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Hua-Xi Zou,1,2,* Tie Hu,1,2,* Jia-Yi Zhao,2,3,* Bai-Quan Qiu,2,4 Chen-Chao Zou,2,4 Qi-Rong Xu,1 Ji-Chun Liu,1,2 Song-Qing Lai,1,2 Huang Huang1,2 1Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Institute of Cardiovascular Diseases, Jiangxi Academy of Clinical Medical Sciences, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Medical Innovation Experimental Program, Huan Kui College, Nanchang University, Nanchang, People’s Republic of China; 4Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huang Huang; Song-Qing Lai, Email jack19871212@hotmail.com; ndyfy03743@ncu.edu.cnIntroduction: Sepsis is currently a common condition in emergency and intensive care units, and is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Cardiac dysfunction caused by septic myocardial injury (SMI) is associated with adverse prognosis and has significant economic and human costs. The pathophysiological mechanisms underlying SMI have long been a subject of interest. Recent studies have identified ferroptosis, a form of programmed cell death associated with iron accumulation and lipid peroxidation, as a pathological factor in the development of SMI. However, the current understanding of how ferroptosis functions and regulates in SMI remains limited, particularly in the absence of direct evidence from human heart.Methods: We performed a sequential comprehensive bioinformatics analysis of human sepsis cardiac transcriptome data obtained through the GEO database. The lipopolysaccharide-induced mouse SMI model was used to validate the ferroptosis features and transcriptional expression of key genes.Results: We identified widespread dysregulation of ferroptosis-related genes (FRGs) in SMI based on the human septic heart transcriptomes, deeply explored the underlying biological mechanisms and crosstalks, followed by the identification of key functional modules and hub genes through the construction of protein-protein interaction network. Eight key FRGs that regulate ferroptosis in SMI, including HIF1A, MAPK3, NOX4, PPARA, PTEN, RELA, STAT3 and TP53, were identified, as well as the ferroptosis features. All the key FRGs showed excellent diagnostic capability for SMI, part of them was associated with the prognosis of sepsis patients and the immune infiltration in the septic hearts, and potential ferroptosis-modulating drugs for SMI were predicted based on key FRGs.Conclusion: This study provides human septic heart transcriptome-based evidence and brings new insights into the role of ferroptosis in SMI, which is significant for expanding the understanding of the pathobiological mechanisms of SMI and exploring promising diagnostic and therapeutic targets for SMI.Keywords: septic myocardial injury, ferroptosis, heart transcriptome, key genes, database

Jun-Chen Liu, Hong-Jing Yu Department of Clinical Pharmacy, The First People’s Hospital of Jiande, Jiande, People’s Republic of ChinaCorrespondence: Hong-Jing Yu, Department of Medical Oncology, The First People’s Hospital of jiande, No. 599 Yanzhou Avenue, Xin’anjiang street, Jiande, Zhejiang, 311600, People’s Republic of China, Tel +86 15869196365, Fax +86-571-64721520, Email hongjingyu1560@163.comAbstract: Immune checkpoint inhibitors (ICIs) have been shown to be significant in improving the overall survival rate in certain malignancies with poor prognoses. However, only 20– 40% of patients achieve long-term benefits, highlighting the relevance of the factors that influence the treatment, which can help clinicians improve their results and guide the development of new immune checkpoint therapies. In this study, the current pharmacokinetic aspects associated with the ICIs and the factors influencing clinical efficacy were characterised, including in terms of drug metabolism, drug clearance, hormonal effects and immunosuppressive effects.Keywords: immune checkpoint inhibitors, pharmacokinetics, influencing factors

Li-Jun Wang,1,* Bai-Quan Qiu,1,* Ming-Ming Yuan,2,* Hua-Xi Zou,1 Cheng-Wu Gong,1 Huang Huang,2 Song-Qing Lai,3 Ji-Chun Liu1 1Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Department of Cardiothoracic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ji-Chun Liu, Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13907913502, Email liujichun999@yeah.net Song-Qing Lai, Institute of Cardiovascular Diseases, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China, Tel +86 13699562160, Email ndyfy03743@ncu.edu.cnPurpose: Dilated cardiomyopathy (DCM) is a type of cardiomyopathy that can easily cause heart failure and has a high mortality rate. Therefore, there is an urgent need to study the underlying mechanism of action of dilated cardiomyopathy. In the present study, we aimed to explore potential miRNA–mRNA pairs and drugs related to DCM.Methods: The Microarray data were collected from the Gene Expression Omnibus (GEO) database. Bioinformatics analysis differentially expressed miRNAs and mRNAs in each microarray were obtained. The target genes of miRNAs were obtained from the miRWalk 2.0 database, and the intersection of these two gene sets (miRNA target genes and differentially expressed mRNAs in the microarray) was obtained. Pathway and Gene Ontology (GO) enrichment analyses were performed in the KOBAS database. Cytoscape software was used to construct the miRNA–mRNA network, and the final hub genes were obtained. Furthermore, we predicted several candidate drugs related to hub genes using DSigDB database. To confirm the abnormal expression of hub genes, qRT-PCR was performed.Results: In total, eight differentially expressed miRNAs and 92 differentially expressed mRNAs were identified. In addition, 47 differentially expressed miRNA target genes were identified. According to the analysis results of the miRNA-mRNA network, we identified hsa-miR-551b-3p, hsa-miR-770-5p, hsa-miR-363-3p, PIK3R1, DDIT4, and CXCR4 as hub genes in DCM. Several candidate drugs, which are related to the hug genes, were identified.Conclusion: In conclusion, in our study, we identified several hub genes that may be involved in the pathogenesis of DCM. Several drugs related to these hub genes may be used as clinical therapeutic candidates.Keywords: dilated cardiomyopathy, miRNA, mRNA, public database, drugs

