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We investigate the two-dimensional t–J model at a hole doping of n¯ h= 1 / 8 using recently developed high accuracy fermionic projected entangled pair states method. By applying the stochastic gradient descent method combined with the Monte Carlo sampling technique, we obtain the ground state hole energy Ehole = −1.621 for J/t = 0.4. We show that the ground state has stable diagonal stripes instead of vertical stripes with a width of 4 unit cells, and stripe filling ρl = 0.5. We further show that the long-range superconductivity order is suppressed at this point.

Yong Suk Jo,1 Myoung Nam Lim,2 Young-Ji Han,3 Woo Jin Kim4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 2Data Analysis Center, 3Department of Environmental Science, Kangwon National University, 4Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Gangwon-do, Korea Background and objective: Aside from smoking, which is already recognized as a strong risk factor for COPD, interest in the impact of particulate matter (PM) on COPD is increasing. This study aimed to investigate the effect of PM, especially with an aerodynamic diameter ≤2.5 µm (PM2.5), and its chemical constituents on the exacerbation of COPD.Methods: Data on hospital visits including admission and outpatient clinic visits for exacerbation of COPD in Chuncheon, Korea, between 2006 and 2012 were extracted from the National Health Insurance Service database. PM2.5 and its chemical constituents were measured on the roof of the four-story Kangwon National University Natural Sciences building once every 3 days. Meteorological data were provided by the Korean Meteorological Administration.Results: During the study period, the mean level of PM2.5 was 35.0±25.2 µg/m3, and the number of daily hospital visits were 6.42±4.28 and 2.07±1.93 for males and females, respectively. The number of COPD-related hospital visits increased with increasing PM2.5 after adjusting for meteorological covariates and females tended to be more affected sooner than males. Among the PM2.5 constituents, Al, Si, and elemental carbon were associated with increased hospital visits and there was a difference according to sex. In males, some constituents of PM2.5 were related to an increased risk of a hospital visit, mainly on the first and second days of measurement (Lag1 and Lag2). In contrast, there was no significant increase in the risk of hospital visits due to any of the PM2.5 constituents in females.Conclusion: Concentrations of PM2.5 mass and some of the PM2.5 constituents were associated with increased COPD-related hospital visits in Chuncheon. Keywords: COPD, PM2.5, constituents, hospital visit

Chondrosarcoma is a type of bone cancer that originates from cartilage cells. In clinical practice, surgical resection is the primary treatment for chondrosarcoma, but chemotherapy becomes essential for patients with metastasis or tumors in surgically inaccessible sites. However, drug resistance often leads to treatment failure. Tumor microenvironment proteins modulate intercellular communication, contributing to drug resistance. Doxorubicin (Dox) is a common chemotherapeutic agent. The present study aimed to establish Dox-resistant chondrosarcoma cells and compare their secretome with parental cells using antibody arrays. Results showed significantly heightened secretion of hepatocyte growth factor (HGF). Knockdown of both HGF and its receptor MET increased Dox sensitivity in chondrosarcoma cells. Treatment of chondrosarcoma cells with conditioned media (CM) from cells secreting high levels of HGF resulted in MET activation. Additionally, the expression levels of HGF and MET were significantly elevated in chondrosarcoma tissues compared to normal cartilage tissues, as confirmed by analysis of GEO database. RNA sequencing and Gene Set Enrichment Analysis (GSEA) elucidated the mechanism involving HGF. Additionally, genes with log fold change > 1 underwent bioinformatics analysis using the ShinyGO web server. The results from both GSEA and ShinyGO analyses corroborate each other, indicating the significance of HGF in cellular signal transduction, regulation of cell motility, developmental processes, immune-inflammatory responses, and functions related to blood and neural systems. In summary, highly secreted HGF can activate signaling pathways through its receptor MET, particularly Ras and Akt activation, enhancing drug resistance in chondrosarcoma cells. The present study may guide the development of novel therapeutic strategies targeting HGF, ultimately improving treatment outcomes and prognosis for malignant chondrosarcoma patients., 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 Inc. All rights reserved.)

A medical specialty prediction system for remote diagnosis can reduce the unexpected costs incurred by first-visit patients who visit the wrong hospital department for their symptoms. To develop medical specialty prediction systems, several researchers have explored clinical predictive models using real medical text data. Medical text data include large amounts of information regarding patients, which increases the sequence length. Hence, a few studies have attempted to extract entities from the text as concise features and provide domain-specific knowledge for clinical text classification. However, it is still insufficient to inject them into the model effectively. Thus, we propose Entity-enhanced BERT (E-BERT), which utilizes the structural attributes of BERT for medical specialty prediction. E-BERT has an entity embedding layer and entity-aware attention to inject domain-specific knowledge and focus on relationships between medical-related entities within the sequences. Experimental results on clinical questionnaire data demonstrate the superiority of E-BERT over the other benchmark models, regardless of the input sequence length. Moreover, the visualization results for the effects of entity-aware attention prove that E-BERT effectively incorporate domain-specific knowledge and other information, enabling the capture of contextual information in the text. Finally, the robustness and applicability of the proposed method is explored by applying it to other Pre-trained Language Models. These effective medical specialty predictive model can provide practical information to first-visit patients, resulting in streamlining the diagnostic process and improving the quality of medical consultations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The quantum circuit model is the most widely used theoretical model for quantum computing. Therefore, determining whether two quantum circuits whose internal structures cannot be seen have the same functionality will be a fundamental problem in future quantum industries, which however turns out to be QMA-hard. Here, based on a photonic system we experimentally implement the equivalence checking of two unknown quantum circuits with real unitary matrix representations, where quantum nonlocality plays a key role and allows us to measure an "average-case" distance between the two quantum circuits very efficiently. Particularly, we also experimentally apply such protocols to verify the correctness of quantum circuit optimizations, which is another crucial topic in future quantum industries. Our work constitutes a proof of concept for the equivalence checking of quantum circuits without relying on their detailed structures.

