functional genes for MP degradation, we proposed a hypothetical degradation mechanism for the three major MP pollutants, namely, PS, PET, and DEHP, which mainly consist of oxidoreductase, hydrolase, transferase, ligase, laccase, and isomerase. The degradation process involves the breakdown of long polymer chains, the oxidation of short-chain oligomers, the conversion of catechols, and the achievement of complete mineralization. Our findings provide insights into the function of MP degradation genes and their host microorganisms in the porcine colon.

Comparison between Three Radiomics Models and Clinical Nomograms for Prediction of Lymph Node Involvement in PCa Patients Combining Clinical and Radiomic Features.

PURPOSE: We aim to compare the performance of three different radiomics models (logistic regression (LR), random forest (RF), and support vector machine (SVM)) and clinical nomograms (Briganti, MSKCC, Yale, and Roach) for predicting lymph node involvement (LNI) in prostate cancer (PCa) patients. MATERIALS AND METHODS: The retrospective study includes 95 patients who underwent mp-MRI and radical prostatectomy for PCa with pelvic lymphadenectomy. Imaging data (intensity in T2, DWI, ADC, and PIRADS), clinical data (age and pre-MRI PSA), histological data (Gleason score, TNM staging, histological type, capsule invasion, seminal vesicle invasion, and neurovascular bundle involvement), and clinical nomograms (Yale, Roach, MSKCC, and Briganti) were collected for each patient. Manual segmentation of the index lesions was performed for each patient using an open-source program (3D SLICER). Radiomic features were extracted for each segmentation using the Pyradiomics library for each sequence (T2, DWI, and ADC). The features were then selected and used to train and test three different radiomics models (LR, RF, and SVM) independently using ChatGPT software (v 4o). The coefficient value of each feature was calculated (significant value for coefficient ≥ ±0.5). The predictive performance of the radiomics models and clinical nomograms was assessed using accuracy and area under the curve (AUC) (significant value for p ≤ 0.05). Thus, the diagnostic accuracy between the radiomics and clinical models were compared. RESULTS: This study identified 343 features per patient (330 radiomics features and 13 clinical features). The most significant features were T2_nodulofirstordervariance and T2_nodulofirstorderkurtosis. The highest predictive performance was achieved by the RF model with DWI (accuracy 86%, AUC 0.89) and ADC (accuracy 89%, AUC 0.67). Clinical nomograms demonstrated satisfactory but lower predictive performance compared to the RF model in the DWI sequences. CONCLUSIONS: Among the prediction models developed using integrated data (radiomics and semantics), RF shows slightly higher diagnostic accuracy in terms of AUC compared to clinical nomograms in PCa lymph node involvement prediction.

Microplastic accumulation and oxidative stress in sweet pepper (Capsicum annuum Linn.): Role of the size effect.

Microplastics (MPs), which are widely dispersed in terrestrial environments, threaten crop growth and human food security. However, plant accumulation and phytotoxicity related to the size effects of MPs remain insufficiently explored. This study investigated the accumulation and toxicity of two sizes of MPs on Capsicum annuum Linn. (C. annuum) through fluorescence tracing and antioxidant defense system assessment. The results revealed that the size of MPs significantly impacts their accumulation characteristics in C. annuum roots, leading to variations in toxic mechanisms, including oxidative stress and damage. Smaller MPs and higher exposure concentrations result in more pronounced growth inhibition. C. annuum roots have a critical size threshold for the absorption of MPs of approximately 1.2 µm. MPs that enter the root tissue exhibit an aggregated form, with smaller-sized MPs displaying a greater degree of aggregation. MP exposure induces oxidative stress in root tissues, with high concentrations of smaller MPs causing lipid peroxidation. Analysis of the IBR values revealed that C. annuum roots utilize ascorbic acid (ASA) to prevent oxidative damage caused by larger MPs. Conversely, smaller MPs primarily induce superoxide dismutase (SOD) and glutathione (GSH). These results emphasize the significant impact of MP size on plant antioxidant defense response mechanisms, laying the foundation for further investigating the implications for human health.

Tris(1-chloro-2-propyl) phosphate enhances the adverse effects of biodegradable polylactic acid microplastics on the mussel Mytilus coruscus.

