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Background: This study aimed to investigate the risk factors for nonrecovery of left ventricular ejection fraction (LVEF) during follow‐up in patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI) combined with reduced LVEF, and establish and verify a risk prediction model based on these factors. Methods: In this study, patients with AMI who underwent PCI in a high‐volume PCI center between December 2018 and December 2021 were consecutively enrolled, screened, and randomly assigned to the model establishment and validation cohorts. A predictive model method based on least absolute shrinkage and selection operator regression was used for establishment and validation. Results: Cardiac troponin I, myoglobin, left ventricular end‐diastolic dimension, multivessel disease, and no‐reflow were identified as potential predictors of LVEF recovery failure. The areas under the curve were 0.703 and 0.665 in the model establishment and validation cohorts, respectively, proving that the prediction model had some predictive ability. The calibration curves of the two cohorts showed good agreement with those of the nomogram model. In addition, the decision curve analysis showed that the model had a net clinical benefit. Conclusion: This prediction model can assess the risk of nonrecovery of LVEF in patients with AMI undergoing PCI combined with LVEF reduction during follow‐up, and conveniently screen high‐risk patients with nonrecoverable LVEF early. [ABSTRACT FROM AUTHOR]

The self‐centering energy dissipative (SCED) brace can limit the maximum story drift and eliminate residual drift during an earthquake. The inadequate reliability or excessive complexity of the energy dissipative system, the contradiction between the energy dissipative system and self‐centering system, the limited elongation capacity, and the difficulty in replacement and reuse are the main challenges faced by the existing developed SCED brace. To solve these problems, a variable friction adaptive self‐centering energy dissipative (VFA‐SCED) brace has been proposed. First, the details of the VFA‐SCED brace are introduced, and the force analysis of each component and the working mechanism of the brace are expounded. Then, the equations that govern the brace performance have been derived, key parameters and mathematical models have been identified. Finally, the feasibility of the new system was demonstrated with a set of experiments, in which five specimens with different key parameters were fabricated, tested, and analyzed. The test results show that the hysteretic curve of the VFA‐SCED brace is typically flag‐shaped, and there is almost no residual deformation after multiple cyclic loadings, which means that the brace has good energy dissipative capacity and self‐centering ability, replaceable and recyclable for each component, and stable working performance. The elongation capacity, friction, energy dissipative capacity, and self‐centering ability can be changed by adjusting the relevant key parameters of the spring and wedge block, and the proposed mathematical model can well predict the force‐deformation hysteresis of the brace with different parameters. The results show that the VFA‐SCED brace successfully avoids the main obstacles of previous SCED braces. [ABSTRACT FROM AUTHOR]

Objective: To compare the antidepressant effects and tolerability of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) treatments in patients with post‐stroke depression (PSD). Methods: We included randomized controlled trials comparing active stimulation with sham stimulation. Primary outcomes were the depression score after treatment, presented as standardized mean differences with 95% confidence intervals. Response/remission and long‐term antidepressant efficacy were also examined. We estimated effect‐size using pairwise and Bayesian network meta‐analysis (NMA) with random‐effects model. Results: We identified 33 studies (total n = 1793). In NMA, 5 of 6 treatment strategies were associated with higher effect compared with sham therapy: dual rTMS (standardized mean differences = −1.5; 95% confidence interval = −2.5 to −0.57), dual LFrTMS (−1.5, −2.4 to −0.61), dual tDCS (−1.1, −1.5 to −0.62), HFrTMS (−1.1, −1.3 to −0.85) and LFrTMS (−0.90, −1.2 to −0.6). And dual rTMS, dual LFrTMS or HFrTMS may be more effective than other interventions for achieving antidepressant effects. Regarding secondary outcomes, rTMS can promote depression remission and response, and alleviate depression for at least 1 month. rTMS and tDCS were well tolerated. Conclusions: Bilateral rTMS and HFrTMS are considered top‐priority non‐invasive brain stimulation (NIBS) interventions for improving PSD. Dual tDCS and LFrTMS are also efficient. Significance: The findings of this study provide evidence for considering NIBS techniques as alternative or add‐on treatments for patients with PSD. This work also emphasizes the need for future clinical trials to address the inadequacies identified in this review to optimize methodological quality. Key points: Bilateral repetitive transcranial magnetic stimulation (rTMS) and high‐frequency rTMS are considered top‐priority non‐invasive brain stimulation interventions for improving post‐stroke depression.Dual transcranial direct current stimulation and low‐frequency rTMS are also efficient.Clinical trials must optimize methodological quality by addressing the inadequacies identified in this review. [ABSTRACT FROM AUTHOR]