Competing Interests: Disclosure: The authors have no financial disclosures or conflicts of interest to report.

Background: To investigate prenatal ultrasound findings and the chromosomal outcomes of mosaic embryo transfer., Methods: This retrospective study was conducted on pregnant women who underwent mosaic embryo transfer following blastocyst-stage preimplantation genetic testing for aneuploidy (PGT-A) at CHA Gangnam Medical Center from January 2021 to July 2024. Trophectoderm biopsy specimens were collected using standard protocols, and next-generation sequencing profiles were defined as mosaics when displaying copy number counts in the 20-80% range. The results of the PGT-A, the amniocentesis results, the findings of prenatal ultrasounds, and the pregnancy outcomes were analyzed., Results: A total of 88 mosaic embryos were transferred, of which 77 embryos were successfully implanted. Sixty-seven embryo-maintained pregnancies went beyond 11 weeks (87.0%), all among 58 patients with singleton pregnancies. The chaotic subtype showed the lowest ongoing pregnancy rate, and high-level mosaicism was less frequent in the ongoing group, compared to the total study group and the successful implantation group. Amniocentesis was performed on 33 mothers (56.9%), revealing two cases with abnormal findings that did not correlate with the PGT-A results. Two cases showed abnormalities in the second trimester detailed ultrasound, and both subsequently demonstrated normal findings in the third trimester and after birth. The average gestational age at birth was 38.4 weeks, and the average birth weight was 3313 g. No congenital anomalies were detected in 16 postnatal cases., Conclusions: Our study indicated that mosaic embryos can develop into euploid healthy infants with various levels or types of mosaicism, although the postnatal follow-up data are limited. This study is invaluable for counseling clinical results after mosaic embryo transfer, reassuring that, if patients do not have euploid embryos available, mosaic embryos can also be a viable option for transfer.

By braiding non-Abelian anyons it is possible to realize fault-tolerant quantum algorithms through the computation of Jones polynomials. So far, this has been an experimentally formidable task. In this Letter, a photonic quantum system employing two-photon correlations and nondissipative imaginary-time evolution is utilized to simulate two inequivalent braiding operations of Majorana zero modes. The resulting amplitudes are shown to be mathematically equivalent to Jones polynomials. The high fidelity of our optical platform allows us to distinguish between a wide range of links, such as Hopf links, Solomon links, Trefoil knots, Figure Eight knots and Borromean rings, through determining their corresponding Jones polynomials. Our photonic quantum simulator represents a significant step towards executing fault-tolerant quantum algorithms based on topological quantum encoding and manipulation.

Various combination therapies have been investigated to overcome the limitations of using immune checkpoint inhibitors. However, determining the optimal combination therapy remains challenging. To overcome the therapeutical limitation, we conducted a translational research to elucidate the mechanisms by which AXL inhibition enhances the anti-tumor effects when combined with anti-PD-1 antibody therapy. Herein, we demonstrated improved antitumor effects through combination treatment with denfivontinib and pembrolizumab which resulted in enhanced differentiation into effector CD4+ and CD8+ memory T cells, accompanied by an increase in IFN-γ expression in the YHIM-2004 xenograft model derived from patients with NSCLC. Concurrently, a reduction in the number of immunosuppressive M2 macrophages and myeloid-derived suppressor cells was observed. Mechanistically, denfivontinib potentiated the NOD-like receptor pathway, thereby facilitating the NLRP3 inflammasome formation. This leads to macrophage activation via the NF-kB signaling pathway activation. We have confirmed that the positive interaction between macrophages and T cells arises from the enhanced antigen-presenting machinery of activated macrophages. Furthermore, the observed tumor effects in AXL knock-out mice confirmed that AXL inhibition by denfivontinib enhances the anti-tumor effects, thus opening new avenues for therapeutic interventions aimed at overcoming limitations in immunotherapy. To demonstrate the extent to which our findings reflect clinical results, we analyzed bulk-RNA sequencing data from 21 NSCLC patients undergoing anti-PD-1 immunotherapy. The NLRP3 inflammasome score influenced enhanced immune responses in patient data undergoing anti-PD-1 immunotherapy, suggesting a role for NLRP3 inflammasome in activating immune responses during treatment.

