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Ga Eun Park,1 Jae-Hoon Ko,2 Hyun Kyun Ki1 1Division of Infectious Disease, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea; 2Division of Infectious Diseases, Department of Internal Medicine, Samsung Medical Center, Seoul, KoreaCorrespondence: Hyun Kyun KiDivision of Infectious Diseases, Konkuk University Medical Center, Konkuk University School of Medicine, 120-1, Neungdong-Ro, Gwangjin-gu, Seoul 05030, Republic of KoreaTel +82-2-2030-7546Email kihkdr@kuh.ac.krPurpose: There is an increasing prevalence of multidrug-resistant (MDR) organisms worldwide. Therefore, broad-spectrum antibiotics are recommended in the treatment of hospital-acquired pneumonia (HAP). However, it remains controversial whether patients with early onset, non-ventilator HAP (NV-HAP) should also be empirically treated with broad-spectrum antibiotics. We compared the clinical benefit of ceftriaxone plus clindamycin vs piperacillin/tazobactam as the initial empirical treatment of adults with early NV-HAP.Patients and Methods: Retrospective cohort study was conducted in adult patients who were diagnosed with early, NV-HAP between January 2013 and June 2017 at a community-based tertiary care hospital. Patients were eligible for inclusion if they had received empiric treatment with either ceftriaxone and clindamycin or piperacillin/tazobactam for at least 3 days. Patients with increased risk of MDR pathogens were excluded.Results: A total of 89 patients were treated with ceftriaxone and clindamycin, while 124 received piperacillin/tazobactam. There were no significant differences between the two antibiotic groups with regard to median age, sex, or risk of pneumonia. The 30-day all-cause mortality did not differ significantly between the ceftriaxone plus clindamycin and piperacillin/tazobactam groups (4.5% vs 1.6%, P=0.202, respectively). However, in multivariate analysis, clinical failure was more frequent in the ceftriaxone plus clindamycin group than in the piperacillin/tazobactam group (HR 3.316; 95% CI, 1.589– 6918, P=0.001).Conclusion: Treatment with piperacillin/tazobactam was more effective than that with ceftriaxone plus clindamycin in patients with early NV-HAP. This study supports the recent treatment recommendations that patients with early NV-HAP should be treated empirically with broad-spectrum antibiotics.Keywords: empirical antibiotics, hospital-acquired infection, pneumonia, multiple drug resistance

The lubricating properties of water have been discussed extensively for millennia. Water films can exhibit wearless high friction in the form of cold ice, or act as lubricants in skating and skiing when a liquid. At the fundamental level, friction is the result of a balance between the rate of energy generation by phonon excitation during sliding and drainage of the energy from the interface by coupling with bulk atoms. Using atomic force microscopy, we found that when H2O intercalates between graphene and mica, it increases the friction between the tip and the substrate, dependent on the thickness of the water and graphene layers, while the magnitude of the increase in friction was reduced by D2O intercalation. With the help of first-principles density functional theory calculations, we explain this unexpected behavior by the increased spectral range of the vibration modes of graphene caused by water, and by better overlap of the graphene vibration modes with mica phonons, which favors more efficient energy dissipation. The larger increase in friction with H2O versus D2O shows that the high-frequency vibration modes of the water molecules play a very important role in the transfer of the vibrational energy of the graphene to the phonon bath of the substrate.

Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Jeong Seok Lee reports financial support was provided by Korea Advanced Institute of Science and Technology. Jeong Seok Lee reports a relationship with Korea Advanced Institute of Science and Technology that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.]., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Biotin is an essential coenzyme involved in various metabolic processes across all known organisms, with biotinylation being crucial for the activity of carboxylases. BirA from Haemophilus influenzae is a bifunctional protein that acts as a biotin protein ligase and a transcriptional repressor. This study reveals the crystal structures of Hin BirA in both its apo- and holo-(biotinyl-5'-AMP bound) forms. As a class II BirA, it consists of three domains: N-terminal DNA binding domain, central catalytic domain, and C-terminal SH3-like domain. The structural analysis shows that the biotin-binding loop forms an ordered structure upon biotinyl-5'-AMP binding. This facilitates its interaction with the ligand and promotes protein dimerization. Comparative studies with other BirA homologs from different organisms indicate that the residues responsible for binding biotinyl-5'-AMP are highly conserved. This study also utilized AlphaFold2 to model the potential heterodimeric interaction between Hin BirA and biotin carboxyl carrier protein, thereby providing insights into the structural basis for biotinylation. These findings enhance our understanding of the structural and functional characteristics of Hin BirA, highlighting its potential as a target for novel antibiotics that disrupt the bacterial biotin synthesis pathways., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although most impacted third molars (ITMs) are extracted in the teens and early 20s, some undergo extractions after their 40s. It is unclear whether the reasons for extraction, the degree of impaction, and complications differ in patients in an older age group compared with a younger age group., Purpose: The purpose of this study was to measure the association between age and 1) reason for extraction and 2) postoperative complications., Study Design, Setting, Sample: This was a retrospective cohort study of patients who had undergone surgical extraction of at least one mandibular ITM at a single institution. We excluded 1) age under 20 years, 2) follow-up period of less than 1 week, and 3) tooth extraction under general anesthesia., Predictor Variable: The primary predictor variable was age, classified into 3 groups (20s:20-29; 30s:30-39; over 40s: 40 and greater)., Main Outcome Variable(s): The primary outcome variables were the reason for extraction (prophylactic or symptomatic) and the presence of complications. The secondary outcome variable was type of complication (postoperative infection, dry socket, neurosensory disturbance, presenting pain over 1 month, retained root requiring secondary treatment)., Covariates: The covariates were sex, laterality of ITM, and difficulty of extraction as measured by the difficulty index, a measure based on depth, orientation, and ramus relationship/space available, with a higher score indicating greater difficulty., Analyses: χ 2 test was performed to analyze the association of categorical outcome variables and covariates. Level of statistical significance was set at P < .05., Results: Of a total of 831 eligible subjects, there were 555 (66.8%), 159 (19.1%), and 117 (14.1%) in the 20s, 30s, and over 40s age groups, respectively. The percentage of symptomatic extraction of ITM was significantly higher in the over-40 age group compared with the 20s group (92.3 vs 69.4%, (P < .001). Complication rate also significantly differed between over 40s group and the 20s group (7.7 vs 1.8%, P < .001). Difficulty index and indications for ITM extraction were significantly different between groups (P < .001)., Conclusion and Relevance: Symptoms, difficulty, and complications related to ITM increase at over 40 years of age. This should be taken into consideration during the joint clinical decision-making process with patients with ITM., (Copyright © 2024 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Zwitterionic polymers have been found to be biocompatible alternatives to poly(ethylene glycol) (PEG) for conjugation to proteins. This work reports the site-selective conjugation of poly(caprolactone-carboxybetaine) (pCLZ) to human growth hormone receptor antagonist (GHA) B2036-alkyne and investigation of safety, activity, and pharmacokinetics. Azide-end-functionalized pCLZs were synthesized and conjugated to GHA B2036-alkyne via copper-catalyzed click reaction. The resulting inhibitory bioactivity concentration responses in Ba/F3-GHR cells were compared to those of PEGylated GHA B2036. IgG and IgM antibody production was tested in mice, and no measurable antibody or cytokine production was detected for the pCLZ conjugate. Using 18 F-labeled PET/CT imaging, the pCLZ conjugate showed an increase in circulation time compared to that of GHA B2036. Acute toxicity of the polymer was investigated in vivo and found to be nontoxic. Ex vivo degradation of the polymer on the conjugate was investigated. The results suggest that pCLZ-GHA is a potentially safe alternative to PEG-GHA.

