bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxidative DNA base modifications in peripheral blood mononuclear cells of patients treated with high-dose infusional doxorubicin
Authors: Doroshow James H. , Synold Timothy W. , Somlo George , Akman Steven A. , Gajewski Ewa
Published: July 2002

In prior studies, it was demonstrated that the redox metabolism of doxorubicin leads to the formation of promutagenic oxidized DNA bases in human chromatin, suggesting a potential mechanism for doxorubicin-related second malignancies. To determine whether a similar type of DNA damage is produced in the clinic, peripheral blood mononuclear cell DNA from 15 women treated with infusional doxorubicin (165 mg/m2) as a single agent was examined for 14 modified bases by gas chromatography/mass spectrometry with selected ion monitoring. Prior to the 96-hour doxorubicin infusion, 13 different oxidized bases were present in all DNA samples examined. Chemotherapy, producing a steady-state level of 0.1 μM doxorubicin, increased DNA base oxidation up to 4-fold compared to baseline values for 9 of the 13 bases studied. Maximal base oxidation was observed 72 to 96 hours after doxorubicin treatment was begun; the greatest significant increases were found for Thy Gly (4.2-fold), 5-OH-Hyd (2.5-fold), FapyAde (2.4-fold), and 5-OH-MeUra (2.4-fold). The level of the promutagenic base FapyGua increased 1.6-fold (P < .02), whereas no change in 8-OH-Gua levels was observed in peripheral blood mononuclear cell DNA during the doxorubicin infusion. These results suggest that DNA base damage similar to that produced by ionizing radiation occurs under clinical conditions in hematopoietic cells after doxorubicin exposure. If doxorubicin-induced DNA base oxidation occurs in primitive hematopoietic precursors, these lesions could contribute to the mutagenic or toxic effects of the anthracyclines on the bone marrow.
Pharmacogenetics of methotrexate: toxicity among marrow transplantation patients varies with the methylenetetrahydrofolate reductase C677T polymorphism
Authors: Ulrich Cornelia M. , Yasui Yutaka , Storb Rainer , Schubert Mark M. , Wagner John L. , Bigler Jeannette , Ariail Kiley S. , Keener Cassie L. , Li Sue , Liu Hao , Farin Federico M. , Potter John D.
Published: July 2002

This study investigated whether a polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene (C677T) modifies responses to methotrexate (MTX) in patients undergoing bone marrow transplantation. About 10% to 12% of the population carry the MTHFR TT genotype (enzyme activity, 30% of wild type [CC]). Patients (n = 220) with chronic myelogenous leukemia underwent marrow allografts and were given a short course of MTX. MTX toxicity measures included the oral mucositis index (OMI), speed of engraftment (platelet and granulocyte counts), and bilirubin. Patients with lower MTHFR activity (TT genotype) had 36% higher mean OMI during days 1 to 18 (+5.7, P = .046) and 20% higher OMI between days 6 and 12 (+3.8, P = .27). Platelet counts recovered more slowly among patients with the TT genotype compared to wild type (24% slower recovery to 10 000 platelets/μL, P = .23; 34% slower to 20 000/μL, P = .08). Patients with decreased MTHFR activity appear at risk of higher MTX toxicity. Because of the high prevalence of the TT genotype, these results may have implications for MTX dosage.
Tumor cells of hairy cell leukemia express multiple clonally related immunoglobulin isotypes via RNA splicing
Authors: Forconi Francesco , Sahota Surinder S. , Raspadori Donatella , Mockridge Christopher I. , Lauria Francesco , Stevenson Freda K.
Published: July 2002

Hairy cell leukemia (HCL) derives from a mature B cell and expresses markers associated with activation. Analysis of immunoglobulin variable region genes has revealed somatic mutation in most cases, consistent with an origin from a cell that has encountered the germinal center. One unusual feature of hairy cells (HCs) is the frequent expression of multiple immunoglobulin heavy chain isotypes, with dominance of immunoglobulin (Ig)–G3, but only a single light chain type. The origin and clonal relationship of these isotype variants have been unclear. In order to probe the isotype switching status of HCL, RNA transcripts of VHDJH– constant region sequences from 5 cases of typical HCL, all expressing multiple surface immunoglobulin isotypes, were analyzed. Tumor VHDJH-Cμ sequences were identified and found to be somatically mutated (range, 1.4% to 6.5%), with a low level of intraclonal heterogeneity. Additional immunoglobulin isotypes of identical VHDJHsequence were also identified, including IgD (5 of 5), IgG3 (5 of 5), IgG1 (3 of 5), IgG2 (2 of 5), IgA1 (4 of 5), and IgA2 (1 of 5). Derivation of multiple isotypes from individual cells was demonstrated by analyzing transcripts in single sorted cells from one patient, with evidence for coexistence of isotype variants in 10 of 10 cells. These findings indicate that clonally related multiple isotypes coexist in single HCs, with individual isotypes presumably generated via RNA splicing. Production of IgG3 appears common, but IgG1, IgG2, IgA1, and IgA2 also arise, indicating a continuing influence of a directed process on the tumor clone. These HCs appear to be arrested at the point of isotype switch, where RNA processing may precede deletional recombination.
Catheter-related deep venous thrombosis in children with hemophilia
Authors: Journeycake Janna M. , Quinn Charles T. , Miller Kim L. , Zajac Joy L. , Buchanan George R.
Published: July 2002