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington disease (HD), and Multiple sclerosis (MS), pose a significant global health challenge due to their intricate pathology and limited therapeutic interventions. Natural products represent invaluable reservoirs for combating these neurodegenerative diseases by targeting key pathological hallmarks such as protein aggregation, synaptic dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, inflammation, and neuronal cell death. This review provides an in-depth analysis of the mechanisms and therapeutic targets of natural products for their neuroprotective effects. Furthermore, it elucidates the current progress of clinical trials investigating the potential of natural products in delaying neurodegeneration. The objective of this review is to enhance the comprehension of natural products in the prevention and treatment of neurodegenerative diseases, offering new insights and potential avenues for future pharmaceutical research., Competing Interests: Declaration of competing interest All of the authors declared there are no conflicts of interest for this manuscript., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: We aimed to comprehensively analyze the immune cell and stromal components of tumor microenvironment at the single-cell level and identify tumor heterogeneity among the major top-derived oncogene mutations in non-small cell lung cancer (NSCLC) using single-cell RNA sequencing (scRNA-seq) data., Materials and Methods: The scRNA-seq dataset utilized in this study comprised 64369 primary tumor tissue cells from 21 NSCLC patients, focusing on mutations in EGFR , ALK , BRAF , KRAS , TP53 , and the wild-type., Results: Tumor immune microenvironment (TIM) analysis revealed differential immune responses across NSCLC mutation subtypes. TIM analysis revealed different immune responses across the mutation subtypes. Two mutation clusters emerged: KRAS , TP53 , and EGFR + TP53 mutations (MC1); and EGFR , BRAF , and ALK mutations (MC2). MC1 showed higher tertiary lymphoid structures signature scores and enriched populations of C2-T-IL7R, C3-T/NK-CXCL4, C9-T/NK-NKG, and C1-B-MS4A1 clusters than cluster 2. Conversely, MC2 cells exhibited higher expression levels of TNF , IL1B , and chemokines linked to alternative immune pathways. Remarkably, co-occurring EGFR and TP53 mutations were grouped as MC1. EGFR + TP53 mutations showed upregulation of peptide synthesis and higher synthetic processes, as well as differences in myeloid and T/NK cells compared to EGFR mutations. In T/NK cells, EGFR + TP53 mutations showed a higher expression of features related to cell activity and differentiation, whereas EGFR mutations showed the opposite., Conclusion: Our research indicates a close association between mutation types and tumor microenvironment in NSCLC, offering insights into personalized approaches for cancer diagnosis and treatment., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Objectives: To determine the effects of cerclage on twin pregnancies., Methods: A multicenter, retrospective, cohort study was conducted at 10 tertiary centers using a web-based data collection platform. The study population included twin pregnancies delivered after 20 weeks of gestation. Patients with one or two fetal deaths before 20 weeks of gestation were excluded. Maternal characteristics, including prenatal cervical length (CL) and obstetric outcomes, were retrieved from the electronic medical records., Results: A total of 1,473 patients had available data regarding the CL measured before 24 weeks of gestation. Seven patients without CL data obtained prior to cerclage were excluded from the analysis. The study population was divided into two groups according to the CL measured during the mid-trimester: the CL ≤2.5 cm group ( n  = 127) and the CL >2.5 cm group ( n  = 1,339). A total of 127 patients (8.7%) were included in the CL ≤2.5 cm group, including 41.7% (53/127) who received cerclage. Patients in the CL >2.5 cm group who received cerclage had significantly lower gestational age at delivery than the control group (hazard ratio (HR): 1.8; 95% confidence interval (CI): 1.11-2.87; p  = .016). Patients in the CL ≤2.5 cm group who received cerclage had a significantly higher gestational age at delivery than the control group (HR: 0.5; 95% CI: 0.30-0.82; p value = .006)., Conclusions: In twin pregnancies with a CL ≤2.5 cm, cerclage significantly prolongs gestation. However, unnecessary cerclage in women with a CL >2.5 cm may result in a higher risk of preterm labor and histologic chorioamnionitis although this study has a limitation originated from retrospective design.