Aims: Muscleblind-like 2 (MBNL2) plays a crucial role in regulating alternative splicing during development and mouse loss of MBNL2 recapitulates brain phenotypes in myotonic dystrophy (DM). However, the mechanisms underlying DM neuropathogenesis during brain development remain unclear. In this study, we aim to investigate the impact of MBNL2 elimination on neuronal development by Mbnl2 conditional knockout (CKO) mouse models. Methods: To create Mbnl2 knockout neurons, cDNA encoding Cre-recombinase was delivered into neural progenitors of Mbnl2flox/flox mouse brains by in utero electroporation. The morphologies and dynamics of dendritic spines were monitored by confocal and two-photon microscopy in brain slices and live animals from the neonatal period into adulthood. To investigate the underlying molecular mechanism, we further detected the changes in the splicing and molecular interactions of proteins associated with spinogenesis. Results: We found that Mbnl2 knockout in cortical neurons decreased dendritic spine density and dynamics in adolescent mice. Mbnl2 ablation caused the adducin 1 (ADD1) isoform to switch from adult to fetal with a frameshift, and the truncated ADD1 failed to interact with alpha-II spectrin (SPTAN1), a critical protein for spinogenesis. In addition, expression of ADD1 adult isoform compensated for the reduced dendritic spine density in cortical neurons deprived of MBNL2. Conclusion: MBNL2 plays a critical role in maintaining the dynamics and homeostasis of dendritic spines in the developing brain. Mis-splicing of downstream ADD1 may account for the alterations and contribute to the DM brain pathogenesis. [ABSTRACT FROM AUTHOR]

Aims: Muscleblind‐like 2 (MBNL2) plays a crucial role in regulating alternative splicing during development and mouse loss of MBNL2 recapitulates brain phenotypes in myotonic dystrophy (DM). However, the mechanisms underlying DM neuropathogenesis during brain development remain unclear. In this study, we aim to investigate the impact of MBNL2 elimination on neuronal development by Mbnl2 conditional knockout (CKO) mouse models. Methods: To create Mbnl2 knockout neurons, cDNA encoding Cre‐recombinase was delivered into neural progenitors of Mbnl2flox/flox mouse brains by in utero electroporation. The morphologies and dynamics of dendritic spines were monitored by confocal and two‐photon microscopy in brain slices and live animals from the neonatal period into adulthood. To investigate the underlying molecular mechanism, we further detected the changes in the splicing and molecular interactions of proteins associated with spinogenesis. Results: We found that Mbnl2 knockout in cortical neurons decreased dendritic spine density and dynamics in adolescent mice. Mbnl2 ablation caused the adducin 1 (ADD1) isoform to switch from adult to fetal with a frameshift, and the truncated ADD1 failed to interact with alpha‐II spectrin (SPTAN1), a critical protein for spinogenesis. In addition, expression of ADD1 adult isoform compensated for the reduced dendritic spine density in cortical neurons deprived of MBNL2. Conclusion: MBNL2 plays a critical role in maintaining the dynamics and homeostasis of dendritic spines in the developing brain. Mis‐splicing of downstream ADD1 may account for the alterations and contribute to the DM brain pathogenesis.In Mbnl2‐knockout mouse model of myotonic dystrophy (DM), the density and dynamics of dendritic spines of cortical neurons were decreased during adolescence. Meanwhile, adducin 1 (ADD1) switched from adult to fetal isoform with a frameshift, causing the truncated ADD1 failing to interact with alpha‐II spectrin (SPTAN1), a critical protein for spinogenesis. Their roles in maintaining the dynamics and homeostasis of dendritic spines in the developing brain may underlie the neurological symptoms in DM patients. [ABSTRACT FROM AUTHOR]

