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Excessive load on the temporomandibular joint (TMJ) is a significant factor in the development of TMJ osteoarthritis, contributing to cartilage degeneration. The specific mechanism through which excessive load induces TMJ osteoarthritis is not fully understood; however, mechanically‐activated (MA) ion channels play a crucial role. Among these channels, Piezo1 has been identified as a mediator of chondrocyte catabolic responses and is markedly increased in osteoarthritis. Our observations indicate that, under excessive load conditions, endoplasmic reticulum stress in chondrocytes results in apoptosis of the TMJ chondrocytes. Importantly, using the Piezo1 inhibitor GsMTx4 demonstrates its potential to alleviate this condition. Furthermore, Piezo1 mediates endoplasmic reticulum stress in chondrocytes by inducing calcium ion influx. Our research substantiates the role of Piezo1 as a pivotal ion channel in mediating chondrocyte overload. It elucidates the link between excessive load, cell apoptosis, and calcium ion influx through Piezo1. The findings underscore Piezo1 as a key player in the pathogenesis of TMJ osteoarthritis, shedding light on potential therapeutic interventions for this condition. [ABSTRACT FROM AUTHOR]

Detachment faults at slow‐ and ultraslow‐spreading mid‐ocean ridges are essential for lithosphere‐hydrosphere interactions. However, their coupling with subseafloor hydrothermal circulation is poorly understood. Here, we investigated shallow hydrothermal fluid circulations in the active Dragon Horn detachment fault system of the Southwest Indian Ridge using combined near‐bottom magnetic anomaly data and rock magnetic analyses. We observed enhanced magnetic anomalies related to the high magnetization of basaltic country rocks and highly serpentinized (>80%) peridotite, whereas the hydrothermally altered basalts and sulfide deposits had weak magnetization and reduced magnetic anomalies. Therefore, the low‐magnetization zone was interpreted as a proxy for the hydrothermal fluid channel. The spatial distribution of the low‐magnetization zone revealed that the inactive Suye field expanded more than 500 m in diameter horizontally and ∼100 m vertically, and the active Longqi hydrothermal field had a >1 km fluid channel, both centered around the detachment fault fracture zone. Our results establish a robust link between detachment faulting and shallow hydrothermal circulation in which the detachment fault system provides critical fluid paths. Therefore, detachment tectonics are important elements for evolving seafloor hydrothermal fields along the Southwest Indian Ridge and possibly other slow‐ and ultraslow‐spreading mid‐ocean ridges globally. Plain Language Summary: The detachment faults of slow‐ and ultraslow‐spreading mid‐ocean ridges are geological structures motivated by seafloor spreading. Intermitted movements of detachment faults exhume deep oceanic crust or mantle rocks and provide pathways for seafloor hydrothermal systems. The magnetic properties of rocks in seafloor detachment fault systems are sensitive to hydrothermal fluids and can be used to study fluid circulation within seafloor detachment fault systems. Using magnetic methods, we found that magnetic minerals in fresh basalt and highly serpentinized peridotite created positive magnetic anomalies, whereas the absence of magnetic minerals in hydrothermally altered basalts and sulfides decreased the magnetic anomalies. As represented by the low‐magnetization zones, the shallow hydrothermal fluid channels sit on the detachment fault, highlighting the close relationship between detachment tectonics and the evolution of seafloor hydrothermal systems. We conclude that the detachment fault system primarily controls the formation of black‐smoker chimneys along the magma‐poor mid‐ocean ridges. Key Points: Altered basalt and sulfide deposits attenuated the magnetic anomaly of the normal‐polarity zone in the Dragon Horn areaSerpentinized peridotite (>80%) produced significant positive magnetic anomalies in the Dragon Horn areaDetachment faulting controls the formation of fluid channels for hydrothermal circulation [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of congenital unilateral first permanent molar occlusal loss (CUMOL) on the morphology and position of temporomandibular joint (TMJ). Materials and Methods: Cone‐beam computed tomography (CBCT) images of 37 patients with CUMOL (18 males and 19 females, mean age: 13.60 ± 4.38 years) were divided into two subgroups according to the status of second molar (G1: the second molar not erupted, n = 18, G2: second molar erupted, n = 19). The control group consisted of 33 normal occlusion patients (9 males and 24 females, mean age: 16.15 ± 5.44 years) and was divided into 2 subgroups accordingly (G3: the second molar had not erupted, n = 18, G4: the second molar had erupted and made contact with the opposing tooth, n = 15). Linear and angular measurements were used to determine the characteristics of TMJ. Results: In G1, the condyle on the side of the CUMOL shifts posteriorly, with significant side differences observed in Anterior space (AS, P <.05) and Posterior space (PS, P <.05). However, with the eruption of the second permanent molars, in G2, the condyle on the CUMOL side moves posteriorly and inferiorly. This results in significant lateral differences in the AS (P <.05), PS (P <.05), and Superior space (SS, P <.05). Additionally, there is an increase in the thickness of the roof of the glenoid fossa (TRF) on the CUMOL side (P <.05), and a decrease in the inclination of the bilateral articular eminences (P <.05). Conclusions: CUMOL can affect the position and the morphology of the condyle and was associated with the eruption of the second permanent molars. Before the eruption of the second permanent molars, CUMOL primarily affects the position of the condyle. After the emergence of the second permanent molars, CUMOL leads to changes in both the condyle's position and the morphology of the glenoid fossa. [ABSTRACT FROM AUTHOR]

Objective: To compare the prevalence of fenestration and dehiscence between pre‐ and post‐orthodontic treatment and to explore the factors related to fenestration and dehiscence in the anterior teeth after treatment. Methods: This study included 1000 cone‐beam computed tomography (CBCT) scans of 500 patients before (T1) and after (T2) orthodontic treatment. These images were imported into Dolphin 11.9 software to detect alveolar fenestration and dehiscence in the anterior teeth area. The chi‐square test and Fisher's exact test were performed to compare the prevalence of alveolar bone defects between time points T1 and T2. A total of 499 patients were selected for logistic regression analysis to examine the correlation among age, sex, crowding, sagittal facial type, extraction, miniscrew use and fenestration or dehiscence post‐treatment. Results: Except for the maxillary lingual fenestration and labial fenestration of mandibular canines, a significant change in the prevalence of fenestration and dehiscence was noted between time points T1 and T2 (P <.025). Multinomial logistic regression showed that age, miniscrew use and extraction highly influenced the prevalence of anterior lingual dehiscence (P <.05). Dehiscence of the mandibular labial side (skeletal Class III vs. I, OR = 2.368, P =.000) and fenestration of the mandibular lingual side (skeletal Class II vs. I, OR = 2.344, P =.044) were strongly correlated with the sagittal facial type. Dehiscence of the maxillary labial side (moderate vs. mild, OR = 1.468, P =.017) was significantly associated with crowding. Conclusions: Older age, maxillary moderate crowding, skeletal Class III, extraction and miniscrew potentially significantly affect the prevalence of anterior teeth dehiscence. Adult females, skeletal Class III patients on the mandibular labial side and skeletal Class II patients on the mandibular lingual side should be monitored for anterior teeth fenestration. [ABSTRACT FROM AUTHOR]