Microglia are strongly implicated in demyelinating neurodegenerative diseases with increasing evidence for roles in protection and healing, but the mechanisms that control CNS remyelination are poorly understood. Here, we show that microglia-specific deletion of tumor necrosis factor receptor 1 (TNFR1) and pharmacological inhibition of soluble TNF (solTNF) or downstream interleukin-1 receptor (IL-1R) allow maturation of highly activated disease-associated microglia with increased size and myelin phagocytosis capacity that accelerate cortical remyelination and motor recovery. Single-cell transcriptomic analysis of cortex at disease onset reveals that solTNF inhibition enhances reparative IL-10-responsive while preventing damaging IL-1-related signatures of disease-associated microglia. Longitudinal brain transcriptome analysis through disease reveals earlier recovery upon therapeutic loss of microglia TNFR1. The functional relevance of microglia inflammatory polarization pathways for disease is validated in vivo. Furthermore, disease-state microglia producing downstream IL-1/IL-18/caspase-11 targets are identified in human demyelinating lesions. Overall, redirecting disease microglia polarization by targeting cytokines is a potential approach for improving CNS repair in demyelinating disorders., Competing Interests: Declaration of interests R.J.T. is CEO and C.J.B. is vice president of Neuroscience of INmune Bio. Both R.J.T. and C.J.B. own shares in INmuneBio. INmune Bio owns a patent application related to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Haplotype-level allelic characterization facilitates research on the functional, evolutionary and breeding-related features of extremely large and complex plant genomes. We report a 21.7-Gb chromosome-level haplotype-resolved assembly in Pinus densiflora. We found genome rearrangements involving translocations and inversions between chromosomes 1 and 3 of Pinus species and a proliferation of specific long terminal repeat (LTR) retrotransposons (LTR-RTs) in P. densiflora. Evolutionary analyses illustrated that tandem and LTR-RT-mediated duplications led to an increment of transcription factor (TF) genes in P. densiflora. The haplotype sequence comparison showed allelic imbalances, including presence-absence variations of genes (PAV genes) and their functional contributions to flowering and abiotic stress-related traits in P. densiflora. Allele-aware resequencing analysis revealed PAV gene diversity across P. densiflora accessions. Our study provides insights into key mechanisms underlying the evolution of genome structure, LTR-RTs and TFs within the Pinus lineage as well as allelic imbalances and diversity across P. densiflora., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: The treatment outcomes of ruptured intracranial aneurysms using the Neuroform Atlas stent were evaluated., Methods: This study represents a retrospective review that included patients who underwent endovascular treatment for ruptured aneurysms at a single institution. Between January 2018 and September 2022, endovascular treatments including simple coiling or Neuroform Atlas stent-assisted coil embolization were performed in 191 patients with ruptured intracranial aneurysms., Results: Intraprocedural rupture was observed in 11 (8.7%) patients in the Simple Coiling (SC) group, which was slightly higher than that in 4 (6.3%) patients in the Neuroform Atlas stent-assisted coiling (NASAC) group (p=0.241). However, Thromboembolic event (TEE) was slightly more prevalent in the NASAC group, with 4 (6.3%) cases as compared to the 5 (3.9%) cases in the SC group (p=0.235). The retreatment rate was slightly higher in the SC group, with 19 (26.4%) patients as compared to the 10 patients (22.2%) in the NASAC group (p=0.342)., Conclusions: The use of the Neuroform Atlas stent (NAS) for ruptured aneurysms might be safe and effective.

Background: Several studies have investigated the relationship between ursodeoxycholic acid (UDCA) and COVID-19 infection. However, complex and conflicting results have generated confusion in the application of these results., Objective: We aimed to investigate whether the association between UDCA and COVID-19 infection can also be demonstrated through the analysis of a large-scale cohort., Methods: This retrospective study used local and nationwide cohorts, namely, the Jeonbuk National University Hospital into the Observational Medical Outcomes Partnership common data model cohort (JBUH CDM) and the Korean National Health Insurance Service claim-based database (NHIS). We investigated UDCA intake and its relationship with COVID-19 susceptibility and severity using validated propensity score matching., Results: Regarding COVID-19 susceptibility, the adjusted hazard ratio (aHR) value of the UDCA intake was significantly lowered to 0.71 in the case of the JBUH CDM (95% CI 0.52-0.98) and was significantly lowered to 0.93 (95% CI 0.90-0.96) in the case of the NHIS. Regarding COVID-19 severity, the UDCA intake was found to be significantly lowered to 0.21 (95% CI 0.09-0.46) in the case of JBUH CDM. Furthermore, the aHR value was significantly lowered to 0.77 in the case of NHIS (95% CI 0.62-0.95)., Conclusions: Using a large-scale local and nationwide cohort, we confirmed that UDCA intake was significantly associated with reductions in COVID-19 susceptibility and severity. These trends remained consistent regardless of the UDCA dosage. This suggests the potential of UDCA as a preventive and therapeutic agent for COVID-19 infection., (©Hyunjun Lee, Min Gul Kim, Sang Woo Yeom, Sang Jae Noh, Cho Yun Jeong, Min Ji Kim, Min Gu Kang, Ji Hoon Ko, Su Cheol Park, Hyeok Tae Kweon, Sang Il Sim, Hyun Lee, Yeon Seok You, Jong Seung Kim. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 07.10.2024.)

