Causal inference analysis of the radiologic progression in the chronic obstructive pulmonary disease.

There is limited evidence regarding the causal inference of emphysema and functional small airway disease in the subsequent progression of chronic obstructive pulmonary disease (COPD). Patients consisting of two independent cohorts diagnosed with COPD and underwent two serial chest CT scans were included. Total percent emphysema (PRMEmph) and fSAD (PRMfSAD) was quantified via PRM. To investigate the progression of emphysema, we divided COPD patients with PRMEmph < 10% into low and high PRMfSADgroup, matched with similar baseline characteristics, and conducted nonparametric hypothesis tests based on randomization inference using Wilcoxon signed rank test and Huber's M statistics. In patients with baseline PRMEmph < 10%, there were 26 and 16 patients in the low PRMfSA group and 52 and 64 patients in the high PRMfSA in the derivation and validation cohorts, respectively. In the both low and high PRMfSAD groups, there were 0.11 and 1.43 percentage point increases (Huber's M statistic p = 0.016) and 0.58 and 2.09 percentage point increases (p = 0.038) in the proportion of emphysema in the derivation and validation cohorts, respectively. On the contrary, among patients with baseline PRMfSAD < 20%, there was no significant differences in the interval changes of PRMfSAD between the low and high PRMEmph groups in both cohorts. In COPD patients with low emphysema, group with baseline high PRMfSAD showed greater change of PRMEmph than those with low PRMfSAD in both the derivation and validation cohorts. Imaging-based longitudinal quantitative analysis may provide important evidence that small airway disease precedes emphysema in CT-based early COPD patients.

Surface-Templated Polymer Microparticle Synthesis Based on Droplet Microarrays.

Polymer microparticle synthesis based on the surface-templated method is a simple and environmentally friendly method to produce various microparticles. Unique particles with different compositions can be fabricated by simply annealing a polymer on a liquid-repellent surface. However, there are hurdles to producing particles of homogeneous sizes with large quantities and varying the shape of particles. Here, a new approach to synthesizing multiple polymer microparticles using micropatterns with wettability contrast is presented. Polymer microparticles are formed in two steps. First, a layer of poly(sodium-4-styrenesulfonate) is deposited on the hydrophilic regions by dipping and withdrawing this micropattern from a polymer solution, and an array of microdroplets is formed. A dewetting-inducing layer on the pattern is introduced, and then target polymer patches are sequentially generated on it. By annealing over Tg, the contact line of the target polymer patch is freely receded, creating a particle form. The size and shape of the microparticle can be controlled by varying the micropatterns. In addition, it is demonstrated that microparticles made of polymer blends or polymer/nanoparticle composite are easily produced. This versatile method offers the potential of surface-templated synthesis to tailor polymer microparticles with different sizes, shapes, and functionalities in various research and applications.

Revisiting o-Phenylenediamine as a Nanomaterial-Catalyzed Signaling Agent: Dimerization versus Polymerization.

o-Phenylenediamine (OPD) is commonly used as a reliable signaling agent for colorimetric assays via oxidative dimerization to 2,3-diaminophenazine (DAP) (λmax = 425 nm), which is catalyzed by conventional horseradish peroxidase (HRP) or its nanoparticle mimics. Recently, it has been reported that catalytic and electrochemical oxidation of OPD produces a mixture of polymerized OPD molecules (polyOPDs), which could potentially affect the colorimetric signal due to the difference in optical properties between DAP and polyOPDs. In our study, we present for the first time that the gold nanoparticle-catalyzed oxidation of OPD could exhibit nonmonotonic extinction transitions at 425 nm. Using various spectroscopic and microscopic techniques such as UV-vis spectroscopy, transmission electron microscopy, dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) spectroscopy, we verify that the production of polyOPDs is specifically responsible for the unexpected decrease in extinction at 425 nm. This discovery presents a potential challenge to the conventionally accepted role of OPD as a signaling agent. Furthermore, we find that the modification of reaction variables, including reactant concentrations, anion types, and temperature, determines how nonmonotonic the extinction transition could be. Lastly, we develop an OPD-based colorimetric DNA detection scheme using DNA-functionalized gold nanoparticles to demonstrate the potential problems in accurately quantifying the target. Our proposal of using NaNO3 instead of NaCl to provide the desired ionic strength could be a suitable solution to overcome the obstacles of detection.