Temporomandibular joint osteoarthritis (TMJOA), prevalent in adolescents and the elderly, has serious physical and psychological consequences. TMJOA is a degenerative disease of the cartilage and bone, mostly driven by inflammation, and synoviocytes are the first and most important inflammatory factor releasers. Receptor‐interacting serine/threonine‐protein kinase (RIPK1) promotes inflammatory response and cell death during an array of illnesses. This research aimed to explore the impacts of RIPK1 inhibitor therapy in TMJOA and the mechanism of RIPK1 in inducing inflammation during TMJOA. Herein, inhibition of RIPK1 suppressed the elevated levels of inflammatory factors, nuclear factor kappa B (NF‐κB), along with markers of apoptosis and necroptosis after tumour necrosis factor (TNF)‐α/cycloheximide (CHX) treatment in synoviocytes. Moreover, inflammation models were constructed in vivo through complete Freund's adjuvant (CFA) induction and disc perforation, and the findings supported that RIPK1 inhibition protected TMJ articular cartilage against progressive degradation. RIPK1 regulates NF‐κB activation via cellular inhibitor of apoptosis proteins (cIAP), apoptosis via caspase‐8, and necroptosis via RIPK3/mixed lineage kinase domain‐like (MLKL) in synoviocytes, which in turn facilitates TMJOA inflammation progression. [ABSTRACT FROM AUTHOR]

Since the Mesozoic, eastern NE Asia has experienced multiple tectonic events, resulting in a complex structure and forming one of the world's largest Meso‐Cenozoic lacustrine basin systems. Presently, basin evolution models require further elucidation regarding the simultaneous generation of diverse rift basins and the potential impact stemming from the closure of the Mudanjiang Ocean, whose oceanic closure demarcated the boundary between the Songliao Basin and the eastern basins, raises questions about its influence on the development of the basin‐and‐range system. To address these questions, we augment new low‐temperature thermochronological data on basement highs separating the eastern NE Asia basins to investigate the shallow‐deep coupling process of tectonic evolution since the Mesozoic. The new cooling age pattern shows non‐overlapping and spatial differences among major basement highs. Inverse thermal modeling revealed five‐stage cooling episodes among the basement highs, but with different onset and cooling rates of each episode, indicating a significant differential uplift mode. A major reburial stage was identified throughout eastern NE Asia during the mid‐Cretaceous. Compiling cooling age patterns and inverse thermal modeling, we note the existence of a proto‐basin covering an area much larger than the previously contemplated "Pan‐Sanjiang" Basin. In general, our study indicates the final closure of the Mudanjiang Ocean occurred at ca. 150–140 Ma. Since the Early Cretaceous, with changes in the subduction direction, two‐stage flat slab subduction of the Paleo‐Pacific plate and the consequent subduction of the Pacific plate co‐dominated the basements' differential uplift and the formation of the eastern NE Asia basin‐and‐range framework. Key Points: Comprehensive analysis of new cooling age patterns reveals distinct non‐overlapping spatial differences among the major basement highsBasement highs in eastern NE Asia were mainly exhumed by differential uplift and deconstructed the proto‐basin since the Early CretaceousDuring the mid‐Cretaceous, the "Pan‐Sanjiang" Basin reached its maximum extension and connected with the Songliao Basin [ABSTRACT FROM AUTHOR]

Fusing condensed aromatics into multi‐resonance (MR) frameworks has been an exquisite strategy to modulate the optoelectronic properties, which, however, always sacrifices the small full width at half maxima (FWHM). Herein, we strategically embed B−N/B−O contained heterocycles as fusion locker into classical MR prototypes, which could enlarge the π‐extension and alleviate the steric repulsion for an enhanced planar skeleton to suppress the high‐frequency stretching/ scissoring vibrations for ultra‐narrowband emissions. Sky‐blue emitters with extremely small FWHMs of 17–18 nm are thereafter obtained for the targeted emitters, decreased by (1.4–1.9)‐fold compared with the prototypes. Benefiting from their high photoluminescence quantum yields of >90 % and fast radiative decay rates of >108 s−1, one of those emitters shows a high maximum external quantum efficiency of 31.9 % in sensitized devices, which remains 25.8 % at a practical luminance of 1,000 cd m−2 with a small FWHM of merely 19 nm. Notably a long operation half‐lifetime of 1,278 h is also recorded for the same device, representing one of the longest lifetimes among sky‐blue devices based on MR emitters. [ABSTRACT FROM AUTHOR]

This study investigates the marginal distributions of grafted stiff polymer tips in a 2D embedding space using both analytical methods and Monte Carlo simulations. By mapping active Brownian particle (ABP) trajectories in the short‐time regime, analytical expressions for the elongation of the free end of the polymer under horizontal and vertical forces are derived and these expressions are validated using Monte Carlo simulations. These results indicate that the theoretical predictions match well with the simulation results when the chain length is short or the force is large. However, a slight discrepancy is observed between the theoretical and simulation results when the chain is extremely long, although the qualitative asymptotic results remain valid. Additionally, expressions are provided for the horizontal and vertical force versus displacement for the wormlike chain under the weakly bending approximation. This research provides insights into how the trajectories of an ABP correspond to the equilibrium configuration of a semiflexible polymer. These findings have potential applications in various fields, including biophysics and materials science, where understanding the behavior of grafted polymers is crucial. [ABSTRACT FROM AUTHOR]