Objective: Pathogenic variants in DCX on the X chromosome lead to lissencephaly and subcortical band heterotopia (SBH), brain malformations caused by neuronal migration defects. Its product doublecortin (DCX) binds to microtubules to modulate microtubule polymerization. How pathogenic DCX variants affect these activities remains not fully investigated. Methods: DCX variants were identified using whole exome and Sanger sequencing from six families with lissencephaly/SBH. We examined how these variants affect DCX functions using microtubule binding, regrowth, and colocalization assays. Results: We found novel DCX variants p.Val177AlafsTer31 and p.Gly188Trp, as well as reported variants p.Arg196His, p.Lys202Met, and p.Thr203Ala. Incidentally, all of the missense variants were clustered on the C‐terminal DCX domain. The microtubule binding ability was significantly decreased in p.Val177AlafsTer31, p.Gly188Trp, p.Lys202Met, and previously reported p.Asp262Gly variants. Furthermore, expression of p.Val177AlafsTer31, p.Gly188Trp, p.Arg196His, p.Lys202Met, and p.Asp262Gly variants hindered microtubule growth in cells. There were also decreases in the colocalization of p.Val177AlafsTer31, p.Thr203Ala, and p.Asp262Gly variants to microtubules. Significance: Our results indicate that these variants in the C‐terminal DCX domain altered microtubule binding and dynamics, which may underlie neuronal migration defects during brain development. [ABSTRACT FROM AUTHOR]

Bioluminescence has been hypothesized as aposematic signalling, intersexual communication and a predatory strategy, but origins and relationships among bioluminescent beetles have been contentious. We reconstruct the phylogeny of the bioluminescent elateroid beetles (i.e. Elateridae, Lampyridae, Phengodidae and Rhagophthalmidae), analysing genomic data of Sinopyrophorus Bi & Li, and in light of our phylogenetic results, we erect Sinopyrophoridae Bi & Li, stat.n. as a clicking elaterid‐like sister group of the soft‐bodied bioluminescent elateroid beetles, that is, Lampyridae, Phengodidae and Rhagophthalmidae. We suggest a single origin of bioluminescence for these four families, designated as the 'lampyroid clade', and examine the origins of bioluminescence in the terminal lineages of click beetles (Elateridae). The soft‐bodied bioluminescent lineages originated from the fully sclerotized elateroids as a derived clade with clicking Sinopyrophorus and Elateridae as their serial sister groups. This relationship indicates that the bioluminescent soft‐bodied elateroids are modified click beetles. We assume that bioluminescence was not present in the most recent common ancestor of Elateridae and the lampyroid clade and it evolved among this group with some delay, at the latest in the mid‐Cretaceous period, presumably in eastern Laurasia. The delimitation and internal structure of the elaterid‐lampyroid clade provides a phylogenetic framework for further studies on the genomic variation underlying the evolution of bioluminescence. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the feasibility of arthroplasty with varisized three‐dimensional(3D) printing lunate prosthesis for the treatment of advanced Kienböck's disease (KD). Methods: From 2016 November to 2018 September, a retrospective study was performed for the patients of KD in our hospital. Five patients (two males, three females) were included in this study. The mean age of the patients at the time of surgery was 51.6 years (range, 37–64 years). Varisized prosthesis identical to the live model in a ratio of 1:0.85, 1:1, and 1:1.1 were fabricated by 3D printing. All patients (one in Lichtman IIIA stage, two in Lichtman IIIB stage, one in Lichtman IIIC stage, and one in Lichtman IV stage) were treated with lunate excision and 3D printing prosthetic arthroplasty. Visual analog scale score (VAS), the active movement of wrist (extension, flexion) and strength were assessed preoperatively and postoperatively. The Mayo Modified Wrist Score (MMWS), Disabilities of the Arm, Shoulder and Hand (DASH) Score, and patient's satisfaction were evaluated during the follow‐up. Results: Prosthesis identical to the live model in a ratio of 1:0.85 or 1:1 were chosen for arthroplasty. The mean operation time (range, 45 to 56 min) was 51.8 ± 4.44 min. Follow‐up time ranged from 11 months to 33 months with the mean value of 19.4 months. The mean extension range of the wrist significantly increased from preoperative 44° ± 9.6° to postoperative 60° ± 3.5° (P < 0.05). The mean flexion range of the wrist significantly increased from preoperative 40° ± 10.6° to postoperative 51° ± 6.5° (P < 0.05). The active movement of wrist and strength were improved significantly in all patients. VAS was significantly reduced from 7.3 preoperatively to 0.2 at the follow‐up visit (P < 0.05). The mean DASH score was 10 (range, 7.2–14.2), and the mean MMWS was 79 (range, 70–90). There were no incision infection. All patients were satisfied with the treatment. Conclusions: For patients suffering advanced Kienböck's disease, lunate excision followed by 3D printing prosthetic arthroplasty can reconstruct the anatomical structure of the carpal tunnel, alleviate pain, and improve wrist movement. [ABSTRACT FROM AUTHOR]

