bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid extracellular release of cytochrome c is specific for apoptosis and marks cell death in vivo
Authors: Renz Andrea , Berdel Wolfgang E. , Kreuter Michael , Belka Claus , Schulze-Osthoff Klaus , Los Marek
Published: July 2002

Diverse death stimuli including anticancer drugs trigger apoptosis by inducing the translocation of cytochrome c from the outer mitochondrial compartment into the cytosol. Once released, cytochrome c cooperates with apoptotic protease-activating factor-1 and deoxyadenosine triphosphate in caspase-9 activation and initiation of the apoptotic protease cascade. The results of this study show that on death induction by chemotherapeutic drugs, staurosporine and triggering of the death receptor CD95, cytochrome c not only translocates into the cytosol, but furthermore can be abundantly detected in the extracellular medium. The cytochrome c release from the cell is a rapid and apoptosis-specific process that occurred within 1 hour after induction of apoptosis, but not during necrosis. Interestingly, elevated cytochrome c levels were observed in sera from patients with hematologic malignancies. In the course of cancer chemotherapy, the serum levels of cytochrome c in the majority of the patients grew rapidly as a result of increased cell death. These data suggest that monitoring of cytochrome c in the serum of patients with tumors might serve as a useful clinical marker for the detection of the onset of apoptosis and cell turnover in vivo.
Regulation of the inhibitor-of-apoptosis family member survivin in normal cord blood and bone marrow CD34+ cells by hematopoietic growth factors: implication of survivin expression in normal hematopoiesis
Authors: Fukuda Seiji , Pelus Louis M.
Published: July 2002

The inhibitor-of-apoptosis protein survivin is expressed in most cancers and leukemias and during fetal development, but not in most normal adult tissues. Survivin expression was analyzed in umbilical cord blood (UCB) and adult bone marrow CD34+cells and in the factor-dependent MO7e cell line; also investigated was whether survivin expression was regulated by hematopoietic growth factors. Survivin messsenger RNA (mRNA) and protein were expressed in fresh UCB and marrow CD34+ cells. The combination of thrombopoietin, Flt3 ligand, and stem cell factor upregulated survivin expression in CD34+ cells within 24 hours; survivin expression was cell-cycle related and highest during G2/M, whereas growth-factor withdrawal resulted in decreased survivin expression. Cell-cycle fractionation of UCB CD34+ with Hoechst-33342/pyronin-Y demonstrated that survivin message was undetectable in freshly isolated G0 cells, but present in G1 cells. After cytokine stimulation, survivin mRNA and protein expression were observed in both G0 and G1 CD34+ cells as well as in cells that had progressed to S and G2/M phase, indicating that survivin expression is regulated in all phases of the cell cycle. This contrasts with the expression of survivin predominantly during G2/M in cancer cells. In CD34+ cells and MO7e cells, growth factor–mediated upregulation of survivin was associated with inhibition of apoptosis, and downregulation of survivin was coincident with increased apoptosis. Furthermore, an inverse correlation between survivin and active caspase-3 was observed in CD34+ cells. These findings demonstrate that survivin is not a cancer-specific antiapoptotic protein and plays a regulatory role in normal adult hematopoiesis.
Isotype-switched immunoglobulin genes with a high load of somatic hypermutation and lack of ongoing mutational activity are prevalent in mediastinal B-cell lymphoma
Authors: Leithäuser Frank , Bäuerle Martin , Huynh Minh Quang , Möller Peter
Published: July 2002

Primary mediastinal B-cell lymphoma (PMBL) is a subentity of diffuse large B-cell lymphoma with characteristic clinical, histomorphologic, immunophenotypical, and genetic features. Unlike other B-cell lymphomas, PMBL has not yet been the subject of comprehensive molecular studies on the rearranged immunoglobulin (Ig) gene. Such investigations have proved essential to obtaining information about the differentiation stage of the lymphomagenic B cell. In the present study, the clonally rearranged immunoglobulin heavy-chain gene of 13 PMBL cases is analyzed by polymerase chain reaction (PCR) in conjunction with cloning and DNA sequencing. Twelve of 13 rearrangements were potentially functional. All clonally rearranged immunoglobulin genes bore a high load of somatic mutations (average, 13.0%), which appeared to be selected for a functional antibody in the majority of cases. The comparison of cloned PCR products revealed no evidence of ongoing mutation of the immunoglobulin variable gene. By means of reverse-transcriptase PCR, lymphoma-specific immunoglobulin transcripts were detected in 8 of 13 cases, all of which were of the postswitched type, whereas immunoglobulin protein expression was undetectable except for 1 case. A PMBL cell line, MedB-1, generated from an IgG− parental tumor, constitutively expressed IgG protein in a subset of cells, which was moderately suppressed by interleukin-4 and up-regulated in the presence of dexamethasone. PMBL is thus characterized by a heavily mutated, class-switched immunoglobulin gene without evidence of ongoing mutational activity. Moreover, our data indirectly suggest that regulation by extrinsic signals contributes to the immunoglobulin-negative phenotype of PMBL.
Interleukin-3 and interferon β cooperate to induce differentiation of monocytes into dendritic cells with potent helper T-cell stimulatory properties
Authors: Buelens Christel , Bartholomé Emmanuel J. , Amraoui Zoulikha , Boutriaux Michael , Salmon Isabelle , Thielemans Kris , Willems Fabienne , Goldman Michel
Published: July 2002