The practical applications of two‐dimensional (2D) transition‐metal borides (MBenes) have been severely hindered by the lack of accessible MBenes because of the difficulties in the selective etching of traditional ternary MAB phases with orthorhombic symmetry (ort‐MAB). Here, we discover a family of ternary hexagonal MAB (h‐MAB) phases and 2D hexagonal MBenes (h‐MBenes) by ab initio predictions and experiments. Calculations suggest that the ternary h‐MAB phases are more suitable precursors for MBenes than the ort‐MAB phases. Based on the prediction, we report the experimental synthesis of h‐MBene HfBO by selective removal of In from h‐MAB Hf2InB2. The synthesized 2D HfBO delivered a specific capacity of 420 mAh g−1 as an anode material in lithium‐ion batteries, demonstrating the potential for energy‐storage applications. The discovery of this h‐MBene HfBO added a new member to the growing family of 2D materials and provided opportunities for a wide range of novel applications. [ABSTRACT FROM AUTHOR]

With the emerging demand of implantable microelectronics, it essentially requires the fully integrated and reliable power supplies. The study reports a stretchable and flexible electrospinning‐based glucose/O2 biofuel cell with glucose oxidase bioanode, Pt/C cathode and thermoplastic polyurethane substrate, which is capable for adapting to the various stresses and strains caused by individual movement. The rigid benzene rings and elastic chain segments of thermoplastic polyurethane ensure its superior tensile property. Furthermore, the stable covalent connections between the activated carbon nanotubes (CNTs‐COOH) and glucose oxidase inside 3D thermoplastic polyurethane network are established by amide reaction to ensure the rapid direct electron transfer of bioanode and stable power output of device in flexible environments. The biofuel cell exhibits an open circuit voltage of 0.575 V, and high‐power density of 57 µW cm−2 in 5 mM glucose. Moreover, the power‐generation properties of implantable biofuel cell keep steady, and its power density exhibits limited fluctuations on the dorsum of rat when bending, stretching, and twisting in 28 days. There is no obvious local inflammation or systemic abnormalities in rats. It satisfies the impressive biocompatible requirement, demonstrating the promising potential of electrospinning‐based biofuel cell as a robust self‐sustained power source for implantable electronics. [ABSTRACT FROM AUTHOR]

Summary: This paper considers the ℋ∞$$ {\mathscr{H}}_{\infty } $$ stabilization of uncertain switched neural networks with external disturbance and reaction‐diffusion. A weight learning rule that ensures the ℋ∞$$ {\mathscr{H}}_{\infty } $$ stability of the network is proposed utilizing the Lyapunov–Krasovskii functional method. Then, a useful lemma concerning the equivalence of matrix inequities is derived. With the aid of the lemma and Schur complement, a more concise existence condition on the learning rule is developed. Finally, theoretical comparisons and a numerical example are given, which show that the obtained results are extensions and improvements of an existing result. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Emitters with narrowband spectra are of great importance nowadays because of the growing demand for ultra‐high‐definition displays in the fields of panel displays and solid‐state lighting. Though the reported multiple resonance (MR) emitters have been widely studied with extremely sharp spectra and color‐tunable emissions, the electrophilic borylation synthetic strategies and stable narrowband blue devices still face great challenges. Herein, by virtue of the advantages of both the MR effect of conventional indolocarbazole skeleton and the easy‐to‐access of B—N covalent bonds, the linear tert‐butyl benzene and carbazole groups modified 6,12‐diphenyl‐5,11‐dihydroindolo[3,2‐b]carbazole derivatives (tPh[BN] and Cz[BN]) containing two B—N covalent bonds are easily constructed through amine‐directed double borylation strategy. Both emitters behaved bright blue emission with full‐width‐at‐half‐maximum (FWHM) of 20—27 nm in solution, high fluorescence quantum efficiency over 90%, and excellent stability toward moisture. By employing triplet‐triplet annihilation electroluminescent mechanism, blue OLED devices based on them showed a small FWHM of 48 nm and maximum external quantum efficiency of ~7.1% with negligible efficiency roll‐off, and long operational lifetime (LT80) of 87 h at an initial brightness of 1000 cd·m−2, demonstrating the enormous application potential of B—N bonds embedded emitters in achieving ideal narrowband blue emitters. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Emitters with narrowband spectra are of great importance nowadays because of the growing demand for ultra‐high‐definition displays in the fields of panel displays and solid‐state lighting. Though the reported multiple resonance (MR) emitters have been widely studied with extremely sharp spectra and color‐tunable emissions, the electrophilic borylation synthetic strategies and stable narrowband blue devices still face great challenges. Herein, by virtue of the advantages of both the MR effect of conventional indolocarbazole skeleton and the easy‐to‐access of B—N covalent bonds, the linear tert‐butyl benzene and carbazole groups modified 6,12‐diphenyl‐5,11‐dihydroindolo[3,2‐b]carbazole derivatives (tPh[BN] and Cz[BN]) containing two B—N covalent bonds are easily constructed through amine‐directed double borylation strategy. Both emitters behaved bright blue emission with full‐width‐at‐half‐maximum (FWHM) of 20—27 nm in solution, high fluorescence quantum efficiency over 90%, and excellent stability toward moisture. By employing triplet‐triplet annihilation electroluminescent mechanism, blue OLED devices based on them showed a small FWHM of 48 nm and maximum external quantum efficiency of ~7.1% with negligible efficiency roll‐off, and long operational lifetime (LT80) of 87 h at an initial brightness of 1000 cd·m−2, demonstrating the enormous application potential of B—N bonds embedded emitters in achieving ideal narrowband blue emitters. [ABSTRACT FROM AUTHOR]

Despite the remarkable multiple resonance (MR) optoelectronic properties of organic nanographenes with boron and nitrogen atoms disposed para to each other, the synthetic procedures are sophisticated with low yields and the molecular skeletons are limited. Here, a new paradigm of easy‐to‐access MR emitter is constructed by simplifying the multiborylation through amine‐directed formation of B−N bonds while introducing an additional para‐positioned nitrogen atom to trigger the MR effect. The proof‐of‐concept molecules exhibit narrowband emissions at 480 and 490 nm, with full width at half maxima (FWHMs) of only 29 and 34 nm. The devices based on them showed external quantum efficiencies (EQE) of >33.0 %, which remained above 24.0 % even at a high brightness of 5000 cd m−2. This is the first example of MR emitters with a B−N covalent bond, not only decreasing the synthesis difficulty but also increasing the diversity of MR skeletons for emerging new optoelectronic properties. [ABSTRACT FROM AUTHOR]