Microplastics (MPs) and organophosphate flame retardants (OPFRs) have recently become ubiquitous and cumulative pollutants in the oceans. Since OPFRs are added to or adsorbed onto MPs as additives, it is necessary to study the composite contamination of OPFRs and MPs, with less focus on bio-based PLA. Therefore, this study focused on the ecotoxicity of the biodegradable MP polylactic acid (PLA) (5 µm, irregular fragments, 102 and 106 particles/L), and a representative OPFRs tris(1-chloro-2-propyl) phosphate (TCPP, 0.5 and 50 µg/L) at environmental and high concentrations. The mussel Mytilus coruscus was used as a standardised bioindicator for exposure experiments. The focus was on examining oxidative stress (catalase, CAT, superoxide dismutase, SOD, malondialdehyde, MDA), immune responses acid (phosphatase, ACP, alkaline phosphatase, AKP, lysozyme, LZM), neurotoxicity (acetylcholinesterase, AChE), energy metabolism (lactate dehydrogenase, LDH, succinate dehydrogenase, SDH, hexokinase, HK), and physiological indices (absorption efficiency, AE, excretion rate, ER, respiration rate, RR, condition index, CI) after 14 days exposure. The results of significantly increased oxidative stress and immune responses, and significantly disturbed energy metabolism and physiological activities, together with an integrated biomarker response (IBR) analysis, indicate that bio-based PLA MPs and TCPP could cause adverse effects on mussels. Meanwhile, TCPP interacted significantly with PLA, especially at environmental concentrations, resulting in more severe negative impacts on oxidative and immune stress, and neurotoxicity. The more severe adverse effects at environmental concentrations indicate higher ecological risks of PLA, TCPP and their combination in the real marine environment. Our study presents reliable data on the complex effects of bio-based MP PLA, TCPP and their combination on marine organisms and the environment.

Microplastics in Indonesian land and aquatic environment: From research activities to regulation policies.

Indonesia is suspected as one of the largest plastic waste contributors to the ocean, resulting in microplastic (MP) contamination of the marine environment. Likewise, >250 MP research in Indonesia have been published in the last decade, including review articles. However, a comprehensive review covering MP observations in all areas, i.e. land, freshwater, and ocean, and the regulation aspect in Indonesia remains unexplored. This review finds that the current MP studies are not sufficient to provide the big picture of MP distribution in Indonesia, suggesting the need for research guidelines and coordination among scholars in this field. In addition, the currently implemented local regulation in plastic item limitation should be supported by effective monitoring, sanction, and education for citizens, as well as investment in waste management facilities. Overall, this review suggests the improvement of MP studies and national regulation as countermeasures for MP pollution problems.

Free-breathing time-resolved 4D MRI with improved T1-weighting contrast.

This work proposes MP-Grasp4D (magnetization-prepared golden-angle radial sparse parallel 4D) MRI, a free-breathing, inversion recovery (IR)-prepared, time-resolved 4D MRI technique with improved T1-weighted contrast. MP-Grasp4D MRI acquisition incorporates IR preparation into a radial gradient echo sequence. MP-Grasp4D employs a golden-angle navi-stack-of-stars sampling scheme, where imaging data of rotating radial stacks and navigator stacks (acquired at a consistent rotation angle) are alternately acquired. The navigator stacks are used to estimate a temporal basis for low-rank subspace-constrained reconstruction. This allows for the simultaneous capture of both IR-induced contrast changes and respiratory motion. One temporal frame of the imaging volume in MP-Grasp4D MRI is reconstructed from a single stack and an adjacent navigator stack on average, resulting in a nominal temporal resolution of 0.16 seconds per volume. Images corresponding to the optimal inversion time (TI) can be retrospectively selected for providing the best image contrast. Reader studies were conducted to assess the performance of MP-Grasp4D MRI in liver imaging across 30 subjects in comparison with standard Grasp4D MRI without IR preparation. MP-Grasp4D MRI received significantly higher scores (P < 0.05) than Grasp4D in all assessment categories. There was a moderate to almost perfect agreement (kappa coefficient from 0.42 to 0.9) between the two readers for image quality assessment. When the scan time is reduced, MP-Grasp4D MRI preserves image contrast and quality, demonstrating additional acceleration capability. MP-Grasp4D MRI improves T1-weighted contrast for free-breathing time-resolved 4D MRI and eliminates the need for explicit motion compensation. This method is expected to be valuable in different MRI applications such as MR-guided radiotherapy.