In mammals, microRNAs can be actively secreted from cells to blood. miR‐29b‐3p has been shown to play a pivotal role in muscle atrophy, but its role in intercellular communication is largely unknown. Here, we showed that miR‐29b‐3p was upregulated in normal and premature aging mouse muscle and plasma. miR‐29b‐3p was also upregulated in the blood of aging individuals, and circulating levels of miR‐29b‐3p were negatively correlated with relative appendicular skeletal muscle. Consistently, miR‐29b‐3p was observed in exosomes isolated from long‐term differentiated atrophic C2C12 cells. When C2C12‐derived miR‐29b‐3p‐containing exosomes were uptaken by neuronal SH‐SY5Y cells, increased miR‐29b‐3p levels in recipient cells were observed. Moreover, miR‐29b‐3p overexpression led to downregulation of neuronal‐related genes and inhibition of neuronal differentiation. Interestingly, we identified HIF1α‐AS2 as a novel c‐FOS targeting lncRNA that is induced by miR‐29b‐3p through down‐modulation of c‐FOS and is required for miR‐29b‐3p‐mediated neuronal differentiation inhibition. Our results suggest that atrophy‐associated circulating miR‐29b‐3p may mediate distal communication between muscle cells and neurons. [ABSTRACT FROM AUTHOR]

Background and Aims: Heat shock factor (HSF4) plays a vital role in carcinogenesis and tumour progression. However, its clinical significance implications in hepatocellular carcinoma (HCC) remained elusive. Methods: RT‐PCR and western blot were used to detect the HSF4 expression levels in HCC cells and tissues. Immunohistochemistry staining was performed on a tissue microarray containing 104 HCC patients received radical resection. In vitro effects of HSF4 on proliferation, migration and invasion were determined by colony formation and transwell assays in HCCLM3, Huh7, MHCC97L and SMMC7721 cells. Epithelial‐mesenchymal transition (EMT) was identified by RT‐PCR, WB and immunofluorescence in HCCLM3 and MHCC97L cells. AKT pathway activation was detected by WB and dual luciferase report system in HCCLM3 and MHCC97L cells. Results: HSF4 expression was higher in primary HCC tissues derived from recurrent patients, and positively correlated with invasiveness potentials of cell lines. Clinically, patients with high HSF4 expression had significant poorer prognosis. In vitro experiments showed HSF4 silencing inhibited HCC cell proliferation, migration and invasion, whereas HSF4 overexpression had inverse effects. Moreover, silence of HSF4 induced an epithelial‐like phenotype, whereas the overexpression of HSF4 resulted in a mesenchymal‐like phenotype in HCC by activating AKT pathway. Further experiments showed that HSF4 could activate AKT pathway in a hypoxia‐inducible factor‐1α (HIF‐1α) dependent, but transforming growth factor‐β (TGF‐β) independent manner. Conclusions: HSF4 is upregulated in HCC, resulting in greater proliferation, migration and invasion capacities. Moreover, high HSF4 expression is a promising predictive indicator of poor outcome after radical resection. HSF4 may promote aggressive tumour behaviour by enhancing EMT through activating AKT pathway in a HIF1α‐dependent manner. [ABSTRACT FROM AUTHOR]