Summary: PAM‐relaxed Cas9 nucleases, cytosine base editors and adenine base editors are promising tools for precise genome editing in plants. However, their genome‐wide off‐target effects are largely unexplored. Here, we conduct whole‐genome sequencing (WGS) analyses of transgenic plants edited by xCas9, Cas9‐NGv1, Cas9‐NG, SpRY, nCas9‐NG‐PmCDA1, nSpRY‐PmCDA1 and nSpRY‐ABE8e in rice. Our results reveal that Cas9 nuclease and base editors, when coupled with the same guide RNA (gRNA), prefer distinct gRNA‐dependent off‐target sites. De novo generated gRNAs by SpRY editors lead to additional, but insubstantial, off‐target mutations. Strikingly, ABE8e results in ~500 genome‐wide A‐to‐G off‐target mutations at TA motif sites per transgenic plant. ABE8e's preference for the TA motif is also observed at the target sites. Finally, we investigate the timeline and mechanism of somaclonal variation due to tissue culture, which chiefly contributes to the background mutations. This study provides a comprehensive understanding on the scale and mechanisms of off‐target and background mutations occurring during PAM‐relaxed genome editing in plants. [ABSTRACT FROM AUTHOR]

Heart failure is a condition caused by a variety of pathophysiological factors. One important pathological change of chronic heart failure is myocardial hypertrophy. In recent years, several studies have found that dysregulated microRNAs are involved in regulating the pathological process of heart failure. In this study, cardiac hypertrophy models were constructed using isoproterenol (ISO)‐/angiotensin‐II (Ang‐II) to explore the role of miR‐384‐5p in cardiac hypertrophy and its molecular mechanism in vivo and in vitro. Echocardiography, invasive pressure–volume analysis and hematoxylin–eosin staining were used to explore cardiac structure and function. ALPK3 mRNA and protein expression were detected using quantitative reverse transcription polymerase chain reaction (RT‐qPCR) and western blot analysis and miR‐384‐5p expression were assessed via RT‐qPCR. Our findings determined that miR‐384‐5p was notably decreased in cardiac hypertrophic tissues and cells, and overexpression of miR‐384‐5p could ameliorate pressure overload. Furthermore, ALPK3 was determined to downregulate the ALPK3 expression to aggravate cardiomyocyte hypertrophy. Our findings provided a potential therapeutic target for the treatment of cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Amyloid-𝜷 (A𝜷) toxicity is considered to be companioned by Tau phosphorylation in Alzheimer's disease (AD). The clinical AD therapy is usually subjected to low blood-brain barrier (BBB) penetration and complex interaction mechanisms between A𝜷 and phosphorylated Tau. A "Drug-Carrier" synergy therapy is herein designed to simultaneously target A𝜷 and Tau-associated pathways for AD treatment. To imitate natural nanoparticle configuration, the endogenous apolipoprotein A-I and its mimicking peptide 4F fused angiopep-2 (Ang) are sequentially grafted onto lipid nanocomposite (APLN), providing liberty of BBB crossing and microglia targeted A𝜷 clearance. For synergy treatment, methylene blue (MB) is further assembled into APLN (APLN/MB) for Tau aggregation inhibition. After intravenous administration, the optimized density (5 wt%) of Ang ligands dramatically enhances APLN/MB intracerebral shuttling and accumulation, which is 2.15-fold higher than that Ang absent-modification. The site-specific release of MB collaborates APLN to promote A𝜷 capture for microglia endocytosis clearance and reduce p-Tau level by 25.31% in AD pathogenesis. In AD-A𝜷-Tau bearing mouse models, APLN/MB can relieve AD symptoms, rescue neuron viability and cognitive functions. Collectively, it is confirmed that "Drug-Carrier" synergy therapy of APLN/MB is a promising approach in the development of AD treatments. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the morphometric changes in maxillary and mandibular anterior alveolar bone after orthodontic treatment and retention for 18‐24 months by cone‐beam computed tomography (CBCT). Setting and Sample Population: Thirty‐four adolescent patients (12 males and 22 females; mean age: 14.29 ± 1.24 years) diagnosed with bimaxillary dentoalveolar protrusion and with extractions of the 4 first premolars were included. Materials and Methods: The labial and lingual (palatal) alveolar bone thickness, height and root length of the maxillary and mandibular anterior teeth were assessed using CBCT imaging at the pre‐treatment (T1), post‐treatment (T2) and retention phases (T3). Voxel‐based superimpositions of the T2 and T3 images were performed, and the distances of incisal and apical movement between T2 and T3 were measured to determine whether relapses occurred. Results: After orthodontic treatment, the labial and lingual (palatal) bone height decreased significantly (P <.05) and the labial thickness at the crestal (L1), midroot (L2), and apical levels (L3) had no significant change, while the lingual (palatal) bone thickness at all three levels decreased significantly (P <.05). After 18‐24 months of retention, the lingual (palatal) height and the lingual (palatal) thickness at the crestal (L1) level increased significantly (P <.05). There were no obvious incisal and apical movements of the anterior teeth between T2 and T3 (P >.05), indicating that no relapses occurred. Conclusions: Even though lingual (palatal) alveolar loss occurred due to the orthodontic treatment, the cervical alveolar bone seemed to recover over time. Therefore, appropriate camouflage treatment can be used in patients with bimaxillary dentoalveolar protrusion, and this treatment will not irreversibly deteriorate periodontal health and affect the orthodontic treatment stability. [ABSTRACT FROM AUTHOR]

Summary: Cytosine base editors (CBEs) can install a predefined stop codon at the target site, representing a more predictable and neater method for creating genetic knockouts without altering the genome size. Due to the enhanced predictability of the editing outcomes, it is also more efficient to obtain homozygous mutants in the first generation. With the recent advancement of CBEs on improved editing activity, purify and specificity in plants and animals, base editing has become a more appealing technology for generating knockouts. However, there is a lack of design tools that can aid the adoption of CBEs for achieving such a purpose, especially in plants. Here, we developed a user‐friendly design tool named CRISPR‐BETS (base editing to stop), which helps with guide RNA (gRNA) design for introducing stop codons in the protein‐coding genes of interest. We demonstrated in rice and tomato that CRISPR‐BETS is easy‐to‐use, and its generated gRNAs are highly specific and efficient for generating stop codons and obtaining homozygous knockout lines. While we tailored the tool for the plant research community, CRISPR‐BETS can also serve non‐plant species. [ABSTRACT FROM AUTHOR]