Complexes of Hydrogen Peroxide, the Simplest Chiral Molecule, with L- and D-Serine Enantiomers and Their Clusters: MP2 and DFT Calculations.

The interaction between natural amino acids and hydrogen peroxide is of paramount importance due to the widespread use of hydrogen peroxide in biological and environmentally significant processes. Given that both amino acids and hydrogen peroxide occur in nature in two enantiomeric forms, it is crucial to investigate the formation of complexes between them, considering the role of molecular chirality. In this work, we report a theoretical study on the hydrogen peroxide enantiomers and their interactions with L- and S-serine and their clusters. We aimed to evaluate the non-covalent interactions between each hydrogen peroxide enantiomer and the L- and D-enantiomers of the non-essential amino acid serine and their clusters. First, the potential energy surfaces (PES) of transitions between enantiomers of the simplest chiral molecule, hydrogen peroxide, in the gas phase and in aqueous solution were studied using the Møller-Plesset theory method MP2/aug-cc-pVDZ. The activation energies of such transitions were calculated. The interactions of both hydrogen peroxide enantiomers (P and M) with L- and D-serine enantiomers were analyzed by density functional theory (DFT) with ωb97xd/6-311+G**, B3Lyp/6-311+G**, B3P86/6-311+G**, and M06/6-311+G** functionals. We found that both enantiomers of hydrogen peroxide bind more strongly to L-serine and its clusters than to D-serine, especially highlighting that the L form is the predominant natural form of this and other chiral amino acids. The optimized geometric parameters, interaction energies, and HOMO-LUMO energies for various complexes were estimated. Furthermore, circular dichroism (CD) spectra, which are optical chirality characteristics, were simulated for all the complexes under study.

Construction of a predictive model of respiratory endoscopic intervention in children with lobar pneumonia caused by Mycoplasma pneumoniae infection.

Background: This study aimed to analyze the clinical features of children with lobar pneumonia caused by Mycoplasma pneumoniae (MP) infection, to explore the independent risk factors for bronchoscopic intervention in children with lobar pneumonia caused by MP infection. There is a lack of objective assessment tools to guide the use of bronchoscopy in clinical practice. For children with lobar pneumonia caused by MP infection, whether line shall be actively bronchoscope intervention therapy remains to be further defined. We also aimed to construct an early warning model of bronchoscopic intervention to provide an objective evaluation tool for clinicians. Methods: We collected the clinical data of 533 children with lobar pneumonia caused by MP infection. The patients were divided into three groups according to the interventional indications for bronchoscopy and whether they were treated with bronchoscopic intervention, and the clinical features and prognosis of the three groups were compared. A binary logistic regression analysis was performed on the indicators with a significance value of P<0.05, which we retrieved from the comparative analysis between the first two groups to uncover the independent risk factors and regression equations concerning bronchoscopic intervention. The regression coefficient (ß) of our regression model was then used to score related values in the model to construct a predictive scoring model of bronchoscopic intervention for the treatment of children with lobar pneumonia caused by MP infection. Results: Children with lobar pneumonia caused by MP infection who demonstrated absolute indications for bronchoscopy exhibited more severe clinical manifestations, and children without absolute indications for bronchoscopy had a better prognosis even without bronchoscopic intervention. To establish our early warning model of bronchoscopic intervention for children with lobar pneumonia caused by MP infection, we used the following indices: C-reactive protein ≥20.94 mg/L (ß1=2.253) received 3 points, while a fever duration before bronchoscopy ≥6.5 d (ß2=1.424), lactate dehydrogenase ≥461.5 U/L (ß3=1.246), or fever (ß4=1.223) each received 2 points, and the complication of pleural effusion (ß5=0.841) received 1 point, for a total possible score of 10 points. Conclusions: When the score for the children with lobar pneumonia caused by MP infection was ≥6, the possibility of bronchoscopic intervention for treatment was >80%. The higher the score, the greater the possibility of bronchoscopic intervention.