It was observed that interferon β (IFN-β) prevents the down-regulation of the interleukin-3 receptor α chain (IL-3Rα), which spontaneously occurs during culture of human monocytes. The functionality of IL-3R was demonstrated by the fact that IL-3 rescued IFN-β–treated monocytes from apoptosis. Monocytes cultured in the presence of IFN-β and IL-3 acquire a dendritic morphology and express high levels of HLA antigen class I and class II and costimulatory molecules. When stimulated by either lipopolysaccharide or fibroblasts expressing CD40 ligand (CD40L) transfectants, dendritic cells (DCs) generated in IFN-β and IL-3 secreted high levels of IL-6, IL-8, and tumor necrosis factor-α but low levels of IL-12 in comparison with DCs generated in IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF). In mixed leukocyte culture, IL-3–IFN-β DCs induced a vigorous proliferative response of allogeneic cord blood T cells and elicited the production of high levels of IFN-γ and IL-5 by naive adult CD4+ T cells. Finally, IL-3–IFN-β DCs were found to produce much higher levels of IFN-α than IL-4–GM-CSF DCs in response to Poly (I:C) but not to influenza virus. It was concluded that monocytes cultured in the presence of IL-3 and IFN-β differentiate into DCs with potent helper T-cell stimulatory capacity despite their low secretion of IL-12.
In vivo manipulation of dendritic cells to induce therapeutic immunity
Authors: Merad Miriam , Sugie Tomoharu , Engleman Edgar G. , Fong Lawrence
Published: July 2002

Efficient antigen presentation and T-cell priming are essential components of effective antitumor immunity. Dendritic cells are critical to both of these functions but to date no method has been devised that both targets antigen to these cells and activates them, in situ, in a manner that induces systemic immunity. In this study we combined a dendritic cell growth factor, Flt3 ligand, with a dendritic cell activator, immunostimulatory DNA, and a tumor antigen to activate and load dendritic cells in vivo. Initial studies showed that immunostimulatory DNA not only activates dendritic cells but also prolongs their survival in vivo and in vitro. Following treatment of mice with Flt3 ligand, coadministration of immunostimulatory DNA and antigen induced potent antitumor immunity, resulting in both tumor prevention and regression of existing tumors. CD8 cytotoxic T lymphocytes but not CD4 T cells were required for tumor protection. Natural killer cells also contributed to tumor protection. These results show that dendritic cells can be loaded with antigen and activated, in situ, and provide the basis for dendritic cell- targeted clinical strategies.
A tyrosine703serine polymorphism of CD109 defines the Gov platelet alloantigens
Authors: Schuh Andre C. , Watkins Nick A. , Nguyen Quang , Harmer Nicholas J. , Lin Martin , Prosper Joseph Y. A. , Campbell Kate , Sutherland D. Robert , Metcalfe Paul , Horsfall Wendy , Ouwehand Willem H.
Published: July 2002

The biallelic platelet-specific Gov antigen system—implicated in refractoriness to platelet transfusion, neonatal alloimmune thrombocytopenia, and posttransfusion purpura—is carried by the glycosylphosphatidylinositol (GPI)–linked protein CD109. The recent identification of the human CD109 complementary DNA (cDNA) has allowed the molecular nature of the Gov alleles to be elucidated. By using reverse transcriptase–polymerase chain reaction (RT-PCR) to amplify CD109 cDNAs from 6 phenotypically homozygous Govaa and Govbb individuals, we have determined that the Gov alleles differ by an A to C single nucleotide polymorphism (SNP) at position 2108 of the coding region, resulting in a Tyr/Ser substitution at CD109 amino acid 703. Allele-specific PCR sequence-specific primers (SSP), PCR-restriction fragment length polymorphism, and real-time PCR studies of 15 additional donors (5 Govaa, 5 Govbb, and 5 Govab) confirmed that this SNP correlates with the Gov phenotype. In addition, Chinese hamster ovary cells transiently expressing nucleotide 2108 A>C CD109 cDNA variants were recognized specifically by allele-specific Gov antisera, indicating that this polymorphism defines the Gov alloantigenic determinants. Real-time PCR was then used to genotype 85 additional Gov phenotyped donors. In all but 3 cases, genomic testing concurred with the Gov phenotype. Repeat testing corrected 2 of these discrepancies in favor of the genotyping result. The third discrepancy could not be resolved, likely reflecting low-level CD109 expression below the sensitivity of the phenotyping assay. We conclude that the Gov alleles are defined by a 2108 A>C SNP that results in a Tyr703Ser substitution of CD109 and that genotyping studies are more accurate for Gov alloantigen determination than are conventional serologic methods.
Tumor Vascularity in the Prognostic Assessment of Primary Cutaneous Melanoma
Authors: Kashani-Sabet Mohammed , Sagebiel Richard W. , Ferreira Carlos M.M. , Nosrati Mehdi , Miller James R.
Published: July 2002

PURPOSE: The vascular supply of the primary tumor is recognized to play an important role in the progression of a number of solid tumors. However, the role of tumor vascularity in the prognostic assessment of melanoma remains unclear. The purpose of this study was to determine the prognostic impact of patterns of vascularity on the outcome associated with cutaneous melanoma.

PATIENTS AND METHODS: Tumor vascularity was documented prospectively using routine histopathologic analysis of 417 primary cutaneous melanomas from the University of California at San Francisco Melanoma Center database. Four patterns of tumor vascularity were recorded: absent, sparse, moderate, and prominent.