Summary: MicroRNA168 (MIR168) is a key miRNA that targets the main RNA‐induced silencing complex component Argonaute 1 (AGO1) to regulate plant growth and environmental stress responses. However, the regulatory functions of MIR168 need to be further elucidated in rice. In this paper, we generated clean OsMIR168a deletion mutants by CRISPR‐Cas9 strategy. We then phenotypically and molecularly characterized these mutants. The rice OsMIR168a mutants grew rapidly at the seedling stage, produced more tillers and matured early. Compared to the wild‐type plants, the mutants were shorter at maturity and produced smaller spikelets and seeds. Analysis of gene expression showed that the transcription levels of OsMIR168a's target genes such as OsAGO1a, OsAGO1b and OsAGO1d were elevated significantly in the OsMIR168a mutants. Intriguingly, OsAGO18, a member of a new AGO clade that is conserved in monocots, was confirmed to be a target of OsMIR168a not only by informatic prediction but also by expression analysis and a cell‐based cleavage assay in the OsMIR168a mutants. Many protein‐coding genes and miRNAs showed differential expression in the OsMIR168a mutants, suggesting OsMIR168a exerts a major transcriptional regulatory role, likely through its potential target genes such as OsAGO1s and OsAGO18. KEGG enrichment analysis of these differentially expressed genes pointed to OsMIR168a's involvement in important processes such as plant hormone signalling transduction and plant–pathogen interaction. These data collectively support that the complex regulation module of OsMIR168a‐OsAGO1/OsAGO18‐miRNAs‐target genes contributes to agronomically important traits, which sheds light on miRNA‐mediated crop breeding. [ABSTRACT FROM AUTHOR]

Summary: This article deals with the issue of input‐to‐state ℋ∞ stabilization for recurrent neural networks with delay and external disturbance. The goal is to design a suitable weight‐learning law to make the considered network input‐to‐state stable with a predefined ℒ2‐gain. Based on the solution of linear matrix inequalities, two schemes for the desired learning law are presented via using decay‐rate‐dependent and decay‐rate‐independent Lyapunov functionals, respectively. It is shown that, in the absence of external disturbance, the proposed learning law also guarantees the exponential stability of the network. To illustrate the applicability of the present weight‐learning law, two numerical examples with simulations are given. [ABSTRACT FROM AUTHOR]

Herein, Nb is used as an intermediate layer to assist the pulsed laser welding of titanium (Ti) alloy/stainless steel (SS), and the formation of brittle Ti–Fe intermetallics is prevented. Microstructures of the joints are analyzed by means of scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), transmission electron microscope (TEM), and X‐ray diffraction (XRD). Mechanical properties of the joints are evaluated by tensile tests. The laser is concentrated on the side of the Ti alloy, and the formation of the Ti–Fe intermetallics is avoided due to the unmelted Nb. A eutectic reaction occurs at the Nb–SS interface to form a reaction layer. The width of the reaction layer increases as the heat input increases. Reasonable control of laser offset and laser current can keep the thickness of the Nb–Fe composite layer at a low level to obtain a small amount of Nb–Fe intermetallics, thereby improving the mechanical properties of the reaction layer. [ABSTRACT FROM AUTHOR]

Summary: CRISPR‐Cas9 is an emerging genome editing tool for reverse genetics in plants. However, its application for functional study of non‐coding RNAs in plants is still at its infancy. Despite being a major class of non‐coding RNAs, the biological roles of circle RNAs (circRNAs) remain largely unknown in plants. Previous plant circRNA studies have focused on identification and annotation of putative circRNAs, with their functions largely uninvestigated by genetic approaches. Here, we applied a multiplexed CRISPR‐Cas9 strategy to efficiently acquire individual null mutants for four circRNAs in rice. We showed each of these rice circRNA loci (Os02circ25329, Os06circ02797, Os03circ00204 and Os05circ02465) can be deleted at 10% or higher efficiency in both protoplasts and stable transgenic T0 lines. Such high efficiency deletion enabled the generation of circRNA null allele plants without the CRISPR‐Cas9 transgene in the T1 generation. Characterization of the mutants reveals these circRNAs' participation in salt stress response during seed germination and in particular the Os05circ02465 null mutant showed high salt tolerance. Notably, the seedlings of the Os06circ02797 mutant showed rapid growth phenotype after seed germination with the seedlings containing higher chlorophyll A/B content. Further molecular and computational analyses suggested a circRNA–miRNA–mRNA regulatory network where Os06circ02797 functions to bind and sequester OsMIR408, an important and conserved microRNA in plants. This study not only presents genetic evidence for the first time in plants that certain circRNAs may serve as sponges to negatively regulate miRNAs, a phenomenon previously demonstrated in mammalian cells, but also provides important insights for improving agronomic traits through gene editing of circRNA loci in crops. [ABSTRACT FROM AUTHOR]

Using silk fibroin as the base material, the drug‐loaded microspheres are prepared by an emulsification method. In order to determine the drug‐loading and drug‐release performance parameters of the microspheres, the central composite design method is used to design and investigate the effects of the parameters of the microsphere preparation process, such as the oil–water ratio, stirring temperature, and stirring rate, on the microsphere particle size, drug‐loading rate, and drug release rate. The "overall desirability" is taken as a comprehensive evaluation index, and the response surface method (RSM) and genetic algorithm–backpropagation (GA–BP) neural network GA–BP model are used to predict and evaluate the parameters of the drug‐loaded microsphere preparation process. The root‐mean‐square error values obtained from the RSM and BP–GA model experiments are 0.000325 and 0.00022, respectively. The results show that the BP–GA model has better prediction accuracy and optimization ability than the RSM. The optimal microsphere preparation process conditions were determined to be as follows: a water–oil ratio of 10:1, at a temperature of 45°C with stirring at a speed of 400 rpm, the particle size of the microspheres is 1.392 μm, the drug‐loading rate is 3.218%, and the drug release rate is 51.991%. The results of this study indicate that this approach is an effective method for the optimization of the parameters of the drug‐loaded microsphere preparation process. [ABSTRACT FROM AUTHOR]

Mafic lavas of Cenozoic age are widely distributed in northeast China and received much attention as an important part of the Circum‐Pacific volcanic belt. The age constraints for the volcanic activity were determined mostly by K/Ar and 40Ar/39Ar methods. We present zircon (U–Th)/He ages obtained on the thermally overprinted sands directly underlying a basaltic lava. This thermochronometer is insensitive to weathering and not biased by excess argon, thus it can express accurately the age of thermal effect of the lava flow. As a regional cooling age reference, three granite samples were dated from basement units that have not been thermally influenced by the basalt eruptions. The reference granite samples revealed well‐defined Cretaceous (U–Th)/He‐ages, while 20 zircon crystals from the sand below the basalt lava revealed a prominent Miocene (U–Th)/He age component of 9.33 ± 0.24 Ma. Raman spectroscopy of these zircon crystals supports their thermally overprinted character. We infer that the sand sample has experienced significant thermal overprint by the overlying basalt lava leading to thermal reset of the majority of the detrital zircon crystals. The obtained age is thus interpreted as the eruption age of the basalt lava. The Huanan basalt flow thus belongs to volcanics of the Laoyeling episode in NE China. [ABSTRACT FROM AUTHOR]