Background: Nuclear receptor interaction protein (NRIP) is versatile and engages with various proteins to execute its diverse biological function. NRIP deficiency was reported to cause small myofibre size in adult muscle regeneration, indicating a crucial role of NRIP in myoblast fusion., Methods: The colocalization and interaction of NRIP with actin were investigated by immunofluorescence and immunoprecipitation assay, respectively. The participation of NRIP in myoblast fusion was demonstrated by cell fusion assay and time-lapse microscopy. The NRIP mutants were generated for mechanism study in NRIP-null C2C12 (termed KO19) cells and muscle-specific NRIP knockout (NRIP cKO) mice. A GEO profile database was used to analyse NRIP expression in Duchenne muscular dystrophy (DMD) patients., Results: In this study, we found that NRIP directly and reciprocally interacted with actin both in vitro and in cells. Immunofluorescence microscopy showed that the endogenous NRIP colocalized with components of invadosome, such as actin, Tks5, and cortactin, at the tips of cells during C2C12 differentiation. The KO19 cells were generated and exhibited a significant deficit in myoblast fusion compared with wild-type C2C12 cells (3.16% vs. 33.67%, p < 0.005). Overexpressed NRIP in KO19 cells could rescue myotube formation compared with control (3.37% vs. 1.00%, p < 0.01). We further confirmed that NRIP directly participated in cell fusion by using a cell-cell fusion assay. We investigated the mechanism of invadosome formation for myoblast fusion, which depends on NRIP-actin interaction, by analysing NRIP mutants in NRIP-null cells. Loss of actin-binding of NRIP reduced invadosome (enrichment ratio, 1.00 vs. 2.54, p < 0.01) and myotube formation (21.82% vs. 35.71%, p < 0.05) in KO19 cells and forced NRIP expression in KO19 cells and muscle-specific NRIP knockout (NRIP cKO) mice increased myofibre size compared with controls (over 1500 μm 2 , 61.01% vs. 20.57%, p < 0.001). We also found that the NRIP mRNA level was decreased in DMD patients compared with healthy controls (18 072 vs. 28 289, p < 0.001, N = 10 for both groups)., Conclusions: NRIP is a novel actin-binding protein for invadosome formation to induce myoblast fusion., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Cases of depression among adolescents are gradually increasing. The study of the physiological basis of cognitive function from a biochemical perspective has therefore been garnering increasing attention. Depression has been hypothesized to be associated with the brain biochemical metabolism of the anterior cingulate gyrus, frontal lobe white matter, and the thalamus., Aim: To explore the application of proton magnetic resonance spectroscopy ( 1 H-MRS) in the metabolic alterations in the prefrontal white matter (PWM) and gray matter (GM) in adolescents with depression., Methods: 1 H-MRS was performed for semi-quantitative analysis of the biochemical metabolites N-acetylaspartate (NAA), choline (Cho) complexes, creatine (Cr), and myo-inositol (mI) in bilateral PWM, anterior cingulate GM, and thalami of 31 adolescent patients with depression (research group) and 35 healthy adolescents (control group), and the NAA/Cr, Cho/Cr, and mI/Cr ratios were calculated. Meanwhile, Hamilton Depression Scale (HAMD) and Wechsler Memory Scale were used to assess the degree of depression and memory function in all adolescents. The correlation of brain metabolite levels with scale scores was also analyzed., Results: The research group had markedly higher HAMD-24 scores and lower memory quotient (MQ) compared with the control group ( P < 0.05). Adolescents with depression were found to have lower bilateral PWM NAA/Cr and Cho/Cr ratios compared with healthy adolescents ( P < 0.05). The mI/Cr ratios were found to be similar in both groups ( P > 0.05). The bilateral anterior cingulate GM NAA/Cr, Cho/Cr, and mI/Cr also did not demonstrate marked differences ( P > 0.05). No statistical inter-group difference was determined in NAA/Cr of the bilateral thalami ( P > 0.05), while bilateral thalamic Cho/Cr and mI/Cr were reduced in teenagers with depression compared with healthy adolescents ( P < 0.05). A significant negative correlation was observed between the HAMD-24 scores in adolescents with depression with bilateral PWM NAA/Cr and Cho/Cr and were inversely linked to bilateral thalamic Cho/Cr and mI/Cr ( P < 0.05). In adolescents with depressions, MQ positively correlated with right PWH NAA/Cr, left PWH Cho/Cr, and bilateral thalamic Cho/Cr and mI/Cr., Conclusion: PWM and thalamic metabolic abnormalities might influence teen depression, and the reduction in bilateral PWM NAA/Cr and Cho/Cr could be related to the neuropathology of adolescents with depression suffering from memory impairment. There exists a possibility of dysfunction of nerve cell membrane phospholipids in the thalami of adolescent patients with depression., Competing Interests: Conflict-of-interest statement: The authors declare that they have no competing interests., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: The ultrasound examination (USE) feature of taller-than-wide (TTW) shape is highly specific but low sensitive in diagnosis of thyroid carcinoma. Relationships between other USE malignant features (such as irregular margin, ill-defined, markedly hypoechoic, and microcalcification) with histopathological features have been well investigated, while studies about the histopathologic features of TTW shape are rare., Aim: The present study aimed to investigate the histopathological features of thyroid nodules with TTW shapes., Methods: A total of 85 thyroid nodules with TTW were selected from 1680 consecutive patients who underwent thyroid resection. USE features of the nodules, including size, location, boundary, margin, composition, echogenicity, and calcification, were recorded according to the China Thyroid Imaging Reporting and Data System (C-TIRADS). Hypoechoic lesions were further categorized as mild, moderate or markedly hypoechoic lesions. The histological features of the specimens were evaluated according to the arrangement of follicular cells, presence of papillary structures or psammoma bodies, degree of fibrosis, and amount of lymphoid infiltration. Differences in the USE and histological features between benign and malignant nodules were compared., Results: Among the 85 nodules, 72 (84.71%) were malignant, and 13 (15.29%) were benign. Only echogenicity showed a statistically significant difference between benign and malignant nodules ( P =0.003). Apart from microfoci, papillary structures, and psammoma bodies, the degree of fibrosis was also significantly different between benign and malignant tumors (all P <0.05). Regression analysis showed a trend of decreasing nodule echogenicity with increasing fibrosis frequency (odds ratio [OR] = 4.500)., Conclusion: Extensive fibrosis is the most common histopathological feature of thyroid cancer and corresponds to hypoechogenicity in USE. TTW-shaped thyroid nodules are highly suggestive of malignancy, especially those with moderate or markedly hypoechogenicity., Competing Interests: The authors declare no conflicts of interest., (© 2024 Yang et al.)