Wen-Shuo Kuo, 1, 2 Chia-Yuan Chang, 3 Jui-Chang Liu, 4 Jian-Hua Chen, 5, 6,* Edmund Cheung So, 5– 7,* Ping-Ching Wu 8,* 1School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing, Jiangsu 210044, People’s Republic of China; 2Allergy & Clinical Immunology Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan Republic of China; 3Department of Mechanical Engineering, National Cheng Kung University, Tainan 701, Taiwan Republic of China; 4Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan 701, Taiwan Republic of China; 5Department of Anesthesia & Medicine Research, An Nan Hospital, China Medical University, Tainan 709, Taiwan Republic of China; 6Department of Anesthesia, China Medical University, Taichung 404, Taiwan Republic of China; 7Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan 711, Taiwan Republic of China; 8Department of Biomedical Engineering, National Cheng Kung University, Tainan 701, Taiwan Republic of China*These authors contributed equally to this workCorrespondence: Jian-Hua Chen; Ping-Ching Wu Email aptx4869jfk@gmail.com; wbcxyz@bme.ncku.edu.twBackground: Multidrug-resistant (MDR) bacterial strain is a serious medical problem. Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to many antibiotics and is often associated with several diseases such as arthritis, osteomyelitis, and endocarditis. The development of an alternative treatment for eliminating MDR bacteria such as MRSA has attracted a considerable amount of research attention. Moreover, the development of a material for highly efficient generation of reactive oxygen species (ROS) involving two-photon photodynamic therapy (PDT) is currently desirable.Materials and Methods: We present an example demonstrating that the use of water-soluble C 60(OH) 30 fullerenol with a 0.89 singlet oxygen quantum yield serving as a photosensitizer in PDT has the superior ability in effectively generating ROS.Results: It has ultra-low energy (228.80 nJ pixel− 1) and can perform 900 scans under two-photon excitation (TPE) in the near-infrared region (760 nm) to completely eliminate the MDR species. Furthermore, the favorable two-photon properties are absorption of approximately 760 nm in wavelength, absolute cross-section of approximately 1187.50 Göeppert–Mayer units, lifetime of 6.640 ns, ratio of radiative to nonradiative decay rates of approximately 0.053, and two-photon stability under TPE.Conclusion: This enabled water-soluble C 60(OH) 30 fullerenol to act as a promising two-photon photosensitizer proceeding with PDT to easily eliminate MDR species.Keywords: methicillin-resistant Staphylococcus aureus, two-photon photodynamic therapy, water-soluble fullerenol, two-photon excitation, near-infrared region

Wen-Shuo Kuo,1,2,* Tien-Sung Yeh,3,* Chia-Yuan Chang,4 Jui-Chang Liu,2 Chang-Hsin Chen,5 Edmund Cheung So,6,7 Ping-Ching Wu8 1School of Chemistry and Materials Science, Nanjing University of Information Science and Technology, Nanjing 210044, Jiangsu, People’s Republic of China; 2Allergy & Clinical Immunology Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan, Republic of China; 3Department of Physical Medicine and Rehabilitation, An Nan Hospital, China Medical University, Tainan 709, Taiwan, Republic of China; 4Department of Mechanical Engineering, National Cheng Kung University, Tainan 701, Taiwan, Republic of China; 5AbVision Inc., Milpitas, CA 95035, USA; 6Department of Anesthesia & Medicine Research, An Nan Hospital, China Medical University, Tainan 709, Taiwan, Republic of China; 7Graduate Institute of Medical Sciences, Chang Jung Christian University, Tainan 711, Taiwan, Republic of China; 8Department of Biomedical Engineering, National Cheng Kung University, Tainan, 701, Taiwan, Republic of China*These authors contributed equally to this workCorrespondence: Edmund Cheung So; Ping-Ching Wu Email edmundsotw@gmail.com; wbcxyz@bme.ncku.edu.twBackground: Although graphene quantum dots (GQDs) have received considerable research attention for their applications in various fields, the use of GQDs, such as nitrogen-doped GQDs (N-GQDs) and amino-functionalized N-GQDs (amino-N-GQDs), as photosensitizers to facilitate photodynamic therapy (PDT) has received limited research intention. To address this research gap, this study prepared novel amino-N-GQDs and investigated their properties.Methods: The amino-N-GQDs subjected to two-photon excitation (TPE) exhibited remarkable bactericidal capability in PDT. The bonding compositions of nitrogen and the amino-functionalized group played a critical role in their antimicrobial effects.Results: Compared with amino-group-free N-GQDs and amino-N-free GQDs, the amino-N-GQDs generated a higher amount of reactive oxygen species, demonstrating their superior efficacy for two-photon PDT. Additionally, the intrinsic luminescence properties and high photostability of the amino-N-GQDs demonstrate their suitability as an effective two-photon contrast agent for tracking bacteria during two-photon biomedical imaging.Conclusion: The amino-N-GQD and their remarkable properties may provide an efficient alternative approach for observing and easily eliminating malignant microbes in the future.Keywords: nitrogen atom-doped graphene quantum dots, amino-functionalized and nitrogen atom-doped graphene quantum dots, two-photon photodynamic therapy, two-photon contrast agent, two-photon biomedical imaging

Wei-Chang Xu,1,* Xiao Dong,1,* Jing-Li Ding,2 Ji-Chun Liu,1 Jian-Jun Xu,1 Yan-Hua Tang,1 Ying-Ping Yi,3 Chao Lu,1 Wei Yang,1 Jue-Sheng Yang,1 Yi Gong,1 Jian-Liang Zhou1 1Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, China; 2Department of Gastroenterology, The Second Affiliated Hospital of Nanchang University, Nanchang, China; 3Department of Science and Education, The Second Affiliated Hospital of Nanchang University, Nanchang, China *These authors contributed equally to this work Background: Macrophages play important roles in the immune response to, and successful implantation of, biomaterials. Titanium nanotubes are considered promising heart valve stent materials owing to their effects on modulation of macrophage behavior. However, the effects of nanotube-regulated macrophages on endothelial cells, which are essential for stent endothelialization, are unknown. Therefore, in this study we evaluated the inflammatory responses of endothelial cells to titanium nanotubes prepared at different voltages. Methods and results: In this study we used three different voltages (20, 40, and 60 V) to produce titania nanotubes with three different diameters by anodic oxidation. The state of macrophages on the samples was assessed, and the supernatants were collected as conditioned media (CM) to stimulate human umbilical vein endothelial cells (HUVECs), with pure titanium as a control group. The results indicated that titanium dioxide (TiO2) nanotubes induced macrophage polarization toward the anti-inflammatory M2 state and increased the expression of arginase-1, mannose receptor, and interleukin 10. Further mechanistic analysis revealed that M2 macrophage polarization controlled by the TiO2 nanotube surface activated the phosphatidylinositol 3-kinase/AKT and extracellular signal-regulated kinase 1/2 pathways through release of vascular endothelial growth factor to influence endothelialization. Conclusion: Our findings expanded our understanding of the complex influence of nanotubes in implants and the macrophage inflammatory response. Furthermore, CM generated from culture on the TiO2 nanotube surface may represent an integrated research model for studying the interactions of two different cell types and may be a promising approach for accelerating stent endothelialization through immunoregulation. Keywords: TiO2 nanotubes, axitinib, stent implant, endothelial cells, conditioned medium