Central venous catheters (CVCs) are a common adjunct to hemophilia therapy, but the risk of CVC-related deep venous thrombosis (DVT) in hemophiliacs is not well defined. In a previous study, 13 patients with CVCs had no radiographic evidence of DVT. However, recent abstracts and case studies demonstrate that DVT does occur. Therefore, this study sought to determine the frequency of DVT in children with hemophilia and long-term CVCs and to correlate venographic findings with clinical features. All hemophilia patients with tunneled subclavian CVCs in place for 12 months or more were candidates for evaluation. Patients were examined for physical signs of DVT and questioned about catheter dysfunction. Contrast venograms were obtained to identify DVT. Fifteen boys with severe hemophilia were evaluated, including 9 from the initially studied group of 13. Eight patients had evidence of DVT, 5 of whom previously had normal venograms. Five of 15 patients had clinical problems related to the CVC, all of whom had DVT. Four of 15 patients had suggestive physical signs; 3 had DVT. The mean duration of catheter placement for all patients was 57.5 months (range, 12-102 months). For patients with DVT, the mean duration was 66.6 ± 7.5 months, compared to 49.5 ± 7.2 months for patients without DVT (P = .06). No patient whose CVC was in place fewer than 48 months had an abnormal venogram. Many hemophilia patients with CVCs develop DVT of the upper venous system, and the risk increases with duration of catheter placement.
The alternatively spliced αEC domain of human fibrinogen-420 is a novel ligand for leukocyte integrins αMβ2 and αXβ2
Authors: Lishko Valeryi K. , Yakubenko Valentin P. , Hertzberg Kathe M. , Grieninger Gerd , Ugarova Tatiana P.
Published: July 2002

The interaction of human plasma fibrinogen with leukocyte integrins αMβ2 (CD11b/CD18, Mac-1) and αXβ2 (CD11c/CD18, p150,95) is an important component of the inflammatory response. Previously, it was demonstrated that binding of fibrinogen to these integrins is mediated by γC, the globular C-terminal domain of the γ chain. In this study, evidence was found of another fibrinogen domain that can serve as a ligand for the 2 leukocyte integrins: αEC, a homologous domain that extends the α chains in a recently discovered subclass of fibrinogen known as fibrinogen-420. Recombinant αEC supported strong adhesion and migration of cells expressing αMβ2 and αXβ2, including nonactivated and activated U937 and THP-1 monocytoid cells, and neutrophils. Cells transfected with complementary DNA for these integrins also bound αEC. The specificity of interaction was substantiated by inhibition of cell adhesion with antibodies against αM, αX, and β2subunits. Also, neutrophil inhibitory factor, a specific inhibitor of αMβ2 and αXβ2function, efficiently blocked cell adhesion to αEC. In αMβ2 and αXβ2, the I domain is the binding site for αEC, since αEC bound to recombinant αM I and αXI domains in a dose-dependent and saturable manner. Synthetic peptides that duplicated sequences γ190 to 202 and γ377 to 395, previously considered putative binding sites in γC, effectively inhibited αMβ2- and αXβ2-mediated adhesion to αEC, suggesting that recognition of αEC by the I domain involves structural features in common with those of γC. These findings identify αEC as a second domain in fibrinogen-420 that binds αMβ2 and αXβ2 and can mediate leukocyte adhesion and migration.
Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma
Authors: Møller Holger Jon , Peterslund Niels Anker , Graversen Jonas Heilskov , Moestrup Søren Kragh
Published: July 2002

The hemoglobin scavenger receptor (HbSR/CD163) is an interleukin-6– and glucocorticoid-regulated macrophage/monocyte receptor for uptake of haptoglobin-hemoglobin complexes. Moreover, there are strong indications that HbSR serves an anti-inflammatory function. Immunoprecipitation and immunoblotting enabled identification of a soluble plasma form of HbSR (sHbSR) having an electrophoretic mobility equal to that of recombinant HbSR consisting of the extracellular domain (scavenger receptor cysteine-rich 1-9). A sandwich enzyme-linked immunosorbent assay was established and used to measure the sHbSR level in 130 healthy subjects (median, 1.87 mg/L; range, 0.73-4.69 mg/L). To evaluate the sHbSR levels in conditions with increased leukocyte stimulation and proliferation, 140 patients admitted to a hematological department were screened. Several patients, with a broad spectrum of diagnoses, had a level of sHbSR above the range of healthy persons. Patients with myelomonocytic leukemias and pneumonia/sepsis exhibited the highest levels (up to 67.3 mg/L). In conclusion, sHbSR is an abundant plasma protein potentially valuable in monitoring patients with infections and myelomonocytic leukemia.
The ABCG2 transporter is an efficient Hoechst 33342 efflux pump and is preferentially expressed by immature human hematopoietic progenitors
Authors: Scharenberg Christian W. , Harkey Michael A. , Torok-Storb Beverly
Published: July 2002