Unveiling the inhibition mechanism of Clostridioides difficile by Bifidobacterium longum via multiomics approach.

Antibiotic-induced gut microbiota disruption constitutes a major risk factor for Clostridioides difficile infection (CDI). Further, antibiotic therapy, which is the standard treatment option for CDI, exacerbates gut microbiota imbalance, thereby causing high recurrent CDI incidence. Consequently, probiotic-based CDI treatment has emerged as a long-term management and preventive option. However, the mechanisms underlying the therapeutic effects of probiotics for CDI remain uninvestigated, thereby creating a knowledge gap that needs to be addressed. To fill this gap, we used a multiomics approach to holistically investigate the mechanisms underlying the therapeutic effects of probiotics for CDI at a molecular level. We first screened Bifidobacterium longum owing to its inhibitory effect on C. difficile growth, then observed the physiological changes associated with the inhibition of C. difficile growth and toxin production via a multiomics approach. Regarding the mechanism underlying C. difficile growth inhibition, we detected a decrease in intracellular adenosine triphosphate (ATP) synthesis due to B. longum-produced lactate and a subsequent decrease in (deoxy)ribonucleoside triphosphate synthesis. Via the differential regulation of proteins involved in translation and protein quality control, we identified B. longum-induced proteinaceous stress. Finally, we found that B. longum suppressed the toxin production of C. difficile by replenishing proline consumed by it. Overall, the findings of the present study expand our understanding of the mechanisms by which probiotics inhibit C. difficile growth and contribute to the development of live biotherapeutic products based on molecular mechanisms for treating CDI.

Multiomics analysis reveals the biological effects of live Roseburia intestinalis as a high-butyrate-producing bacterium in human intestinal epithelial cells.

Butyrate-producing bacteria play a key role in human health, and recent studies have triggered interest in their development as next-generation probiotics. However, there remains limited knowledge not only on the identification of high-butyrate-producing bacteria in the human gut but also in the metabolic capacities for prebiotic carbohydrates and their interaction with the host. Herein, it was discovered that Roseburia intestinalis produces higher levels of butyrate and digests a wider variety of prebiotic polysaccharide structures compared with other human major butyrate-producing bacteria (Eubacterium rectale, Faecalibacterium prausnitzii, and Roseburia hominis). Moreover, R. intestinalis extracts upregulated the mRNA expression of tight junction proteins (TJP1, OCLN, and CLDN3) in human intestinal epithelial cells more than other butyrate-producing bacteria. R. intestinalis was cultured with human intestinal epithelial cells in the mimetic intestinal host-microbe interaction coculture system to explore the health-promoting effects using multiomics approaches. Consequently, it was discovered that live R. intestinalis only enhances purine metabolism and the oxidative pathway, increasing adenosine triphosphate levels in human intestinal epithelial cells, but that heat-killed bacteria had no effect. Therefore, this study proposes that R. intestinalis has potentially high value as a next-generation probiotic to promote host intestinal health.

Evaporation-driven Supraparticle Synthesis by Self-Lubricating Colloidal Dispersion Microdrops.

The surface-templated evaporation-driven (S-TED) method that uses liquid-repellent surfaces has attracted considerable attention for its use in fabricating supraparticles of defined shape, size, and porosity. However, challenges in achieving mass production have impeded the widespread adoption of the S-TED method. To overcome this limit, we introduce an evaporation-driven "multiple supraparticle" synthesis by drying arrays of self-lubricating colloidal dispersion microdrops. To facilitate this synthetic method, a hydrophilic micropattern is prepared on a hydrophobic substrate as a template. During the removal of the substrate out of a dispersion, liquid drops are trapped and generate a microdrop array. To produce supraparticles, the contact lines of the trapped drops must be able to recede freely during evaporation. However, hydrophilic micropatterns induce strong contact line pinning for microdrops that hinders supraparticle formation. Herein, we solve this contradiction by employing an Ouzo-like colloidal dispersion, where we can control the wettability of the drop trapping domain. The self-lubrication effect provided by the Ouzo-like solution enables smooth movement of the drops' contact lines during evaporation, thereby resulting in the successful fabrication of supraparticle arrays even within the trapping domain. This strategy offers a promising and scalable approach for large-scale evaporation-driven supraparticle synthesis with a potential for extension to various primary colloidal particles, further broadening its applicability.