Xiaowu Wang,1,* Bo Xu,1,* Hongliang Liang,1 Shuyun Jiang,1 Hongmei Tan,1 Xinrong Wang,1 Xia Wang,2 Shiqiang Yu,1 Jincheng Liu1 1Department of Cardiovascular Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China; 2Department of Health Statistics, Faculty of Preventive Medicine, Fourth Military Medical University, Xi’an 710032, Shaanxi, People’s Republic of China *These authors contributed equally to this work Purpose: Oral warfarin anticoagulation is a long-term treatment that is required after heart valve replacement. This treatment can prevent serious complications, such as embolism, thereby increasing patients’ postoperative survival rates and quality of life. Patients treated with artificial mechanical heart valve replacement were followed up over the phone at different times after the procedure, which is an effective method for preventing accidents related to postoperative oral warfarin anticoagulation. Our goal was to determine a method for providing theoretical guidance to patients on oral warfarin anticoagulation following heart valve replacement. Patients and methods: The participants of this study were patients who received artificial mechanical heart valve replacements and were followed up for 2 years after the procedure. Patient adherence to medical advice was calculated, and the distribution characteristics of adherence to prescribed timing, prescribed dose, and regular clinical follow-up among patients of both sexes and of different ages, regions, and educational levels attained were compared. Results: Univariate and multifactorial logistic regression analyses were used to evaluate the factors influencing adherence. Our analyses showed that adherence to oral warfarin anticoagulation in patients after heart valve replacement is influenced by sex, age, residential location, and educational attainment. The medication habits of patients can be evaluated accordingly via phone follow-up. As such, dose adjustment recommendations can be provided, significantly increasing the adherence to oral warfarin anticoagulation in patients after heart valve replacement. Conclusion: Adherence to oral warfarin anticoagulation among patients after heart valve replacement is affected by sex, age, type of residence, and educational level, as well as adherence to clinical follow-up over the phone. The follow-up sessions help establish good doctor–patient communication, which is critical for timely medication guidance, thus shortening medication administration delays and decreasing the overall length of therapy. Keywords: warfarin, artificial mechanical heart valve replacement, AMHVR, telephone follow-up, adherence, distribution characteristics

Study Design: A retrospective clinical study. Objective: To investigate clinical and radiographic outcomes following the surgical treatment of fixed cervical kyphosis with myelopathy. Summary Of Background Data: To our knowledge, a study specifically addressing the surgical treatment of fixed cervical sagittal deformity has never before been published. Methods: Sixteen patients treated surgically for fixed cervical kyphosis and myelopathy were followed for a mean of 4.5 years (range, 25-112 months). The study group consisted of 9 males and 7 females, with an average age of 52 years (range, 31-78 years). The principal etiologies of cervical deformity were prior laminectomy (63%), advanced spondylosis (19%), infection (6%), neuromuscular disease (6%), and metabolic disease (renal osteodystrophy) (6%). All patients were clinically evaluated by the Nurick classification and Odom criteria both before surgery and at the time of most recent follow-up. Radiographic analysis was performed using thin-cut CT scans, dynamic radiographs, and 14 x 36-inch scoliosis films. Results: The mean preoperative cervical Cobb angle as measured from the C2-C7 was +38 degrees and improved to -10 degrees at final follow-up, yielding an average correction of 48 degrees . The mean number of anterior and posterior segments fused was 4.8 (range, 2-6) and 7.2 (range, 3-14), respectively. The mean Nurick score improved from 2.4 before surgery to 1.5 at the time of follow-up. According to Odom criteria, outcomes were as follows: excellent (38%), good (50%), fair (6%), and poor (6%). At the time of most recent follow-up, solid bony arthrodesis and maintenance of correction occurred in all patients; however, revision was required in one patient. Conclusion: The treatment of fixed cervical kyphosis with myelopathy using circumferential spinal osteotomies and instrumented reconstruction is technically demanding; however, restoration and maintenance of a neutral or lordotic cervical profile and excellent clinical outcomes are achievable. [ABSTRACT FROM AUTHOR]

Nanozyme catalytic therapeutic efficacy is limited by the finite enzyme activity and specificity. In this work, nitrogen-doped carbon loaded with a cerium single-atom nanozyme (Ce SAs@NC) is synthesized, exhibiting tumor specificity and excellent multiple enzyme-like activities. Compared with nitrogen-doped carbon loaded with CeO 2 nanoparticles, Ce SAs@NC shows excellent peroxidase-like and catalase-like activity. Ce SAs@NC can convert intracellular hydrogen peroxide into cytotoxic hydroxyl radical and O 2 , which can be further transferred to superoxide radicals. Cascade enzyme reactions not only alleviate the hypoxic microenvironment of tumors but also induce lipid peroxidation and apoptosis or necrosis of tumor cells. The mild photothermal action will enhance the enzyme-like activities of Ce SAs@NC rather than induce the production of heat shock proteins to protect tumor cells. In addition, Ce SAs@NC can regulate the immune environment, stimulate M1 macrophages to trigger immune responses, and inhibit tumor proliferation. Thanks to the combination of the size effect of the single atoms, photothermal influence, multiple enzyme-like activities, and immunological effect, the Ce SAs@NC platform appears to have tumor specificity, less toxic side effects, and a high curative effect both in vitro and in vivo .

The surface chemistry of CeO 2 is dictated by the well-defined facets, which exert great influence on the supported metal species and the catalytic performance. Here we report Pt 1 /CeO 2 catalysts exhibiting specific structures of Pt-O coordination on different facets by using adequate preparation methods. The simple impregnation method results in Pt-O 3 coordination on the predominantly exposed {111} facets, while the photo-deposition method achieves oriented atomic deposition for Pt-O 4 coordination into the "nano-pocket" structure of {100} facets at the top. Compared to the impregnated Pt 1 /CeO 2 catalyst showing normal redox properties and low-temperature activity for CO oxidation, the photo-deposited Pt 1 /CeO 2 exhibits uncustomary strong metal-support interaction and extraordinary high-temperature stability. The preparation methods dictate the facet-dependent diversity of Pt-O coordination, resulting in the further activity-selectivity trade-off. By applying specific preparation routes, our work provides an example of disentangling the effects of support facets and coordination environments for nano-catalysts., (© 2024 Wiley-VCH GmbH.)

