A Comparison of Tracheal Intubation Using Direct Laryngoscope and Video Laryngoscope in the Sellick and Trendelenburg Position with That Using Direct Laryngoscope in the Supine Sniffing Position: A Randomized Controlled Trial.

Background: Tracheal intubation in the Sellick and Trendelenburg position (ST position) can prevent pulmonary aspiration but increase the difficulty of tracheal intubation. We compared tracheal intubation using video and direct laryngoscopy in the ST position with direct laryngoscopy in the supine sniffing position to evaluate the overall intubation performance. Methods: One hundred and twenty patients were randomly assigned to three groups: direct laryngoscope in the supine sniffing position (control), direct laryngoscope in the ST position (ST direct), and video laryngoscope in the ST position (ST video). The primary outcome was the intubation time; secondary outcomes included the first attempt success rate of tracheal intubation, intubation difficulty scale score, operator's subjective assessment of intubation difficulty, and modified Cormack-Lehane grades. Results: The median intubation times were greater in the ST direct (36.0 s) and video (34.5 s) than the control (28.0 s) groups. The first attempt success rate decreased in the ST direct (77.5%) but not the video (95.0%) group compared with the control group (100%). Conclusions: The challenges of tracheal intubation in the ST position, aimed at reducing the risk of pulmonary aspiration, can be mitigated by using a video laryngoscope, despite slightly longer intubation times.

Acid tolerance responses and their mechanisms in Lactiplantibacillus plantarum LM1001.

This study investigated the acid tolerance responses of Lactiplantibacillus plantarum LM1001 at physiological and molecular levels. Upon exposure to low pH, L. plantarum LM1001 demonstrated increased ATPase activity and ammonia consumption, which contributed to a higher intracellular pH. Comparative analysis of cell membrane fatty acids revealed that acid-stressed cells had a significantly higher proportion of unsaturated fatty acids than those of unstressed cells. There was differential upregulation of several genes, notably those involved in alkali production (arcB, argG, and argH) and in class I and class III stress responses (clpE, clpP, hrcA, dnaK, grpE, groEL, and groES). Following 2-h exposure to pH 2.5, L. plantarum LM1001 not only exhibited enhanced survival but also showed increased auto-aggregation and improved mucin adhesion capability, albeit with a reduction in hydrophobicity. These findings indicate that acid stress induces adaptive physiological and metabolic changes in L. plantarum LM1001, enhancing its acid resistance and adherence properties. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01582-4.

Wet tissue adhesive polymeric powder hydrogels for skeletal muscle regeneration.

Volumetric muscle loss (VML) frequently results from traumatic incidents and can lead to severe functional disabilities. Hydrogels have been widely employed for VML tissue regeneration, which are unfortunately ineffective because of the lack of intimate contact with injured tissue for structural and mechanical support. Adhesive hydrogels allow for strong tissue connections for wound closure. Nevertheless, conventional adhesive hydrogels exhibit poor tissue adhesion in moist, bleeding wounds due to the hydration layer at the tissue-hydrogel interfaces, resulting in insufficient performance. In this study, we developed a novel, biocompatible, wet tissue adhesive powder hydrogel consisting of dextran-aldehyde (dex-ald) and gelatin for the regeneration of VML. This powder absorbs the interfacial tissue fluid and buffer solution on the tissue, spontaneously forms a hydrogel, and strongly adheres to the tissue via various molecular interactions, including the Schiff base reaction. In particular, the powder composition with a 1:4 ratio of dex-ald to gelatin exhibited optimal characteristics with an appropriate gelation time (258 s), strong tissue adhesion (14.5 kPa), and stability. Dex-ald/gelatin powder hydrogels presented strong adhesion to various organs and excellent hemostasis compared to other wet hydrogels and fibrin glue. A mouse VML injury model revealed that the dex-ald/gelatin powder hydrogel significantly improved muscle regeneration, reduced fibrosis, enhanced vascularization, and decreased inflammation. Consequently, our wet-adhesive powder hydrogel can serve as an effective platform for repairing various tissues, including the heart, muscle, and nerve tissues.

