bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Mycoplasma Contamination on the Concentration and Composition of Extracellular RNA
Authors: MOROZKIN EVGENIY S. , RYKOVA ELENA Y. , VLASSOV VALENTIN V. , LAKTIONOV PAVEL P.
Published: November 2006

Abstract:  Kinetics of extracellular RNA accumulation in culture medium and at the cell surface along with their composition and distribution among cell‐free and cell‐surface‐bound fractions were investigated in mycoplasma‐contaminated and mycoplasma‐free HeLa cells. It was shown that the mycoplasma infection influenced the concentration and kinetics of accumulation of total extracellular RNA and the distribution of specific RNA fragments among cell‐free and cell‐surface‐bound fractions. Fragments of immature rRNA were found in culture of mycoplasma‐infected HeLa cells. The data obtained indicate the existence of selective mechanisms providing binding of RNA with cell surface and their excretion out of cells.
Direct control of neurogenesis by selector factors in the fly eye:regulation ofatonalby Ey and So
Authors: Zhang Tianyi , Ranade Swati , Cai Chuan Qi , Clouser Christopher , Pignoni Francesca
Published: November 2006

During eye development, the selector factors of the Eyeless/Pax6 or Retinal Determination (RD) network control specification of organ-type whereas the bHLH-type proneural factor Atonal drives neurogenesis. Although significant progress has been made in dissecting the acquisition of `eye identity' at the transcriptional level, the molecular mechanisms underlying the progression from neuronal progenitor to differentiating neuron remain unclear. A recently proposed model for the integration of organ specification and neurogenesis hypothesizes that atonal expression in the eye is RD-network-independent and that Eyeless works in parallel or downstream of atonal to modify the neurogenetic program. We show here that distinct cis-regulatory elements control atonal expression specifically in the eye and that the RD factors Eyeless and Sine oculis function as direct regulators. We find that these transcription factors interact in vitro and provide indirect evidence that this interaction may be required in vivo. The subordination of neurogenesis to the RD pathway in the eye provides a direct mechanism for the coordination of neurogenesis and tissue specification during sensory organ formation.
Sprinter: a novel transmembrane protein required for Wg secretion and signaling
Authors: Goodman Robyn M. , Thombre Shreya , Firtina Zeynep , Gray Dione , Betts Daniella , Roebuck Jamie , Spana Eric P. , Selva Erica M.
Published: November 2006

Wingless (Wg) is a secreted ligand that differentially activates gene expression in target tissues. It belongs to the Wnt family of secreted signaling molecules that regulate cell-to-cell interactions during development. Activation of Wg targets is dependent on the ligand concentration in the extracellular milieu; cellular mechanisms that govern the synthesis,delivery and receipt of Wg are elaborate and complex. We have identified sprinter (srt), which encodes a novel, evolutionarily conserved transmembrane protein required for the transmission of the Wg signal. Mutations in srt cause the accumulation of Wg in cells that express it, and retention of the ligand prevents activation of its target genes in signal-receiving cells. In the absence of Srt activity, levels of Wg targets (including Engrailed in embryos lacking maternal and zygotic srt, and Senseless and Achaete in wing discs) are reduced. Activation of Wg targets in the receiving cells does not require srt. Hence, the function of Srt is restricted to events occurring within the Wg-producing cells. We show that srt is not required for any aspect of Hedgehog(Hh) signal transduction, suggesting specificity of srt for the Wg pathway. We propose that srt encodes a protein required for Wg secretion that regulates maturation, membrane targeting or delivery of Wg. Loss of srt function in turn diminishes Wg-pathway activation in receiving cells.
Direct and sensitive miRNA profiling from low-input total RNA
Authors: Wang Hui , Ach Robert A. , Curry Bo
Published: November 2006

We have developed a sensitive, accurate, and multiplexed microRNA (miRNA) profiling assay that is based on a highly efficient labeling method and novel microarray probe design. The probes provide both sequence and size discrimination, yielding in most cases highly specific detection of closely related mature miRNAs. Using a simple, single-vial experimental protocol, 120 ng of total RNA is directly labeled using Cy3 or Cy5, without fractionation or amplification, to produce precise and accurate measurements that span a linear dynamic range from 0.2 amol to 2 fmol of input miRNA. The results can provide quantitative estimates of the miRNA content for the tissues studied. The assay is also suitable for use with formalin-fixed paraffin-embedded clinical samples. Our method allows rapid design and validation of probes for simultaneous quantitative measurements of all human miRNA sequences in the public databases and to new miRNA sequences as they are reported.
Expression of Mutated Mouse Myocilin Induces Open-Angle Glaucoma in Transgenic Mice
Authors: Senatorov Vladimir , Malyukova Irina , Fariss Robert , Wawrousek Eric F. , Swaminathan Srividya , Sharan Shyam K. , Tomarev Stanislav
Published: November 2006

We developed a genetic mouse model of open-angle glaucoma by expression of mutated mouse myocilin (Myoc) in transgenic (Tg) mice. The Tyr423His point mutation, corresponding to the severe glaucoma-causing Tyr437His mutation in the humanMYOCgene, was introduced into bacterial artificial chromosome DNA encoding the full-length mouseMyocgene and long flanking regions. Both wild-type (Wt) and Tg animals expressed Myoc in tissues of the irido-corneal angle and the sclera. Expression of mutated Myoc induced the accumulation of Myoc in cell cytoplasm and prevented its secretion into the extracellular space. The levels of ATPase-1 were reduced in the irido-corneal angle of Tg mice compared with Wt animals. Tg mice demonstrated a moderate elevation of intraocular pressure, the loss of ∼20% of the retinal ganglion cells (RGCs) in the peripheral retina, and axonal degeneration in the optic nerve. RGC depletion was associated with the shrinkage of their nuclei and DNA fragmentation in the peripheral retina. Pathological changes observed in the eyes of Tg mice are similar to those observed in glaucoma patients.
Physiologic Regulation of a Tetrodotoxin-Sensitive Sodium Influx That Mediates a Slow Afterdepolarization Potential in Gonadotropin-Releasing Hormone Neurons: Possible Implications for the Central Regulation of Fertility
Authors: Chu Zhiguo , Moenter Suzanne M.
Published: November 2006