Background: Noninvasive and functional imaging of the focal liver lesion (FLL) vasculature at microscopic scales is clinically challenging. We investigated the feasibility of using super-resolution ultrasound (SR-US) imaging for visualizing and quantifying the microvasculature of intraparenchymal FLLs., Methods: Patients with FLLs between June 2022 and February 2023 were prospectively screened. Following bolus injection of microbubbles at clinical concentration, SR-US was performed using a high frame rate (350-500 Hz) modified ultrasound scanner and a convex array transducer with a central frequency of 3.1 MHz., Results: In total, 47 pathologically proven FLLs at a depth of 5.7 ± 1.7 cm (mean ± standard deviation) were included: 30 hepatocellular carcinomas (HCC), 11 liver metastases (LM), and 6 focal nodular hyperplasias (FNH). The smallest detectable vessel size of the hepatic microvasculature was 128.4 ± 18.6 μm (mean ± standard deviation) at a depth of 8 cm. Significant differences were observed among the three types of lesions in terms of pattern categories, vessel density, minimum flow velocity, and perfusion index. We observed higher vessel density for FNH versus liver parenchyma (p < 0.001) as well as fractal dimension and local flow direction entropy value for FNH versus HCC (p = 0.002 and p < 0.001, respectively) and for FNH versus LM (p = 0.006 and p = 0.002, respectively)., Conclusion: Multiparametric SR-US showed that these three pathological types of FLLs have specific microvascular phenotypes. Vessel density, fractal dimension and local flow direction entropy served as valuable parameters in distinguishing between benign and malignant FLLs., Trial Registration: ClinicalTrials.gov (NCT06018142)., Relevance Statement: Multiparametric SR-US imaging offers precise morphological and functional assessment of the microvasculature of intraparenchymal focal liver lesions, providing insights into tumor heterogeneity and angiogenesis., Key Points: Super-resolution (SR)-US imaging allowed morphological and functional evaluation of intraparenchymal hepatic lesion microvasculature. Hepatocellular carcinoma, liver metastasis, and focal nodular hyperplasia exhibit distinct microvascular architectures and hemodynamic profiles. Multiparametric microvasculature characterization via SR-US imaging facilitates the differentiation between benign and malignant microvascular phenotypes., Competing Interests: Declarations. Ethics approval and consent to participate: Our study was registered on ClinicalTrials.gov (NCT06018142), and the study protocol was approved by the Institutional Review Board. Consent to participate was obtained from all patients in this study. Consent for publication: Not applicable. Competing interests: The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article., (© 2024. The Author(s).)

Developing selective kinase inhibitors remains a formidable challenge in drug discovery because of the highly conserved structural information on adenosine triphosphate (ATP) binding sites across the kinase family. Tailoring docking protocols to identify promising kinase inhibitor candidates for optimization has long been a substantial obstacle to drug discovery. Therefore, we introduced "Kinase-Bench," a pioneering benchmark suite designed for an advanced virtual screen, to improve the selectivity and efficacy of kinase inhibitors. Our comprehensive data set includes 6875 selective ligands and 422,799 decoys for 75 kinases, using extensive bioactivity and structural data from the ChEMBL database and decoys generated by the Directory of Useful Decoys-Enhanced version. Our benchmarking sets and retrospective case studies were designed to provide useful guidance in discovering selective kinase inhibitors. We employed a Glide High-Throughput Virtual Screen and Standard Precision complemented by three scoring functions and customized protein-ligand interaction filters that target specific kinase residue interactions. These innovations were successfully implemented in our virtual screen efforts targeting JAK1 inhibitors, achieving selectivity against its family member, TYK2. Consequently, we identified novel potential hits: Compound 2 (JAK1 IC 50 : 980.5 nM, TYK2 IC 50 : 4.5 μM) and the approved pan-AKT inhibitor Capivasertib (JAK1 IC 50 : 275.9 nM, TYK2 IC 50 : 10.9 μM). Using the Kinase-Bench protocol, both compounds demonstrated substantial JAK1 selectivity, making them strong candidates for further investigation. Our pharmaceutical results underscore the utility of tailored virtual screen protocols in identifying selective kinase inhibitors with substantial implications for rational drug design. Kinase-Bench offers a robust toolset for selective kinase drug discovery with the potential to effectively guide future therapeutic strategies effectively.

We report a case highlighting the global prevalence of atrial fibrillation (Afib) and the increased use of ablation therapy, underscoring the importance of understanding its complications, especially atrio-esophageal fistula (AEF), a rare but potentially fatal outcome. This case involves a 38-year-old male who underwent radiofrequency ablation for Afib and was subsequently hospitalized with abrupt left-sided weakness. Initially presumed to be a transient ischemic attack (TIA), his condition progressed to seizures and reduced consciousness. The computed tomography scans revealed pneumocranium, leading to a diagnosis of AEF. Despite the rapid identification of this complication, the patient's condition deteriorated quickly, resulting in his death on the 10th day. This case exemplifies that while AEF is an infrequent complication (0.1%-0.2%) following Afib ablation, it is of critical concern. The initial symptoms of AEF can be misleading, which accentuates the necessity for prompt recognition and timely intervention. Employing appropriate diagnostic techniques and ablation strategies are crucial to enhance patient outcomes and reduce the risks associated with AEF.

Meta-analyses have reported conflicting data on the whole blood cell count (WBCC) derived indexes (neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR], and lymphocyte-to-monocyte ratio [LMR]) and cancer prognosis. However, the strength and quality of this evidence has not been quantified in aggregate. To grade the evidence from published meta-analyses of cohort studies that investigated the associations between NLR, PLR, and LMR and cancer prognosis. A total of 694 associations from 224 articles were included. And 219 (97.8%) articles rated as moderate-to-high quality according to AMSTAR. There were four associations supported by convincing evidence. Meanwhile, 165 and 164 associations were supported by highly suggestive and suggestive evidence, respectively. In this umbrella review, we summarized the existing evidence on the WBCC-derived indexes and cancer prognosis. Due to the direction of effect sizes is not completely consistent between studies, further research is needed to assess causality and provide firm evidence., 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.)