Solvent Engineering of Thermo-Responsive Hydrogels Facilitates Strong and Large Contractile Actuations.

Thermo-responsive hydrogels can generate the actuation force through volumetric transitions in response to temperature changes. However, their weak mechanical properties and fragile actuation performance limit robust applications. Existing approaches to enhance these properties have typically depended on additional components, leading to an unavoidable interference to the actuation performance. In this work, robust thermo-responsive hydrogels are fabricated through solvent engineering. A particular solvent, N-methylformamide, interacts affinitively with the carbonyl group of N-isopropylacrylamide monomer, solubilizes the monomer with extremely high concentration, stabilizes chain propagation during polymerization, and greatly increases chain lengths and entanglements of the resulting polymer. The synthesized hydrogels are highly elastic, strong, and tough, displaying remarkable thermo-responsive contractile actuation. The simple synthetic process can broaden its applicability in designing robust functional hydrogel applications.

Socioeconomic Disparities in Six Common Cancer Survival Rates in South Korea: Population-Wide Retrospective Cohort Study.

Background: In South Korea, the cancer incidence rate has increased by 56.5% from 2001 to 2021. Nevertheless, the 5-year cancer survival rate from 2017 to 2021 increased by 17.9% compared with that from 2001 to 2005. Cancer survival rates tend to decline with lower socioeconomic status, and variations exist in the survival rates among different cancer types. Analyzing socioeconomic patterns in the survival of patients with cancer can help identify high-risk groups and ensure that they benefit from interventions. Objective: The aim of this study was to analyze differences in survival rates among patients diagnosed with six types of cancer-stomach, colorectal, liver, breast, cervical, and lung cancers-based on socioeconomic status using Korean nationwide data. Methods: This study used the Korea Central Cancer Registry database linked to the National Health Information Database to follow up with patients diagnosed with cancer between 2014 and 2018 until December 31, 2021. Kaplan-Meier curves stratified by income status were generated, and log-rank tests were conducted for each cancer type to assess statistical significance. Hazard ratios with 95% CIs for any cause of overall survival were calculated using Cox proportional hazards regression models with the time since diagnosis. Results: The survival rates for the six different types of cancer were as follows: stomach cancer, 69.6% (96,404/138,462); colorectal cancer, 66.6% (83,406/125,156); liver cancer, 33.7% (23,860/70,712); lung cancer, 30.4% (33,203/109,116); breast cancer, 91.5% (90,730/99,159); and cervical cancer, 78% (12,930/16,580). When comparing the medical aid group to the highest income group, the hazard ratios were 1.72 (95% CI 1.66-1.79) for stomach cancer, 1.60 (95% CI 1.54-1.56) for colorectal cancer, 1.51 (95% CI 1.45-1.56) for liver cancer, 1.56 (95% CI 1.51-1.59) for lung cancer, 2.19 (95% CI 2.01-2.38) for breast cancer, and 1.65 (95% CI 1.46-1.87) for cervical cancer. A higher deprivation index and advanced diagnostic stage were associated with an increased risk of mortality. Conclusions: Socioeconomic status significantly mediates disparities in cancer survival in several cancer types. This effect is particularly pronounced in less fatal cancers such as breast cancer. Therefore, considering the type of cancer and socioeconomic factors, social and medical interventions such as early cancer detection and appropriate treatment are necessary for vulnerable populations.

Sequential Effect of Dual-Layered Hybrid Graphite Anodes on Electrode Utilization During Fast-Charging Li-Ion Batteries.

To recharge lithium-ion batteries quickly and safely while avoiding capacity loss and safety risks, a novel electrode design that minimizes cell polarization at a higher current is highly desired. This work presents a dual-layer electrode (DLE) technology via sequential coating of two different anode materials to minimize the overall electrode resistance upon fast charging. Electrochemical impedance spectroscopy and distribution of relaxation times analysis revealed the dynamic evolution of electrode impedances in synthetic graphite (SG) upon a change in the state of charge (SOC), whereas the natural graphite (NG) maintains its original impedance regardless of SOC variation. This disparity dictates the sequence of the NG and SG coating layers within the DLE, considering the temporal SOC gradient developed upon fast charging. Simulation and experimental results suggest that DLE positioning NG and SG on the top (second-layer) and bottom (first-layer), respectively, can effectively reduce the overall resistance at a 4 C-rate (15-min charging), demonstrating two times higher capacity retention (61.0%) over 200 cycles than its counterpart with reversal sequential coating, and is higher than single-layer electrodes using NG or NG/SG binary mixtures. Hence, this study can guide the combinatorial sequence for multi-layer coating of various active materials for a lower-resistivity, thick-electrode design.