RESULTS: Increasing tumor vascularity significantly increased the risk of relapse and death associated with melanoma, corresponding to reduced relapse-free and overall survival. By multivariate analysis, tumor vascularity was the most important determinant of overall survival, surpassing tumor thickness. Increasing tumor vascularity was associated with increased incidence of ulceration in the primary tumor.

CONCLUSION: Tumor vascularity is an important prognostic factor in melanoma, rivaling tumor thickness. Increasing tumor vascularity is highly correlated with ulceration, possibly helping to explain the biologic basis of this known prognostic factor.
Place of Death and Its Predictors for Local Patients Registered at a Comprehensive Cancer Center
Authors: Bruera Eduardo , Russell Nancy , Sweeney Catherine , Fisch Michael , Palmer J. Lynn
Published: July 2002

PURPOSE: To help with planning of a palliative care program, we reviewed the place of death of patients who were registered at our comprehensive cancer center and explored factors that predicted death in the hospital versus death at home.

PATIENTS AND METHODS: A retrospective study was undertaken of local patients who were registered at the University of Texas M.D. Anderson Cancer Center and died during the 1997/1998 fiscal year. Data from the institutional tumor registry and from the State of Texas Bureau of Vital Statistics file were collected and analyzed. The main outcome measures were place of death, patient characteristics associated with place of death, and time from registration at the institution to death.

RESULTS: Of 1,793 local patients, 251 (14%) died at M.D. Anderson Cancer Center; the remaining 86% died elsewhere. A total of 617 (34%) died at home, and 929 (52%) died in an acute hospital setting (including M.D. Anderson). A total of 1,040 (58%) died within 2 years of registration. The risk of hospital death versus home death increased for patients with cancer at a hematologic site (odds ratio [OR], 4.4; 95% confidence interval [CI], 2.8 to 6.8) and black ethnicity (OR, 1.9; 95% CI, 1.4 to 2.6) and decreased for patients who paid with Medicare (OR, 0.71; 95% CI, 0.57 to 0.90).

CONCLUSION: Most patients died in an acute care hospital setting and within 2 years of registration. Our data show some predictors of hospital death for cancer patients and suggest that better hospital palliative care services and integrated palliative care systems that bridge community and acute hospitals are needed.
Effect of Electric Fans on Body Core Temperature in Older Adults Exposed to Extreme Indoor Heat
Authors: O’Connor Fergus K. , Meade Robert D. , Wagar Katie E. , Harris-Mostert Roberto C. , Tetzlaff Emily J. , McCormick James J. , Kenny Glen P.
Published: October 2024

This study assessed whether electric fans limit core temperature increases in adults aged 65 to 85 years exposed to conditions similar to those experienced in homes during heat waves in North America.
Enhancing Antibacterial Properties and Biocompatibility of Titanium Surfaces through Synergy of Plasma Electrolytic Oxidation and Hydrothermal Process
Authors: Mazinani Arash , Nine Md Julker , Rastin Hadi , Chiesa Roberto , Candiani Gabriele , Tarsini Paolo , Ghomashchi Reza , Losic Dusan
Published: October 2024

Plasma electrolytic oxidation (PEO) is a well‐established electrochemical method to modify titanium (Ti) surfaces for various industrial applications, including automobile, aerospace, nuclear, sports, defense, and biomedical industries. However, PEO surfaces, with their subsequent nanostructural modification to achieve enhanced antibacterial properties, osseointegration, and biocompatibility on biomedical implants are barely explored. This study investigates the combined approach of PEO and hydrothermal (HT) processes to introduce a range of nanostructures on PEO‐induced porous titania for enhanced antibacterial and improved osseointegration properties. Different fabrication conditions of combined PEO and HT process enabled the fabrication of multidimensional nano‐morphologies, such as blades, needles, belts, and grass that exhibit mechano‐bactericidal properties with enhanced biocompatibility. Antibacterial performance shows that nanostructures generated using HT on the acidic PEO process have excellent antibacterial activity, destroying 88% of E. coli and ≈99% of S. aureus colonies after 24 h incubation. All these fabricated structures show very high biomineralization ability, as confirmed by simulated body fluid (SBF) tests. This study provides valuable contributions showing the potential of low‐cost PEO technology combined with other surface engineering methods for scalable modification and improvements of titanium implants with advanced antibacterial and biointegration properties.
4D Printing of PLA/PBS Biopolymers: Impact of Polymer Grade Variations on Thermomechanical Performance
Authors: Ghalayaniesfahani Ava , Oostenbrink Betty , van Kasteren Han , Mehrpouya Mehrshad
Published: October 2024

The adoption of biobased polymers is growing in the additive manufacturing industry, offering alternatives to petrochemical‐based plastics, known for their environmental impact. However, finding a single polymer with all desirable properties is challenging. Blending polymers allows for the combination of distinct features, optimizing performance for specific applications. This study formulates two biopolymer blends of poly(butylene succinate) (PBS) and poly(lactic acid) (PLA) (80/20 wt%) using different PBS grades to examine their effects on thermomechanical and functional properties. The addition of PLA, a shape memory polymer, enables dynamic changes in 3D printed structures, causing them to deform under stimuli and revert to their original shape—an effect known as 4D printing. The blend pellets are then used in filament extrusion, and smart sandwich samples are produced using fused filament fabrication. The thermomechanical and functional characteristics of the printed samples are evaluated. This research highlights the differences arising from using different PBS grades in 3D printed structures with high energy absorption. Results show that melt flow rate is a crucial factor, significantly affecting the thermomechanical and shape memory behavior, with variation between 86% and 93%.
Fabricating and Engineering Woody‐Biomass Aerogels for High‐Performance Triboelectric Nanogenerators for Energy Harvesting and Biomechanical Monitoring
Authors: Li Longwen , Wang Ruolin , Fu Yang , Jin Zhenhui , Chen Jiansong , Du Haishun , Pan Xuejun , Wang Yi‐Cheng
Published: October 2024