Wound closure in surgeries is traditionally achieved using invasive methods such as sutures and staples. Adhesion-based wound closure methods such as tissue adhesives, sealants, and hemostats are slowly replacing these methods due to their ease of application. Although several chemistries have been developed and used commercially for wound closure, there is still a need for better tissue adhesives from the point of view of toxicity, wet-adhesion strength, and long-term bonding. Catechol chemistry has shown great promise in developing wet-set adhesives that meet these criteria. Herein, we have studied the biocompatibility of a catechol-based copolymer adhesive, poly([dopamine methacrylamide]-co-[methyl methacrylate]-co-[poly(ethylene glycol) methyl ether methacrylate]) or poly(catechol-MMA-OEG), which is soluble in water. The adhesive was injected subcutaneously in a mouse model on its own and in combination with a sodium periodate crosslinker. After 72 h, 4 weeks, and 12 weeks, the mice were euthanized and subjected to histopathological analysis. Both adhesives were present and still palpable at the end of 12 weeks. The moderate inflammation observed for the poly(catechol-MMA-OEG) cohort at 72 h had reduced to mild inflammation at the end of 12 weeks. However, the moderate inflammatory response observed for the poly(catechol-MMA-OEG) + crosslinker cohort at 72 h had not subsided at 12 weeks., (© 2024 The Author(s). Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

In order to guide the formulation of post-stroke treatment strategy in time, it is necessary to have real-time feedback on collateral circulation and revascularization. Currently used near-infrared II (NIR-II) probes have inherent binding with endogenous albumin, resulting in significant background signals and uncontrollable pharmacokinetics. Therefore, the albumin-escaping properties of the new probe, IR-808AC, was designed, which achieved timely excretion and low background signal, enabling the short-term repeatable injection for visualization of cerebral vessels and perfusion. We further achieved continuous observation of changes in collateral vessels and perfusion during the 7-d period in middle cerebral artery occlusion mice using IR-808AC in vivo. Furthermore, using IR-808AC, we confirmed that remote ischemic conditioning could promote collateral vessels and perfusion. Finally, we evaluated the revascularization after thrombolysis on time in embolic stroke mice using IR-808AC. Overall, our study introduces a novel methodology for safe, non-invasive, and repeatable assessment of collateral circulation and revascularization in real-time that is crucial for the optimization of treatment strategies., 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 Ltd. All rights reserved.)

Lung adenocarcinoma metastatic to the ovary is rarely detected in clinical practice, and only a few cases have been reported. Its clinicopathological features, molecular genetics, and prognosis have not been well characterised. The data of 17 patients diagnosed with this disease between 2013 and 2022 were analysed retrospectively. All patients were non-smokers, with a median age of 46 years (range 30-71 years). Unilateral ovarian involvement was more frequent than bilateral involvement (58.8% vs 41.2%). Lesions presented as solid ovarian or mixed cystic and solid masses, and nearly two-thirds of the tumours (11/17, 64.7%) had a diameter greater than 10 cm. Solid adenocarcinoma was the most common histological subtype (9/17, 52.9%), and three of the cases showed abundant intracellular mucin and signet ring cells. Acinar adenocarcinoma was the second most common type (6/17, 35.3%), usually of moderate to poor differentiation. The remaining two cases were identified as micropapillary adenocarcinoma and mucinous adenocarcinoma. Multinodular growth, necrosis, and lymphovascular invasion were observed in half of the cases, and most of them had a marked stromal response. The most prevalent molecular alteration was ALK-rearranged (8/17, 47.1%), followed by EGFR gene mutations (5/17, 29.4%). A total of 34 cases, comprising 17 from the cohort and 17 from the literature, were included in the survival analysis. Patients with ALK-rearranged genes demonstrated an 80.0% 2-year overall survival rate, whereas those without ALK rearrangement exhibited a lower rate of 33.7%. Although there appears to be a potentially better prognosis for patients with ALK-rearranged genes, further cases and an extended follow-up period are necessary to substantiate this observation., (Copyright © 2024 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

The effects and mechanisms of four exogenous proteins, soy protein isolate (SPI), pea protein isolate (PPI), egg white protein (EWP), and whey protein isolate (WPI), on the gelation of Meretrix meretrix (MM) surimi were investigated. The exogenous protein addition significantly increased the G* of samples to 1.36-1.60 folds compared to the MM group, and the MM/EWP sample presented a better time-stable structure. Furthermore, the incorporation of SPI and EWP reduced expressible water content by 17.51 % and 21.61 % in MM gel, respectively. Moreover, SPI and PPI interacted with water to act as fillers within the MM matrix, where SPI formed larger self-aggregations than PPI. A double cross-linked network was generated by EWP and MM protein, and WPI increased the interaction with MM protein as a binder. This research could provide a theoretical basis for the processing and utilization of exogenous proteins in MM., 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 Ltd. All rights reserved.)

Background: Numerous prospective cohort studies have investigated the influence of dietary patterns on the risks of various cancers, although the findings differed., Objective: To evaluate the associations of dietary patterns with risks of various cancers and assess the strength and validity of the evidence., Methods: Relevant articles were retrieved from the PubMed, EMBASE, Web of Science, and Cochrane library databases from inception to February 22, 2024. The included systematic reviews were meta-analyses of prospective cohort studies that reported an effect size to calculate the association between dietary patterns and cancer risk. The quality of the included studies was evaluated using a measurement tool to assess systematic reviews and the certainty of evidence was assessed using credibility assessment of evidence. Outcomes of interest included any incident cancers. This study was registered with PROSPERO (CRD42023425237)., Results: Overall, 74 meta-analyses from 30 articles were identified. Three meta-analyses (4.1%) were graded as convincing evidence and included associations between adherence to the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) dietary recommendations (per 1-unit score increase) and lower risk of all cancers (relative risk [RR] = 0.93, 95% confidence interval [CI]: 0.92-0.95), while negative associations were found comparing the highest vs. lowest categories for a prudent diet (RR = 0.89, 95% CI: 0.85-0.93) and vegetable-fruit-soybean diet (RR = 0.87, 95% CI: 0.83-0.92) in relation to breast cancer. After credibility assessment of evidence by Grading of Recommendations, Assessment, Development, and Evaluation, four (5.4%) meta-analyses were classified as high, including adherence to the 2007 WCRF/AICR dietary recommendations and decreased risks of all cancers, breast cancer, colorectal cancer, and prostate cancer., Conclusion: These findings suggest that adherence to certain healthy dietary patterns is associated with lower risk of all cancers and certain individual cancers., Register: This study was registered with PROSPERO (CRD42023425237). crd.york.ac.uk/PROSPERO/display&#95;record.php?RecordID=425237., 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 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Efficient photocatalytic CO 2 reduction coupled with the photosynthesis of pure H 2 O 2 is a challenging and significant task. Herein, using classical CO 2 photoreduction site iron porphyrinate as the linker, Ag(I) clusters were spatially separated and evenly distributed within a new metal-organic framework (MOF), namely Ag 27 TPyP-Fe. With water as electron donors, Ag 27 TPyP-Fe exhibited remarkable performances in artificial photosynthetic overall reaction with CO yield of 36.5 μmol g -1  h -1 and ca. 100 % selectivity, as well as H 2 O 2 evolution rate of 35.9 μmol g -1  h -1 . Since H 2 O 2 in the liquid phase can be more readily separated from the gaseous products of CO 2 photoreduction, high-purity H 2 O 2 with a concentration up to 0.1 mM was obtained. Confirmed by theoretical calculations and the established energy level diagram, the reductive iron(II) porphyrinates and oxidative Ag(I) clusters within an integrated framework functioned synergistically to achieve artificial photosynthesis. Furthermore, photoluminescence spectroscopy and photoelectrochemical measurements revealed that the robust connection of Ag(I) clusters and iron porphyrinate ligands facilitated efficient charge separation and rapid electron transfer, thereby enhancing the photocatalytic activity., (© 2024 Wiley-VCH GmbH.)