Polyphenols are well known for their health-related benefits, including antioxidant activities, but most of them are hydrophobic, decreasing their bioavailability. This study reports water-soluble trimeric antioxidants synthesized with L-carnosine and the hydrophobic ortho-methoxy-substituted phenolic unit, syringaldehyde or vanillin. In the DPPH assay, carnosine-syringaldehyde (7.5 μM) and carnosine-vanillin (19 μM) derivatives showed much lower IC50 values than ascorbic acid (27.5 μM) and sodium ascorbate (30.5 μM) standards. According to the AAPH assay, carnosine-syringaldehyde and carnosine-vanillin protect DNA at concentrations as low as 6.5 μM and 26 μM, respectively, while both sodium ascorbate and ascorbic acid protected until 52 μM. Another notable property of these antioxidants is they can protect DNA well against hydroxyl radicals, produced via the Fenton reaction: carnosine-syringaldehyde showed DNA protection at all tested concentrations (833-1.6 μM), but the protection was slightly weaker between 26-1.6 μM. Carnosine-vanillin showed strong protection in the 833-104 μM range and some protection between 52-3.2 μM. Conversely, both sodium ascorbate and ascorbic acid did not protect DNA at any test concentration. In the pro-oxidant potential assessments, the synthesized antioxidants did not show any pro-oxidant effects at all concentrations, whereas sodium ascorbate showed severe pro-oxidant effects between 833-13 μM and ascorbic acid, 833-52 μM. Our study stresses the importance of ortho-methoxy group(s) for antioxidants as its electron-donating nature contributes to enhancing antioxidant activities, while steric bulk eliminates pro-oxidant effects by preventing the effective binding of transition metal ions to the phenolic hydroxyl group. The hydrophobicity of hindered phenols can be overcome if attached to a water-soluble scaffold., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Minor ginsenosides produced by β-glucosidase are interesting biologically and pharmacologically. In this study, new ginsenoside-hydrolyzing glycosidase from Furfurilactobacillus rossiae DCYL3 was cloned and expressed in Escherichia coli strain BL21. The enzyme converted Rb1 and Gyp XVII into Rd and compound K following the pathways: Rb1→Rd and Gyp XVII→F2→CK, respectively at optimal condition: 40 °C, 15 min, and pH 6.0. Furthermore, we examined the cytotoxicity, NO production, ROS generation, and gene expression of Gynostemma extract (GE) and bioconverted Gynostemma extract (BGE) in vitro against A549 cell lines for human lung cancer and macrophage RAW 264.7 cells for antiinflammation, respectively. As a result, BGE demonstrated significantly greater toxicity than GE against lung cancer at a dose of 500 µg/mL but in normal cells showed lower toxicity. Then, we indicated an enhanced generation of ROS, which may be boosting cancer cell toxicity. By blocking the intrinsic way, BGE increased p53, Bax, Caspase 3, 9, and while Bcl2 is decreased. At 500 µg/mL, the BGE sample was less toxic in normal cells and decreased the LPS-treated NO and ROS level to reduce inflammation. In addition, BGE inhibited the expression of pro-inflammatory genes COX-2, iNOS, IL-6, and IL-8 in RAW 264.7 cells than the sample of GE. In conclusion, FrBGL3 has considerable downstream applications for high-yield, low-cost, effective manufacture of minor ginsenosides. Moreover, the study's findings imply that BGE would be potential materials for anti-cancer and anti-inflammatory agent after consideration of future studies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reservoir computing (RC) system is based upon the reservoir layer, which non-linearly transforms input signals into high-dimensional states, facilitating simple training in the readout layer-a linear neural network. These layers require different types of devices-the former demonstrated as diffusive memristors and the latter prepared as drift memristors. The integration of these components can increase the structural complexity of RC