The brain controls fertility through release of gonadotropin-releasing hormone (GnRH), but the mechanisms underlying action potential patterning and GnRH release are not understood. We investigated whether GnRH neurons exhibit afterdepolarizing potentials (ADPs) and whether these are modified by reproductive state. Whole-cell current-clamp recordings of GnRH neurons in brain slices from ovariectomized mice revealed a slow ADP (sADP) after action potentials generated by brief current injection. Generating two or four spikes enhanced sADP amplitude and duration. sADP amplitude was not affected by blocking selected neurotransmitter/neuromodulator receptors, delayed-rectifier potassium channels, calcium-dependent cation channels, or hyperpolarization-activated cation channels but was halved by the calcium channel blocker cadmium and abolished by tetrodotoxin. Cadmium also reduced peak latency. Intrinsic mechanisms underlying the sADP were investigated using voltage-clamp protocols simulating action potential waveforms. A single action potential produced an inward current, which increased after double and quadruple stimulation. Cadmium did not affect current amplitude but reduced peak latency. Pretreatment with blockers of calcium-activated potassium currents (IKCa) reproduced this shift and blocked subsequent cadmium-induced changes, suggesting cadmium changes latency indirectly by blockingIKCa. Tetrodotoxin abolished the inward current, suggesting that it is carried by sodium. In contrast,IKCablockers increased the inward current, indicating thatIKCamay oppose generation of the sADP. Strong sADPs were suprathreshold, generating repetitive spontaneous firing.IADP, sADP, and excitability were enhanced byin vivoestradiol, which triggers a preovulatory surge of GnRH release. Physiological feedback modification of this inward current and resulting sADP may modulate action potential firing and subsequent GnRH release.
Stable Rhodopsin/Arrestin Complex Leads to Retinal Degeneration in a Transgenic Mouse Model of Autosomal Dominant Retinitis Pigmentosa
Authors: Chen Jiayan , Shi Guang , Concepcion Francis A. , Xie Guifu , Oprian Daniel , Chen Jeannie
Published: November 2006

Over 100 rhodopsin mutation alleles have been associated with autosomal dominant retinitis pigmentosa (ADRP). These mutations appear to cause photoreceptor cell death through diverse molecular mechanisms. We show that K296E, a rhodopsin mutation associated with ADRP, forms a stable complex with arrestin that is toxic to mouse rod photoreceptors. This cell death pathway appears to be conserved from flies to mammals. A genetics approach to eliminate arrestin unmasked the constitutive activity of K296E and caused photoreceptor cell death through a transducin-dependent mechanism that is similar to light damage. Expressing K296E in the arrestin/transducin double knock-out background prevented transducin signaling and led to substantially improved retinal morphology but did not fully prevent cell death caused by K296E. The adverse effect of K296E in the arrestin/transducin knock-out background can be mimicked by constant exposure to low light. Furthermore, we found that arrestin binding causes K296E to mislocalize to the wrong cellular compartment. Accumulation of stable rhodopsin/arrestin complex in the inner segment may be an important mechanism for triggering the cell death pathway in the mammalian photoreceptor cell.
The Development of Cortical Multisensory Integration
Authors: Wallace Mark T. , Carriere Brian N. , Perrault Thomas J. , Vaughan J. William , Stein Barry E.
Published: November 2006

Although there are many perceptual theories that posit particular maturational profiles in higher-order (i.e., cortical) multisensory regions, our knowledge of multisensory development is primarily derived from studies of a midbrain structure, the superior colliculus. Therefore, the present study examined the maturation of multisensory processes in an area of cat association cortex [i.e., the anterior ectosylvian sulcus (AES)] and found that these processes are rudimentary during early postnatal life and develop only gradually thereafter. The AES comprises separate visual, auditory, and somatosensory regions, along with many multisensory neurons at the intervening borders between them. During early life, sensory responsiveness in AES appears in an orderly sequence. Somatosensory neurons are present at 4 weeks of age and are followed by auditory and multisensory (somatosensory–auditory) neurons. Visual neurons and visually responsive multisensory neurons are first seen at 12 weeks of age. The earliest multisensory neurons are strikingly immature, lacking the ability to synthesize the cross-modal information they receive. With postnatal development, multisensory integrative capacity matures. The delayed maturation of multisensory neurons and multisensory integration in AES suggests that the higher-order processes dependent on these circuits appear comparatively late in ontogeny.
Reduktion von Überschwingern bei der 3D-Streifenprojektion durch „Inverse Filterung“ (Reduction of Overshooting in 3D Fringe Projection Measurements by Inverse Filtering)
Authors: Kohler Christian , Droste Ulrich , Körner Klaus , Osten Wolfgang
Published: November 2006