Construction of a nomogram for early diagnosis of refractory Mycoplasma pneumoniae pneumonia in children.

Background: Refractory Mycoplasma pneumoniae pneumonia (RMPP) has a serious, rapid progression that can easily cause a variety of extra-pulmonary complications. Therefore, the early identification of RMPP is crucial. This study aimed to construct and validate a risk prediction model based on clinical manifestations, laboratory blood indicators, and radiological findings to help clinicians identify patients who are at high risk of RMPP. Methods: We retrospectively analyzed the medical records of 369 children with Mycoplasma pneumoniae pneumonia (MPP) admitted to Xi'an Children's Hospital, China. The demographics, clinical features, laboratory data, and radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and subjected to univariate and multivariate logistic regression analyses. Results: The fever peak and duration of the children in the RMPP group (n=86) were higher and longer compared with those in the GMPP group (n=283) (P<0.05). There was a significant difference in the incidence of lobar pneumonia and pleural effusion in pulmonary imaging between the two groups (P<0.05). Laboratory tests showed that the children with RMPP had lower serum uric acid (SUA) and albumin (ALB) as compared with the GMPP group (P<0.05). White blood cells (WBCs), neutrophil count (NEP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT), C-reactive protein (CRP), and neutrophil-to-lymphocyte ratio (NLR) were higher in the RMPP group (P<0.05). Binary logistic regression analysis showed that the fever duration, pleural effusion, WBC, NEP, lactate dehydrogenase (LDH), CRP, NLR, and SUA levels were independent predictors of RMPP (P<0.05). The receiver operator characteristic (ROC) curve results showed fever duration, WBC, NEP, CRP, LDH, SUA, and NLR had good predictive value. The areas under the curve (AUCs) were 0.861, 0.730, 0.758, 0.837, 0.868, 0.744, and 0.713 and the best cutoff values were 10.50, 10.13, 6.43, 29.45, 370.50, 170.50, and 3.47, respectively. Finally, fever duration of more than 10.5 days, pleural effusion, WBC >10.13×109/L, NEP >6.43×109/L, CRP >29.45 mg/L, LDH >370.50 U/L, NLR >3.47, and SUA <170.5 µmol/mL constructed a prediction model of RMPP. According to internal validation, the mean AUC of the nomogram based on the development dataset was 0.956 [95% confidence interval (CI): 0.937-0.974] with good discrimination ability for predicting RMPP patients. The calibration plot and Hosmer-Lemeshow test (P=0.70) of the prediction model showed good consistency between the predicted probability and actual probability. Decision curve analysis (DCA) showed that the nomogram is clinically useful. Conclusions: The simple and easy-to-use nomogram can help clinicians, especially primary doctors, to make early diagnoses of RMPP.

Metagenome comparison (MC): A new framework for detecting unique/enriched OMUs (operational metagenomic units) derived from whole-genome sequencing reads.

BACKGROUND: Current methods for comparing metagenomes, derived from whole-genome sequencing reads, include top-down metrics or parametric models such as metagenome-diversity, and bottom-up, non-parametric, model-free machine learning approaches like Naïve Bayes for k-mer-profiling. However, both types are limited in their ability to effectively and comprehensively identify and catalogue unique or enriched metagenomic genes, a critical task in comparative metagenomics. This challenge is significant and complex due to its NP-hard nature, which means computational time grows exponentially, or even faster, with the problem size, rendering it impractical for even the fastest supercomputers without heuristic approximation algorithms. METHOD: In this study, we introduce a new framework, MC (Metagenome-Comparison), designed to exhaustively detect and catalogue unique or enriched metagenomic genes (MGs) and their derivatives, including metagenome functional gene clusters (MFGC), or more generally, the operational metagenomic unit (OMU) that can be considered the counterpart of the OTU (operational taxonomic unit) from amplicon sequencing reads. The MC is essentially a heuristic search algorithm guided by pairs of new metrics (termed MG-specificity or OMU-specificity, MG-specificity diversity or OMU-specificity diversity). It is further constrained by statistical significance (P-value) implemented as a pair of statistical tests. RESULTS: We evaluated the MC using large metagenomic datasets related to obesity, diabetes, and IBD, and found that the proportions of unique and enriched metagenomic genes ranged from 0.001% to 0.08 % and 0.08%-0.82 % respectively, and less than 10 % for the MFGC. CONCLUSION: The MC provides a robust method for comparing metagenomes at various scales, from baseline MGs to various function/pathway clusters of metagenomes, collectively termed OMUs.