A promising and increasingly exploited property of hematopoietic stem cells is their ability to efflux the fluorescent dye Hoechst 33342. The Hoechst-negative cells are isolated by fluorescence-activated cell sorting as a so-called side “population” (SP) of bone marrow. This SP from bone marrow, as well as other tissues, is reported to contain immature stem cells with considerable plasticity. Some cell lines also efflux Hoechst and generate SP profiles. Reverse transcription–polymerase chain reaction (RT-PCR) and efflux inhibition studies with the lung carcinoma cell line, A549, implicated the ABCG2 transporter as a Hoechst efflux pump. Furthermore, it is shown that transient expression of ABCG2 generates a robust SP phenotype in human embryonic kidney (HEK293) cells. The results allow the conclusion thatABCG2 is a potent Hoechst efflux pump. Semiquantitative RT-PCR was used to characterize the developmental pattern of expression of ABCG2 in hematopoiesis. It is expressed at relatively high levels in putative hematopoietic stem cells (isolated as SP, 34+/38− or 34+/KDR+populations) and drops sharply in committed progenitors (34+/38+, 34+/33+, or 34+/10+). Expression remains low in most maturing populations, but rises again in natural killer cells and erythroblasts. Comparison of messenger RNA (mRNA) levels for the 3 major multidrug-resistant efflux pumps, MDR1,MRP1, and ABCG2, in bone marrow SP cells reveals that ABCG2 is the predominant form in these cells. These data suggest that ABCG2 contributes significantly to the generation of the SP phenotype in hematopoietic stem cells. Furthermore, the sharp down-regulation of ABCG2 at the stage of lineage commitment suggests that this gene may play an important role in the unique physiology of the pluripotent stem cell.
Peculiarities of SQUID magnetometer application in TEM
Authors: Panaitov G. , Bick M. , Zhang Y. , Krause H.‐J.
Published: July 2002

Due to progress in high‐temperature superconductor (HTS) technology, research in the application of superconducting quantum interference devices (SQUIDs) in time‐domain transient electromagnetics (TEM) has intensified. Several TEM systems using HTS SQUIDs have been developed and tested in numerous field trials. In this paper, the reliability of SQUID TEM data is investigated by comparison with commonly used induction‐coil data. Generally, a good agreement between SQUID and coil TEM data was found. However, two effects were observed with the SQUID TEM system which were not visible in coil measurements. The first effect is a “frequency dependence”: the response signal measured by the SQUID depends on the base frequency of the transmitter signal, decaying faster for higher frequencies. The second effect is a “zero‐crossover”: the SQUID response data becomes negative for late times. We propose a model for magnetometer TEM measurements that provides a possible explanation for these two effects. This model takes into account remnant responses induced in the ground by repetitive transmitter signals. Our simulations of coil and magnetometer responses show that, at moderately conducting ground, the influence of remnant responses is negligible in coil recordings, whereas it leads to a typical frequency dependence of magnetometer recordings. We show also that the influence of remnant responses may lead to the sign reversal of magnetometer data over highly conducting ground structures. To optimize magnetometer TEM measurements, it is advantageous to use lower transmitter frequencies than typical frequencies used for induction coil measurements. A recalculation of the original ground response on the basis of the proposed model may also be of advantage.
Simultaneous computation of gravity and magnetic anomalies resulting from a 2‐D object
Authors: Singh Bijendra
Published: July 2002

This paper presents a new algorithm for the simultaneous computation of gravity and magnetic anomalies resulting from an infinitely long (2‐D) body with an arbitrary polygonal cross‐section. With the assumption of uniform volume density and magnetization, the gravity or magnetic field may be expressed as the field resulting from an equivalent distribution of surface mass density or surface pole density, respectively, over the surface of the source body. The resulting surface integrals are reduced to new line integrals using Stokes' theorem. The components of the fields for each bounding surface are expressed in terms of a new line integral and the solid angle subtended by the surface at the point of observation. Since these analytical solutions are similar in form, a direct relation is derived between gravity and magnetic fields, which allows their simultaneous computation. Hence, the same computer program can be used to compute the gravity field, the magnetic field, or both fields simultaneously. This new approach will find wide applications in the joint inversion of potential field data, as it will make the numerical computations much faster.
Acoustic velocity of seismic‐while‐drilling (SWD) borehole guided waves
Authors: Poletto Flavio , Carcione José M. , Lovo Massimo , Miranda Francesco
Published: July 2002

Borehole guided waves, other than the extensional waves traveling through the drillstring, can be used as pilot signals to obtain seismic‐while‐drilling (SWD) seismograms and information about the drilling conditions. This occurs when there is no rotation of the drillstring while drilling and when the contacts between the drillpipe and the borehole wall preclude the propagation of the extensional wave. To obtain the velocity of the guided waves, we model the compressional‐wave velocity of drilling mud with different compositions of low‐ and high‐gravity solids, corresponding to a given drilling plan and taking into account the presence of formation cuttings and in‐situ conditions. Then we compute the velocities of the tube wave (with and without casing) and the guided wave traveling in the mud inside the drillstring (pipe wave). The results indicate the pipe wave constitutes a reliable pilot signal in the absence of drillpipe rotation. This allows us to obtain a complete depth reverse vertical seismic profile.
NMO‐velocity surfaces and Dix‐type formulas in anisotropic heterogeneous media
Authors: Grechka Vladimir , Tsvankin Ilya
Published: July 2002

Reflection moveout of pure modes recorded on conventional‐length spreads is described by a normal‐moveout (NMO) velocity that depends on the orientation of the common‐midpoint (CMP) line. Here, we introduce the concept of NMO‐velocity surfaces, which are obtained by plotting the NMO velocity as the radius‐vector along all possible directions in 3‐D space, and use it to develop Dix‐type averaging and differentiation algorithms in anisotropic heterogeneous media.

The intersection of the NMO‐velocity surface with the horizontal plane represents the NMO ellipse that can be estimated from wide‐azimuth reflection data. We demonstrate that the NMO ellipse and conventional‐spread moveout as a whole can be modeled by Dix‐type averaging of specifically oriented cross‐sections of the NMO‐velocity surfaces along the zero‐offset reflection raypath. This formalism is particularly simple to implement for a stack of homogeneous anisotropic layers separated by plane dipping boundaries. Since our method involves computing just a single (zero‐offset) ray for a given reflection event, it can be efficiently used in anisotropic stacking‐velocity tomography.