Background: Patients with chronic ankle instability (CAI) often experience recurrent swelling and pain, which hinder their ability to walk long distances. Emerging evidence suggests that joint mobilization can enhance ankle function in patients with CAI., Objective: The aim of this study is to investigate the effects of subtalar joint mobilization on enhancing ankle stability, alleviating ankle pain, and improving the walking ability of patients diagnosed with CAI., Methods: A retrospective analysis was conducted on 46 patients who were treated between April 2022 and October 2023. They were randomly divided into two groups: a treatment group with 23 cases receiving conventional treatment along with subtalar joint mobilization treatment, and a control group with 23 cases receiving only conventional treatment. The treatment duration was eight weeks. Pain levels and walking ability were assessed before and after the treatment period., Results: After eight weeks of treatment, the treatment group showed significant increases in the number of heel raises on the affected leg (NLHSL), improvements in the star excursion balance test (SEBT), and higher American Orthopedic Foot and Ankle Society (AOFAS) scores compared to the control group. Additionally, resting pain (RVAS) and walking pain (WVAS) scores were significantly lower in the treatment group. However, there was no statistically significant difference in single-leg standing time (SLT) between the two groups. Within the control group, post-treatment assessments indicated significant improvements in dynamic balance and control measures (SLT, NLHSL, SEBT), but no significant changes were observed in pain levels (RVAS, WVAS) or rear foot function (AOFAS). In contrast, the treatment group showed significant improvements across all measured parameters (RVAS, WVAS, SLT, NLHSL, SEBT, and AOFAS) following treatment., Conclusion: Subtalar joint mobilization effectively reduces ankle pain and enhances walking ability among patients with CAI by improving ankle stability. The observed improvements in walking ability may stem from mitigating compensatory mechanisms associated with varus of the calcaneus and ankle instability., (© 2024. The Author(s).)

Introduction: Restoring a balanced, healthy gut microbiota through fecal microbiota transplantation (FMT) has the potential to be a treatment option for sepsis, despite the current lack of evidence. This study aimed to investigate the effect of FMT on sepsis in relation to the gut microbiota through a sepsis model in juvenile mice., Methods: Three-week-old male mice were divided into three groups: the antibiotic treatment (ABX), ABX-FMT, and control groups. The ABX and ABX-FMT groups received antibiotics for seven days. FMT was performed through oral gavage in the ABX-FMT group over the subsequent seven days. On day 14, all mice underwent cecal ligation and puncture (CLP) to induce abdominal sepsis. Blood cytokine levels and the composition of fecal microbiota were analyzed, and survival was monitored for seven days post-CLP., Results: Initially, the fecal microbiota was predominantly composed of the phyla Bacteroidetes and Firmicutes. After antibiotic intake, an extreme predominance of the class Bacilli emerged. FMT successfully restored antibiotic-induced fecal dysbiosis. After CLP, the phylum Bacteroidetes became extremely dominant in the ABX-FMT and control groups. Alpha diversity of the microbiota decreased after antibiotic intake, was restored after FMT, and decreased again following CLP. In the ABX group, the concentrations of interleukin-1β (IL-1β), IL-2, IL-6, IL-10, granulocyte macrophage colony-stimulating factor, tumor necrosis factor-α, and C-X-C motif chemokine ligand 1 increased more rapidly and to a higher degree compared to other groups. The survival rate in the ABX group was significantly lower (20.0%) compared to other groups (85.7%)., Conclusion: FMT-induced microbiota restoration demonstrated a protective effect against sepsis. This study uniquely validates the effectiveness of FMT in a juvenile mouse sepsis model, offering potential implications for clinical research in critically ill children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Han, Kim, Shin, Kim and Park.)

Bacteria are becoming an increasingly serious threat to human health. The emergence of super bacteria makes clinical treatment more difficult. Vaccines are one of the most effective means of preventing and treating bacterial infections. As a new class of vaccines, killed but metabolically active (KBMA) vaccines provide the immunogenicity of live vaccines and the safety of inactivated vaccines. Herein, a promising strategy is proposed to improve the stability and immunogenicity of KBMA vaccines. KBMA vaccines were produced at low temperature (4 °C), and the bacterial surface was engineered using mesoporous silica nanoparticle (MSN) coating. Compared to vaccines prepared at room temperature, the metabolic activity of KBMA vaccines prepared at 4 °C remarkably improved. Benefiting from the induction of MSNs, the stability of KBMA vaccines was increased and the preservation time was prolonged at 4 °C. Meanwhile, metabolomics analysis showed that the metabolite spectrum of live bacteria changed after photochemical treatment and MSN coating, which interfered with organic acid metabolism pathways, lipid metabolism and biosynthesis of secondary metabolites. Furthermore, the immune response in the mice treated with KBMA/MSN vaccines was similar to that in those treated with live vaccines and stronger than that in those treated with inactivated vaccines. In comparison with the control group, bacteria tissue burdens of KBMA/MSN group were significantly reduced. CD4 + T cells dominated immune responses for the protection of mice. Thus, the current work promotes the application of KBMA vaccines, providing an alternative choice for treating bacterial infections.