The pH‐insensitive beetle luciferases cloned from Rhagophthalmidae, Phengodidae, and Elateridae exhibit great potential application as reporter assays for monitoring gene expression. At present, however, only one luciferase has been reported from the enigmatic and predominantly Asian distributed luminous family Rhagophthalmidae. Here, we cloned the second rhagophthalmid luciferase from the Chinese glow‐worm Menghuoius giganteus (Rhagophthalmidae: Elateroidea) by combining reverse transcription polymerase chain reaction (RT‐PCR) with rapid amplification of complementary DNA ends (RACE). The luciferase consisted of 546 amino acids and showed high identity to that of Rhagophthalmus ohbai (90.4%). The recombinant M. giganteus luciferase was produced in vitro and exhibited significant bioluminescent activity under neutral conditions (pH 7.8), with low KM for D‐luciferin (2.2 μm) and ATP (53 μm). Activity was highest at 10°C and inactivation occurred at 45°C. This luciferase showed pH‐insensitivity and maximum emission spectrum at 560 nm. Phylogenetic analyses based on the deduced amino acids indicated a close relationship between the M. giganteus luciferase and that of R. ohbai. These results increase our understanding of rhagophthalmid luciferases and provide a new resource for the application of luciferases. [ABSTRACT FROM AUTHOR]

Lamprigera (Lampyridae) is a small genus with only 17 species distributing in Asian countries. Its larviform females and alate males can produce continuously strong yellow‐green light at night. However, no luciferase gene was reported for this genus and its subfamily‐level phylogenetic position still remains uncertain. Here, we cloned the luciferase gene from one Chinese species, Lamprigera yunnana, by reverse transcription‐polymerase chain reaction (RT‐PCR) and rapid amplification of cDNA ends (RACE). This luciferase includes 551 deduced amino acids (AA) with the sequence identity of 71.8–76.8%, 67.5–70.7%, 68.4–75.3%, 77.8% and 59.5% to those from Lampyrinae, Luciolinae, Ototretinae, Cyphonocerinae and Photurinae, respectively. Phylogenetic analyses of deduced AA of luciferases suggest that Lamprigera locates outside Lampyrinae, in which it was originally placed in traditional taxonomy. The luciferase was produced in vitro as recombinant protein, and its biochemical properties were characterized. It possesses significant luminescence activity at pH 7.8, and its KM for D‐luciferin and ATP are 61 μm and 122 μm, respectively. It shows the highest activity at 37°C and is completely inactivated at 55°C. It is pH‐sensitive with the maximum emission spectrum of 566 nm at pH 7.8. Our data provide new insights into Lamprigera luciferase and its phylogenetic position. [ABSTRACT FROM AUTHOR]

Summary: Objective: Variants in human PRRT2 cause paroxysmal kinesigenic dyskinesia (PKD) and other neurological disorders. Most reported variants resulting in truncating proteins failed to localize to cytoplasmic membrane. The present study identifies novel PRRT2 variants in PKD and epilepsy patients and evaluates the functional consequences of PRRT2 missense variations. Methods: We investigated two families with PKD and epilepsies using Sanger sequencing and a multiple gene panel. Subcellular localization of mutant proteins was investigated using confocal microscopy and cell surface biotinylation assay in Prrt2‐transfected cells. Results: Two novel PRRT2 variants, p.His232Glnfs*10 and p.Leu298Pro, were identified, and functional study revealed impaired localization of both mutant proteins to the plasma membrane. Further investigation of other reported missense variants revealed decreased protein targeting to the plasma membrane in eight of the 13 missense variants examined (p.Trp281Arg, p.Ala287Thr, p.Ala291Val, p.Arg295Gln, p.Leu298Pro, p.Ala306Asp, p.Gly324Glu, and p.Gly324Arg). In contrast, all benign variants we tested exhibited predominant localization to the plasma membrane similar to wild‐type Prrt2. Most likely pathogenic variants were located at conserved amino acid residues near the C‐terminus, whereas truncating variants spread throughout the gene. Significance: PRRT2 missense variants clustering at the C‐terminus often lead to protein mislocalization. Failure in protein targeting to the plasma membrane by PRRT2 variants may be a key mechanism in causing PKD and related neurological disorders. [ABSTRACT FROM AUTHOR]