Silk fibroin (SF)/polyvinyl alcohol (PVA) composite hydrogel and SF/PVA/hydroxyapatite (HA) composite were prepared by two methods: drying at room temperature and repeated freezing–thawing cycles. A comparative analysis was carried out for the composite material under various conditions, focusing on the properties of SF/PVA/HA composites, studied by Fourier transform infrared, scanning electron microscope, swelling characteristics, mechanical compression, cytotoxicity, in vitro degradation, and drug carrying release experiment. The results show that compared with the SF/PVA/HA composites prepared by cooled at room temperature method, SF/PVA composite hydrogel was heated at 80°C after repeated freezing–thawing for three times, with HA blended, the SF/PVA/HA composites were obtained after freeze‐dried. The content of β‐sheet structure noticeably increased, which has the better mechanical properties and aqueous solution stability, good cell compatibility, moderate in vitro degradation rate and stable drug release rate, and can also be beneficial for material used in drug‐loaded tissue engineering bone scaffold to improve degradation of uniform rate and drug release stability. It provides a significant technique to achieve the treatment of anti‐bone tuberculosis and lesion bone defect repair. POLYM. COMPOS., 40:3131–3139, 2019. © 2018 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Unwanted interference noise often causes problems during seismic reflection data acquisition and processing. In this paper we present two novel data‐regrouping methods that enable improved shot‐to‐shot coherent interference noise attenuation in marine seismic data. The two approaches are based on line mixing and/or shot skipping: (1) for a 3‐D marine seismic reflection data acquisition which is typically carried out by shooting closely spaced parallel lines, we propose to mix the shot gathers from two adjacent sail lines to break up shot‐to‐shot coherent noise. This approach takes advantage of the fact that adjacent sail lines are usually acquired with a significant time interval, resulting in different types of noise; (2) for a 2‐D/3‐D acquisition, we propose an algorithm to skip and reorder the original shots to decrease the continuity of the shot‐to‐shot coherent noise. This approach could also supply more aperture data for the first or last shot from both sides, which is beneficial for the coherent noise removal at the edge area. After regrouping the original data, the coherent noise can then be further randomized or isolated by sorting and transforming to other domains, typically the common p‐shot domain where a random noise attenuation tool could be applied to identify and attenuate such noise. Field data examples confirm the effectiveness of the methods. Key Points: This paper illustrates the generation and distribution characteristics of coherent noise, especially the rig noise and seismic interferenceThis paper presents two novel approaches to break up the consistency of shot‐to‐shot coherent noise resulting in very good denoised resultStatistics show that data‐regrouping methods combined with cross‐party vessel cooperation significantly reduced the time‐sharing cost [ABSTRACT FROM AUTHOR]

Background: The roles of TMEM206, a new transmembrane protein, in cancer, including colorectal cancer (CRC), are unknown. Related family members, including TMEM16A, TMEM132A, and TMEM176B, have been shown to be involved in various biological behaviors. In addition, TMEM88 has been reported to promote non‐small‐cell lung cancer. In this study, we examined the roles of TMEM206 in CRC. Method: Real‐time reverse transcription polymerase chain reaction was used to measure TMEM206 messenger RNA (mRNA) levels in clinical specimens and transfected cell lines. Immunohistochemistry was used to determine the relationship between TMEM206 expression levels and clinical data. Plasmids and small interfering RNA were used to upregulate and silence TMEM206, respectively. Protein expression levels and signaling pathway modulation were validated through western blot analysis. Colony formation, MTT, cell migration and invasion assays, and flow cytometry analyses were used to test the potential roles of TMEM206 in CRC. Co‐immunoprecipitation was used to evaluate the interaction between TMEM206 and AKT. Results: Investigation of the clinical significance of TMEM206 expression in CRC tissues revealed that TMEM206 mRNA and protein levels were higher in CRC tissues than in paired normal adjacent tissues (p < 0.05). TMEM206 overexpression was positively associated with T stage of cancer and UICC stage (p < 0.05) and negatively related to differentiation of CRC (p = 0.015). Upregulation or silencing of TMEM206 promoted or inhibited the proliferation of CRC cells and positively or negatively regulated the levels of phospho‐AKT and downstream signaling pathway components (phospho‐glycogen synthase kinase 3β and cyclin D1), respectively. Moreover, silencing of TMEM206 in cell lines arrested CRC cells in the G1 stage of the cell‐cycle. In addition, upregulating or silencing TMEM206 increased or decreased cell invasion and migration in vitro and positively or negatively altered levels of the phospho‐extracellular signal‐regulated kinase (ERK) and phospho‐focal adhesion kinase 397, respectively. Co‐immunoprecipitation demonstrated that AKT and TMEM206 proteins interacted. Furthermore, TMEM206 promoted the development and progression of CRC by enhancing the interactions between the AKT and ERK signaling pathways. Conclusion: TMEM206 controlled the progression of CRC by accelerating CRC cell proliferation and promoting CRC cell migration and invasion. The target of TMEM206 may be AKT, which is known to be involved in modulating the biological behaviors of various cancers. [ABSTRACT FROM AUTHOR]

ZC3H13 is a canonical CCCH zinc finger protein, which harbors a somatic frame‐shift mutation in colorectal cancer (CRC). However, its expression and biological function were still uncertain. In the current study, we found that ZC3H13 was served as a tumor suppressor in CRC cells, which decreased the expression of Snail, Cyclin D1, and Cyclin E1, and increased the expression of Occludin and Zo‐1 through inactivating Ras–ERK signaling pathway. Furthermore, reduction of ZC3H13 associated with advanced TNM stage (p = 0.02), positive regional lymph node metastasis (p = 0.01). Taken together, the current study indicated that ZC3H13 may be an upstream regulator of Ras–ERK signaling pathway and suppressed invasion and proliferation of CRC. Zinc finger CCCH domain‐containing protein 13 (ZC3H13) suppresses colorectal cancer proliferation and invasion via inactivating Ras–ERK signaling. [ABSTRACT FROM AUTHOR]