Unveiling the Role of Precursors in the Byproduct Formation of AgCl-Replicated Bimetallic Nanostructures and Their Stability-Dependent Photothermal Properties.

AgCl nanomaterials recently attracted scientific interest as useful structural building blocks for producing metallic nanomaterials owing to their facile synthesis, controllable morphology, and ease of removal under ambient conditions. However, their complex chemical reactivity has primarily been studied in association with water solubility or reducibility. This study investigates the pivotal role of precursor ligands in the photochemical synthesis of metallic cubic mesh nanostructures on the AgCl templates. The side reactions between AgCl and Au precursors with different ligands are thoroughly discussed along with their influence on the byproduct formation and the structural stability of the resulting metallic nanostructures. Importantly, we introduce for the first time the partial destruction of AgCl and the formation of undesirable byproducts caused by the presence of highly oxidizing and Cl-containing AuCl4-. In addition, a synthetic route for producing highly pure and stable metallic nanostructures using a halogen-free Au precursor or Pt-priming is proposed. Further, the photothermal properties of these replicated metallic nanostructures are presented as a new evaluation tool for analyzing their overall structural stability. Discovering the role of precursor ligands in the reaction system will prove useful as a guide for the synthesis of functional noble metal nanomaterials using silver halide templates.

Codeine prescription pattern and treatment responses in patients with chronic cough: a routinely collected institutional database analysis.

Background: Codeine has been long used as an antitussive drug in several countries. However, a prescription pattern of codeine, such as dose or treatment duration, has not been reported in detail. Furthermore, there is few scientific evidence on the efficacy and safety. We aimed to examine codeine prescription pattern and explore treatment response in patients with chronic cough in real-world practice. Methods: This was a retrospective cohort analysis of patients with chronic cough who were newly referred to tertiary allergy and asthma clinics between July 2017 and July 2018. Routinely collected electronic healthcare records (EHRs), including medical notes, prescriptions, and outpatient visits, were analyzed. Codeine prescription records were examined for duration, mean daily dose, and 1-year cumulative dose. Codeine responses were evaluated by manual EHR reviews. Results: Among a total of 1,233 newly referred patients with chronic cough, 666 were prescribed codeine for a median [interquartile range (IQR)] of 27.5 days (IQR 14-60 days); the median daily dose was 30 mg/year (IQR 21.6-30 mg/year), and the 1-year cumulative dose was 720 mg/year (IQR 420-1,800 mg/year). About 14.0% of patients were prescribed codeine for >8 weeks; they were older and had a longer cough duration, throat abnormal sensation and less dyspnea than patients prescribed codeine for ≤8 weeks or who did not receive codeine. Codeine prescription and duration was positively associated with the number of other cough-related medications, diagnostic tests, or outpatient visits. Cough status change was noted in 61.3% of codeine-prescribed patients (as 'improved' in 40.1% and 'not improved' in 21.2%), but not documented in 38.7%. Side effects were described in 7.8%. Conclusions: Codeine prescription may be frequent and chronic in real-world practice of patients with chronic cough, despite the lack of robust clinical evidence on the efficacy. High prescription rates suggest unmet clinical needs. Prospective studies are warranted to identify codeine treatment responses and safety, and to build up clinical evidence to guide appropriate use of narcotic antitussives.

Chest computed tomography scan utilization and diagnostic outcomes in chronic cough patients with normal chest X-rays: analysis of routinely collected data of a tertiary academic hospital.