An iridescent chameleon-like material that can change its colors under different circumstances is always desired in color-on-demand applications. Herein, a strategy based on trichromacy and the dynamically tunable fluorescence resonance energy transfer (FRET) process to design and prepare these chameleon-like fluorescent materials is proposed. A set of trichromic (red, green, and blue), solid fluorescent materials are synthesized by covalently attaching spiropyran, fluorescein, and pyrene onto cellulose chains independently. After simply mixing them together, a full range of color is realized. The chameleon-like nature of these materials is based on the dynamic tunable FRET process between donors (green and blue) and acceptors (red) in which the energy transfer efficiency can be finely tuned by irradiation. Ultimately, the reversible and nonlinear regulation of fluorescence properties, including color and intensity, is achieved on a timescale recognizable by the naked eye. Benefited by the excellent processability inherited from the cellulose derivatives, the as-prepared materials are feasibly transformed into different forms. Particularly, a fluorescent ink with the complicated fluorescent input-output dependence suggests more than a proof-of-concept; indeed, it suggests a unique method of information encryption, security printing, and dynamic anticounterfeiting. [ABSTRACT FROM AUTHOR]

The cover image is based on the Original Article Muscleblind‐Like 2 knockout shifts adducin 1 isoform expression and alters dendritic spine dynamics of cortical neurons during brain development by Chia‐Wei Huang et al., https://doi.org/10.1111/nan.12890. [ABSTRACT FROM AUTHOR]

In China, a large burden of gastric cancer has remained, and endoscopic screening was expected to reduce gastric cancer mortality. Therefore, a population-based case-control study was conducted to evaluate the screening effect. The gastric cancer screening program was initiated in Linzhou in the year 2005, and endoscopic examination with indicative biopsy, for residents aged 40-69 years, was used to detect early cancer and precancerous lesion. In this study, cases were defined as individuals who had died of gastric cancer, which were selected from Linzhou Cancer Registry database. Controls were residents (six per case), who had not died of gastric cancer, from the same area as the case, and matched by gender and age (±2 years). The exposure status, whether cases and controls ever attended the screening or not, was acquired by inspecting the well-documented screening records. Conditional logistic regression model was used to estimate the odds ratios ( OR) and their 95% confidence intervals (95% CI). A total of 313 cases and 1876 controls were included in our analysis. Compared with subjects who never participated in screening, the overall OR for individuals who ever participated in screening was 0.72(95% CI: 0.54-0.97). The OR for lag time 4 years or longer was 0.68(95% CI: 0.47-0.98) and the OR for those who were aged 50-59 years were 0.56 (0.37-0.85). The results suggest a 28% reduction in risk of gastric cancer mortality by endoscopic screening, which may have significant implications for gastric cancer screening in rural areas of China. [ABSTRACT FROM AUTHOR]

In the cold strip rolling process, tension plays a great role in the stability of rolling, reduction of rolling force and power consumption, coordination of thickness control, and improvement of flatness quality. The correcting and attenuating effect of tension on flatness deviation is gradually revealed, but quantitative analysis of their inherent effect is still insufficient. Thus, a roll-strip-tension coupling model with both accuracy and efficiency was established to analyze the influence of tension on flatness deviation. In the model, a strip plastic deformation model based on a 3-dimensional differential method was corrected by a strip transverse flow factor obtained by an finite element method simulation model and was consequently combined with a rolls elastic deformation model based on the influence function method and the tension calculation module. By the coupling model, the mechanism of the self-correction effect of front tension and the attenuation effect of back tension on flatness deviation was further discussed, and the calculation results of the corresponding correction coefficient and attenuation coefficient were obtained. The present paper brings more insight into the effect of tension on flatness, and lays a foundation for the optimization of the shape control model in the cold rolling process with tension. [ABSTRACT FROM AUTHOR]