Bei 3D-Messsystemen, die nach dem Prinzip der Streifentriangulation arbeiten, kommt es in Bereichen mit hohem Gradienten, zu Sprüngen in der Oberflächengeometrie sowie an Stellen mit abrupt wechselnder Reflektivität zu Messartefakten, welche sich in Form von Überschwingern äußern. Es gibt hierfür bereits unterschiedliche Erklärungsansätze, welche jedoch in unserem Fall nicht zu einer Lösung des Problems geführt haben. Daher präsentieren wir hier einen weiteren Ansatz, um diese Artefakte zumindest zu reduzieren. Der Ansatz basiert auf der Technik des “inverse filtering”. In dieser Arbeit werden zunächst eine Simulation und anschließend ein Messbeispiel gezeigt, die unseren Ansatz verifizieren.
Verringerung und Abschätzung der Messunsicherheit bei der optischen Verzahnungsmessung mit Streifenprojektion (Reduction and Evaluation of the Uncertainty of Measurement of Optical Gear Measurement using Fringe Projection)
Authors: Meeß Karsten , Kästner Markus , Seewig Jörg
Published: November 2006

Für die fertigungsnahe Prüfung Präzisionsgeschmiedeter Verzahnungen bietet sich der Einsatz der Streifenprojektionstechnik als bildgebendes Triangulationsverfahren an. Im Gegensatz zu der konventionellen Verzahnungsprüfung steht bei dem vorgestellten Ansatz die flächige Erfassung der Verzahnungsgeometrie bei gleichzeitiger Reduzierung der erforderlichen Messzeiten im Vordergrund. Anhand einer ausgewählten Verzahnung wird erstmals mithilfe taktiler Referenzmessungen die Messunsicherheit des Gesamtsystems experimentell angeschätzt. Dabei wird deutlich, dass die numerische Korrektur der Messwerte einen entscheidenden Anteil zur Verringerung der Unsicherheit beiträgt.
Allozyme and Microsatellite DNA Analyses of Lingcod from Puget Sound, Washington, and Adjoining Waters
Authors: LeClair Larry L. , Young Sewall F. , Shaklee James B.
Published: November 2006

In all, 472 lingcod Ophiodon elongatus from six areas of Puget Sound, the Strait of Juan de Fuca, and the outer coast of Washington were assayed for 44 allozyme and 9 microsatellite DNA loci to investigate possible population subdivision. Levels of genetic variation at many of the allozyme loci and all of the microsatellite DNA loci were reasonably high, and there was no evidence of significant Hardy–Weinberg or linkage disequilibrium. Pairwise genotypic tests of population differentiation showed no evidence of genetic structuring among the 23 variable allozyme loci, the 9 microsatellite loci, or all 32 variable loci combined. The results of this investigation are consistent with the existence of a single genetic stock of lingcod throughout the greater Puget Sound region, including the Strait of Juan de Fuca and San Juan Islands. Despite the fact that most of the collections we analyzed did not consist of spawning fish from the spawning grounds, we believe that the combined absence of significant outcomes in the population differentiation tests and the absence of significant heterozygote deficits at any of the 32 variable loci make it highly unlikely that there is significant genetic divergence among the greater Puget Sound populations analyzed in this study. Allozyme data obtained from inland populations in this study were compared with previously published allozyme data from the outer coast. No difference was detected when summed over all variable loci.
Influence of Stream Discharge on Reproductive Success of a Prairie Stream Fish Assemblage
Authors: Durham Bart W. , Wilde Gene R.
Published: November 2006

We studied the relationship between stream discharge and reproductive success for five members of a prairie stream fish assemblage. Based on information obtained from the literature, we constructed seven models relating stream discharge to successful reproduction. To assess the utility of our models, we collected larval and juvenile Arkansas River shiners Notropis girardi, peppered chub Macrhybopsis tetranema, plains minnow Hybognathus placitus, flathead chub Platygobio gracilis, and red shiners Cyprinella lutrensis from the Canadian River, Texas, during 2000–2001. We removed otoliths and counted daily growth increments to determine ages. Models were parameterized by use of age and discharge data. Models were evaluated with the Akaike information criterion likelihood statistic to assess which model(s) best described reproductive success for each species. Of the seven models evaluated, the best overall model predicted that reproductive success was uniform across dates when discharge was present in the river; however, reproduction was predicted to be unsuccessful during periods when the river was confined to isolated pools. These results suggest that the presence of discharge in the river may be more important for successful reproduction of prairie stream cyprinids than the magnitude of discharge.
Treatment Issues in Clear Cell Carcinoma of the Ovary: A Different Entity?
Authors: Pectasides Dimitrios , Pectasides Eirini , Psyrri Amanda , Economopoulos Theofanis
Published: November 2006

Learning Objectives

After completing this course, the reader will be able to: Discuss the clinical features of OCCC.Discuss the current data regarding treatment strategies and outcome of patients with OCCC.Explain the rationale for using alternative treatment approaches (i.e., clinical trials) in patients with OCCC.

Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com

Background. Ovarian clear cell carcinoma (OCCC) is a distinct histopathologic subtype of epithelial ovarian cancer (EOC) with an incidence of <5% of all ovarian malignancies. Our goal was to review the clinical features and management of patients with OCCC.

Methods and Results. We performed a PubMed search using the phrase “clear cell ovarian cancer.” We reviewed 54 articles referring to OCCC. OCCC patients have a high incidence of stage I disease and frequently present with a large pelvic mass. Recurrences are more frequent with this entity than with other types of EOC. The clinical management of advanced EOC includes maximal cytoreduction and platinum plus paclitaxel–based chemotherapy. The survival rates of patients with advanced OCCC are lower than those of patients with advanced serous EOC (serous subtype). The poor response rate to platinum-based regimens may be related to the intrinsic chemoresistance of these tumors. Despite their aggressive clinical course, OCCCs are still treated similarly to the other EOCs at the present time, because the rarity of these tumors prevents the conduction of randomized studies.