Woody biomass is an abundant renewable resource. In this study, aerogels for versatile triboelectric devices are fabricated from poplar biomass via a dissolution‐and‐regeneration method with concentrated lithium bromide solution as the solvent. To improve the aerogels' structural homogeneity, two treatments—ball‐milling the raw poplar woody biomass before its dissolution, and, separately, ultrasonication following its dissolution—were applied. These treatments altered the porous structures and mechanical properties of the resulting aerogels, leading to a marked increase in their triboelectric performance. Removing the majority of the lignin from the aerogels was also explored, and resulted in triboelectric output ≈5 times greater than that of pristine woody biomass aerogel (i.e., without ball milling, ultrasonication, or lignin reduction). The underlying mechanisms of such increases were found to be both chemical and physical. Next, triboelectric devices were fabricated using the optimal (i.e., low‐lignin) aerogel for energy harvesting and biomechanical monitoring. These devices were able to: 1) respond sensitively to force, likely due to the aerogel's porous structures; 2) capture mechanical energy, charge capacitors, and power small portable electronics; and 3) monitor biomechanical movements including respiration, joint motions, and gait‐pattern changes.
Sergeant‐and‐Soldier Effect in an Organic Room‐Temperature Phosphorescent Host‐Guest System
Authors: Law Anthony W. K. , Cheung Tsz Shing , Zhang Jianyu , Leung Nelson L. C. , Kwok Ryan T. K. , Zhao Zheng , Sung Herman H. Y. , Williams Ian D. , Qiu Zijie , Alam Parvej , Lam Jacky W.Y. , Tang Ben Zhong
Published: October 2024

Host‐guest systems have emerged as an efficient strategy for promoting organic room temperature phosphorescence (RTP). Despite the advantages of doping guest molecules into a host matrix, the complexity of these systems and the lack of techniques to visualize host‐guest interactions at the molecular scale pose significant challenges in understanding the underlying mechanisms. Here, a novel host‐guest RTP system is developed by incorporating low concentrations (1–10 mol%) of TPP‐4C‐BI (guest) into crystalline TPP‐4C‐Cz (host). Utilizing structural isomerism, the guest molecules are regularly incorporated into the host crystal lattice, resulting in phosphorescence quantum yields almost ten times higher than the pure compounds. The system enabled resolution of the molecular packing of the single crystal through X‐ray diffraction, providing unprecedented visualization of host‐guest interactions. A “sergeant‐and‐soldier” effect, where the minority dopant molecules (sergeants) significantly influence the packing arrangement of the host molecules (soldiers), enhances RTP is identified. Further analyses revealed that due to the host molecule's inefficient phosphorescence pathway, its long‐lived dark triplets are channeled to the guest via triplet‐triplet energy transfer (TTET), allowing the excited energy to radiatively decay more efficiently. These insights advance the understanding of RTP mechanisms and offer practical implications for designing high‐efficiency phosphorescent materials.
Optoelectric‐Driven Wetting Transition on Artificially Micropatterned Surfaces With Long‐Range Virtual Electrodes
Authors: Zamboni Riccardo , Ray Debdatta , Denz Cornelia , Imbrock Jörg
Published: October 2024

The manipulation of droplets and wetting properties is crucial in many applications that involve surface‐liquid interactions, especially on artificial superhydrophobic substrates. This study presents an active optoelectronic method to achieve transport and transition between two wetting states on patterned surfaces, namely Cassie–Baxter (CB) and Wenzel (W). The approach employs a photovoltaic iron‐doped lithium niobate crystal placed on the bottom of a micropatterned substrate without any adhesive or sticky bonding. Taking advantage of the bulk photovoltaic effect, charge separation can be induced by light inside the crystal, thus leading to virtual electrodes. The long‐range interaction between these virtual electrodes and the droplets on the top of the substrate allows for transitions between wetting states and droplet transport. Superhydrophobic wetting transitions between Cassie–Baxter and Wenzel are observed on different substrates using this technique. The forces acting on the droplet that cause the transition are determined numerically. The evolution of droplet deformation and contact angle during the generation of the virtual electrode depends on the shape and intensity of the light beam used for photoinduction, as well as on the compositional properties of the crystal.
Filaments for 3D Printing of Iridescent Structural Colors
Authors: Siegwardt Lukas , Hemkemeier Georg , Gallei Markus
Published: October 2024

Inspired by nature, this work presents a scalable method to produce opalescent 3D printing filaments with angle‐dependent structural color. Compared to conventional colorants, these colors provide a more vivid appearance, possess the ability to dynamically change in response to alterations of illumination, and may feature superior longevity as well as durability. Particle synthesis via emulsion polymerization in starved‐feed mode is utilized to achieve a tailored core–shell particle architecture. During processing, the thermoplastic polyacrylate‐based shells form a continuous matrix, wherein the pristine polystyrene cores self‐assemble. The colloidal ordered structure thus formed selectively scatters light according to Bragg's law. Adjusting particle size makes the perceived colors easily tunable over the visible spectrum. The filaments are printable on entry‐level printers with comparable settings to commercial filaments and state‐of‐the‐art print quality. With this work, sustainable 3D printing of iridescent objects with a novel and superior coloration strategy becomes possible for everyone – from hobbyists over customized goods and industrial prototypes to serial production.
Biodegradable Substrates for Rigid and Flexible Circuit Boards: A Review
Authors: Dušek Karel , Koc Daniel , Veselý Petr , Froš Denis , Géczy Attila
Published: October 2024