Serine/arginine protein‐specific kinase 2 (SRPK2) plays a vital role in the progression of a range of different malignancies, including pancreatic cancer. However, the mechanisms are poorly understood. Previous studies have shown that in hepatocellular carcinoma, SRPK2 knockdown leads to the upregulation of the cell fate determining protein Numb, and in pancreatic cancer cells, Numb knockdown prevents ubiquitin‐mediated degradation of p53. In this study, we investigated the relationship between SRPK2, Numb and p53 in the development of pancreatic cancer with or without chemical agent treatment in vitro. SRPK2 expression was upregulated in pancreatic cancer tissues and associated with decreased overall survival in pancreatic cancer patients, indicating that expression of this protein can be used as a marker of unfavourable prognosis. Expression of SRPK2 was positively associated with tumour T stage and Union for International Cancer Control (UICC) stage, and negatively associated with Numb expression in serial tissue sections. In pancreatic cancer cells, SRPK2 downregulation or overexpression led to modulation of Numb and wild‐type p53 protein expression in response to oxaliplatin treatment. Furthermore, these three endogenous proteins could be coimmunoprecipitated as a triple complex. Numb or p53 knockdown reversed the upregulation of p53 that was induced by silencing SRPK2. SRPK2 overexpression promoted cell invasion and migration, and decreased chemosensitivity of cancer cells to gemcitabine or oxaliplatin treatment. Conversely, SRPK2 silencing decreased cell invasion and migration and increased chemosensitivity; these effects were reversed by silencing p53 in oxaliplatin‐treated pancreatic cancer cells. Our data suggest that SRPK2 negatively regulates p53 by downregulating Numb under chemical agent treatment. Thus, SRPK2 promotes the development and progression of pancreatic cancer in a p53‐dependent manner. [ABSTRACT FROM AUTHOR]

The Late Palaeozoic Solonker‐Xar Moron‐Changchun‐Yanji Suture (SXCYS) is considered to mark the location of the final closure of the Paleo‐Asian Ocean, which separated the North China Craton to the south and the amalgamated blocks to the north in Northeast China. There has always been controversy about its eastern extension in Northeast China and the final closure time of the Paleo‐Asian Ocean. To explore this issue, we collected gabbro and quartz‐diorite samples in the Hunchun area for the genesis of mafic magma and age dating, and five groups of Permian to Triassic sandstones belonging to both sides of the potential suture locations in the middle and east Jilin Province for the provenance analysis to discuss the final closure time of the Paleo‐Asian Ocean and the possible positions of the eastward termination of the SXCYS. The gabbro reveals a Middle Permian concordia average age of 266.9 ± 5.2 Ma, and the quartz diorite reveals a Late Permian Concordia average age of 258.8 ± 4.8 Ma. Lithological and geochemical analysis reveal the two rock samples belong to low‐K arc tholeiites from the oceanic island and calk‐alkaline volcanics from the active continental margin, respectively, which implies that during the middle to late Permian, the SW margin of the Jiamusi–Khanka Block (JB) continuously experienced the subduction process from the Paleo‐Asian Ocean Plate. The final closure time of the Paleo‐Asian Ocean should be later than the Late Permian. Meanwhile, four groups of sandstone from the east Jilin reveal typically Jiamusi–Mongolia Block (JMB) provenance features, with age components of ~500 Ma, ~0.9–1.5 Ga implying that the Wangqing, Hunchun, Kaishantun area belongs to the northern part of the SXCYS from late Early Permian to Middle Triassic, with youngest age components of 288.2 ± 2.8, 275.5 ± 1.8, 250 ± 1.7, and 244.9 ± 1.7 Ma, respectively. The late Early Permian sandstone from the middle Jilin reveals the youngest age component of 273.8 ± 3.4 Ma and the age component of 487 ± 3 Ma also revealing JMB feature. Comparing to previous studies, we propose that the Paleo‐Asian Ocean finally closed during Middle to Late Triassic. A possible ENE fault separates the eastern extension of SXCYS into two parts, which means the possible position of the eastward extension of the SXCYS should go along the Wangqing‐Kaishantun with NNW direction in the west, Hunchun‐Laoheishan with NW direction in the east. [ABSTRACT FROM AUTHOR]

Nanocarriers capable of circumventing various biological barriers between the site of administration and the therapeutic target hold great potential for cancer treatment. Herein, a redox-sensitive, hyaluronic acid-decorated graphene oxide nanosheet (HSG) is developed for tumor cytoplasm-specific rapid delivery using near-infrared (NIR) irradiation controlled endo/lysosome disruption and redox-triggered cytoplasmic drug release. Hyaluronic acid (HA) modification through redox-sensitive linkages permits HSG a range of advantages over the standard graphene oxide, including high biological stability, enhanced drug-loading capacity for aromatic molecules, HA receptor-mediated active tumor targeting, greater NIR absorption and thermal energy translation, and a sharp redox-dependent response for accelerated cargo release. Results of in vivo and in vitro testing indicate a high loading of doxorubicin (DOX) onto HSG. Selective delivery to HA-receptor overexpressing tumors is achieved through passive and active targeting with minimized unfavorable interactions with blood components. Cytoplasm-specific DOX delivery is then achieved through NIR controlled endo/lysosome disruption along with redox-triggered release of DOX in glutathione rich areas. HSG's specificity is resulted in enhanced cytotoxicity of chemotherapeutics with minimal collateral damage to healthy tissues in a xenograft animal tumor model. HSG is validated the programmed delivery of therapeutic agents in a spatiotemporally controlled manner to overcome multiple biological barriers results in specific and enhanced cancer treatment. [ABSTRACT FROM AUTHOR]

Boron-Nitrogen Covalent Bonds, Device Lifetime, High Efficiency, Multiple Resonance, Narrowband Emission Eine Amin-dirigierte B-N-Bindungsbildung für die Synthese von BN-fusionierten polycyclischen aromatischen Mehrfachresonanzemittern wird in der Zuschrift (e202207293) von Dongdong Zhang, Lian Duan et al. vorgestellt. Keywords: Boron-Nitrogen Covalent Bonds; Device Lifetime; High Efficiency; Multiple Resonance; Narrowband Emission EN Boron-Nitrogen Covalent Bonds Device Lifetime High Efficiency Multiple Resonance Narrowband Emission 1 1 1 09/28/22 20221004 NES 221004 B Organische Halbleiter b . [Extracted from the article]