Conclusion. Novel treatment approaches should be adopted in OCCC. Molecular-targeted therapies and effective new agents without cross-resistance to platinum compounds should be evaluated in a prospective clinical trial in OCCC.
Factors associated with shedding of Cryptosporidium parvum versus Cryptosporidium bovis among dairy cattle in New York State
Authors: Starkey Simon R. , Zeigler Peter E. , Wade Susan E. , Schaaf Stephanie L. , Mohammed Hussni O.
Published: November 2006

Objective—To isolate and speciate Cryptosporidium DNA from fecal samples obtained from dairy cattle in New York State and identify factors associated with whether cattle were shedding Cryptosporidium parvum versus Cryptosporidium bovis.

Design—Cross-sectional study.

Sample Population—115 fecal samples positive for DNA coding for the Cryptosporidium 18S rRNA gene from dairy cattle in New York State.

Procedures—A PCR assay was used to amplify DNA from fecal samples; amplification products were submitted for bidirectional DNA sequencing. Logistic regression was used to test for associations between various host factors and Cryptosporidium spp.

Results—70 of the 115 (61%) fecal samples were found to have C parvum DNA, 42 (37%) were determined to have C bovis DNA, and 3 (3%) were found to have C parvum deer-type DNA. The presence of diarrhea at the time of fecal sample collection, oocyst count, and breed were associated with whether cattle were infected with C parvum or C bovis, with animals more likely to be infected with C parvum if they had diarrhea, had a high oocyst count, or were Holsteins.

Conclusions and Clinical Relevance—Results suggest that C parvum and C bovis can be isolated from dairy cattle in New York State and that various factors affect whether cattle infected with Cryptosporidium spp are infected with C parvum or C bovis. Findings also lend credence to the theory that C bovis may be more host adapted and thus less pathogenic to dairy cattle than C parvum.
Fabrication of Metal–Organic Framework‐Derived LaCo/C‐Decorated Ti3C2Tx Composites with High Electromagnetic Wave Absorption
Authors: Huang Yufei , Zhao Jia , Chen Guojing , Han Xuhui , Chai Chunpeng , Ma Huiling
Published: March 2024

Thin‐thickness and lightweight electromagnetic wave (EMW) absorption materials are critically needed for stealth technology in the military stealth field. The special structure of a material is important for improving its good EMW absorption. Herein, a series of porous metal–organic framework‐derived LaCo/C‐decorated Ti3C2Tx (LaCo/C/Ti3C2Tx) composites are prepared by carbonization at high temperatures. Impressively, the minimum reflection loss of LaCo/C/Ti3C2Tx–2 is −47.72 dB at 10.26 GHz (thickness 2.3 mm), and the optimal effective absorption bandwidth is 5.45 GHz (thickness 1.9 mm). The excellent EMW absorption properties are due to multiple electromagnetic loss mechanisms, such as polarization loss, magnetic loss, and multiple reflections and scattering. This work provides a new route for the application of Ti3C2Tx‐based derivatives.
Self‐Reporting Microsensors Inspired by Noctiluca Scintillans for Small‐Defect Positioning and Electrical‐Stress Visualization in Polymers
Authors: Sima Wenxia , Yang Yuhang , Sun Potao , Shi Yuning , Yuan Tao , Yang Ming , Xiong Hongbo , Tang Xinyu , Niu Chaolu
Published: March 2024

Small defects induce concentrated electrical stress in dielectric polymers, leading to premature failure of materials. Existing sensing methods fail to effectively visualize these defects owing to the invisible‐energy state of the electric field. Thus, it is necessary to establish a nondestructive method for the real‐time detection of small defects in dielectric polymers. In this study, a self‐reporting microsensor (SRM) inspired by Noctiluca scintillans is designed to endow materials with the ability of self‐detection for defects and electrical stress. The SRM leverages the energy of a nearby electric field to emit measurable fluorescence, enabling defect localization and diagnosis as well as electrical‐stress visualization. A controllable dielectric microsphere is constructed to achieve an adjustable electroluminescence threshold for the SRM, thereby increasing its detection accuracy while decreasing the electroluminescence threshold. The potential degradation in the polymer performance owing to SRM implantation is addressed by assembling long molecular chains on the SRM surface to spontaneously generate an interpenetrating network. Results of finite element analyses and experiments demonstrate that the SRM can effectively realize nondestructive visualization and positioning of small defects and concentrated electrical stress in polymers, positioning it as a promising sensing method for monitoring the electric field and charge distribution in materials.
Bio‐Inspired Ultrathin Perfect Absorber for High‐Performance Photothermal Conversion
Authors: Liao Qihua , Zhu Kaixuan , Hao Xuanzhang , Wu Chunxiao , Li Jing , Cheng Huhu , Yan Jianfeng , Jiang Lan , Qu Liangti
Published: March 2024

Ultrathin perfect absorber (UPA) enables efficient photothermal conversion (PC) in renewable chemical and energy systems. However, it is challenging so far to obtain efficient absorption with thickness significantly less than the wavelength, especially considering the common view that an ultrathin film can absorb at most 50% of incident light. Here, a highly light‐absorbing and mechanically stable UPA is reported by learning from the honeycomb mirror design of the crab compound eyes. With the hollow apertures enclosed by the self‐supporting ultrathin film of reduced graphene oxide and gold nanoparticles, the absorber achieves spoof‐plasmon enhanced broadband absorption in solar spectrum and low radiative decay in infrared. Specifically, a strong absorption (87%) is realized by the apertures with cross‐section thickness of 1/20 of the wavelength, which is 7.3 times stronger than a planar counterpart with the identical material. Its high PC efficiency up to 64%, with hot‐electron temperature as high as 2344 K, is also experimentally demonstrated. Utilizing its low thermal mass nature, a high‐speed visible‐to‐infrared converter is constructed. The absorber can enable high‐performance PC processes for future interfacial catalysis and photon‐detection.
Nanoscale Methods for Longitudinal Extraction of Intracellular Contents
Authors: Quek Ying Jie , Tay Andy
Published: March 2024