Biodegradable materials represent a promising path toward green and sustainable electronics on a global scale in the future. Plastics play a pivotal role in contemporary electronics, including printed circuit boards (PCB), where petroleum‐based polymers such as epoxies form the base insulating substrate. In this review paper, several promising bio‐based alternatives to conventional PCB materials that are recently developed and investigated are stated and discussed regarding their properties, practical utilization, and further perspective. The given list includes polylactic acid (PLA), cellulose acetate (CA), polyvinyl alcohol (PVA), and others, with the development of PLA‐based PCB substrates being the furthest along regarding the use in industry practice. Yet, all of the provided solutions are still only suitable for prototypes or low‐cost electronics without high‐reliability requirements. The reason for this is inferior mechanical and thermal properties of biopolymers compared to traditional petroleum‐based polymers. Further development is therefore essential, including new types of reinforcements and other additives. However, as Life Cycle Assessment analyses discussed in the paper show, biopolymers are capable of significantly reducing the environmental impact and are likely to play a major role in shaping a sustainable path for the electronics industry, which will be a key challenge in the current decade.
Insufficient Mechanical Loading Downregulates Piezo1 in Chondrocytes and Impairs Fracture Healing Through ApoE‐Induced Senescence
Authors: Jia Siming , Liu Weijian , Zhang Mo , Wang Lijun , Ren Chuan , Feng Chen , Zhang Tao , Lv Hongzhi , Hou Zhiyong , Zou Weiguo , Zhang Yingze , Tong Wei , Wang Juan , Chen Wei
Published: October 2024

Insufficient mechanical loading impairs fracture healing; however, the underlying mechanisms remain unclear. Increasing evidence indicates that Piezo1 plays an important role in fracture healing, although the effect of Piezo1 on the endochondral ossification of chondrocytes has been overlooked. This study reports that mechanical unloading down‐regulates the expression of Piezo1 in chondrocytes and leads to fracture nonunion. Single‐cell sequencing of calluses revealed that specific deletion of Piezo1 in chondrocytes upregulated the expression of apolipoprotein E (ApoE) in hypertrophic chondrocytes, resulting in delayed cartilage‐to‐bone transition due to enhanced chondrocyte senescence. Based on these results, an injectable and thermosensitive hydrogel is developed, which released an ApoE antagonist in situ at the fracture site. This hydrogel effectively attenuated chondrocyte senescence and, thus, promoted cartilage‐to‐bone transition as well as the fracture healing process. Overall, this data provide a new perspective on the activity of chondrocytes in fracture healing and a new direction for the treatment of fracture nonunion caused by insufficient mechanical loading.
Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets
Authors: Xu Ganfei , Yu Juan , Lyu Jiacheng , Zhan Mengna , Xu Jie , Huang Minjing , Zhao Rui , Li Yan , Zhu Jiajun , Feng Jinwen , Tan Subei , Ran Peng , Su Zhenghua , Liu Xinhua , Zhao Jianyuan , Zhang Hongwei , Xu Chen , Chang Jun , Hou Yingyong , Ding Chen
Published: October 2024

Multi‐omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi‐step progression of BRDC, such as tumor protein P53 (TP53) mutation‐associated estrogen receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification‐associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS_Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T‐cell lymphoma invasion and metastasis 1, androgen receptor, and aldo‐keto reductase family 1 member C1 (TIAM1‐AR‐AKR1C1) axis promotes cell invasion and migration in DCIS_adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi‐omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.
Glycerol Kinase Drives Hepatic de novo Lipogenesis and Triglyceride Synthesis in Nonalcoholic Fatty Liver by Activating SREBP‐1c Transcription, Upregulating DGAT1/2 Expression, and Promoting Glycerol Metabolism
Authors: Ouyang Shuyu , Zhuo Shu , Yang Mengmei , Zhu Tengfei , Yu Shuting , Li Yu , Ying Hao , Le Yingying
Published: October 2024

Glycerol kinase (GK) participates in triglyceride (TG) synthesis by catalyzing glycerol metabolism. Whether GK contributes to nonalcoholic fatty liver (NAFL) is unclear. The expression of hepatic Gk is found to be increased in diet‐induced and genetic mouse models of NAFL and is positively associated with hepatic SREBP‐1c expression and TG levels. Cholesterol and fatty acids stimulate GK expression in hepatocytes. In HFD‐induced NAFL mice, knockdown of hepatic Gk decreases expression of SREBP‐1c and its target lipogenic genes as well as DGAT1/2, increases serum glycerol levels, decreases serum TG levels, and attenuates hepatic TG accumulation. Overexpression of GK in hepatocytes in mice or in culture produces opposite results. Mechanistic studies reveal that GK stimulates SREBP‐1c transcription directly by binding to its gene promoter and indirectly by binding to SREBP‐1c protein, thereby increasing lipogenic gene expression and de novo lipogenesis. Studies with truncated GK and mutant GKs indicate that GK induces SREBP‐1c transcription independently of its enzyme activity. GK contributes to lipid homeostasis under physiological conditions by catalyzing glycerol metabolism rather than by regulating SREBP‐1c transcription. Collectively, these results demonstrate that increased hepatic GK promotes de novo lipogenesis and TG synthesis in NAFL by stimulating SREBP‐1c transcription and DGAT1/2 expression and catalyzing glycerol metabolism.
High‐Energy LiNiO2 Li Metal Batteries Enabled by Hybrid Electrolyte Consisting of Ionic Liquid and Weakly Solvating Fluorinated Ether
Authors: Liu Qian , Xu Jiayi , Jiang Wei , Gim Jihyeon , Tornheim Adam P. , Pathak Rajesh , Zhu Qijia , Zuo Peng , Yang Zhenzhen , Pupek Krzysztof Z. , Lee Eungje , Wang Chongmin , Liu Cong , Croy Jason R. , Xu Kang , Zhang Zhengcheng
Published: October 2024