system. Here, a reconfigurable resistive switching memory (RSM) capable of implementing both diffusive and drift dynamics is demonstrated. This reconfigurability is achieved by preparing a medium with a 3D ion transport channel (ITC), enabling precise control of the metal filament that determines memristor operation. The 3D ITC-RSM operates in a volatile threshold switching (TS) mode under a weak electric field and exhibits short-term dynamics that are confirmed to be applicable as reservoir elements in RC systems. Meanwhile, the 3D ITC-RSM operates in a non-volatile bipolar switching (BS) mode under a strong electric field, and the conductance modulation metrics forming the basis of synaptic weight update are validated, which can be utilized as readout elements in the readout layer. Finally, an RC system is designed for the application of reconfigurable 3D ITC-RSM, and performs real-time recognition on Morse code datasets., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Influenza A virus (IAV) induces acute respiratory infections in birds and various mammals, including humans, and presents a significant global public health concern, with considerable economic consequences. Recently, researchers have shown keen interest in noncanonical small noncoding RNAs (sncRNAs) as carriers of epigenetic information, including tRNA-derived small RNAs (tsRNAs), rRNA-derived small RNA (rsRNAs), and Y RNA-derived small RNAs (ysRNAs). Particularly, tsRNAs and rsRNAs are detected in diverse species and demonstrate evolutionary conservation. We analyzed sncRNAs sequencing data in the pulmonary tissue of two genetically distinct mouse strains, C57BL/6J and DBA/2J, to explore strain-specific variations of sncRNAs in response to IAV infection. We systematically compiled information on noncanonical sncRNAs in these two strains and investigated the tsRNAs/rsRNAs/ysRNAs profiles influenced by IAV infection. Specifically, four noncanonical sncRNA families, including rsRNA-12S, GtsRNA-Arg-CCT, GtsRNA-Arg-TCT, and GtsRNA-Lys-TTT, exhibited upregulation upon IAV infection. Notably, DBA/2J mice showed earlier systemic differential expression of noncanonical sncRNAs after IAV infection compared to C57BL/6J mice. Additionally, our study revealed a strain-specific biogenesis of MtsRNAs in response to IAV infection. Also, distinct co-expression patterns of MtsRNAs were observed between C57BL/6J and DBA/2J mice, with DBA/2J mice showing broader positive co-expression of MtsRNAs with various sncRNA families compared to C57BL/6J mice. Our study provides a novel insight into noncanonical sncRNAs and their implications in IAV pathology and mouse strain specificity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

This study explores the utilization of municipal solid waste incineration fly ash (MSWIFA) in geopolymer concrete, focusing on compressive strength and heavy metal leachability. MSWIFA was sourced from a Shenzhen waste incineration plant and pretreated by washing to remove soluble salts. Geopolymer concrete was prepared incorporate with washed or unwashed MSWIFA and tested under different pH conditions (2.88, 4.20, and 10.0). Optimal compressive strength was achieved with a Si/Al ratio of 1.5, water/Na ratio of 10, and sand-binder ratio of 0.6. The washing pretreatment significantly enhanced compressive strength, particularly under alkaline conditions, with GP-WFA (washed MSWIFA) exhibiting a 49.6% increase in compressive strength, compared to a 21.3% increase in GP-FA (unwashed MSWIFA). Additionally, GP-WFA's compressive strength reached 41.7 MPa, comparable to that of the control (GP-control) at 43.7 MPa. Leaching tests showed that acidic conditions (pH 2.88) promoted heavy metal leaching, which increased over the leaching time, while an alkaline environment significantly reduced the leachability of heavy metals. These findings highlight the potential of using washed MSWIFA in geopolymer concrete, promoting sustainable construction practices, particularly in alkaline conditions.