Application of the Dix‐type averaging to layered transversely isotropic media with a vertical symmetry axis (VTI) shows that the presence of dipping interfaces above the reflector makes the P‐wave NMO ellipse dependent on the vertical velocity and anisotropic coefficients ε and δ. In contrast, P‐wave moveout in VTI models with a horizontally layered overburden is fully controlled by the NMO velocity of horizontal events and the Alkhalifah‐Tsvankin coefficient η ≈ ε − δ. Hence, in some laterally heterogeneous, layered VTI models P‐wave reflection data may provide enough information for anisotropic depth processing.
Cellular liquid biopsy provides unique chances for disease monitoring, preclinical model generation and therapy adjustment in rare salivary gland cancer patients
Authors: Stojanović Gužvić Nataša , Lüke Florian , Treitschke Steffi , Coluccio Andrea , Hoffmann Martin , Feliciello Giancarlo , Varadarajan Adithi Ravikumar , Lu Xin , Weidele Kathrin , Botteron Catherine , Materna–Reichelt Silvia , Keil Felix , Evert Katja , Weber Florian , Schamberger Thomas , Althammer Michael , Grosse Jirka , Hellwig Dirk , Schulz Christian , Seitz Stephan , Ugocsai Peter , Schlenska‐Lange Anke , Mayr Roman , Kaiser Ulrich , Dietmaier Wolfgang , Polzer Bernhard , Warfsmann Jens , Honarnejad Kamran , Pukrop Tobias , Heudobler Daniel , Klein Christoph A. , Werno Christian
Published: October 2024

While cell‐free liquid biopsy (cfLB) approaches provide simple and inexpensive disease monitoring, cell‐based liquid biopsy (cLB) may enable additional molecular genetic assessment of systemic disease heterogeneity and preclinical model development. We investigated 71 blood samples of 62 patients with various advanced cancer types and subjected enriched circulating tumor cells (CTCs) to organoid culture conditions. CTC‐derived tumoroid models were characterized by DNA/RNA sequencing and immunohistochemistry, as well as functional drug testing. Results were linked to molecular features of primary tumors, metastases, and CTCs; CTC enumeration was linked to disease progression. Of 52 samples with positive CTC counts (≥1) from eight different cancer types, only CTCs from two salivary gland cancer (SGC) patients formed tumoroid cultures (P = 0.0005). Longitudinal CTC enumeration of one SGC patient closely reflected disease progression during treatment and revealed metastatic relapse earlier than clinical imaging. Multiomics analysis and functional in vitro drug testing identified potential resistance mechanisms and drug vulnerabilities. We conclude that cLB might add a functional dimension (to the genetic approaches) in the personalized management of rare, difficult‐to‐treat cancers such as SGC.
Genomic landscape and preclinical models of angiosarcoma
Authors: Benton Annaleigh , Liu Bozhi , Gartenhaus Lauren E. , Hanna Jason A.
Published: October 2024

Angiosarcoma is a cancer that develops in blood or lymphatic vessels that presents a significant clinical challenge due to its rarity and aggressive features. Clinical outcomes have not improved in decades, highlighting a need for innovative therapeutic strategies to treat the disease. Genetically, angiosarcomas exhibit high heterogeneity and complexity with many recurrent mutations. However, recent studies have identified some common features within anatomic and molecular subgroups. To identify potential therapeutic vulnerabilities, it is essential to understand and integrate the mutational landscape of angiosarcoma with the models that exist to study the disease. In this review, we will summarize the insights gained from reported genomic alterations in molecular and anatomic subtypes of angiosarcoma, discuss several potential actionable targets, and highlight the preclinical disease models available in the field.
Evaluating post‐thrombectomy effective connectivity changes in anterior circulation stroke
Authors: Xu Jiaona , Chen Weiwei , Niu Guozhong , Meng Yuting , Qiu Kefan , Li Tongyue , Wang Luoyu , Zhang Liqing , Lv Yating , Ding Zhongxiang
Published: October 2024

Objective

Granger causal analysis (GCA) and amplitude of low‐frequency fluctuation (ALFF) are commonly used to evaluate functional alterations in brain disorders. By combining the GCA and ALFF, this study aimed to investigate the effective connectivity (EC) changes in patients with acute ischemic stroke (AIS) and anterior circulation occlusion after mechanical thrombectomy (MT).

Methods

Resting‐state functional magnetic resonance imaging (rs‐fMRI) data were collected from 43 AIS patients with anterior circulation occlusion within 1 week post‐MT and 37 healthy controls. ALFF and GCA were calculated for each participant. Patients were further divided into groups based on prognosis and perfusion levels. The differences in ALFF and EC were compared between AIS patients and healthy controls and between subgroups of patients. Pearson correlations between EC, ALFF values, and clinical characteristics of patients were calculated.

Results

Compared to healthy controls, post‐MT, AIS patients exhibited significant ALFF increases in the left precuneus and decreases in the left fusiform gyrus and right caudate. Increased EC from the contralesional lingual gyrus, contralesional putamen, ipsilesional thalamus, and contralesional thalamus to the contralesional caudate was obsrved, while decrease in EC were found for contralesional caudate to the ipsilesional thalamus and medial superior frontal gyrus. EC differences were particularly notable between perfusion groups, with significantly lower EC in the poorly perfused group. EC values were also positively correlated with National Institutes of Health Stroke Scale (NIHSS) scores pre‐MT.