Generic Reporter Sets for Colorimetric Multiplex dPCR Demonstrated with 6-Plex SNP Quantification Panels.

Digital PCR (dPCR) is a powerful method for highly sensitive and precise quantification of nucleic acids. However, designing and optimizing new multiplex dPCR assays using target sequence specific probes remains cumbersome, since fluorescent signals must be optimized for every new target panel. As a solution, we established a generic fluorogenic 6-plex reporter set, based on mediator probe technology, that decouples target detection from signal generation. This generic reporter set is compatible with different target panels and thus provides already optimized fluorescence signals from the start of new assay development. Generic reporters showed high population separability in a colorimetric 6-plex mediator probe dPCR, due to their tailored fluorophore and quencher selection. These reporters were further tested using different KRAS, NRAS and BRAF single-nucleotide polymorphisms (SNP), which are frequent point mutation targets in liquid biopsy. We specifically quantified SNP targets in our multiplex approach down to 0.4 copies per microliter (cp/µL) reaction mix, equaling 10 copies per reaction, on a wild-type background of 400 cp/µL for each, equaling 0.1% variant allele frequencies. We also demonstrated the design of an alternative generic reporter set from scratch in order to give detailed step-by-step guidance on how to systematically establish and optimize novel generic reporter sets. Those generic reporter sets can be customized for various digital PCR platforms or target panels with different degrees of multiplexing.

Challenges of Protein-Protein Docking of the Membrane Proteins.

Despite the recent advances in the determination of high-resolution membrane protein (MP) structures, the structural and functional characterization of MPs remains extremely challenging, mainly due to the hydrophobic nature, low abundance, poor expression, purification, and crystallization difficulties associated with MPs. Whereby the major challenges/hurdles for MP structure determination are associated with the expression, purification, and crystallization procedures. Although there have been significant advances in the experimental determination of MP structures, only a limited number of MP structures (approximately less than 1% of all) are available in the Protein Data Bank (PDB). Therefore, the structures of a large number of MPs still remain unresolved, which leads to the availability of widely unplumbed structural and functional information related to MPs. As a result, recent developments in the drug discovery realm and the significant biological contemplation have led to the development of several novel, low-cost, and time-efficient computational methods that overcome the limitations of experimental approaches, supplement experiments, and provide alternatives for the characterization of MPs. Whereby the fine tuning and optimizations of these computational approaches remains an ongoing endeavor.Computational methods offer a potential way for the elucidation of structural features and the augmentation of currently available MP information. However, the use of computational modeling can be extremely challenging for MPs mainly due to insufficient knowledge of (or gaps in) atomic structures of MPs. Despite the availability of numerous in silico methods for 3D structure determination the applicability of these methods to MPs remains relatively low since all methods are not well-suited or adequate for MPs. However, sophisticated methods for MP structure predictions are constantly being developed and updated to integrate the modifications required for MPs. Currently, different computational methods for (1) MP structure prediction, (2) stability analysis of MPs through molecular dynamics simulations, (3) modeling of MP complexes through docking, (4) prediction of interactions between MPs, and (5) MP interactions with its soluble partner are extensively used. Towards this end, MP docking is widely used. It is notable that the MP docking methods yet few in number might show greater potential in terms of filling the knowledge gap. In this chapter, MP docking methods and associated challenges have been reviewed to improve the applicability, accuracy, and the ability to model macromolecular complexes.

A high-resolution 7 Tesla resting-state fMRI dataset optimized for studying the subcortex.