SPATA20 deficiency enhances the metastatic and angiogenic potential of cancer cells by promoting HIF-1α synthesis.

Hypoxia-inducible factors (HIFs) regulate cellular oxygen balance and play a central role in cancer metastasis and angiogenesis. Despite extensive research on HIFs, successful therapeutic strategies remain limited due to the intricate nature of their regulation. In this study, we identified SPATA20, a relatively understudied protein with a thioredoxin-like domain, as an upstream regulator of HIF-1α. Depleting SPATA20 induced HIF-1α expression, suggesting a tumor-suppressive role for SPATA20 in cancer cells. SPATA20 depletion increased HIF-1α protein levels and transcriptional activity without affecting its degradation. It appears that SPATA20 inhibits the de novo synthesis of HIF-1α, possibly by repressing the cap-dependent translation process involving AKT phosphorylation. Additionally, depletion of SPATA20 promoted cancer cell migration and invasion, which can be reversed by pharmacological inhibition of HIF-1α. Clinical data analysis revealed an inverse correlation between SPATA20 expression and colorectal cancer progression, providing evidence of its role as a potential biomarker. Utilizing SPATA20 as an indicator for HIF-1α-targeting therapy may be an attractive strategy for treating patients with hypoxia-driven cancers. In conclusion, this study demonstrates that SPATA20 deficiency promotes cancer progression by activating the HIF-1α signaling pathway.

Safety Assessment of Levilactobacillus brevis KU15006: A Comprehensive Analysis of its Phenotypic and Genotypic Properties.

Levilactobacillus brevis KU15006, isolated from kimchi, exhibits pathogen-antagonistic and anti-diabetic activities; however, the safety of this strain has not been assessed. In the present study, L. brevis KU15006 was evaluated to elucidate its safety as a probiotic strain using phenotypic and genotypic analyses. Its safety was assessed using a minimum inhibitory concentration test comprising nine antibiotics, 26 antibiotic resistance genes, a single conjugative element, virulence gene analysis, hemolysis, cell cytotoxicity, mucin degradation, and toxic metabolite production. L. brevis KU15006 exhibited equal or lower minimum inhibitory concentration for the nine antibiotics than the cut-off value established by the European Food Safety Authority. It did not harbor antibiotic resistance and virulence genes. L. brevis KU15006 lacked ß-hemolysis, mucin degradation, cytotoxicity against Caco-2 cells, gelatin liquefaction, bile salt deconjugation, and toxic metabolite production abilities. Based on the results, L. brevis KU15006, which has antagonistic and anti-diabetic effects, could be marketed as a probiotic in the future.

"Three-in-one": A Photoactivable Nanoplatform Evokes Anti-Immune Response by Inhibiting BRD4-cMYC-PDL1 Axis to Intensify Photo-Immunotherapy.