Background: The role of chest computed tomography (CT) scan is controversial in the management of chronic cough patients with normal chest X-rays. We investigated the utilization pattern and diagnostic outcomes of chest CT scans using institutional routinely collected data (RCD) in South Korea. Methods: This is a retrospective analysis of adults with chronic cough (>8 weeks in duration) identified from routinely collected electronic health records (EHRs). Structured data were retrieved, including demographics, medical history, symptoms, and diagnostic test results (including chest X-rays and CT scans). Chest CT scan outcomes were classified into major abnormal findings (malignancy, infectious diseases, or other critical conditions that warrant immediate treatment decisions), minor abnormal findings (other abnormal findings), or normal CT. Results: A total of 5,038 chronic cough patients with normal chest X-rays were analyzed. Chest CT scans were performed in 1,006 patients. Prescription of CT scans was significantly associated with older age, male sex, smoking history, and physician-diagnosed history of lung disease. Only 8 of 1,006 (0.8%) patients had major abnormal findings (4 pneumonia, 2 pulmonary tuberculosis, and 2 lung cancer), while 367 (36.5%) had minor findings, and 631 (62.7%) had normal CT scans. However, no baseline parameters were significantly associated with major CT findings. Conclusions: Chest CT scans were frequently prescribed for chronic cough patients with normal chest X-rays, and abnormal findings were frequently found (37.3%). However, the diagnostic yield for malignancy or infectious disease were low (<1%). Given the potential radiation harm, a routine chest CT scan may not be warranted in chronic cough patients with normal chest X-rays.

Surface Functionalization and Reversible Disassembly of DNA-Assembly Nanoparticles for Sensitive and Multiplexed Detection of DNA Targets Without Enzymatic and Catalytic Amplification.

Recently, DNA-assembly nanoparticles based on DNA-metal ion interactions are emerging as new building blocks for drug delivery and metal nanostructure synthesis. However, the surface modification of DNA-assembly nanoparticles using functional biomolecules that can identify specific targets has rarely been explored. In this study, we developed a new immobilization chemical strategy to efficiently functionalize the barcode DNA-assembly nanoparticles (bcDNA NPs) with thiolated probe DNA (pDNA) for synthesizing pDNA-functionalized bcDNA NPs (pDNA-bcDNA NPs). We used them as nanoprobes to successfully demonstrate the sensitive and selective detection of multiple DNA targets. Importantly, Au ions played an essential role as anchoring sites via their conjugation with both thiolated pDNA and bcDNA NPs. In addition, we could reversibly and rapidly disassemble the pDNA-bcDNA NPs into the initial bcDNA strands with a recovery rate of 91%; this process significantly amplified the signal by releasing a million bcDNA strands, which enabled DNA quantification from a single pDNA-bcDNA NP. The Au3+ concentration, pH, and surface passivation conditions were carefully investigated to maximize the pDNA loading to 8500 strands/bcDNA NP. The limit of detection was determined to be 221 fM, which is the most sensitive among the absorbance-based methods without polymerase chain reaction, hybridization chain reactions, catalytic hairpin assembly, and other reactions involving enzymes and catalysts. The reversible disassembly of DNA strands and Au ion-mediated conjugation chemistry could be extended for the detection of other types of targets, such as proteins, metal ions, and small molecules, using other organic functionalities that are or can be thiolated, including polypeptides, aptamers, and antibodies.

Acrylamide: New Organic Solvent with Chemically Tunable Viscosity for Rapid Gram-Scale Synthesis of Gold Nanoparticles.

Noble metal nanoparticles have demonstrated various biomedical, optical, and electronic applications owing to their unique chemical and physical properties. However, their gram-scale synthesis remains a challenge. We have developed a method for the gram-scale synthesis of gold nanoparticles (AuNPs) using acrylamide (AAm) as a solvent. AAm possesses unique properties such as low melting temperature, high solvating power, and high solubility of its polymer (polyacrylamide(pAAm)) in water. The viscosity of the AAm solvent can be chemically tuned by the polymerization of AAm and addition of a low-volatile diluent, which can stabilize highly concentrated as-synthesized AuNPs in gram quantities. The synthesized AuNPs are substantially stable and catalytically active under high ionic strength conditions owing to the pAAm protection on the particle surface. Further, the synthesis mechanism of the AuNPs has been thoroughly investigated. The versatility of the synthesis method is proved by synthesizing other mono-(Ag and Pd) and bimetallic (Au + Pd and Ag + Pd) nanoparticles using the AAm solvent with controlled viscosity. Importantly, the productivity of this synthetic strategy is the highest among the previously reported gram-scale synthesis methods of AuNPs. To the best of our knowledge, our study presents the use of acrylic monomer as a solvent for the gram-scale synthesis of noble metal nanoparticles for the first time. This study significantly extends the list of solvents with chemically tunable viscosity by including other acrylic reagents for nanomaterial synthesis, functionalization, and catalytic, optical, and electrical reactions under highly localized reaction conditions.