To achieve a comprehensive understanding of spontaneous brain dynamics in humans, in vivo acquisition of intrinsic activity across both cortical and subcortical regions is necessary. Here we present advanced whole-brain, resting-state functional magnetic resonance imaging (rs-fMRI) data acquired at 7 Tesla with 1.5 mm isotropic voxel resolution. Functional images were obtained from 56 healthy adults (33 females, ages 19-39 years) in two runs of 15 min eyes-open wakeful rest. The high spatial resolution and short echo times of the multiband echo-planar imaging (EPI) protocol optimizes blood oxygen level-dependent (BOLD)-sensitivity for the subcortex while concurrent respiratory and cardiac measures enable retrospective correction of physiological noise, resulting in data that is highly suitable for researchers interested in subcortical BOLD signal. Functional timeseries were coregistered to high-resolution T1-weighted structural data (0.75 mm isotropic voxels) acquired during the same scanning session. To accommodate data reutilization, functional and structural images were formatted to the Brain Imaging Data Structure (BIDS) and preprocessed with fMRIPrep.

The Use of Azelastine Hydrochloride/Fluticasone Propionate in the Management of Allergic Rhinitis in Asia: A Review.

The incidence of allergic rhinitis (AR) in Asia and the world is steadily rising. Patients experience incomplete symptom relief despite existing treatment options, which warrants the need for new therapeutic regimes. Azelastine hydrochloride/fluticasone propionate (MP-AzeFlu), a novel intranasal formulation of azelastine hydrochloride and fluticasone propionate has been indicated in the treatment of AR. The current review discusses the effects of MP-AzeFlu versus conventional therapies in achieving superior clinical improvement with a very rapid onset of action (5 minutes). The superiority of MP-AzeFlu in offering complete symptom control with sustained relief in patients with AR compared to the existing therapeutic options is also discussed. MP-AzeFlu has been shown to improve the quality of life for patients with AR, thereby enhancing patient adherence to therapy and establishing its preference for the treatment of AR. Currently, the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines recommend the use of a combination of intranasal corticosteroids and intranasal antihistamines as first-line treatment in patients with persistent AR with visual analog scores ≥5 or when prior treatment with single agents has been ineffective. Widely published data on the efficacy and safety of its prolonged use in adults and children have validated that effective treatment of AR can be achieved with MP-AzeFlu.

Bio-based microplastic polylactic acid exerts the similar toxic effects to traditional petroleum-based microplastic polystyrene in mussels.

Microplastics (MPs) have accumulated in the oceans, causing adverse effects on marine organisms and the environment. Biodegradable polylactic acid (PLA) is considered as an excellent substitute for traditional petroleum-based plastics, but it is difficult to degrade completely and easily become MPs in the marine environment. To test the ecological risk of bio-based PLA, we exposed thick-shelled mussels (Mytilus coruscus) to bio-based PLA and petroleum-based polystyrene (PS) (at 102, 104, and 106 particles/L) for 14 days. The significant increase in enzyme activities related to oxidative stress and immune response showed that mussels were under physiological stress after MP ingestion. While enzyme activities of nerve conduction and energy metabolism were significantly disturbed after exposure. Meanwhile, normal physiological activities in respiration, ingestion and assimilation were also suppressed in association with enzyme changes. The negative effects of PS and PLA in mussels were not differentiated, and further integration analysis of integrated biomarker response (IBR) and principal component analysis (PCA) also showed that PLA would induce adverse effects in mussels and ecological risks as PS, especially at environmental concentrations. Therefore, it is necessary to pay more attention to the environmental and ecological risk of bio-based MP PLA accumulating in the marine environment.

Discovery of TCP-(MP)-caffeic acid analogs as a new class of agents for treatment of osteoclastic bone loss.

Inhibition of LSD1 was proposed as promising and attractive therapies for treating osteoporosis. Here, we synthesized a series of novel TCP-(MP)-Caffeic acid analogs as potential LSD1 inhibitors to assess their inhibitory effects on osteoclastogenesis by using TRAP-staining assay and try to explore the preliminary SAR. Among them, TCP-MP-CA (11a) demonstrated osteoclastic bone loss both in vitro and in vivo, showing a significant improvement in the in vivo effects compared to the LSD1 inhibitor GSK-LSD1. Additionally, we elucidated a mechanism that 11a and its precursor that 11e directly bind to LSD1/CoREST complex through FAD to inhibit LSD1 demethylation activity and influence its downstream IκB/NF-κB signaling pathway, and thus regulate osteoclastic bone loss. These findings suggested 11a or 11e as potential novel candidates for treating osteoclastic bone loss, and a concept for further development of TCP-(MP)-Caffeic acid analogs for therapeutic use in osteoporosis clinics.