Combinatorial immuno-cancer therapy is recognized as a promising approach for efficiently treating malignant tumors. Yet, the development of multifunctional nanomedicine capable of precise tumor targeting, remote activation, and immune-regulating drug delivery remains a significant challenge. In this study, nanoparticles loaded with an immune checkpoint inhibitor (JQ-1) using polypyrrole/hyaluronic acid (PPyHA/JQ-1) are developed. These nanoparticles offer active tumor targeting, photothermal tumor ablation using near-infrared light, and laser-controlled JQ-1 release for efficient breast cancer treatment. When the molecular weight of HA varies (from 6.8 kDa to 3 MDa) in the PPyHA nanoparticles, it is found that the nanoparticles synthesized using 1 MDa HA, referred to as PPyHA (1 m), show the most suitable properties, including small hydrodynamic size, high surface HA contents, and colloidal stability. Upon 808 nm laser irradiation, PPyHA/JQ-1 elevates the temperature above 55 °C, which is sufficient for thermal ablation and active release of JQ-1 in the tumor microenvironment (TME). Notably, the controlled release of JQ-1 substantially inhibits the expression of cancer-promoting genes. Furthermore, PPyHA/JQ-1 effectively suppresses the expression of programmed cell death ligand 1 (PD-L1) and prolongs dendritic cell maturation and CD8+ T cell activation against the tumor both in vitro and in vivo. PPyHA/JQ-1 treatment simultaneously provides a significant tumor regression through photothermal therapy and immune checkpoint blockade, leading to a durable antitumor-immune response. Overall, "Three-in-one" immunotherapeutic photo-activable nanoparticles have the potential to be beneficial for a targeted combinatorial treatment approach for TNBC.

CD200Rhigh neutrophils with dysfunctional autophagy establish systemic immunosuppression by increasing regulatory T cells.

Distinct neutrophil populations arise during certain pathological conditions. The generation of dysfunctional neutrophils during sepsis and their contribution to septicemia-related systemic immune suppression remain unclear. In this study, using an experimental sepsis model that features immunosuppression, we identified a novel population of pathogenic CD200Rhigh neutrophils that are generated during the initial stages of sepsis and contribute to systemic immune suppression by enhancing regulatory T (Treg) cells. Compared to their CD200Rlow counterparts, sepsis-generated CD200Rhigh neutrophils exhibit impaired autophagy and dysfunction, with reduced chemotactic migration, superoxide anion production, and TNF-α production. Increased soluble CD200 blocks autophagy and neutrophil maturation in the bone marrow during experimental sepsis, and recombinant CD200 treatment in vitro can induce neutrophil dysfunction similar to that observed in CD200Rhigh neutrophils. The administration of an α-CD200R antibody effectively reversed neutrophil dysfunction by enhancing autophagy and protecting against a secondary infection challenge, leading to increased survival. Transcriptome analysis revealed that CD200Rhigh neutrophils expressed high levels of Igf1, which elicits the generation of Treg cells, while the administration of an α-CD200R antibody inhibited Treg cell generation in a secondary infection model. Taken together, our findings revealed a novel CD200Rhigh neutrophil population that mediates the pathogenesis of sepsis-induced systemic immunosuppression by generating Treg cells.

Neutrophil extracellular traps promote ΔNp63+ basal cell hyperplasia in chronic rhinosinusitis.

BACKGROUND: Neutrophil extracellular traps (NETs) are observed in chronic rhinosinusitis (CRS), although their role remains unclear. OBJECTIVES: This study aimed to investigate the influence of NETs on the CRS epithelium. METHODS: Forty-five sinonasal biopsy specimens were immunofluorescence-stained to identify NETs and p63+ basal stem cells. Investigators treated human nasal epithelial cells with NETs and studied them with immunofluorescence staining, Western blotting, and quantitative real-time PCR. NET inhibitors were administered to a murine neutrophilic nasal polyp model. RESULTS: NETs existed in tissues in patients with CRS with nasal polyps, especially in noneosinophilic nasal polyp tissues. p63+ basal cell expression had a positive correlation with the release of NETs. NETs induced the expansion of Ki-67+p63+ cells. We found that ΔNp63, an isoform of p63, was mainly expressed in the nasal epithelium and controlled by NETs. Treatment with deoxyribonuclease (DNase) I or Sivelestat (NET inhibitors) prevented the overexpression of ΔNp63+ epithelial stem cells and reduced polyp formation. CONCLUSIONS: These results reveal that NETs are implicated in CRS pathogenesis via basal cell hyperplasia. This study suggests a novel possibility of treating CRS by targeting NETs.

The Defined TLR3 Agonist, Nexavant, Exhibits Anti-Cancer Efficacy and Potentiates Anti-PD-1 Antibody Therapy by Enhancing Immune Cell Infiltration.