Plants make complex and potent therapeutic molecules, but difficulties in sourcing from natural producers or chemical synthesis can challenge their use in the clinic. A prominent example is the anti-cancer therapeutic paclitaxel (Taxol ® ). Identification of the full paclitaxel biosynthetic pathway would enable heterologous drug production, but it has eluded discovery despite a half century of intensive research. Within the search space of Taxus' large, enzyme-rich genome, we suspected the complex paclitaxel pathway would be difficult to resolve using conventional gene co-expression analysis and small sample sets. To improve the resolution of gene set identification, we developed a multiplexed perturbation strategy to transcriptionally profile cell states spanning tissues, cell types, developmental stages, and elicitation conditions. This approach revealed a set of paclitaxel biosynthetic genes that segregate into expression modules that suggest consecutive biosynthetic sub-pathways. These modules resolved seven new genes that, when combined with previously known enzymes, are sufficient for the de novo biosynthesis and isolation of baccatin III, an industrial precursor for Taxol, in Nicotiana benthamiana leaves at levels comparable to the natural abundance in Taxus needles. Included are taxane 1β-hydroxylase (T1βH), taxane 9α-hydroxylase (T9αH), taxane 7β- O -acyltransferase (T7AT), taxane 7β- O -deacetylase (T7dA), taxane 9α- O -deacetylase (T9dA), and taxane 9-oxidase (T9ox). Importantly, the T9αH we discovered is distinct and independently evolved from those recently reported, which failed to yield baccatin III with downstream enzymes. Unexpectedly, we also found a nuclear transport factor 2 (NTF2)-like protein (FoTO1) crucial for high yields of taxanes; this gene promotes the formation of the desired product during the first taxane oxidation step, resolving a longstanding bottleneck in paclitaxel pathway reconstitution. Together with a new β-phenylalanine-CoA-ligase, the eight genes discovered in this study enables the complete reconstitution of 3'- N -debenzoyl-2'-deoxy-paclitaxel with a 20-enzyme pathway in Nicotiana plants. More broadly, we establish a generalizable approach for pathway discovery that scales the power of co-expression studies to match the complexity of specialized metabolism, enabling discovery of gene sets responsible for high-value biological functions.

Many complex terpenoids, predominantly isolated from plants and fungi, show drug-like physicochemical properties. Recent advances in genome mining revealed actinobacteria as an almost untouched treasure trove of terpene biosynthetic gene clusters (BGCs). In this study, we characterized a terpene BGC with an unusual architecture. The selected BGC includes, among others, genes encoding a terpene cyclase fused to a truncated reductase domain and a cytochrome P450 monooxygenase (P450) that is split over three gene fragments. Functional characterization of the BGC in a heterologous host led to the identification of several new members of the trans -eunicellane family of diterpenoids, the euthailols, that feature unique oxidation patterns. A combination of bioinformatic analyses, structural modeling studies, and heterologous expression revealed a dual function of the pathway-encoded hypothetical protein that acts as an isomerase and an oxygenase. Moreover, in the absence of other tailoring enzymes, a P450 hydroxylates the eunicellane scaffold at a position that is not modified in other eunicellanes. Surprisingly, both the modifications installed by the hypothetical protein and one of the P450s exhibit partial redundancy. Bioactivity assays revealed that some of the euthailols show growth inhibitory properties against Gram-negative ESKAPE pathogens. The characterization of the euthailol BGC in this study provides unprecedented insights into the partial functional redundancy of tailoring enzymes in complex diterpenoid biosynthesis and highlights hypothetical proteins as an important and largely overlooked family of tailoring enzymes involved in the maturation of complex terpenoids.

Palladium catalysts are highly efficient for a variety of chemical industrial processes but are prone to being affected by poisons during practical application. Sulfur is one of the major poisons in Pd-based catalysts. The recycling of deeply poisoned Pd species like Pd sulfides is challenging due to the strong Pd-S bond. Herein, we proposed a top-down strategy to degrade Pd sulfides and create Pd single-atom sites simultaneously by one-step thermal atomization. Pd 4 S model nanoparticles were successfully converted to Pd single-atom sites supported on nitrogen and sulfur-codoped carbon (Pd 1 /N, S-C) after loading them on ZIF-8 and thermal treatment. PdZn intermediates were formed during the atomization process. Density functional theory revealed that the formation of PdZn helped the generation of vacancies adjacent to metal nanoparticles, which prompted the atomization process. This strategy can be facilely applied to the atomization of sulfur-poisoned commercial Pd/C, which shows the potential for recycling commercial catalysts. The optimal Pd 1 /N, S-C catalyst showed good activity and much enhanced selectivity than Pd 4 S for the semi-hydrogenation of acetylene.