Interpretation

In AIS patients, the caudate nucleus was central to the observed EC changes post‐MT, characterized by decreased outputs and increased inputs. These changes indicate functional remodeling within the cortico‐basal ganglia‐thalamic‐cortical pathway.
Effect of Laser Powder Bed Fusion Parameters on the Evolution of Melt Pool, Densification, Microstructure, and Hardness in 420 Stainless Steel Parts
Authors: Cunha Ângela , Gasik Michael , Silva Filipe Samuel , Trindade Bruno , Bartolomeu Flávio , Carvalho Óscar
Published: October 2024

Laser powder bed fusion (LPBF) involves depositing, melting, and solidifying metal powder particles layer by layer to create 3D components. In this study, a deep fundamental understanding on how process parameters—laser power, scan speed, and hatch spacing—affect the melt pool, densification, microstructure, hardness, and thermal behavior of 420 stainless steel (420SS) parts produced by such technology is provided. The conducted investigation considers five levels of laser power and hatch spacing, and four scan speeds. Optimal single tracks, based on geometry and profile, are achieved with laser powers between 40 and 80 W and a scan speed of 10 mm s−1. In the multitrack analysis, it is indicated that a dense, smooth surface is obtained with a hatch spacing of 250 μm, corresponding to an overlapping rate of ≈30%. The 420SS samples show high densification (≈99%) and low surface roughness (≈3.62 μm). The microstructure consisted of martensite laths and retained austenite. The hardness and thermal conductivity of the samples are measured at 540 HV and 15.3 W m−1 K−1, respectively. In this study, the understanding of the process–structure–property relationships in LPBF of 420SS is expanded.
Photocurrent‐Directed Immunoregulation Accelerates Osseointegration through Activating Calcium Influx in Macrophages
Authors: Zhu Yizhou , Wang Chaofeng , Ai Can , Xiang Yiming , Mao Congyang , Qiao Wei , Wu Jun , Kubi John Akrofi , Liu Xiangmei , Wu Shuilin , Zhao Xin , Li Bin , Yeung Kelvin W. K.
Published: October 2024

Early osteoimmune microenvironment disorder at the interface between bone and implant can lead to implant loosening, which prolongs patient convalescence, exacerbates postoperative complications, and potentially results in implant failure. The timely regulation of macrophages primarily orchestrates the entire long‐term regeneration process. Here, it is proposed to precisely direct macrophage polarization using localized photoelectrical signals generated by an excitable surface in response to remote stimulation via near‐infrared light (NIR). The photocurrent generated from the n–n heterojunction between calcium titanate (CaTiO3) and defective titanium dioxide (TiO2‐Vo) on the excitable surface can accurately direct macrophage polarization, suppressing acute inflammation at the early stage of post‐implantation and establishing a favorable osteoimmune microenvironment that promotes bone‐to‐implant integration. Mechanistic study reveals that photoelectric signals initiate increased calcium influx via voltage‐gated calcium ion channels, subsequently modulating calcium/calmodulin‐dependent protein kinase kinase 2 (Camkk2) and calcium/calmodulin‐dependent protein kinase I (Camk1) expression to regulate macrophage polarization. This optimization of the osteoimmune microenvironment results in enhanced mesenchymal stem cells (MSCs) recruitment and osteogenesis, ultimately accelerating bone‐to‐implant integration within 14 days post‐implantation. This research presents a novel method for adjusting in vivo spatiotemporal immune responses through the use of noninvasive and externally‐controlled targeted stimulations.
Novel Mn[N(CN)2]2 Anode with Cationic and Anionic Redox Chemistry for Li‐Ion Batteries
Authors: Qiao Xianji , Cai Guohong , Müller Peter C. , Wang Liguang , Cai Guanqun , Liu Tiefeng , Qu Shangqing , Yin Yufeng , Li Guobao , Corkett Alex J. , Dronskowski Richard , Lu Jun , Sun Junliang
Published: October 2024

α‐Mn[N(CN)2]2 (Pnnm) with divalent Mn2+ being octahedrally coordinated by six [N(CN)2]− dicyanamide (dca‒) complex anions is known since 1999. A novel β polymorph is now prepared and its structure characterized via powder X‐ray diffraction. β‐Mn[N(CN)2]2 also crystallizes orthorhombically (Cmcm) but with Mn2+ tetrahedrally coordinated to four [N(CN)2]− anions. Property‐wise, α‐Mn[N(CN)2]2 can be efficiently used as a negative electrode material for lithium‐ion batteries, maintaining a large reversible capacity of more than 600 mAh g−1 for 250 cycles tested at 0.5 C, comparing favorably to well‐established negative electrode references such as graphite (≈372 mAh g−1). The electrochemical lithiation/delithiation mechanism of α‐Mn[N(CN)2]2 is investigated using advanced characterization techniques and theoretical calculations. Upon lithiation, α‐Mn[N(CN)2]2 undergoes a reversible conversion reaction, forming LiN(CN)2 and metallic manganese, which are transformed back into α‐Mn[N(CN)2]2 upon delithiation. Further, there is evidence for reversible and additional charge/discharge processes on the dca‒ anion throughout the entire discharge/charge process in α‐Mn[N(CN)2]2, reflecting an anionic charge compensation. Moreover, density‐functional (DFT) and chemical‐bonding theory are employed to investigate the detailed anodic behavior of α‐Mn[N(CN)2]2 via conversion reaction during (de‐)lithiation processes. This mechanism, evidenced for the first time in transition metal dicyanamides, is likely behind its outstanding electrochemical properties.
Conformal Iontronic Sensing Clear Aligner
Authors: Sun Chuanxi , Li Sen , Zhou Ziqi , Chen Xiaoxiao , Liu Zhe , Liao Shenglong , Xing Jian , Sun Hongyan , Cheng Yu , Yi Zhengkun , Chen Jianfeng , Li Zhihua
Published: October 2024