In Situ Tetraalkylammonium Ligand Engineering of Organic-Inorganic Hybrid Perovskite Nanoparticles for Enhancing Long-Term Stability and Optical Tunability.

Organic-inorganic hybrid perovskite nanoparticles (OIHP NPs) have attracted scientific attention owing to their efficient photoluminescence with optical tunability, which is highly advantageous for optoelectronic applications. However, the limited long-term stability of OIHP NPs has significantly hindered their practical application. Despite several synthetic strategies and encapsulation methods to stabilize OIHP NPs, complicated multi-step procedures are often required. In this study, we introduce an in situ ligand engineering method for stabilizing and controlling the optical properties of OIHP NPs using tetraalkylammonium (TAA) halides with various molecular structures at different concentrations. Our one-pot ligand engineering substantially enhanced the stability of the OIHP NPs without post-synthetic processes. Moreover, in certain cases, approximately 90% of the initial photoluminescence (PL) intensity was preserved even after a month under ambient conditions (room temperature, 20-50% relative humidity). To determine the role of ligand engineering in stabilizing the OIHP NPs, the surface binding properties of the TAA ligands were thoroughly analyzed using Raman spectroscopy. Specifically, the permanent positive charge of the TAA cations and consequent effective electrostatic interactions with the surfaces of the OIHP NPs are pivotal for preserving the initial PL intensity. Our investigation is beneficial for developing OIHP nanomaterials with improved stability and controlled photoluminescence for various optoelectronic applications, such as light-emitting devices, photosensitizers, photodetectors, photocatalysis, and solar cells.

Hierarchical Metal-Organic Aerogel as a Highly Selective and Sustainable CO2 Adsorbent.

Typical amorphous aerogels pose great potential for CO2 adsorbents with high surface areas and facile diffusion, but they lack well-defined porosity and specific selectivity, inhibiting utilization of their full functionality. To assign well-defined porous structures to aerogels, a hierarchical metal-organic aerogel (HMOA) is designed, which consists of well-defined micropores (d ∼ 1 nm) by coordinative integration with chromium(III) and organic ligands. Due to its hierarchical structure with intrinsically flexible coordination, the HMOA has excellent porous features of a high surface area and a reusable surface with appropriate binding energy for CO2 adsorption. The HMOA features high CO2 adsorption capacity, high CO2/N2 IAST selectivity, and vacuum-induced surface regenerability (100% through 20 cycles). Further, the HMOA could be prepared via simple ambient drying methods while retaining the microporous network. This unique surface-tension-resistant micropore formation and flexible coordination systems of HMOA make it a potential candidate for a CO2 adsorbent with industrial scalability and reproducibility.

Investigation of metabolic crosstalk between host and pathogenic Clostridioides difficile via multiomics approaches.

Clostridioides difficile is a gram-positive anaerobic bacterium that causes antibiotic-associated infections in the gut. C. difficile infection develops in the intestine of a host with an imbalance of the intestinal microbiota and, in severe cases, can lead to toxic megacolon, intestinal perforation, and even death. Despite its severity and importance, however, the lack of a model to understand host-pathogen interactions and the lack of research results on host cell effects and response mechanisms under C. difficile infection remain limited. Here, we developed an in vitro anaerobic-aerobic C. difficile infection model that enables direct interaction between human gut epithelial cells and C. difficile through the Mimetic Intestinal Host-Microbe Interaction Coculture System. Additionally, an integrative multiomics approach was applied to investigate the biological changes and response mechanisms of host cells caused by C. difficile in the early stage of infection. The C. difficile infection model was validated through the induction of disaggregation of the actin filaments and disruption of the intestinal epithelial barrier as the toxin-mediated phenotypes following infection progression. In addition, an upregulation of stress-induced chaperones and an increase in the ubiquitin proteasomal pathway were identified in response to protein stress that occurred in the early stage of infection, and downregulation of proteins contained in the electron transfer chain and ATP synthase was observed. It has been demonstrated that host cell energy metabolism is inhibited through the glycolysis of Caco-2 cells and the reduction of metabolites belonging to the TCA cycle. Taken together, our C. difficile infection model suggests a new biological response pathway in the host cell induced by C. difficile during the early stage of infection at the molecular level under anaerobic-aerobic conditions. Therefore, this study has the potential to be applied to the development of future therapeutics through basic metabolic studies of C. difficile infection.