Objective: Head and neck cancer affects patient swallowing function. We set out to examine how objective measures of swallowing compare against subjective patient-reported outcomes in a cohort of head and neck cancer patients., Study Design: Retrospective analysis of data collected from a large dysphagia HNC registry., Setting: Tertiary Academic Cancer Center., Methods: Between 2006 and 2019, objective measures of swallowing as scored on Modified Barium Swallow Study or Fiberoptic Endoscopic Evaluation of Swallowing and subjective measures using the SWAL-QOL were collected. Objective measures were scored by the Penetration-Aspiration Score (PAS); subjective measures were assessed by the Dysphagia Domain Score (DDS), collectively forming paired data points. Data on tumor site, T-stage, and treatment modality was collected and evaluated., Results: A total of 253 paired data points were included in this study. A statistically significant relationship between PAS and DDS was observed across all patients (P < .05, chi sq). When stratified by tumor subsite, PAS and DDS relationships were strongest for oral cavity. When stratified by AJCC T-stage, T4 tumors had the strongest relationship between PAS and DDS. The relationship of PAS and DDS was less congruent the further removed from treatment completion., Conclusion: Objective and subjective measures of swallowing provide complementary evaluations of swallow function. The congruency of assessment varies by T stage and tumor subsite. Physicians and allied health professionals can use this information to better understand the value and limitation of objective and subjective swallowing assessments in evaluating head and neck cancer patients., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

As a well-established topic, single-atom catalyst has drawn growing interest for its high utilization of metal. However, researchers prefer to develop various active metals with single-atom form, the intrinsic roles of single-atom promoters are usually underrated, which are significant in boosting reaction activity. In this work, Ba single atoms were in situ prepared in the Co-Ba/Y 2 O 3 catalyst with crystallized BaCO 3 as the precursor under the ammonia decomposition reaction condition. The optimized Co-Ba/Y 2 O 3 catalyst achieves extremely high H 2 production rate of 138.3 mmolH 2  ⋅ g cat -1  ⋅ min -1 at very low temperature (500 °C, GHSV=840,000 mL ⋅ g -1  ⋅ h -1 ) and Co-Ba/Y 2 O 3 exhibits excellent durability during the 350 h test, which realizes the highest activity among all non-noble catalysts, and reaches or even exceeds numerous reported Ru-based catalysts. Both Y 2 O 3 and Co demonstrate positive interactions with Ba, which significantly facilitates the dispersion of Ba species at high temperatures (≥600 °C). Ba single atoms significantly enhance the charge density of Co and form additionally active Co-O-Ba-Y 2 O 3 interfacial sites, which alleviates hydrogen poisoning and decreases the reaction barrier of the N-H bond activation of *NH. The exploration of atomically dispersed promoters is groundbreaking in heterogeneous catalysis, which opens up a whole new domain of catalytic material., (© 2024 Wiley-VCH GmbH.)

Lignocellulose, the most abundant organic waste on Earth, is of economic value because it can be converted into biofuels like ethanol by enzymes such as β-glucosidase. This study involved cloning a β-glucosidase gene named JBG from the rumen fungus Neocallimastix patriciarum J11. When expressed recombinantly in Escherichia coli, the rJBG enzyme exhibited significant activity, hydrolyzing 4-nitrophenyl-β-d-glucopyranoside and cellobiose to release glucose. Surprisingly, the rJBG enzyme also showed hydrolytic activity against β-glucan, breaking it down into glucose, indicating that the rJBG enzyme possesses both β-glucosidase and β-glucanase activities, a characteristic rarely found in β-glucosidases. When the JBG gene was expressed in Saccharomyces cerevisiae and the transformants were inoculated into a medium containing β-glucan as the sole carbon source, the ethanol concentration in the culture medium increased from 0.17 g/L on the first day to 0.77 g/L on the third day, reaching 1.3 g/L on the fifth day, whereas no ethanol was detected in the yeast transformants containing the recombinant plasmid pYES-Sur under the same conditions. These results demonstrate that yeast transformants carrying the JBG gene can directly saccharify β-glucan and ferment it to produce ethanol. This gene, with its dual β-glucosidase and β-glucanase activities, simplifies and reduces the cost of the typical process of converting lignocellulose into bioethanol using enzymes and yeast., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Regulation of mitochondrial calcium uptake by the mitochondrial calcium uniporter (mtCU) complex is crucial for heart function. In a recent study, Hasan et al. demonstrated that mitochondrial calcium uptake (MICU)1 and MICU2, regulatory subunits of the complex, help maintain calcium homeostasis in cardiac mitochondria, providing potential targets for therapies aimed at improving mitochondrial function in heart disease., Competing Interests: Declaration of interests None declared by authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The identification of deceased migrants is a global challenge that is exacerbated by migration distance, post-mortem conditions, access to ante-mortem data for comparison, inconsistent international procedures and lack of communication between arrival and origin countries. Due to low technology requirements, fast speed analysis and ease of transferring digital data, facial image comparison is particularly beneficial in those contexts, especially in challenging scenarios when this may be the only initial ante-mortem data available to identify the deceased. The Facial Identification Scientific Working Group (FISWG) professional guidelines for facial image comparison were developed for living facial appearance, and, therefore, a tailored protocol for the application of post-mortem to ante-mortem facial image comparison was proposed and evaluated in this research. The protocol was investigated via an inter-observer and an accuracy study, using 29 forensic cases (2001-2020) from the University of Milan, provided by the Laboratory of Forensic Anthropology and Odontology. In order to replicate a migrant identification scenario, each post-mortem subject was compared to all 29 ante-mortem targets (841 comparisons). The protocol guided the practitioner through stages of facial image comparison, from broad (phase 1) to more detailed (phase 3), eventually leading to a decision of 'exclusion' or 'potential match' for each post-mortem to ante-mortem case (phase 4). In phase 4, a support scale was also utilised to indicate the level of confidence in a potential match. Each post-mortem subject could be recorded with multiple potential matches. The protocol proved to be useful guide for facial image comparison, especially for less experienced practitioners and the inter-observer study suggested good reproducibility. The majority (82-96%) of ante-mortem subjects were excluded at the first stage of the protocol, and 71 full post-mortem to ante-mortem facial image comparisons were carried out. On average, two or three potential matches were recorded for each post-mortem subject. The overall accuracy rate was 85%, with the majority (79%) of ante-mortem non-targets correctly excluded from the identification process. An increased number and quality of available ante-mortem images produced more successful matches with higher levels of support. All potential matches involving non-targets received low levels of support, and for 73% of the post-mortem subjects, the ante-mortem target was the only recorded potential match. However, two ante-mortem targets were incorrectly excluded (one at the first stage of the protocol) and therefore changes to the protocol were implemented to mitigate these errors. A full protocol and a practical recording chart for practitioner use is included with this paper., (© 2024. The Author(s).)