Preeclampsia (PE) is a hypertensive disorder of pregnancy with various clinical symptoms. However, traditional markers for the disease including high blood pressure and proteinuria are poor indicators of the related adverse outcomes. Here, we performed systematic proteome profiling of plasma samples obtained from pregnant women with PE to identify clinically effective diagnostic biomarkers. Proteome profiling was performed using TMT-based liquid chromatography-mass spectrometry (LC-MS/MS) followed by subsequent verification by multiple reaction monitoring (MRM) analysis on normal and PE maternal plasma samples. Functional annotations of differentially expressed proteins (DEPs) in PE were predicted using bioinformatic tools. The diagnostic accuracies of the biomarkers for PE were estimated according to the area under the receiver-operating characteristics curve (AUC). A total of 1307 proteins were identified, and 870 proteins of them were quantified from plasma samples. Significant differences were evident in 138 DEPs, including 71 upregulated DEPs and 67 downregulated DEPs in the PE group, compared with those in the control group. Upregulated proteins were significantly associated with biological processes including platelet degranulation, proteolysis, lipoprotein metabolism, and cholesterol efflux. Biological processes including blood coagulation and acute-phase response were enriched for down-regulated proteins. Of these, 40 proteins were subsequently validated in an independent cohort of 26 PE patients and 29 healthy controls. APOM, LCN2, and QSOX1 showed high diagnostic accuracies for PE detection (AUC >0.9 and p < 0.001, for all) as validated by MRM and ELISA. Our data demonstrate that three plasma biomarkers, identified by systematic proteomic profiling, present a possibility for the assessment of PE, independent of the clinical characteristics of pregnant women., Competing Interests: Conflict of interests The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: By utilizing both protein and mRNA expression patterns, we can identify more detailed and diverse immune cells, providing insights into understanding the complex immune landscape in cancer ecosystems., Materials and Methods: This study was performed by obtaining publicly available Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) data of peripheral blood mononuclear cells (PBMCs) from the Gene Expression Omnibus database. A total of 94674 total cells were analyzed, of which 32412 were T cells. There were 228 protein features and 16262 mRNA features in the data. The Seurat package was used for quality control and preprocessing, principal component analysis was performed, and Uniform Manifold Approximation and Projection was used to visualize the clusters. Protein and mRNA levels in the CITE-seq were analyzed., Results: We observed that a subset of T cells in the clusters generated at the protein level divided better. By identifying mRNA markers that were highly correlated with the CD4 and CD8 proteins and cross-validating CD26 and CD99 markers using flow cytometry, we found that CD4 + and CD8 + T cells were better discriminated in PBMCs. Weighted Nearest Neighbor clustering results identified a previously unobserved T cell subset., Conclusion: In this study, we used CITE-seq data to confirm that protein expression patterns could be used to identify cells more precisely. These findings will improve our understanding of the heterogeneity of immune cells in the future and provide valuable insights into the complexity of the immune response in health and disease., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Garnet-type Li 7 La 3 Zr 2 O 12 (LLZO) Li-ion solid electrolytes are promising candidates for safe, next-generation solid-state batteries. In this study, we synthesize Ga-doped LLZO (Ga-LLZO) electrolytes using a microwave-assisted solvothermal method followed by low-temperature heat treatment. The nanostructured precursor (<50 nm) produced by the microwave-assisted solvothermal process has a high surface energy, facilitating the reaction for preparing garnet-type Ga-LLZO powders (<800 nm) within a short time (<5 h) at a low calcination temperature (<700 °C). Additionally, the calcined nanostructured Ga-LLZO powder can be sintered to produce a high-density pellet with minimized grain boundaries under moderate sintering conditions (temperature: 1150 °C, duration: 10 h). The optimal doping concentration was determined to be 0.4 mol% Ga, which resulted significantly increased the ionic conductivity (1.04 × 10 -3  S cm -1 at 25 °C) and stabilized the cycling performance over 1700 h at 0.4 mA cm -2 . This approach demonstrates the potential to synthesize oxide-type solid electrolyte materials with improved properties for solid-state batteries., Competing Interests: 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., (© 2024 The Author(s).)

Background: Biliary atresia (BA) is a rare fatal liver disease in children, and the aim of this study was to develop a method to diagnose BA early., Methods: We determined serum levels of matrix metalloproteinase-7 (MMP-7), the results of 13 liver tests, and the levels of 20 bile acids, and integrated computational models were constructed to diagnose BA., Results: Our findings demonstrated that MMP-7 expression levels, as well as the results of four liver tests and levels of ten bile acids, were significantly different between 86 BA and 59 non-BA patients (P < 0.05). The computational prediction model revealed that MMP-7 levels alone had a higher predictive accuracy [area under the receiver operating characteristic curve (AUC) = 0.966, 95% confidence interval (CI): 0.942, 0.989] than liver test results and bile acid levels. The AUC was 0.890 (95% CI 0.837, 0.943) for liver test results and 0.825 (95% CI 0.758, 0.892) for bile acid levels. Furthermore, bile levels had a higher contribution to enhancing the predictive accuracy of MMP-7 levels (AUC = 0.976, 95% CI 0.953, 1.000) than liver test results. The AUC was 0.983 (95% CI 0.962, 1.000) for MMP-7 levels combined with liver test results and bile acid levels. In addition, we found that MMP-7 levels were highly correlated with gamma-glutamyl transferase levels and the liver fibrosis score., Conclusion: The innovative integrated models based on a large number of indicators provide a noninvasive and cost-effective approach for accurately diagnosing BA in children. Video Abstract (MP4 142103 KB)., (© 2023. The Author(s).)