Longitudinal analysis of intracellular contents including gene and protein expression is crucial for deciphering the fundamentally dynamic nature of cells. This offers invaluable insights into complex tissue composition and behavior, and drives progress in disease diagnosis, biomarker discovery, and drug development. Traditional longitudinal analysis workflows, involving the destruction of cells at various timepoints, limit insights to singular moments and fail to account for cellular heterogeneity. Current non‐destructive approaches, like temporal modeling with single‐cell ribonucleic acid sequencing (RNA‐seq) and live‐cell fluorescence imaging, either rely on biological assumptions or possess the risk of cellular perturbation. Recent advances in nanoscale technologies for non‐destructive intracellular content extraction offer a promising solution to these challenges. These novel methods work at the nanoscale to non‐destructively access cellular membranes and can be broadly classified into three mechanisms: tip‐facilitated aspiration, membrane‐based, and probe‐based methods. This perspective focuses on these emerging nanotechnologies for repeated intracellular content extraction. Their potential in longitudinal analysis is discussed, the critical requirements for effective repeated sampling are addressed, and the suitability of each technique for various applications is explored. Furthermore, unresolved challenges in repeated sampling are highlighted to encourage further research in this growing field.
Line Edge Roughness Effects on the Thermoelectric Properties of Armchair Black Phosphorene Nanoribbons
Authors: Pishevar Ebrahim , Karamitaheri Hossein
Published: March 2024

This study delves into the thermoelectric properties of armchair black phosphorene nanoribbons while considering the presence of line edge roughness. Employing the tight‐binding method in conjunction with non‐equilibrium Green's function techniques and Landauer formulas, the impact of various parameters on thermoelectric performance is explored. These findings reveal that the electrical conductivity and, consequently, the power factor exhibits an increasing trend with expanding ribbon length and width. This behavior can be attributed to heightened collision rates, particularly in narrow ribbons, induced by line edge roughness as length increases. Remarkably, the Seebeck coefficient at the Fermi energy corresponding to the maximum power factor remains nearly constant across different widths, lengths, temperatures, and transport regimes. Furthermore, the thermoelectric figure of merit (ZT) demonstrates a positive correlation with both ribbon length and width. In narrow widths and lengths ≈1000 nm, the power factor and figure of merit exhibit an upward trend with ribbon width. However, with further increases in ribbon width, the influence of line edge roughness on thermal conductivity diminishes. Consequently, the figure of merit decreases due to the rise in thermal conductivity. Notably, the thermoelectric figure of merit is higher for short and narrow ribbons and long and wider ribbons.
Matrix Metalloproteinase‐Responsive Hydrogel with On‐Demand Release of Phosphatidylserine Promotes Bone Regeneration Through Immunomodulation
Authors: Zhang Mingjin , Yu Tingting , Li Jing , Yan Huichun , Lyu Liang , Yu Yi , Yang Gengchen , Zhang Ting , Zhou Yanheng , Wang Xing , Liu Dawei
Published: March 2024

Inflammation‐responsive hydrogels loaded with therapeutic factors are effective biomaterials for bone tissue engineering and regenerative medicine. In this study, a matrix metalloproteinase (MMP)‐responsive injectable hydrogel is constructed by integrating an MMP‐cleavable peptide (pp) into a covalent tetra‐armed poly‐(ethylene glycol) (PEG) network for precise drug release upon inflammation stimulation. To establish a pro‐regenerative environment, phosphatidylserine (PS) is encapsulated into a scaffold to form the PEG‐pp‐PS network, which could be triggered by MMP to release a large amount of PS during the early stage of inflammation and retain drug release persistently until the later stage of bone repair. The hydrogel is found to be mechanically and biologically adaptable to the complex bone defect area. In vivo and in vitro studies further demonstrated the ability of PEG‐pp‐PS to transform macrophages into the anti‐inflammatory M2 phenotype and promote osteogenic differentiation, thus, resulting in new bone regeneration. Therefore, this study provides a facile, safe, and promising cell‐free strategy on simultaneous immunoregulation and osteoinduction in bone engineering.
Framework Nucleic Acids‐Based VEGF Signaling Activating System for Angiogenesis: A Dual Stimulation Strategy
Authors: Ge Yichen , Wang Qingxuan , Yao Yangxue , Xin Qin , Sun Jiafei , Chen Wen , Lin Yunfeng , Cai Xiaoxiao
Published: March 2024