Background: The impact of timing of PORT initiation for major salivary gland cancers on survival is unknown. We aim to examine the impact of PORT timeliness on overall survival (OS) of patients with major salivary gland cancers., Methods: This was a cross-sectional analysis using data from the National Cancer Database (2004-2017) and included patients with major salivary gland cancer treated with surgery and PORT., Results: In total, 5701 patients were included (3133 [55%] male, 4644 [82%] white, mean age 59 ± 16 years). For the overall cohort, PORT >6 weeks was not associated with decreased OS (1.00 aHR, 95% CI 0.89-1.11). When specifically examining patients with mucoepidermoid carcinoma, PORT >6 weeks was associated with a decreased OS (1.27 aHR, 95% CI 1.01-1.58)., Conclusions: Overall, this analysis did not demonstrate a survival benefit for initiating PORT within 6 weeks for patients with salivary gland malignancies. Subset analysis did support initiating PORT within 6 weeks after resection for patients with mucoepidermoid carcinomas. This was not demonstrated in other major salivary gland cancer histologies., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Compared to H 2 -assisted activation mode, the direct dissociation of CO 2 into carbonyl (*CO) with a simplified reaction route is advantageous for CO 2 -related synthetic processes and catalyst upgrading, while the stable C = O double bond makes it very challenging. Herein, we construct a subnano MoO 3 layer on the surface of Mo 2 N, which provides a dynamically changing surface of MoO 3 ↔MoO x (x < 3) for catalyzing CO 2 hydrogenation. Rich oxygen vacancies on the subnano MoO x surface with a high electron donating capacity served as a scissor to directly shear the C = O double bond of CO 2 to form CO at a high rate. The O atoms leached in CO 2 dissociation are removed timely by H 2 to regenerate active oxygen vacancies. Owing to the greatly enhanced dissociative activation of CO 2 , this MoO x /Mo 2 N catalyst without any supported active metals shows excellent performance for catalyzing CO 2 hydrogenation to CO. The construction of highly disordered defective surface on heterostructures paves a new pathway for molecule activation., (© 2024. The Author(s).)

Collagen (Col) is commonly used as a natural biomaterial for biomedical applications. Although Col I is the most prevalent col type employed, many collagen types work together in vivo to confer function and biological activity. Thus, blending collagen types can better recapitulate many native environments. This work investigates how hydrogel properties can be tuned through blending collagen types (col I/II and col I/III) and by varying polymerization temperatures. Col I/II results in poorly developed fibril networks, which softened the gels, especially at lower polymerization temperatures. Conversely, col I/III hydrogels exhibit well-connected fibril networks with localized areas of fine fibrils and result in stiffer hydrogels. A decreased molecular mass recovery rate is observed in blended hydrogels. The altered fibril morphologies, mechanical properties, and biological signals of the blended gels can be leveraged to alter cell responses and can be used as models for different tissue types (e.g., healthy vs fibrotic tissue). Furthermore, the biomimetic hydrogel properties are a tool that can be used to modulate the transport of drugs, nutrients, and wastes in tissue engineering applications., (© 2024 The Author(s). Macromolecular Bioscience published by Wiley‐VCH GmbH.)

Background: Previous studies have investigated complexation and coacervation of scallop Patinopecten yessoensis male gonad hydrolysates (SMGHs) and polysaccharides influenced by pH and blending ratio. It has been found that SMGHs/polysaccharide composite shows better gel properties under strongly acidic conditions. Thus, the complexation and coacervation of SMGHs and gellan gum (GG) were investigated via turbidimetric titration at different pH values (1-12) and biopolymer blending ratios (9.5:0.5-6:4)., Results: Both pH c and pH φ1 exhibited ratio-independent behavior with constant values at approximately pH 5.8 and pH 3.8, respectively, dividing SMGHs/GG blends into three phases named mixed polymers, soluble complexes and insoluble coacervates, respectively. Overall, SMGHs and GG exhibited synergistic gelation under neutral and acidic conditions, with the initial storage modulus (G') increasing by approximately 42.5-, 573.7- and 3421-fold and 97.7-, 550.3- and 0.5-fold, respectively, at pH 7, 5 and 3, compared with SMGHs and GG. As pH decreased from 7 to 3, the initial G' and viscosity η values of SMGHs/GG gels increased by 20.1- and 2.3-fold, respectively, exhibiting the greatest increase in gel strength. Moreover, the free water in the SMGHs/GG system significantly shifted toward lower relaxation times attributed to the immobilization of the outer hydration layers. SMGHs/GG gels in the insoluble phase exhibited denser networks and rougher surfaces, supporting the enhanced rheological properties and water retention capacity of the gel., Conclusion: This work provides a basic foundation for the development of pH-driven SMGHs/GG gelation by examining complexation and coacervation processes. © 2024 Society of Chemical Industry., (© 2024 Society of Chemical Industry.)

This Letter reports the first measurement of the oscillation amplitude and frequency of reactor antineutrinos at Daya Bay via neutron capture on hydrogen using 1958 days of data. With over 3.6 million signal candidates, an optimized candidate selection, improved treatment of backgrounds and efficiencies, refined energy calibration, and an energy response model for the capture-on-hydrogen sensitive region, the relative ν[over ¯]&#95;{e} rates and energy spectra variation among the near and far detectors gives sin^{2}2θ&#95;{13}=0.0759&#95;{-0.0049}^{+0.0050} and Δm&#95;{32}^{2}=(2.72&#95;{-0.15}^{+0.14})×10^{-3}  eV^{2} assuming the normal neutrino mass ordering, and Δm&#95;{32}^{2}=(-2.83&#95;{-0.14}^{+0.15})×10^{-3}  eV^{2} for the inverted neutrino mass ordering. This estimate of sin^{2}2θ&#95;{13} is consistent with and essentially independent from the one obtained using the capture-on-gadolinium sample at Daya Bay. The combination of these two results yields sin^{2}2θ&#95;{13}=0.0833±0.0022, which represents an 8% relative improvement in precision regarding the Daya Bay full 3158-day capture-on-gadolinium result.

Brain metastases (BMs) are the most common and among the deadliest brain tumors. Currently, there are no reliable predictors of BM development from primary cancer, which limits early intervention. Lung adenocarcinoma (LUAD) is the most common BM source and here we obtained 402 tumor and plasma samples from a large cohort of patients with LUAD with or without BM (n = 346). LUAD DNA methylation signatures were evaluated to build and validate an accurate model predicting BM development from LUAD, which was integrated with clinical factors to provide comprehensive patient-specific BM risk probabilities in a nomogram. Additionally, immune and cell interaction gene sets were differentially methylated at promoters in BM versus paired primary LUAD and had aligning dysregulation in the proteome. Immune cells were differentially abundant in BM versus LUAD. Finally, liquid biomarkers identified from methylated cell-free DNA sequenced in plasma were used to generate and validate accurate classifiers for early BM detection. Overall, LUAD methylomes can be leveraged to predict and noninvasively identify BM, moving toward improved patient outcomes with personalized treatment., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)