Lithium batteries with solid-state electrolytes are an appealing alternative to state-of-the-art non-aqueous lithium-ion batteries with liquid electrolytes because of safety and energy aspects. However, engineering development at the cell level for lithium batteries with solid-state electrolytes is limited. Here, to advance this aspect and produce high-energy lithium cells, we introduce a cell design based on advanced parametrization of microstructural and architectural parameters of electrode and electrolyte components. To validate the cell design proposed, we assemble and test (applying a stack pressure of 3.74 MPa at 45 °C) 10-layer and 4-layer solid-state lithium pouch cells with a solid polymer electrolyte, resulting in an initial specific energy of 280 Wh kg -1 (corresponding to an energy density of 600 Wh L -1 ) and 310 Wh kg -1 (corresponding to an energy density of 650 Wh L -1 ) respectively., (© 2024. The Author(s).)

Coenzyme Q10 (CoQ10) is an essential medicinal ingredient. In this study, we obtained a high-yielding mutant strain of CoQ10, VK-2-3, by subjecting R. sphaeroides V-0 (V-0) to a 12 C 6+ heavy ion beam and high-voltage prick electric field treatment. To investigate the mutation mechanism, the complete genomes of VK-2-3 and V-0 were sequenced. Collinearity analysis revealed that the nicotinamide adenine dinucleotide-dependent dehydrogenase (NAD) gene underwent rearrangement in the VK-2-3 genome. The NAD gene was overexpressed and silenced in V-0, and this construct was named RS.NAD and RS.ΔNAD. The results showed that the titers of CoQ10 in the RS.NAD and RS.ΔNAD increased and decreased by 16.00 and 33.92%, respectively, compared to those in V-0, and these differences were significant. Our results revealed the mechanism by which the VK-2-3 CoQ10 yield increases through reverse metabolic engineering, providing insights for genetic breeding and mechanistic analysis., Competing Interests: Y-jH, Y-xL, and Z-jT were employed by Shenzhou Biotechnology Co., Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhang, Wang, Han, Liu, Li, Hu, Tian and Liu.)

During the cold season in South Korea, NO 3 - concentrations are known to significantly increase, often causing PM 2.5 to exceed air quality standards. This study investigated the formation mechanisms of NO 3 - in a suburban area with low anthropogenic emissions. The average PM 2.5 was 25.3 μg m -3 , with NO 3 - identified as the largest contributor. Ammonium-rich conditions prevailed throughout the study period, coupled with low atmospheric temperature facilitating the transfer of gaseous HNO 3 into the particulate phase. This result indicates that the formation of HNO 3 played a crucial role in determining particulate NO 3 - concentration. Nocturnal increases in NO 3 - were observed alongside increasing ozone (O 3 ) and relative humidity (RH), emphasizing the significance of heterogeneous reactions involving N 2 O 5 . NO 3 - concentrations at the study site were notably higher than in Seoul, the upwind metropolitan area, during a high concentration episode. This difference could potentially attributed to lower local NO concentrations, which enhanced the reaction between O 3 and NO 2 , to produce NO 3 radicals. High concentrations of Cl - and dust were also identified as contributors to the elevated NO 3 - concentrations., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Immune checkpoint inhibitors are effective first-line therapy for solid cancers. However, low response rate and acquired resistance over time has led to the need for additional therapeutic options. Here, we evaluated synergistic antitumor efficacy of EGFR × MET targeting bispecific antibody, amivantamab with PD-L1 immunotherapy, pembrolizumab in head and neck squamous cell carcinoma (HNSCC) and lung squamous cell carcinoma tumor-bearing humanized patient-derived xenograft (PDX) models. We demonstrated that pembrolizumab or amivantamab alone was ineffective and that combination treatment induced a significant reduction of tumor growth in both models (P < 0.0001 and P < 0.01, respectively). It appeared that combination of amivantamab and pembrolizumab significantly enhanced infiltration of granzyme B-producing CD8 T cells was in the TME of HNSCC PDX (P < 0.01) and enhanced neoantigen-associated central memory CD8 T cells in circulating immune cells. Analysis of single-cell RNA transcriptomics suggested that the tumor cells dramatically upregulated EGFR and MET in response to PD-L1 immunotherapy, potentially creating a metabolic state fit for tumor persistence in the tumor microenvironment (TME) and rendered pembrolizumab ineffective. We demonstrated that EGFRHIGHMETHIGH subcluster displayed an increased expression of genes implicated in production of lactate [SLC16A3 and lactate dehydrogenase A (LDHA)] compared to the EGFRLOWMETLOW cluster. Accumulation of lactate in the TME has been associated with immunosuppression by hindering the infiltration of tumor killing CD8 T and NK cells. This study proved that amivantamab reduced glycolytic markers in the EGFRHIGHMETHIGH subcluster including SLC16A3 and LDHA and highlighted remodeling of the TME by combination treatment, providing rationale for additional therapy of amivantamab with PD-1 immunotherapy., Significance: Amivantamab in synergy with pembrolizumab effectively eradicated EGFRHIGHMETHIGH tumor subcluster in the tumor microenvironment of head and neck squamous cell carcinoma and overcame resistance against anti-PD-1 immunotherapy., (©2024 The Authors, Published by the American Association for Cancer Research.)