Nexavant was reported as an alternative to the TLR3 agonist of Poly(I:C) and its derivatives. The physicochemical properties, signaling pathways, anti-cancer effects, and mechanisms of Nexavant were investigated. The distinctive characteristics of Nexavant compared to that of Poly(I:C) were demonstrated by precise quantification, enhanced thermostability, and increased resistance to RNase A. Unlike Poly(I:C), which activates TLR3, RIG-I, and MDA5, Nexavant stimulates signaling through TLR3 and RIG-I but not through MDA5. Compared to Poly(I:C), an intratumoral Nexavant treatment led to a unique immune response, immune cell infiltration, and suppression of tumor growth in various animal cancer models. Nexavant therapy outperformed anti-PD-1 antibody treatment in all the tested models and showed a synergistic effect in combinational therapy, especially in well-defined cold tumor models. The effect was similar to that of nivolumab in a humanized mouse model. Intranasal instillation of Nexavant led to the recruitment of immune cells (NK, CD4+ T, and CD8+ T) to the lungs, suppressing lung metastasis and improving animal survival. Our study highlighted Nexavant's defined nature for clinical use and unique signaling pathways and its potential as a standalone anti-cancer agent or in combination with anti-PD-1 antibodies.

Heterozygous Kmt2d loss diminishes enhancers to render medulloblastoma cells vulnerable to combinatory inhibition of lysine demethylation and oxidative phosphorylation.

The histone H3 lysine 4 (H3K4) methyltransferase KMT2D (also called MLL4) is one of the most frequently mutated epigenetic modifiers in medulloblastoma (MB) and other types of cancer. Notably, heterozygous loss of KMT2D is prevalent in MB and other cancer types. However, what role heterozygous KMT2D loss plays in tumorigenesis has not been well characterized. Here, we show that heterozygous Kmt2d loss highly promotes MB driven by heterozygous loss of the MB suppressor gene Ptch in mice. Heterozygous Kmt2d loss upregulated tumor-promoting programs, including oxidative phosphorylation and G-protein-coupled receptor signaling, in Ptch-mutant-driven MB genesis. Mechanistically, both downregulation of the transcription-repressive tumor suppressor gene NCOR2 by heterozygous Kmt2d loss and upregulation of the oncogene MycN by heterozygous Ptch loss increased the expression of tumor-promoting genes. Moreover, heterozygous Kmt2d loss extensively diminished enhancer signals (e.g., H3K27ac) and H3K4me3 signature, including those for tumor suppressor genes (e.g., Ncor2). Combinatory pharmacological inhibition of oxidative phosphorylation and the H3K4 demethylase LSD1 drastically reduced tumorigenicity of MB cells bearing heterozygous Kmt2d loss. These findings reveal the mechanistic basis underlying the MB-promoting effect of heterozygous KMT2D loss, provide a rationale for a therapeutic strategy for treatment of KMT2D-deficient MB, and have mechanistic implications for the molecular pathogenesis of other types of cancer bearing heterozygous KMT2D loss.

Is the Direct Fixation of Displaced Quadrilateral Plates in Acetabular Fractures Necessary?

Quadrilateral plate fractures represent a heterogeneous group of acetabular fractures. Accurate reduction is required to prevent post-traumatic arthritis. The purpose of this study is to determine the reduction effect of the direct fixation of quadrilateral plates in acetabular fractures, and to evaluate the strength of direct fixation compared to indirect fixation. Between 2005 and 2021, 49 patients underwent surgery for open reduction and internal fixation in acetabular fractures with severely displaced quadrilateral plates. Twenty-nine patients comprised the indirect fixation group, and twenty patients comprised the direct fixation group. In a comparison of primary outcome between two groups, 10 out of 29 indirect-group patients and 1 out of 20 direct-group patients developed post-traumatic osteoarthritis, wherein the difference between the two groups is statistically significant. In the assessment of postoperative Matta's radiological reduction status, 19 out of 20 patients in the direct group had achieved anatomical and congruent reduction. The treatment using a direct reduction and internal fixation improved the reduction quality of articular displacement and offered a better survivorship of the affected hip joint.

Full-Color Generation via Phototunable Mono Ink for Fast and Elaborate Printings.