The clear aligner, commonly utilized in orthodontic treatment for malocclusion, necessitates the quantification of orthodontic forces, which is highly demanded by doctors for enhancing risk management and treatment efficiency. However, the current technology still faces obstacles in achieving conformal integration of pressure sensors onto clear aligners with large curvature for the quantification and real‐time monitoring of orthodontic forces. In this paper, a conformal iontronic sensing clear aligner (CSA) is proposed based on flexible iontronic sensing mechanism, which conformally integrates the sensor with the aligner to quantify orthodontic forces throughout the treatment process while preserving the aligner's original function. Specifically, the ionic coating is seamlessly integrated onto the diaphragm by applying a layer of ionic paint before molding the clear aligner, while the sensing electrode array, designed using a kirigami‐based structure, is seamlessly adhered to the ionic coating. By integrating the CSA into a dental model, its exceptional sensitivity and precise pressure mapping capabilities have been demonstrated. This enables the identification of various tooth movement patterns, discernment of orthodontic force magnitude, and continuous monitoring of forces throughout the orthodontic treatment. Consequently, this research is expected to significantly advance risk management, outcome prediction, and treatment efficiency in orthodontic treatments.
Impact of Surface Chemistry and Particle Size on Inertial Cavitation Driven Transport of Silica Nanoparticles and Microparticles
Authors: Alina Talaial B. , Saemundsson Sven A. , Mortensen Lillian E. , Xu Yiqi , Medlin J. Will , Cha Jennifer N. , Goodwin Andrew P.
Published: October 2024

This study investigated the high‐intensity focused ultrasound (HIFU)‐mediated propulsion of mesoporous silica nanoparticles (MSNs) and microspheres (MSMs). Nanoparticles are heavily sought as vehicles for drug delivery, but their transport through tissue is often restricted. Here, MSNs and MSMs are hydrophobically modified and coated with phospholipids to facilitate inertial cavitation to promote propulsion under HIFU. Modified nanoparticles show significantly enhanced cavitation and propulsion, achieving a maximum displacement of 250 µm (≈2500 body length) and speed of ≈1600 µm s−1 (16 000 body length s−1), compared to unmodified nanoparticles (2 µm, 20 body length, 60 µm s−1, 600 body length). In contrast, microparticles demonstrate comparable cavitation responses. Modified microparticles reached a maximum speed of 4000 µm s−1 (800 body length s−1) and displacement of 230 µm (46 body length), and unmodified microparticles achieved 2000 µm s−1 (400 body length s−1) and 75 µm (15 body length). In all HIFU‐responsive samples, displacement and speed decreased with successive pulses, implying that particles fatigue with continued pulsing. Analyses of particle trajectories and rotational diffusion times suggest that cavitation occurs uniformly on particle surfaces rather than at specific sites. These principles are important for the design of future drug‐delivery vehicles capable of ultrasound‐triggered motion.
Achieving Highly Durable Intermetallic PtMn3N Electrocatalyst via the Strong Metal‐N Bonds toward Oxygen Reduction Reaction
Authors: Liang Jinhui , Pan Xiankai , Zeng Binwen , Zhong Chengzhi , Zhang Longhai , Zhang Jiaxi , Song Huiyu , Du Li , Liao Shijun , Cui Zhiming
Published: October 2024

Pt‐based intermetallic compounds have been considered promising electrocatalysts in the practical applications of fuel cells; however, the development of Pt‐based catalysts that meet performance targets of high activity, maximized stability, and low cost remains a huge challenge. Herein, an atomically ordered and low‐Pt intermetallic nitride (PtMn3N) catalyst are synthesized consisting of a strained Pt shell and PtMn3N core on carbon support via the KCl‐matrix protection strategy. The PtMn3N catalyst represents a high mass activity of 0.70 A mgPt−1 at 0.9 V and a specific activity degradation of 4.2% after 5000 potential cycles for the oxygen reduction reaction (ORR) in rotating disk electrode (RDE) testing, which substantially outperformed commercial Pt/C (0.25 A mgPt−1 and 17.4%). Density functional theory calculations reveal that the introduction of Mn elements to the Pt lattice is beneficial to produce appropriate compressive strain to weaken the binding energy of oxygen species and the introduction of N elements to promote the strong metal‐N interactions is conducive to alleviating the dissolution of metal atoms, allowing for displaying the prominent durability. This work provides an effective strategy of N‐doped Pt‐based intermetallic compounds to enhance the corrosion resistance of 3d transition metals and to enhance the ORR performance.
Integrating Phosphate Enhances Biomineralization Effect of Methacrylate Cement in Vital Pulp Treatment with Improved Human Dental Pulp Stem Cells Stimulation
Authors: Ryu Jeong‐Hyun , Mangal Utkarsh , Kwon Jae‐Sung , Seo Ji‐Young , Byun Seong‐Yun , Lee Young‐Hee , Jang Sungil , Hwang Geelsu , Ku Hyemin , Shin Yooseok , Kim Dohyun , Choi Sung‐Hwan
Published: October 2024