In pursuit of the highest possible energy density, researchers shift their focus to the ultimate anode material, lithium metal (Li0), and high‐capacity cathode materials with high nickel content (Ni > 80%). The combination of these aggressive electrodes presents unprecedented challenges to the electrolyte. Here, we report a hybrid electrolyte consisting of a highly fluorinated ionic liquid and a weakly solvating fluorinated ether, whose hybridization structure enables the reversible operation of a battery chemistry based on Li0 and LiNiO2 (Ni = 100%), delivering nearly theoretical capacity of the latter (up to 249 mAh g−1) for >300 cycles with retention of 78.6% and in absence of unwanted morphological changes in both electrodes. Extensive characterization assisted by molecular dynamic simulation and density functional theory calculations reveals the function of the fluorinated ether to be far more profound than simple dilution and viscosity reduction. Instead, it induces drastic changes in Li+‐solvation environment, the consequence of which engenders simultaneous stabilization of electrode/electrolyte and interfacing via formation of respective interfacial chemistries. This study further unlocks fundamental knowledge underneath the prevailing “diluent strategy” that is extensively applied by the electrolyte researchers and opens more design space for the next‐generation electrolytes and interphases for these coveted battery chemistries.
Enhanced Coupling Between Soft Ferromagnetism and Displacive Ferroelectricity in the Pb‐Site Modified PbFe1/2Nb1/2O3
Authors: Park Ji‐Hun , Cho Jae‐Hyeon , Lee Nyun Jong , Lee Hyun‐Jae , Lee Ju‐Hyeon , Lee Geon‐Ju , Marlton Frederick P. , Suzuki Motohiro , Hinterstein Manuel , Oh Yoon Seok , Choi Ji‐Won , Hwang Geon‐Tae , Lee Jun Hee , Kim Sanghoon , Kim Kee Hoon , Jo Wook
Published: October 2024

Albeit having great potential toward unprecedented type of applications such as magnetoelectric (ME) sensors and memories, practically useful single‐phase multiferroics that show large coupling between ferromagnetism and ferroelectricity at ambient temperatures are still lacking. Here, the discovery of a new type of perovskite ferroelectrics (Pb,M)(Fe1/2Nb1/2)O3 (M = Fe, Co, Ni) is reported with a magnetically‐active metal ion introduced into a cuboctahedrally‐coordinated Pb position, which exhibits enhanced ME coupling owing to the development of simultaneous soft‐ferromagnetism and lone‐pair ferroelectricity persistent above room temperature. These Pb‐site engineered (Pb,M)(Fe1/2Nb1/2)O3 perovskites exhibit a ME coupling coefficient of ≈40–60 ps m−1, a saturated electric polarization of 14–17 µC cm−2 and a saturation magnetization of 0.15–0.3 µB f.u−1. X‐ray absorption spectroscopy combined with first‐principles calculations demonstrates that the induced ferromagnetism originates from the ferromagnetic superexchange interaction coming from ≈90° bonding between the magnetic ions at the Pb site. The present discovery of the enhanced ME coupling in the Pb‐site engineered perovskite ferroelectrics may provide unforeseen opportunities for applying conventional displacive ferroelectricity in the field of spintronics where ferromagnetism is essentially required.
Application of a Conceptual Stocking Model for Two Recreationally Important Species
Authors: Farrier Sean M. , Koupal Keith D. , Burger Paul R. , Wuellner Melissa R.
Published: October 2024

Fish stocking continues to be an important and often‐used tool in fisheries management. Mortality of fish may be high in the first few days after stocking due to predation and a lack of appropriate food and habitat. The objective of this study was to develop a conceptual model that may identify stocking locations that can help improve the survival of stocked fish. We identified three factors—predator risk, zooplankton (food) availability and measures of habitat that could be important to the survival of stocked Walleye (Sander vitreus) and White Bass (Morone chrysops) fingerlings in Lake McConaughy, Nebraska. The spatial distribution of these factors was used to create a predictive surface to identify those stocking locations hypothesised to lead to higher survival. Final stocking maps identified the best 12.8% and 13.9% of the predicted area of Lake McConaughy for stocking Walleye and White Bass, respectively. Both maps predicted that the best locations were along the south‐central shoreline of Lake McConaughy. The maps for both species were interestingly similar. These results are likely due to the similarities in predators consuming the stocked species and the zooplankton consumed by fingerlings of both species. Habitat availability may be less important, or other aspects of habitat may need to be considered. Identifying the best locations for stocking based on predation risk and the availability of food and habitat could increase the survival of stocked fishes and help managers reach population objectives.
Path analysis for quality traits and minerals in common bean based on data from multi‐environment experiments
Authors: Ribeiro Nerinéia Dalfollo , de Andrade Fabricio Fuzzer , Maziero Sandra Maria , da Silva Argenta Henrique
Published: October 2024