Unlike pigment-based colors, which are determined by their molecular structure, diverse colors can be expressed by a regular arrangement of nanomaterials. However, existing techniques for constructing such nanostructures have struggled to combine high precision and speed, resulting in a narrow gamut, and prolonged color fabrication time. Here, this work reports a phototunable mono ink that can generate a wide range of colors by controlling regularly arranged nanostructure. Core-shell growth controlled by polymerization time precisely regulates the distance between arranged particles at a nanometer-scale, enabling the generation of various colors. Moreover, the wide and thin arrangement induces constrained out-of-plane growth, thus facilitating the intricate color generation at the desired location via photopolymerization. Upon terminating polymerization by oxygen gas, the generated colors are readily fixed and kept stable. Utilizing programmed ultraviolet illumination, large-scale and high-resolution (≈1 µm) full-color printings are demonstrated at high speed (100 mm2 s-1 ).

Contribution of Electrolyte Decomposition Products and the Effect of Temperature on the Dissolution of Transition Metals from Cathode Materials.

A fundamental understanding of aging processes in lithium-ion batteries (LIBs) is imperative in the development of future battery architectures for widespread electrification. Herein, dissolution of transition metals from cathode active materials of LIBs is among the most important degradation processes. Research has demonstrated that elevated operating temperatures accelerate battery degradation. However, the exact mechanism of transition-metal dissolution at elevated temperatures has still to be clarified. Current literature suggests that the reaction rate of dissolution increases with increasing temperature; moreover, the decomposition of electrolytes results in products that also accelerate dissolution processes. Most studies focus on ex situ analyses of thermally treated full cells. This approach is not appropriate to get detailed insights and to distinguish between different contributions. In this work, with the help of real-time dissolution analysis using an electroanalytical flow cell (EFC) coupled to an inductively coupled plasma mass spectrometer (ICP-MS), we present novel details of the temperature effects on in situ dissolution at the cathode electrolyte interface. With fresh electrolytes, we find increased Mn dissolution even at open-circuit conditions as well as with constant voltage polarization when the electrode sample is heated at constant temperatures between 50 and 80 °C. The release of transition metals also responds in a nuanced manner when applying temperature transients. Utilizing electrolytes preheated at 60 and 100 °C, we demonstrate that decomposition products in the bulk electrolyte have no influence on transition-metal (TM) dissolution when constantly flushing the cell with the thermally aged electrolyte samples. Only when keeping the cathode temperature at 60 °C, the dissolution increases by a factor of 2-3. Our findings highlight the interplay between the cathode and electrolyte and provide new insights into the dissolution mechanism of cathode materials.

Diagnosis of Current Flow Patterns Inside Fault-Simulated Li-Ion Batteries via Non-Invasive, In Operando Magnetic Field Imaging.

With the growing popularity of Li-ion batteries in large-scale applications, building a safer battery has become a common goal of the battery community. Although the small errors inside the cells trigger catastrophic failures, tracing them and distinguishing cell failure modes without knowledge of cell anatomy can be challenging using conventional methods. In this study, a real-time, non-invasive magnetic field imaging (MFI) analysis that can signal the battery current-induced magnetic field and visualize the current flow within Li-ion cells is developed. A high-speed, spatially resolved MFI scan is used to derive the current distribution pattern from cells with different tab positions at a current load. Current maps are collected to determine possible cell failures using fault-simulated batteries that intentionally possess manufacturing faults such as lead-tab connection failures, electrode misalignment, and stacking faults (electrode folding). A modified MFI analysis exploiting the magnetic field interference with the countercurrent-carrying plate enables the direct identification of defect spots where abnormal current flow occurs within the pouch cells.

Fabry-Perot Interferometric Fiber-Optic Sensor for Rapid and Accurate Thrombus Detection.