Cough Presentation and Cough-Related Healthcare Utilization in Tertiary Care: Analysis of Routinely Collected Academic Institutional Database.

PURPOSE: Routinely collected data (RCD) from electronic health records (EHR) are useful for studying disease epidemiology in the real world. We examined cough presentation and cough-related healthcare utilization using an academic institutional EHR database in Korea. METHODS: In this retrospective cohort study, patients with subacute (3-8 weeks) or chronic cough (> 8 weeks in duration) referred to allergy and asthma clinics were studied. Cases were identified using the search term "cough" or "coughing," which is the chief complaint, in the data fields. Structured data, including demographics, medical history, symptoms, and diagnostic tests, were analyzed. Healthcare utilization was assessed for drug prescriptions, additional tests, or outpatient visits for 1 year. RESULTS: Cough was the chief complaint in 13,223 cases (46.7%) among 28,312 new referrals for 8 years. A total of 3810 subacute and 7150 chronic cough patients were analyzed. The common demographic profile was middle-aged woman (mean age 52.1 years), reported in 63% of the cases. Cough was frequently accompanied by anterior nasal (about 50%), lower airway (30%), or acid reflux disease symptoms (20%), and by test abnormalities in chest X-rays (14%), spirometry (23%), or T2 inflammation markers (40%). Chronic cough patients frequently required additional tests (chest CT scan: 24%), drug prescriptions (codeine: 21.5% and oral steroids: 9.9%), and long-term healthcare utilization (16.0%) for 1 year. CONCLUSIONS: Cough is a common chief complaint at allergy and asthma clinics, but the clinical presentation may be heterogeneous. Further studies are needed to understand long-term outcomes and reduce the disease burden.

An Integrative Multiomics Approach to Characterize Prebiotic Inulin Effects on Faecalibacterium prausnitzii.

Faecalibacterium prausnitzii, a major commensal bacterium in the human gut, is well known for its anti-inflammatory effects, which improve host intestinal health. Although several studies have reported that inulin, a well-known prebiotic, increases the abundance of F. prausnitzii in the intestine, the mechanism underlying this effect remains unclear. In this study, we applied liquid chromatography tandem mass spectrometry (LC-MS/MS)-based multiomics approaches to identify biological and enzymatic mechanisms of F. prausnitzii involved in the selective digestion of inulin. First, to determine the preference for dietary carbohydrates, we compared the growth of F. prausnitzii in several carbon sources and observed selective growth in inulin. In addition, an LC-MS/MS-based intracellular proteomic and metabolic profiling was performed to determine the quantitative changes in specific proteins and metabolites of F. prausnitzii when grown on inulin. Interestingly, proteomic analysis revealed that the putative proteins involved in inulin-type fructan utilization by F. prausnitzii, particularly ß-fructosidase and amylosucrase were upregulated in the presence of inulin. To investigate the function of these proteins, we overexpressed bfrA and ams, genes encoding ß-fructosidase and amylosucrase, respectively, in Escherichia coli, and observed their ability to degrade fructan. In addition, the enzyme activity assay demonstrated that intracellular fructan hydrolases degrade the inulin-type fructans taken up by fructan ATP-binding cassette transporters. Furthermore, we showed that the fructose uptake activity of F. prausnitzii was enhanced by the fructose phosphotransferase system transporter when inulin was used as a carbon source. Intracellular metabolomic analysis indicated that F. prausnitzii could use fructose, the product of inulin-type fructan degradation, as an energy source for inulin utilization. Taken together, this study provided molecular insights regarding the metabolism of F. prauznitzii for inulin, which stimulates the growth and activity of the beneficial bacterium in the intestine.