Background: Biologic meshes are mostly used for abdominal wall reinforcement in infected fields, but no consensus has been reached on its use for inguinal hernia repairing. The purpose of this study was to compare biologic mesh with synthetic mesh in open inguinal herniorrhaphy. Methods: A systematic literature review and meta-analysis was undertaken to identify studies comparing the outcomes of biologic mesh and synthetic mesh in open inguinal hernia repair. Published studies were identified by the databases PubMed, EMBASE and the Cochrane Library. Results: A total of 382 patients in five randomized controlled trials were reviewed (179 patients in biologic mesh group; 203 patients in synthetic mesh group). The two groups did not significantly differ in chronic groin pain (P = 0.06) or recurrence (P = 0.38). The incidence of seroma trended higher in biologic mesh group (P = 0.03). Operating time was significantly longer with biologic mesh (P = 0.03). There was no significant difference in hematomas (P = 0.23) between the two groups. Conclusions: From the data of this study, biologic mesh had no superiority to synthetic mesh in open inguinal hernia repair with similar recurrence rates and incidence of chronic groin pain, but higher rate of seroma and longer operating time. However, this mesh still needs to be assessed in a large, multicentre, well-designed randomized [ABSTRACT FROM AUTHOR]

Argonaute ( AGO) family proteins are conserved key components of small RNA-induced silencing pathways. In the RNA-directed DNA methylation ( Rd DM) pathway in Arabidopsis, AGO6 is generally considered to be redundant with AGO4. In this report, our comprehensive, genomewide analyses of AGO4- and AGO6-dependent DNA methylation revealed that redundancy is unexpectedly negligible in the genetic interactions between AGO4 and AGO6. Immunofluorescence revealed that AGO4 and AGO6 differ in their subnuclear co-localization with RNA polymerases required for Rd DM. Pol II and AGO6 are absent from perinucleolar foci, where Pol V and AGO4 are co-localized. In the nucleoplasm, AGO4 displays a strong co-localization with Pol II, whereas AGO6 co-localizes with Pol V. These patterns suggest that Rd DM is mediated by distinct, spatially regulated combinations of AGO proteins and RNA polymerases. Consistently, Pol II physically interacts with AGO4 but not AGO6, and the levels of Pol V-dependent scaffold RNAs and Pol V chromatin occupancy are strongly correlated with AGO6 but not AGO4. Our results suggest that AGO4 and AGO6 mainly act sequentially in mediating small RNA-directed DNA methylation. [ABSTRACT FROM AUTHOR]

We studied the clinicopathological significance for Calreticulin (CRT) expression in pancreatic cancer (PC), and its functional relationship with other signaling genes (especially with p53) in regulating the biological behavior of PC cells. IHC, IF, IB, and real-time PCR were used to detect CRT expression in PC, while transfection and drug intervention were used to investigate the functional relationship of CRT with other signaling genes. IHC showed both CRT and p53 expression was significantly increased in PC, compared to that in paired non-cancerous pancreatic tissues ( P < 0.001). High expression of CRT was positively associated with tumor UICC stage and lymph nodes metastasis ( P = 0.034 and P = 0.015), and was an independent adverse prognostic indicator in patients with PC. No relationship was found between CRT and p53 expression in spearman's rank correlation test. Altered expression of CRT did not change p53, MDM2, pho-AKT, pho-p38, and pho-JNK expression, but had a specific regulation on pho-ERK. Meanwhile, CRT-regulated cell proliferation, migration, and invasion of PC cells in MEK/ERK pathway dependent manner. In addition, CRT knockdown significantly decreased pho-ERK expression and cell chemoresistance independent of activated p53 and caspase-3-related apoptosis in gemcitabine- or oxaliplatin-treated Capan-2 cells. Our study first demonstrated that overexpression of CRT contributed to the development and progression of PC through MEK/ERK-signaling pathway but independent of p53. The interaction between CRT and MEK/ERK pathway might provide a new idea for revealing malignant biology and supplying new gene targeted chemotherapy of PC. J. Cell. Physiol. 229: 887-897, 2014. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A programmed drug-delivery system that can transport different anticancer therapeutics to their distinct targets holds vast promise for cancer treatment. Herein, a core-shell-based 'nanodepot' consisting of a liposomal core and a crosslinked-gel shell (designated Gelipo) is developed for the sequential and site-specific delivery (SSSD) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and doxorubicin (Dox). As a small-molecule drug intercalating the nuclear DNA, Dox is loaded in the aqueous core of the liposome, while TRAIL, acting on the death receptor (DR) on the plasma membrane, is encapsulated in the outer shell made of crosslinked hyaluronic acid (HA). The degradation of the HA shell by HAase that is concentrated in the tumor environment results in the rapid extracellular release of TRAIL and subsequent internalization of the liposomes. The parallel activity of TRAIL and Dox show synergistic anticancer efficacy. The half-maximal inhibitory concentration (IC50) of TRAIL and Dox co-loaded Gelipo (TRAIL/Dox-Gelipo) toward human breast cancer (MDA-MB-231) cells is 83 ng mL-1 (Dox concentration), which presents a 5.9-fold increase in the cytotoxicity compared to 569 ng mL-1 of Dox-loaded Gelipo (Dox-Gelipo). Moreover, with the programmed choreography, Gelipo significantly improves the inhibition of the tumor growth in the MDA-MB-231 xenograft tumor animal model. [ABSTRACT FROM AUTHOR]

Aims To study the expression of Gli1, MDM2 and p53 for clinical significance in pancreatic cancer ( PC), and their functional relationship in regulating the biological behaviour of PC cells. Methods and results Immunohistochemistry showed that the expression of Gli1, MDM2 and p53 was much higher in 57 cases of PC than in paired normal pancreatic tissues, and was positively associated with tumour UICC stage and T stage ( P < 0.05). Patients with expression of Gli1 only or coexpression of Gli1 and MDM2 had significantly worse overall survival than patients with negative expression ( P < 0.05). RNA interference showed that p53 knockdown increased the protein level of Gli1 but decreased the level of MDM2, and enhanced cell invasion and migration in wild-type p53 Capan-2 cells; whereas Gli1 or MDM2 knockdown did not change p53 expression, but decreased the protein level of MDM2 or Gli1, respectively, and inhibited cell invasion and migration in mutant p53 PANC-1 cells. Conclusions Overexpression of Gli1, MDM2 and mutant p53 contributes to the development and progression of PC, and plays an important role in predicting PC patients' prognosis. Moreover, we report a positive association between Gli1 and MDM2 in PC cells, but their relationship with p53 is dependent on wild-type or mutant p53 status. [ABSTRACT FROM AUTHOR]