Angiogenesis is crucial for tissue engineering, wound healing, and regenerative medicine. Nanomaterials constructed based on specific goals can be employed to activate endogenous growth factor‐related signaling. In this study, based on the conventional single‐stranded DNA self‐assembly into tetrahedral framework nucleic acids (tFNAs), the Apt02 nucleic acid aptamer and dimethyloxallyl glycine (DMOG) small molecule are integrated into a complex via a template‐based click chemistry reaction and toehold‐mediated strand displacement reaction. Thus, being able to simulate the VEGF (vascular endothelial growth factor) function and stabilize HIF (hypoxia‐inducible factor), a functional whole is constructed and applied to angiogenesis. Cellular studies demonstrate that the tFNAs‐Apt02 complex (TAC) has a conspicuous affinity to human umbilical vein endothelial cells (HUVECs). Further incubation with DMOG yields the tFNAs‐Apt02‐DMOG complex (TACD), which promotes VEGF secretion, in vitro blood vessel formation, sprouting, and migration of HUVECs. Additionally, TACD enhances angiogenesis by upregulating the VEGF/VEGFR and HIF signaling pathways. Moreover, in a diabetic mouse skin defect repair process, TACD increases blood vessel formation and collagen deposition, therefore accelerating wound healing. The novel strategy simulating VEGF and stabilizing HIF promotes blood‐vessel formation in vivo and in vitro and has the potential for broad applications in the vascularization field.
Recent Progress in Nucleic Acid Pulmonary Delivery toward Overcoming Physiological Barriers and Improving Transfection Efficiency
Authors: Wang Qiyue , Bu Chaozhi , Dai Qihao , Chen Jinhua , Zhang Ruitao , Zheng Xiaomin , Ren Hao , Xin Xiaofei , Li Xueming
Published: March 2024

Pulmonary delivery of therapeutic agents has been considered the desirable administration route for local lung disease treatment. As the latest generation of therapeutic agents, nucleic acid has been gradually developed as gene therapy for local diseases such as asthma, chronic obstructive pulmonary diseases, and lung fibrosis. The features of nucleic acid, specific physiological structure, and pathophysiological barriers of the respiratory tract have strongly affected the delivery efficiency and pulmonary bioavailability of nucleic acid, directly related to the treatment outcomes. The development of pharmaceutics and material science provides the potential for highly effective pulmonary medicine delivery. In this review, the key factors and barriers are first introduced that affect the pulmonary delivery and bioavailability of nucleic acids. The advanced inhaled materials for nucleic acid delivery are further summarized. The recent progress of platform designs for improving the pulmonary delivery efficiency of nucleic acids and their therapeutic outcomes have been systematically analyzed, with the application and the perspectives of advanced vectors for pulmonary gene delivery.
Metabolism/Immunity Dual‐Regulation Thermogels Potentiating Immunotherapy of Glioblastoma Through Lactate‐Excretion Inhibition and PD‐1/PD‐L1 Blockade
Authors: Li Tianliang , Xu Dan , Ruan Zhao , Zhou Jie , Sun Wenbo , Rao Bo , Xu Haibo
Published: March 2024

Intrinsic immunosuppressive tumor microenvironment (ITM) and insufficient tumor infiltration of T cells severely impede the progress of glioblastoma (GBM) immunotherapy. In this study, it is identify that inhibiting the expression of glucose transporter 1 (GLUT1) can facilitate the prevention of lactate excretion from tumor glycolysis, which significantly alleviates the lactate‐driven ITM by reducing immunosuppressive tumor‐associated macrophages (TAMs) and regulatory T cells (Tregs). Simultaneously, the findings show that the generated inflammatory cytokine IFN‐γ during immune activation aggravates the immune escape by upregulating immune checkpoint programmed death‐ligand 1 (PD‐L1) in tumor cells and TAMs. Therefore, an injectable thermogel loaded with a GLUT1 inhibitor BAY‐876 and a PD‐1/PD‐L1 blocker BMS‐1 (Gel@B‐B) for dual‐regulation of metabolism and immunity of GBM is developed. Consequently, in situ injection of Gel@B‐B significantly delays tumor growth and prolongs the survival of the orthotopic GBM mouse model. By actively exposing tumor antigens to antigen‐presenting cells, the GBM vaccine combined with Gel@B‐B is found to significantly increase the fraction of effector T cells (Th1/CTLs) in the tumor microenvironment, thereby remarkably mitigating tumor recurrence long‐term. This study may provide a promising strategy for GBM immunotherapy.
Progress in Performance of AlGaN‐Based Ultraviolet Light Emitting Diodes
Authors: Lang Jing , Xu Fujun , Wang Jiaming , Zhang Lisheng , Fang Xuzhou , Zhang Ziyao , Guo Xueqi , Ji Chen , Ji Chengzhi , Tan Fuyun , Wu Yong , Yang Xuelin , Kang Xiangning , Qin Zhixin , Tang Ning , Wang Xinqiang , Ge Weikun , Shen Bo
Published: March 2024

AlGaN‐based ultraviolet light‐emitting diodes (UV‐LEDs) have the advantages of mercury (Hg) pollution free, small size, high efficiency, and so on, and are widely used in military, medical, and industrial fields, which are considered to be the most promising alternative to the traditional Hg lamps. Great efforts are made over the past few decades to improve the device performance, thereby meeting the commercial production and application requirements of UV‐LEDs, which is always accompanied by a series of interesting physical topics. In this review, the recent research progress in performance of AlGaN‐based UV‐LEDs is summarized from the perspectives of electrical injection, electro‐optical conversion, and light extraction, which are responsible for the operation of devices. The detailed discussions include the major challenges, the corresponding technological breakthroughs, and also the outlook of material growth, energy band modulation, as well as device fabrication involved in UV‐LEDs, which are expected to be helpful for the thorough comprehension of device physics and further development of AlGaN‐based UV‐LEDs.
Rural‐urban disparities in the diagnosis and treatment of hypertension and diabetes among aging Indians
Authors: Rai Pooja , Sahadevan Pravin , Mensegere Abhishek L. , Issac Thomas G. , Muniz‐Terrera Graciela , Sundarakumar Jonas S.
Published: March 2024

INTRODUCTION

Hypertension and diabetes are modifiable risk factors for dementia. We aimed to assess rural‐urban disparities in the diagnosis and treatment of these conditions among aging Indians.