Butterfly wings possess distinct micro/nanostructures that contribute to their vibrant coloration, light-trapping capabilities, and sensitivity to various stimuli. These complex features have inspired the creation of diverse devices and systems, such as sensors, photovoltaics, photocatalysis, and robotics. Specifically, the wing scales of the Emerald Swallowtail (Papilio palinurus) display iridescent, polarization-sensitive, and retroreflective colors due to their hierarchical structures. However, current technologies fail to mimic these natural designs fully, limiting their practical application in everyday life. In this study, we introduce a groundbreaking method for fabricating artificial wing scales that emulate the biological structure's functionality with a much simpler geometry. By integrating self-graded lossy media into metallic micro-concavity arrays, we achieve pronounced iridescent effects in both coaxial and non-coaxial arrangements, while preserving retroreflective properties. In particular, the simplified design allows for switchable color patterns based on the viewing angle. Demonstrating the concept, we successfully employ these conspicuous retroreflectors in hydrogen gas detection and the bi-directional/switchable recognition of patterned signals., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The phenylpropanoid pathway is vital for plant growth and development, producing lignin and flavonoids. This study investigates PtrMYB203, a homolog of MYB repressors of proanthocyanidin (PA) biosynthesis in Populus trichocarpa, as a transcriptional repressor in the phenylpropanoid pathway of hybrid poplar (Populus alba x P. glandulosa). Overexpression of PtrMYB203 (35S::PtrMYB203) in hybrid poplar detrimentally impacted plant growth and development. Histological analysis revealed irregular xylem vessel formation and decreased lignin content, corroborated by Klason lignin assays. Moreover, 35S::PtrMYB203 transgenic poplars exhibited significant decreases in anthocyanin and PA accumulations in callus tissues, even under high light conditions. Quantitative RT-PCR analysis and protoplast-based transcriptional activation assay confirmed the downregulation of lignin and flavonoid biosynthesis genes. This genetic modification also alters the expression of several MYB transcription factors, essential for phenylpropanoid pathway regulation. Remarkably, saccharification efficiency in the 35S::PtrMYB203 poplar was improved by over 34% following hot water treatment alone. These findings suggest PtrMYB203 as a potential genetic target for enhancing wood properties for bioenergy production, providing valuable insights into the manipulation of metabolite pathways in woody perennials to advance wood biotechnology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

An atomistic understanding of dry-etching processes with reactive molecules is crucial for achieving geometric integrity in highly scaled semiconductor devices. Molecular dynamics (MD) simulations are instrumental, but the lack of reliable force fields hinders the widespread use of MD in etching simulations. In this work, we develop an accurate neural network potential (NNP) for simulating the etching process of amorphous Si 3 N 4 with HF molecules. The surface reactions in diverse local environments are considered by incorporating several types of training sets: baseline structures, reaction-specific data, and general-purpose training sets. Furthermore, the NNP is refined through iterative comparisons with the density functional theory results. Using the trained NNP, we carry out etching simulations, which allow for detailed observation and analysis of key processes such as preferential sputtering, surface modification, etching yield, threshold energy, and the distribution of etching products. Additionally, we develop a simple continuum model, built from the MD simulation results, which effectively reproduces the surface composition obtained with MD simulations. By establishing a computational framework for atomistic etching simulation and scale bridging, this work will pave the way for more accurate and efficient design of etching processes in the semiconductor industry, enhancing device performance and manufacturing precision.

Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.