Vital pulp treatment (VPT) is crucial for preserving the health and function of the tooth in cases where the pulp tissue remains vital despite exposure. Various materials are introduced for this purpose. However, challenges such as low strength, high solubility, and tooth discoloration persist. Methylmethacrylate‐based cement (MC) offers excellent sealing ability, feasibility, and mechanical properties, making it a promising alternative for VPT. Phosphate‐based glass (PBG) has the potential to promote hard tissue regeneration by releasing key inducers, phosphorus (P) and calcium (Ca), for reparative odontogenesis. This study investigates PBG‐integrated MC (PIMC) by characterizing its properties, assessing human dental pulp stem cell activity related to initial inflammatory adaptation and odontogenic differentiation, and evaluating hard tissue formation using an in vivo dog pulpotomy model. Results indicate that a 5% PBG‐integrated MC (5PIMC) maintains the physicochemical properties of MC. Furthermore, 5PIMC demonstrates cytocompatibility, excellent expression of osteo/odontogenic markers, and resistance to inflammatory markers, significantly outperforming MC. Enhanced hard tissue formation is observed in the dental pulp of mongrel dog teeth treated with 5PIMC. These findings suggest that 5PIMC could be an optimal and suitable material for reparative odontogenesis through VPT.
Intertwined Flexoelectricity and Stacking Ferroelectricity in Marginally Twisted hBN Moiré Superlattice
Authors: Wan Siyuan , Huang Hanying , Liu Huanlin , Liu Heng , Li Zhixiong , Li Yue , Liao Zhimin , Lanza Mario , Zeng Hualing , Zhou Yangbo
Published: October 2024

Moiré superlattices in twisted van der Waals homo/heterostructures present a fascinating interplay between electronic and atomic structures, with potential applications in electronic and optoelectronic devices. Flexoelectricity, an electromechanical coupling between electric polarization and strain gradient, is intrinsic to these superlattices because of the lattice misfit strain at the atomic scale. However, due to its weak magnitude, the effect of flexoelectricity on moiré ferroelectricity has remained underexplored. Here, the role of flexoelectricity in shaping and modulating the moiré ferroelectric patterns in twisted hBN homojunction is unveiled. Enhanced flexoelectric effects induce unique stacking ferroelectric domains with hollow triangular structures. Interlayer bubbles influence domain shape and periodicity through local electric field modulation, and tip‐stress enables the reversible manipulation of domain area and polarization direction. These findings highlight the impact of flexoelectric effects on moiré ferroelectricity, offering a new tuning knob for its manipulation.
Unraveling the Fast Ionic Conduction in NASICON‐Type Materials
Authors: He Yufang , Scivally Elena , Shaji Ajay , Ouyang Bin , Zeng Yan
Published: October 2024

Na Superionic Conductor (NASICON) materials stand out as an important class of ionic conductors, offering high ionic conductivity and notable electrochemical stability for applications such as solid electrolytes. While advances through compositional engineering have been made to enhance the ionic conductivity of NASICONs, the fundamental mechanisms underlying their superionic conducting behavior remain unresolved. In this study, the interplay between local and global factors—specifically, bottleneck volume and Na site ordering— that influence ionic conduction within the NASICON framework is elucidated. Analysis of reported ionic conductivity data indicates that optimal bottleneck volumes exceed 3.7 Å3, adjustable through the choice of metal cations and polyanions. Additionally, the findings imply that weaker Na site ordering, which enhances ionic conduction, can be induced by increasing the Na content, selecting metal cations with a d0 electron configuration, or mixing elements at the cation or polyanion sites. Moreover, it is proposed that the predominant diffusion mechanism can shift between occupancy‐conserved hopping (OCH), occurring under conditions of strong Na site ordering, and single‐ion hopping (SIH), which becomes possible when site ordering is minimal. These insights offer strategic guidelines for designing NASICONs with superionic conductivity, promoting the development of solid electrolytes for safer and more energy‐dense all‐solid‐state batteries.
Copper‐Catalyzed Enantioselective Hydrophosphorylation of Unactivated Alkynes
Authors: Kang Jie , Ding Kang , Ren Si‐Mu , Yang Wen‐Jun , Su Bo
Published: October 2024

P‐stereogenic phosphorus compounds are essential across various fields, yet their synthesis via enantioselective P−C bond formation remains both challenging and underdeveloped. We report the first copper‐catalyzed enantioselective hydrophosphorylation of alkynes, facilitated by a newly designed chiral 1,2‐diamine ligand. Unlike previous methods that rely on kinetic resolution with less than 50 % conversion, our approach employs a distinct dynamic kinetic asymmetric transformation mechanism, achieving complete conversion of racemic starting materials. This reaction is compatible with a broad range of aromatic and aliphatic terminal alkynes, producing products with high yields (up to 95 %), exclusive cis selectivity, and exceptional regio‐ and enantioselectivity (>20 : 1 r.r. and up to 96 % ee). The resulting products were further transformed into a diverse array of enantioenriched P‐stereogenic scaffolds. Preliminary mechanistic studies were conducted to elucidate the reaction details.
Poly(4‐methoxyaniline) composites: Investigating structure–property relationship towards semiconducting applications
Authors: de Carvalho Menezes Diogo , de Oliveira Santiago Pedro Henrique , Souza Paulo Nunes , Andrade Marcelo Barbosa , Oliveira Cristiano Luis Pinto , Souza Sérgio Michielon , Sanches Edgar Aparecido , Mascarenhas Yvonne Primerano
Published: October 2024