METHODS

Participants (n = 6316) were from two parallel, prospective aging cohorts in rural and urban India. Using self‐report and clinical/biochemical assessments, we subdivided participants with diabetes and hypertension into undiagnosed and untreated groups. Logistic regression and Fairlie decomposition analysis were the statistical methods utilized.

RESULTS

There was a significant rural‐urban disparity in undiagnosed hypertension (25.14%), untreated hypertension (11.75%), undiagnosed diabetes (16.94%), and untreated diabetes (11.62%). Further, sociodemographic and lifestyle factors, such as age and tobacco use were the common contributors to the disparities in both undiagnosed hypertension and undiagnosed diabetes, whereas education and body mass index (BMI) were significant contributors to the disparity in untreated hypertension.

DISCUSSION

Rural Indians face significant healthcare disadvantages as compared to their urban counterparts, which prompts the urgent need for strategies for equitable healthcare.
Spark plasma sintering and mechanical properties of two grades of PEKK presenting different Tere/Iso ratios
Authors: Heyer Anthony , Rossit Julie , Moitrier Florence , Gütter Georg , Montmasson Nicolas , Wary Marc , Delorme Fabian , Lemonnier Sebastien , Czarnota Christophe , Bracq Anthony
Published: March 2024

Two grades of PolyEtherKetoneKetone with different Tere/Iso ratios (PEKK 60/40 and PEKK 80/20) were consolidated using spark plasma sintering. Processing parameters were varied and their influence on mechanical properties was assessed. The study reveals that sintering at a temperature close to the melting temperature along with an applied pressure of 18 MPa leads to better mechanical properties, while the effect of dwell time remains limited. A high sintering pressure is shown to promote the cohesion of PEKK 60/40 samples when the temperature is closer to the glass transition temperature, while pressure does not play a significant role for PEKK 80/20. Post‐mortem fractographic analyses provide explanations of the underlying phenomena. PEKK samples sintered with optimal processing parameters display higher compressive yield strength and stiffness than PEKK samples elaborated from conventional processing routes. They however also exhibit a fragile behavior which can be attributed to the incomplete healing between the powder particles.
Regional differences in the umbilical vein and ductus venosus at different stages of normal human development
Authors: Isotani Naoko , Kanahashi Toru , Imai Hirohiko , Yoneyama Akio , Yamada Shigehito , Takakuwa Tetsuya
Published: March 2024

During the fetal period, oxygenated blood from the placenta flows through the umbilical vein (UV), portal sinus, ductus venosus (DV), and inferior vena cava (IVC) to the heart. This venous route varies regionally in many aspects. Herein, we sought to characterize the venous route's morphological features and regional differences during embryonic and early‐fetal periods. Twenty‐nine specimens were selected for high‐resolution digitized imaging; 18 embryos were chosen for histological analysis. The venous route showed a primitive, large, S‐shaped curved morphology with regional narrowing and dilation at Carnegie stage (CS) 15. Regional differences in vessel‐wall differentiation became apparent from approximately CS20. The vessel wall was poorly developed in most DV parts; local vessel‐wall thickness at the inlet was first detected at CS20. The lumen of the venous route changed from a nonuniform shape to a relatively round and uniform morphology after CS21. During the early‐fetal period, two large bends were observed around the passage of the umbilical ring and at the inlet of the liver. The length ratio of the extrahepatic UV to the total venous route increased. The sectional area gradually increased during embryonic development, whereas differences in sectional area between the DV, UV, and IVC became more pronounced in the early‐fetal period. Furthermore, differences in the sectional area between the narrowest part of the DV and other hepatic veins and the transverse sinus became more pronounced. In summary, the present study described morphological, morphometric, and histological changes in the venous route throughout embryonic and early‐fetal development, clarifying regional characteristics.
Carbazole Based Smaragdyrins: Synthesis, Aromaticity Switching, and Formation of a Spiro‐Dimer
Authors: Chen Jinchao , Nie Haigen , Rao Yutao , Xu Ling , Zhou Mingbo , Yin Bangshao , Song Jianxin , Osuka Atsuhiro
Published: March 2024

Carbazole‐incorporated smaragdyrin BF2‐complex 3 was synthesized by SNAr reaction of 3,5‐dibromo‐8‐mesityl‐BODIPY 1 with 3,6‐di(tert‐butyl)‐1,8‐di(pyrrol‐2‐yl)carbazole 2 as a nucleophile. Demetalation of 3 with ZrCl4 gave the corresponding smaragdyrin free base 4 in a good yield. Oxidations of 3 and 4 with MnO2 gave smaragdyrins 5 and 6, respectively, both followed by aromaticity switching, since the oxidized products showed a moderate paratropic ring current owing to their 20π‐electronic circuits. Further, treatment of 4 with [RhCl(CO)2]2 in the presence of NaOAc gave RhI complex 7, and oxidation of 3 with RuCl3 in the presence of triethylamine led to the formation of a spiro dimer product, 8.
The complexities of ligand/receptor interactions: Exploring the role of molecular vibrations and quantum tunnelling
Authors: Pagán Oné R.
Published: March 2024