An integrative multiomics approach to characterize anti-adipogenic and anti-lipogenic effects of Akkermansia muciniphila in adipocytes.

The cellular components of Akkermansia muciniphila are considered potential biotherapeutics for the improvement of obesity, diabetes, and metabolic diseases. However, the molecular-based mechanism of A. muciniphila for treatment of obesity, which can provide important evidence for human research, has rarely been explored. Here, we applied integrative multiomics approaches to investigate the underlying molecular mechanism involved in obesity treatment by A. muciniphila. First, the treatment with a cell lysate of A. muciniphila reduced lipid accumulation in 3T3-L1 cells and downregulated the mRNA expression of proteins involved in adipogenesis and lipogenesis. Our proteomic results revealed that A. muciniphila decreased the expression of proteins involved in fat cell differentiation, fatty acid metabolism, and energy metabolism in adipocytes. Moreover, A. muciniphila significantly reduced the level of metabolites related to glycolysis, the TCA cycle, and ATP in adipocytes. Interestingly, serine protease inhibitor A3 (SERPINA3) homologs were overexpressed in the 3T3-L1 cells treated with A. muciniphila. Small interfering RNA (siRNA) transfection demonstrated that A. muciniphila upregulates SERPINA3G expression and inhibits lipogenesis in adipocytes. Taken together, our multiomics-based approaches enabled to uncover the molecular mechanism of A. muciniphila for treatment of obesity and provide potent anti-lipogenic agents.

A Cost-Effective CNN-LSTM-Based Solution for Predicting Faulty Remote Water Meter Reading Devices in AMI Systems.

Automatic meter infrastructure (AMI) systems using remote metering are being widely used to utilize water resources efficiently and minimize non-revenue water. We propose a convolutional neural network-long short-term memory network (CNN-LSTM)-based solution that can predict faulty remote water meter reading (RWMR) devices by analyzing approximately 2,850,000 AMI data collected from 2762 customers over 360 days in a small-sized city in South Korea. The AMI data used in this study is a challenging, highly unbalanced real-world dataset with limited features. First, we perform extensive preprocessing steps and extract meaningful features for handling this challenging dataset with limited features. Next, we select important features that have a higher influence on the classifier using a recursive feature elimination method. Finally, we apply the CNN-LSTM model for predicting faulty RWMR devices. We also propose an efficient training method for ML models to learn the unbalanced real-world AMI dataset. A cost-effective threshold for evaluating the performance of ML models is proposed by considering the mispredictions of ML models as well as the cost. Our experimental results show that an F-measure of 0.82 and MCC of 0.83 are obtained when the CNN-LSTM model is used for prediction.

Application of M1 macrophage as a live vector in delivering nanoparticles for in vivo photothermal treatment.

Introduction: To enhance photothermal treatment (PTT) efficiency, a delivery method that uses cell vector for nanoparticles (NPs) delivery has drawn attention and studied widely in recent years. Objectives: In this study, we demonstrated the feasibility of M1 activated macrophage as a live vector for delivering NPs and investigated the effect of NPs loaded M1 stimulated by Lipopolysaccharide on PTT efficiency in vivo. Methods: M1 was used as a live vector for delivering NPs and further to investigate the effect of NPs loaded M1 on PTT efficiency. Non-activated macrophage (MФ) was stimulated by lipopolysaccharide (LPS) into M1 and assessed for tumor cell phagocytic capacity towards NPs. Results: We found M1 exhibited a 20-fold higher uptake capacity of NPs per cell volume and 2.9-fold more active infiltration into the tumor site, compared with non-activated macrophage MФ. We injected M1 cells peritumorally and observed that these cells penetrated into the tumor mass within 12 h. Then, we conducted PTT using irradiation of a near-infrared laser for 1 min at 1 W/cm2. As a result, we confirmed that using M1 as an active live vector led to a more rapid reduction in tumor size within 1 day indicating that the efficacy of PTT with NPs-loaded M1 is higher than that with NPs-loaded MФ. Conclusion: Our study demonstrated the potential role of M1 as a live vector for enhancing the feasibility of PTT in cancer treatment.