The number of experiments to be used in path analysis to enhance the efficacy of indirect selection for fast‐cooking common bean (Phaseolus vulgaris L.) lines has not yet been defined. This study sought to break down the correlation coefficient into direct and indirect effects for quality traits and mineral concentration based on data acquired from multi‐environment experiments. Additionally, the study proposed to establish the minimum number of experiments required for path analysis aiming at indirect selection for fast cooking in common bean. Four experiments were conducted in which various quality traits and the concentration of seven minerals were analyzed across 25 common bean cultivars. Variance and path analyses were applied to data from individual experiments and combinations of two, three, and four experiments. Significant cultivar × experiment interaction effects were found for most evaluated traits. The traits exerting the greatest direct effects on cooking time varied across the four experiments. Data from individual experiments were highly variable, resulting in low ability to identify promising traits for indirect selection. However, data from two, three, and four experiments had lower variability and therefore provided a greater ability to identify traits with the greatest direct and indirect effects on cooking time. Mass of 100 grains and calcium concentration emerged as promising traits for indirect selection to achieve fast cooking in common bean. Using data from two experiments allows for an effective interpretation of path analysis results for quality traits and mineral concentration in common bean.
Pore classification method with steady‐state diffusion in complex porous media
Authors: Lee Seunggeon , Kim Dongjae , Nam Jaewook
Published: October 2024

In porous media, the transport and flow through the void phase are influenced by the internal pore network due to its complex morphology. In other words, the contributions of individual pores can vary due to their connectivity within the network and characteristics in physical phenomena. In this study, we propose a pore classification method according to geometries and physical behaviors to understand the role of each pore in microstructure. Our method classifies entire pores into backbone, dead‐end, and isolated pore using connectivity analysis and steady‐state diffusion. The backbone acts as the main pathway for the transportation process. Therefore, backbone fraction can be utilized as a quantitative indicator of the pore network in microstructure. Furthermore, this approach enables us to explore the relationship between classified pores and microstructural properties through numerical experiment using virtual structures. This method can be used for various porous materials, such as battery electrodes, membranes, and soil.
Bimetal anchoring porous MXene nanosheets for driving tandem catalytic high‐efficiency electrochemical nitrate reduction
Authors: Guo Rongyu , Cui Zhijie , Yu Tianyang , Li Jing , Peng Wenchao , Liu Jiapeng
Published: October 2024

Electrochemical nitrate reduction reaction (NO3RR) is considered a promising strategy for ammonia synthesis and nitrate removal, in which catalyst development is crucial. Herein, a series of bimetal (Co and Cu) anchoring porous MXene nanosheets (CoxCuy@PM) catalysts were prepared by combining etching and reduction strategy. On the one hand, Cu and Co bimetals provided tandem catalytic active sites for NO3RR. On the other hand, the in‐plane PM exhibited good electrical conductivity and multiple transport pathways. Consequently, the optimized Co7Cu3@PM catalyst achieved a high ammonia yield of 7.43 mg h−1 mg cat.−1 and an excellent Faraday efficiency (FE) of 95.9%. The mechanism of NO3RR was investigated by analyzing electrolysis products and in situ Fourier transform infrared spectroscopy. Furthermore, the Co7Cu3@PM based ZnNO3− battery exhibited the superior power density of 5.59 mW cm−2 and an NH3 FE of 92.3%. This work presents an effective strategy to design MXene‐based high‐performance NO3RR electrocatalysts.
Numerical study on the hydrodynamics of highly viscous liquid under vertical acoustic vibration
Authors: Yu Lei , Jia Yuxin , Zhan Xiaobin , Ma Wenzhe , Jiang Yalong , Shi Tielin
Published: October 2024

This study investigated the hydrodynamics of highly viscous liquid under vertical acoustic vibration, and examined the effects of vibration parameters and filling ratio on the strain rate, stretching index, and convective intensity of high‐viscosity liquid. A numerical simulation model of gas–liquid flows was developed using computational fluid dynamics method and validated through experiment. Under acoustic vibration, the high‐viscosity liquid predominantly experienced extensional and shearing flows. Significant deformation of the high‐viscosity liquid was observed near the interface between gas and liquid. Increasing the amplitude or frequency of acoustic vibration, selecting a combination of low‐frequency and high amplitude under equal acceleration conditions, as well as appropriately reducing the filling ratio can enhance the stretching and shearing effects on the liquid, and improve the strength of convection. The findings also established a predictive relationship between amplitude and frequency, enabling the determination of optimal mixing conditions.
Risk factors and clinical significance of post‐stroke incident ischemic lesions
Authors: Fang Rong , Duering Marco , Bode Felix J. , Stösser Sebastian , Meißner Julius N. , Hermann Peter , Liman Thomas G. , Nolte Christian H. , Kerti Lucia , Ikenberg Benno , Bernkopf Kathleen , Glanz Wenzel , Janowitz Daniel , Wagner Michael , Neumann Katja , Speck Oliver , Düzel Emrah , Gesierich Benno , Dewenter Anna , Spottke Annika , Waegemann Karin , Görtler Michael , Wunderlich Silke , Zerr Inga , Petzold Gabor C. , Endres Matthias , Georgakis Marios K. , Dichgans Martin ,   the DEMDAS investigators
Published: October 2024

INTRODUCTION

While incident ischemic lesions (IILs) are not unusual on follow‐up magnetic resonance imaging (MRI) following stroke, their risk factors and prognostic significance remain unknown.