Molecular vibrations and quantum tunneling may link ligand binding to the function of pharmacological receptors. The well‐established lock‐and‐key model explains a ligand's binding and recognition by a receptor; however, a general mechanism by which receptors translate binding into activation, inactivation, or modulation remains elusive. The Vibration Theory of Olfaction was proposed in the 1930s to explain this subset of receptor‐mediated phenomena by correlating odorant molecular vibrations to smell, but a mechanism was lacking. In the 1990s, inelastic electron tunneling was proposed as a plausible mechanism for translating molecular vibration to odorant physiology. More recently, studies of ligands’ vibrational spectra and the use of deuterated ligand analogs have provided helpful information to study this admittedly controversial hypothesis in metabotropic receptors other than olfactory receptors. In the present work, based in part on published experiments from our laboratory using planarians as an experimental organism, I will present a rationale and possible experimental approach for extending this idea to ligand‐gated ion channels.
U1 snRNP Biogenesis Defects in Neurodegenerative Diseases
Authors: Campagne Sebastien
Published: March 2024

The U1 small ribonucleoprotein (U1 snRNP) plays a pivotal role in the intricate process of gene expression, specifically within nuclear RNA processing. By initiating the splicing reaction and modulating 3’‐end processing, U1 snRNP exerts precise control over RNA metabolism and gene expression. This ribonucleoparticle is abundantly present, and its complex biogenesis necessitates shuttling between the nuclear and cytoplasmic compartments. Over the past three decades, extensive research has illuminated the crucial connection between disrupted U snRNP biogenesis and several prominent human diseases, notably various neurodegenerative conditions. The perturbation of U1 snRNP homeostasis has been firmly established in diseases such as Spinal Muscular Atrophy, Pontocerebellar hypoplasia, and FUS‐mediated Amyotrophic Lateral Sclerosis. Intriguingly, compelling evidence suggests a potential correlation in Fronto‐temporal dementia and Alzheimer's disease as well. Although the U snRNP biogenesis pathway is conserved across all eukaryotic cells, neurons, in particular, appear to be highly susceptible to alterations in spliceosome homeostasis. In contrast, other cell types exhibit a greater resilience to such disturbances. This vulnerability underscores the intricate relationship between U1 snRNP dynamics and the health of neuronal cells, shedding light on potential avenues for understanding and addressing neurodegenerative disorders.
Bacterial Hydrazine Biosynthetic Pathways Featuring Cupin/Methionyl tRNA Synthetase‐like Enzymes
Authors: Matsuda Kenichi , Wakimoto Toshiyuki
Published: March 2024

Nitrogen‐Nitrogen (N−N) bond‐containing functional groups in natural products and synthetic drugs play significant roles in exerting biological activities. The mechanisms of N−N bond formation in natural organic molecules have garnered increasing attention over the decades. Recent advances have illuminated various enzymatic and nonenzymatic strategies, and our understanding of natural N−N bond construction is rapidly expanding. A group of didomain proteins with zinc‐binding cupin/methionyl‐tRNA synthetase (MetRS)‐like domains, also known as hydrazine synthetases, generates amino acid‐based hydrazines, which serve as key biosynthetic precursors of diverse N−N bond‐containing functionalities such as hydrazone, diazo, triazene, pyrazole, and pyridazinone groups. In this review, we summarize the current knowledge on hydrazine synthetase mechanisms and the various pathways employing this unique bond‐forming machinery.
Synthesis and Crystallization Mechanism for SAPO‐34 Zeolite Derived from Magadiite
Authors: Liu Bo , Gao Yu , Xu Hanlu , Feng Yuhang , Zhou Zihan , Gao Yuan , Jiang Rongli
Published: March 2024

In this work, we explored the hydrothermal synthesize and crystallization process of SAPO‐34 zeolites from two‐dimensional layered silicate magadiite by using tetraethylammonium hydroxide (TEAOH) as a templating agent. Comprehensive characterization was conducted by XRD, SEM, FTIR, Raman, and BET. Time‐resolved PXRD analysis revealed that SAPO‐34 zeolite exhibited a steep growth curve when the crystallization time was 30 h, and the crystallinity reached 98.65 % at 48 h. Specifically, the disruption of the magadiite layer exposed charged silanol groups on the surface, fostering an affinity for AlO4 and PO4 species, thereby initiating the nucleation process. Under the guidance of TEAOH, these nucleation sites transformed into SAPO‐34 nuclei, gradually advancing towards crystallization. FTIR and Raman analyses affirmed the presence of 6Rs, followed by D6R and 4Rs SBUs, along with the characteristic CHA structure. Combined with 29Si NMR established that disaggregated silicate minerals served as zeolite synthesis “seeds”, enhancing nucleation sites and overall crystallization efficiency.
Channel estimation for reconfigurable intelligent surface‐assisted mmWave using multidimensional Runge Kutta orthogonal matching pursuit algorithm in MIMO systems
Authors: Panda Sunita
Published: March 2024

In the context of Reconfigurable Intelligent Surface (RIS) assisted millimeter wave communications within the Multiple Input Multiple Output (MIMO) system, Channel Estimation (CE) poses a significant challenge due to signal sparsity and blockages between transmitters and receivers. Consequently, communication faces difficulties without a direct line‐of‐sight path, leading to increased pilot overhead. To address these obstacles, this research introduces a channel estimation approach for RIS‐aided millimeter wave communication employing the Multidimensional Runge Kutta Orthogonal Matching Pursuit (MRKOMP) algorithm in MIMO systems. The proposed method aims to enhance network coverage and channel capacity for efficient data transmission. By utilizing the multiscale cumulative residual distribution entropy function, the method establishes an indirect path when the line‐of‐sight is obstructed. Furthermore, the multidimensional orthogonal matching pursuit methodology calculates sparsity levels and facilitates sparse recovery. Optimization of the weight parameter through the Runge Kutta optimizer effectively eliminates sparsity, resulting in improved spectral efficiency and RIS gain. Simulation results demonstrate a significant 99.9% enhancement in network capacity and spectral efficiency compared to existing methods.