Conjugated polymers are essential materials for the organic optoelectronic industry, serving a pivotal role in cutting‐edge technologies. In this study, we conducted an integrated characterization approach, including spectroscopic techniques coupled with X‐ray diffraction analysis to explore the structure–property relationship of poly(4‐methoxyaniline), commonly referred to as poly(p‐anisidine) or PPA, along with two distinct ceramic composites: PPA/α‐Al2O3 and PPA/Eu2O3. From powder X‐ray diffraction analysis, a triclinic unit cell in space group P1 is proposed, after the whole powder pattern decomposition (WPPD) refinement is employed for the semicrystalline regions of the polymeric phases. Fractal‐like structures are observed, following analysis of small‐angle X‐ray scattering (SAXS) data and scanning electron microscopy (SEM) from which we could infer the approximate sizes of the fractal clusters. Pure PPA displays a glass transition temperature (Tg) of approximately 80°C and an electrical conductivity slightly above 10−5 S/cm. In contrast, the composite materials do not exhibit a glass transition temperature but perform better in terms of crystallinity and thermal stability. PPA/Eu2O3 present conductivity enhancement exceeding tenfold, surpassing 10−4 S/cm. These findings provide the baseline for further explorations on the development of organic electronic devices and sensors.
Insight into the therapeutic potential of pyrazole‐thiazole hybrids: A comprehensive review
Authors: Sumran Garima , Sharma Manisha , Aggarwal Ranjana
Published: October 2024

Several pyrazole‐thiazole hybrids featuring two potentially bioactive pharmacophores with or without linker have been synthesized using the molecular hybridization approach as target structures by medicinal chemists to modulate multiple drug targets simultaneously. The presented review aims to provide an overview of the diversified and wide array of pharmacological activities of these hybrids bestowing anticancer, antifungal, antibacterial, analgesic, anti‐inflammatory, antioxidant, antitubercular, antiviral, antiparasitic, and miscellaneous activities. The structure–activity relationships and potential mechanism of action are also reviewed to shed light on the development of more effective and biotargeted candidates. This review focuses on the latest research advances in the biological profile of pyrazole‐thiazole hybrids reported from 2015 to the present, providing medicinal researchers with a comprehensive platform to rationally design and develop more promising pyrazole‐thiazole hybrids.
Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications
Authors: Junges Lucas Henrique , Müller‐Santos Marcelo
Published: October 2024

Tryptamines play diverse roles as neurotransmitters and psychoactive compounds found in various organisms. Psilocybin, a notable tryptamine, has garnered attention for its therapeutic potential in treating mental health disorders like depression and anxiety. Despite its promising applications, current extraction methods for psilocybin are labor‐intensive and economically limiting. We suggest biocatalysis as a sustainable alternative, leveraging enzymes to synthesize psilocybin and other tryptamines efficiently. By elucidating psilocybin biosynthesis pathways, researchers aim to advance synthetic methodologies and industrial applications. This review underscores the transformative potential of biocatalysis in enhancing our understanding of tryptamine biosynthesis and facilitating the production of high‐purity psilocybin and other tryptamines for therapeutic and research use.
GC/MS and LC‐ESI‐MS Analysis of Conocarpus erectus Leaves Extract via Regulating Amyloid‐β‐Peptide, Tau Protein, Neurotransmitters, Inflammation and Oxidative Stress against AlCl3‐Induced Alzheimer's Disease in Rats
Authors: Nasr Noha N. , El‐Hagrassi Ali M. , Ahmed Yomna R. , Hamed Manal A.
Published: October 2024

This study investigated the therapeutic effect of Conocarpus erectus leaves methanolic extract against AlCl3 ‐induced Alzheimer's disease (AD) in rats comparing with Donepezil‐hydrochloride as a reference drug. The bioactive compounds of C. erectus leaves were isolated and identified by GC/MS and LC‐ESI‐MS analysis. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor‐alpha (TNF‐α), interleukin‐6 (IL‐6), amyloid‐β‐peptide (Aβ‐peptide), tau protein, acetylcholinesterase (AChE), serotonin (5‐HT), dopamine (DA) and nor‐adrenaline (NE) levels were estimated. The neuromuscular strength, memory behavior and histopathological examination of cerebral cortex region were also conducted. Forty‐three compounds were characterized from the non‐polar fraction of C. erectus L. leaves extract and nineteen compounds were identified from the defatted extract. AlCl3‐ induction caused significant elevation of brain oxidative stress, Aβ‐peptide, tau protein, IL‐6, TNF‐α and AChE levels. A significant decrease in 5‐HT, ND and DA levels were noticed. Additionally, AlCl3 reduced neuromuscular strength and compromised memory function. Treatment of AlCl3‐ induced rats with C. erectuse extract ameliorated these selected parameters by variable degrees. In conclusion, C. erectus protects against AlCl3‐ induced AD in rats through its antioxidant, anti‐inflammatory, and antineural damage. [Correction added on 3 December 2024, after first online publication: The term “antineutron” was corrected to “antineural” in the preceding sentence.]. It could be considered as a new nutraceutical agent for attenuating symptoms associated with Alzheimer's disease.
Precise Modulation of Protein Degradation by Smart PROTACs
Authors: Cheng Junfei , Dong Guoqiang , Wang Wei , Sheng Chunquan
Published: October 2024

Proteolysis‐targeting chimera (PROTAC) has emerged as an attractive therapeutic modality in drug discovery. PROTACs are bifunctional molecules that effectively bridge proteins of interest (POIs) with E3 ubiquitin ligases, such that, the target proteins are tagged with ubiquitin and subsequently degraded via the proteasome. Despite significant progress in the field of targeted protein degradation (TPD), the application of conventional PROTAC degraders still faces significant challenges, including systemic toxicity induced by non‐tissue‐specific targeting. To address this issue, a variety of smart PROTACs that can be activated by specific stimuli, have been developed for achieving conditional and spatiotemporal modulation of protein levels. Here, on the basis of our contributions, we overview recent advances of smart PROTACs, including tumor microenvironment‐, photo‐, and X‐ray radiation‐responsive PROTACs, that enable controllable TPD. The design strategy, case studies, potential applications and challenges will be focused on.