Purpose: Black women experience the highest breast cancer mortality rate compared with women of other racial/ethnic groups. To gain a deeper understanding of breast cancer heterogeneity across diverse populations, we examined a VEGF-hypoxia gene expression signature in breast tumors from women of diverse ancestry., Experimental Design: We developed a NanoString nCounter gene expression panel and applied it to breast tumors from Nigeria (n = 182) and the University of Chicago (Chicago, IL; n = 161). We also analyzed RNA sequencing data from Nigeria (n = 84) and The Cancer Genome Atlas (TCGA) datasets (n = 863). Patient prognosis was analyzed using multiple datasets., Results: The VEGF-hypoxia signature was highest in the basal-like subtype compared with other subtypes, with greater expression in Black women compared with White women. In TCGA dataset, necrotic breast tumors had higher scores for the VEGF-hypoxia signature compared with non-necrosis tumors (P < 0.001), with the highest proportion in the basal-like subtype. Furthermore, necrotic breast tumors have higher scores for the proliferation signature, suggesting an interaction between the VEGF-hypoxia signature, proliferation, and necrosis. T-cell gene expression signatures also correlated with the VEGF-hypoxia signature when testing all tumors in TCGA dataset. Finally, we found a significant association of the VEGF-hypoxia profile with poor outcomes when using all patients in the METABRIC (P < 0.0001) and SCAN-B datasets (P = 0.002)., Conclusions: These data provide further evidence for breast cancer heterogeneity across diverse populations and molecular subtypes. Interventions selectively targeting VEGF-hypoxia and the immune microenvironment have the potential to improve overall survival in aggressive breast cancers that disproportionately impact Black women in the African Diaspora., (©2024 American Association for Cancer Research.)

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

With the rapid improvement of equipment integration technology, multi-spectrum detectors are integrated into compact volumes and widely used for object detection. Confront with this challenge, it is essential to propose a strategy to design a single-layer metasurface with multi-spectrum responses in microwave and infrared ranges. In this work, we proposed a method of designing meta-atoms, which is capable of achieving functional electromagnetic response at microwave and infrared individually. As a demonstration, a metasurface with four different occupation ratios and coding permutation features is designed, fabricated, and tested. In the microwave band, the pixel meta-atom is designed to realize highly efficient cross-polarization conversion between 5.0 and 10.0 GHz, which shows the metasurface can behave as ultra-low Radar Cross Section (RCS) reflectors in the working band; In the infrared band, different occupation ratio of meta-atoms are designed to realize the infrared emissivity from 0.60 to 0.80 in 3-14 μm, which can be used to exhibit digital infrared camouflage pattern. This work promotes the ability to use single-layer design to achieve digital infrared camouflage and microwave RCS reduction simultaneously. The one-layer design is simple in geometry, simplified in process, low cost in economy, and large scale in fabrication, which can promote practical use in compatible microwave stealth and infrared camouflage., Competing Interests: Conflict of interest: Authors state no conflicts of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

(1) Background: Non-invasive prenatal testing (NIPT) is a screening test for fetal aneuploidy using cell-free fetal DNA. The fetal fragments (FF) of cell-free DNA (cfDNA) are derived from apoptotic trophoblast of the placenta. The level of fetal cfDNA is known to be influenced by gestational age, multiple pregnancies, maternal weight, and height. (2) Methods: This study is a single-center retrospective observational study which examines the relationship between the fetal fraction (FF) of cell-free DNA in non-invasive prenatal testing (NIPT) and adverse pregnancy outcomes in singleton pregnancies. A total of 1393 samples were collected between 10 weeks and 6 days, and 25 weeks and 3 days of gestation. (3) Results: Hypertensive disease of pregnancy (HDP) occurred more frequently in the low FF group than the normal FF group (5.17% vs. 1.91%, p = 0.001). Although the rates of small for gestational age (SGA) and placental abruption did not significantly differ between groups, the composite outcome was significantly higher in the low FF group (7.76% vs. 3.64%, p = 0.002). Furthermore, women who later experienced complications such as HDP or gestational diabetes mellitus (GDM) had significantly lower plasma FF levels compared to those without complications ( p < 0.001). After adjustments, the low FF group exhibited a significantly higher likelihood of placental compromise (adjusted odds ratio: 1.946). (4) Conclusions: Low FF in NIPT during the first and early second trimesters is associated with adverse pregnancy outcomes, particularly HDP, suggesting its potential as a predictive marker for such outcomes., Competing Interests: J.E.P. is from CHA Biotech Inc. The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Photonic integrated quantum memories are essential for the construction of scalable quantum networks. Spin-wave quantum storage, which can support on-demand retrieval with a long lifetime, is indispensable for practical applications, but has never been demonstrated in an integrated solid-state device. Here, we demonstrate spin-wave quantum storage based on a laser-written waveguide fabricated in a 151 Eu 3+ :Y 2 SiO 5 crystal, using both the atomic frequency comb and noiseless photon-echo protocols. Qubits encoded with single-photon-level inputs are stored and retrieved with a fidelity of [Formula: see text], which is far beyond the maximal fidelity that can be obtained with any classical device. Our results underline the potential of laser-written integrated devices for practical applications in large-scale quantum networks, such as the construction of multiplexed quantum repeaters in an integrated configuration and high-density transportable quantum memories., (© The Author(s) 2024. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)