We present a fiber-optic sensor based on the principles of a Fabry-Perot interferometer (FPI), which promptly, sensitively, and precisely detects blood clot formation. This sensor has two types of sensor tips; the first was crafted by splicing a tapered fiber into a single-mode fiber (SMF), where fine-tuning was achieved by adjusting the tapered diameter and length. The second type is an ultra-compact blood FPI situated on the core of a single-mode fiber. The sensor performance was evaluated via clot-formation-indicating spectrum shifts induced by the varied quantities of a thrombin reagent introduced into the blood. The most remarkable spectral sensitivity of the micro-tip fiber type was approximately 7 nm/µL, with a power sensitivity of 4.1 dB/µL, obtained with a taper fiber diameter and length of 55 and 300 µm, respectively. For the SMF type, spectral sensitivity was observed to be 8.7 nm/µL, with an optical power sensitivity of 0.4 dB/µL. This pioneering fiber-optic thrombosis sensor has the potential for in situ applications, healthcare, medical monitoring, harsh environments, and chemical and biological sensing. The study underscores the scope of optical technology in thrombus detection, establishing a platform for future medical research and application.

Machine learning-based inverse design methods considering data characteristics and design space size in materials design and manufacturing: a review.

In the last few decades, the influence of machine learning has permeated many areas of science and technology, including the field of materials science. This toolkit of data driven methods accelerated the discovery and production of new materials by accurately predicting the complicated physical processes and mechanisms that are not fully described by existing materials theories. However, the availability of a growing number of increasingly complex machine learning models confronts us with the question of "which machine learning algorithm to employ". In this review, we provide a comprehensive review of common machine learning algorithms used for materials design, as well as a guideline for selecting the most appropriate model considering the nature of the design problem. To this end, we classify the material design problems into four categories of: (i) the training data set being sufficiently large to capture the trend of design space (interpolation problem), (ii) a vast design space that cannot be explored thoroughly with the initial training data set alone (extrapolation problem), (iii) multi-fidelity datasets (small accurate dataset and large approximate dataset), and (iv) only a small dataset available. The most successful machine learning-based surrogate models and design approaches will be discussed for each case along with pertinent literature. This review focuses mostly on the use of ML algorithms for the inverse design of complicated composite structures, a topic that has received a lot of attention recently with the rise of additive manufacturing.

Sphingosylphosphorylcholine inhibits plasma cell differentiation and ameliorates experimental autoimmune encephalomyelitis.

Introduction: Multiple sclerosis (MS) is a potentially disabling disease that damages the brain and spinal cord, inducing paralysis of the body. While MS has been known as a T-cell mediated disease, recent attention has been drawn to the involvement of B cells in its pathogenesis. Autoantibodies from B cells are closely related with the damage lesion of central nervous system and worse prognosis. Therefore, regulating the activity of antibody secreting cell could be related with the severity of the MS symptoms. Methods: Total mouse B cells were stimulated with LPS to induce their differentiation into plasma cells. The differentiation of plasma cells was subsequently analyzed using flow cytometry and quantitative PCR analysis. To establish an experimental autoimmune encephalomyelitis (EAE) mouse model, mice were immunized with MOG35-55/CFA emulsion. Results: In this study, we found that plasma cell differentiation was accompanied by upregulation of autotaxin, which converts sphingosylphosphorylcholine (SPC) to sphingosine 1-phosphate in response to LPS. We observed that SPC strongly blocked plasma cell differentiation from B cells and antibody production in vitro. SPC downregulated LPS-stimulated IRF4 and Blimp 1, which are required for the generation of plasma cells. SPC-induced inhibitory effects on plasma cell differentiation were specifically blocked by VPC23019 (S1PR1/3 antagonist) or TY52159 (S1PR3 antagonist), but not by W146 (S1PR1 antagonist) and JTE013 (S1PR2 antagonist), suggesting a crucial role of S1PR3 but not S1PR1/2 in the process. Administration of SPC against an EAE mouse model significantly attenuated the symptoms of disease, showing decreased demyelinated areas of the spinal cord and decreased numbers of cells infiltrated into the spinal cord. SPC markedly decreased plasma cell generation in the EAE model, and SPC-induced therapeutic effects against EAE were not observed in µMT mice. Conclusion: Collectively, we demonstrate that SPC strongly inhibits plasma cell differentiation, which is mediated by S1PR3. SPC also elicits therapeutic outcomes against EAE, an experimental model of MS, suggesting SPC as a new material to control MS.