METHODS

In a prospective multicenter study of 503 acute stroke patients, we assessed IILs on registered MRI images at baseline and 6 months, analyzing risk factors and clinical outcomes across 36 months.

RESULTS

At 6 months, 78 patients (15.5%) had IILs, mostly diffusion‐weighted imaging‐positive (72%) and clinically covert (91%). Older age and small vessel disease (SVD) lesions were baseline risk factors for IILs. IILs were associated with worse cognitive (beta for global cognition: −0.31, 95% confidence interval [CI]: −0.48 to −0.14) and functional outcomes (beta for modified Rankin scale [mRS]: 0.36, 95% CI: 0.14 to 0.58), and higher recurrent stroke risk (hazard ratio: 3.81, 95% CI: 1.35 to 10.69). IILs partially explained the relationship between SVD and poor cognition.

DISCUSSION

IILs are common and are associated with worse cognitive and functional outcomes and stroke recurrence risk. Assessing IILs following stroke might aid prognostication.

Highlights

Incident ischemic lesions (IILs) were assessed with registered baseline and 6‐month magnetic resonance imaging (MRI) scans in a stroke cohort.

IILs 6 months after stroke are present in one‐sixth of patients and are mostly clinically silent.

Small vessel disease burden is the main baseline risk factor for IILs.

IILs are associated with cognitive and functional impairment and stroke recurrence.

Assessing IILs by follow‐up MRI aids long‐term prognostication for stroke patients.
Successful transition from intravenous to inhalation anesthesia for respiratory management of coronavirus disease pneumonia: A case report
Authors: Kato Reijiro , Irie Yuhei , Izutani Yoshito , Ishikura Hiroyasu
Published: October 2024

Background

In patients with coronavirus disease pneumonia, strong spontaneous breathing increases pulmonary vascular permeability and induces self‐inflicted lung injury, prolonging the intensive care unit stay and worsening prognosis. Therefore, spontaneous respiration must be strictly controlled.

Case Presentation

A 48‐year‐old man was admitted for respiratory management of severe coronavirus disease pneumonia. Despite immediate ventilatory management, ventilatory failure and air leak syndrome developed, necessitating venovenous extracorporeal membrane oxygenation, intravenous sedation, and muscle relaxation. Over time, the patient's inspiratory effort worsened and the requirement for transvenous anesthesia increased. Therefore, management was switched to inhalation anesthesia after discontinuation of all transvenous anesthetics, maintaining morphine‐only analgesia. Subsequent management enabled effective control of spontaneous respiration, allowing eventual discontinuation of inhalation anesthesia, venovenous extracorporeal membrane oxygenation, and ventilation.

Conclusion

Management of spontaneous respiration in coronavirus disease pneumonia can be complicated by resistance to transvenous anesthesia; however, the use of an inhaled anesthetic may present a valuable alternative.
Self‐Adaptive Activation of DNAzyme Nanoassembly for Synergistically Combined Gene Therapy
Authors: Wang Jing , Shang Jinhua , Yu Shanshan , Lin Mengru , Gong Xue , Liu Xiaoqing , Liu Zhihong , Wang Fuan
Published: October 2024

DNAzyme represents a promising gene silencing toolbox yet is obstructed by the poor substrate accessibility in specific cells. Herein, a compact DNA nanoassembly, incorporating multimeric therapeutic DNAzyme, was prepared for selective delivery of gene‐silencing DNAzyme with requisite cofactors and auxiliary chemo‐drugs. By virtue of the sequence‐conservative duplex‐specific nuclease, the endogenous miRNA catalyzes the successive and site‐specific cleavage of DNA nanoassembly substrate (nominated as the localized RNA walking machine) and thus ensures the liberation/activation of therapeutic agents with high accuracy and efficacy. The miR‐10b‐stimulated DNAzyme was designed to downregulate the TWIST transcription factor, an upstream promotor of miR‐10b, thus acquiring the self‐sufficient downregulation of TWIST/miR‐10b signaling nodes (self‐adaptive negative feedback loop) for abrogating tumor metastasis and chemo‐resistance issues.
Stereospecific 3‐Aza‐Cope Rearrangement Interrupted Asymmetric Allylic Substitution‐Isomerization
Authors: Zhuang Hong‐Feng , Gu Jun , Ye Zhiwen , He Ying
Published: October 2024

Transition‐metal catalyzed asymmetric allylic substitution with alkyl and heteroaryl carbon nucleophiles has been well‐established. However, the asymmetric allylic arylation of acyclic internal alkenes with aryl nucleophiles remains challenging and underdeveloped. Herein we report a stereospecific 3‐aza‐Cope rearrangement interrupted asymmetric allylic substitution‐isomerization (Int‐AASI) that enables asymmetric allylic arylation. By means of this stepwise strategy, both enantioenriched allylic arylation products and axially chiral alkenes could be readily obtained in high enantioselectivities. Experimental studies support a mechanism involving a cascade of asymmetric allylic amination, stereospecific 3‐aza‐Cope rearrangement and alkene isomerization. Density functional theory studies detailed the reasons of achieving the high chemoselectivity, regioselectivity, stereoselectivity and stereospecificity, respectively.