In this study, single crystals of (K 1-x Na x )NbO 3 are grown by the self-flux crystal growth method and their phase transitions are studied using a combination of Raman scattering and impedance spectroscopy. X-ray diffraction shows that single crystals have a perovskite structure with monoclinic symmetry. Single crystal X-ray diffraction shows that single crystals have monoclinic symmetry at room temperature with space group P12 1 1. Electron probe microanalysis shows that single crystals are Na-rich and A-site deficient. Temperature-controlled Raman scattering shows that low temperature monoclinic-monoclinic, monoclinic-tetragonal and tetragonal-cubic phase transitions take place at -20 °C, 220 °C and 440 °C. Dielectric property measurements show that single crystals behave as a normal ferroelectric material. Relative or inverse relative permittivity peaks at ~-10 °C, ~230 °C and ~450 °C with hysteresis correspond to the low temperature monoclinic-monoclinic, monoclinic-tetragonal and tetragonal-cubic phase transitions, respectively, consistent with the Raman scattering results. A conduction mechanism with activation energies of about 0.5-0.7 eV was found in the paraelectric phase. Single crystals show polarization-electric field hysteresis loops of a lossy normal ferroelectric. The combination of Raman scattering and impedance spectroscopy is effective in determining the phase transition temperatures of (K 1-x Na x )NbO 3 .

Background: Mesenchymal stem/stromal cells (MSCs) maintain tissue homeostasis in response to microenvironmental perturbations. Toll-like receptors (TLRs) are key sensors for exogenous and endogenous signals produced during injury. In this study, we aimed to investigate whether TLRs affect the homeostatic functions of MSCs after injury. Methods: We examined the expression of TLR2, TLR3 and TLR4 in MSCs, and analyzed the functional significance of TLR2 activation using single-cell RNA sequencing. Additionally, we investigated the effects and mechanisms of TLR2 and its downstream activation in MSCs on the MSCs themselves, on monocytes/macrophages, and in a mouse model of sterile injury-induced inflammatory corneal angiogenesis. Results: MSCs expressed TLR2, which was upregulated by monocytes/macrophages. Activation of TLR2 in MSCs promoted their immunoregulatory and angiostatic functions in monocytes/macrophages and in mice with inflammatory corneal angiogenesis, whereas TLR2 inhibition attenuated these functions. Single-cell RNA sequencing revealed AKR1C1 , a gene encoding aldo-keto reductase family 1 member C1, as the most significantly inducible gene in MSCs upon TLR2 stimulation, though its stimulation did not affect cell compositions. AKR1C1 protected MSCs against ferroptosis, increased secretion of anti-inflammatory cytokines, and enhanced their ability to drive monocytes/macrophages towards immunoregulatory phenotypes, leading to the amelioration of inflammatory corneal neovascularization in mice. Conclusion: Our findings suggest that activation of TLR2-AKR1C1 signaling in MSCs serves as an important pathway for the survival and homeostatic activities of MSCs during injury., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

We evaluated the diagnostic performance of the β-d-glucan (BDG) test (Beijing Gold Mountain River Tech) in diagnosing invasive fungal disease (IFD) and its variations among patients with different risks. Patients ≥18 years old who underwent a serum BDG test (positive cutoff value >80 pg/ml) from April 2017 through May 2018 were collected consecutively. Patients were classified into three groups: group 1, patients with host factors as defined by the prior 2008 European Organization for Research and Treatment (EORTC) criteria; group 2, those with extended host factors in 2020 EORTC criteria; and group 3, those without any risk factor mentioned in the criteria. IFD was defined by 2020 EORTC criteria, but BDG was not considered. Diagnostic performance of the serum BDG test was measured by the area under the curve (AUC) of the receiver-operating characteristic curve. Among 469 patients, 15.4% (72/469) were diagnosed with IFD (48/191 [25.1%], 14/144 [9.7%], and 10/134 [7.5%] in groups 1, 2, and 3, respectively). The BDG assay showed fair performance (AUC 0.748 [95% CI: 0.688-0.810]). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 77.8%, 60.7%, 26.4%, and 93.8%, respectively. PPV was higher in group 1, and NPV was higher in group 3. Additionally, diagnostic odds ratios were 6.73, 2.88, and 5.92 in groups 1, 2, and 3. Immunosuppressant use, non-IFD/Candida colonization, and central venous catheter were associated with false positivity. Clinicians should cautiously interpret the BDG assay, considering the various diagnostic performances depending on the different levels of risk., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)