Abstract: Caenorhabditis elegans microRNAs (miRNAs) bind to partially complementary sequences in the 3′ untranslated region of target mRNAs, resulting in translational repression through mRNA destabilization. High-throughput sequencing of RNA cleavage fragments was performed to directly detect miRNA-directed cleavage targets in adult stage C. elegans. From this analysis, we found that miR-249 directed the cleavage of the ZK637.6 transcript with extensive and evolutionarily conserved complementarity in nematode. In addition, expression of the ZK637.6 transcript was strongly dependent on the expression of miR-249. These findings may lead to a better understanding of miRNA-mediated gene regulation in nematodes. [Copyright &y& Elsevier]

The goal of this study was to develop an aggressive running regimen for modeling osteoarthritis (OA) in rats. Twelve Wistar rats were randomly placed into either a running group or a non-running group to serve as the control. The running rats used a motorized treadmill to run either 30 km in 3 weeks or 55 km in 6 weeks. Each week, the prints of hind paws were obtained when rats were made to walk through a tunnel. The resulting prints were digitalized for analyses of stride length and step angle. The histology of the knees was examined at 3 and 6 weeks and the OA pathology in the knees was quantified by Mankin's score. Osteoarthritic pathology developed in the knees of the running rats, including decreased proteoglycan content, uneven type II collagen distribution in the cartilage matrix, increased MMP-13 expression, expanded calcified cartilage zone, and clefts and defects in articular cartilage. The pathology worsened from running for 3 to 6 weeks. Gait analysis revealed an inverse correlation between paw angle and the grades of OA pathology. In conclusion, excessive running induces joint degeneration and a unique gait pattern in rats. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1604-1610, 2012 [ABSTRACT FROM AUTHOR]

Single crystalline anatase TiO2 tetragonal nanosheet-array film on a transparent conductive fluorine-doped tin oxide (FTO) substrate was successfully prepared by hydrothermal method. The products were characterized with XRD, SEM, and transmission electron microscopy measurements. The formation mechanism of the tetragonal (001) TiO2 nanosheets is discussed and the effect of growth parameters, such as acidity, growth time, growth temperature, initial reactant concentration, and additives, are investigated. This work demonstrates a clean and effective route to the morphology-controlled preparation of large area single-crystalline TiO2 nanostructured array films on FTO glass. [ABSTRACT FROM AUTHOR]

Matrine and oxymatrine are the major bioactive compounds extracted from the root of Sophora flavescens Ait, which have been widely used in traditional Chinese medicines. The objective of the study was to investigate the effects of matrine or oxymatrine on hepatic cytochrome P450 (CYP450) and the underlying molecular mechanisms. Matrine (15, 75 and 150 mg/kg) or oxymatrine (36, 180 and 360 mg/kg) was administered to rats for 14 days and the activities of CYP450 were measured by the quantification of the metabolites from multiple CYP450 probe substrates, using validated liquid chromatography coupled with liquid chromatography-tandem mass spectrometry detection (LC-MS/MS) and high-performance liquid chromatography methods. The mRNA and protein expression levels of CYPs were determined by quantitative real-time reverse-transcription polymerase chain reaction and Western blotting analysis respectively. Interactions between matrine or oxymatrine and human constitutive androstane (CAR), pregnane X receptor were evaluated by means of the reporter gene assay in CV-1 cells. Our study showed that matrine and oxymatrine significantly induced the activity and gene expression of CYP2B1 in a dose-dependent manner; matrine (150 mg/kg) slightly induced the mRNA and protein expression of CYP2E1 and mildly inhibited the mRNA and protein expression of CYP3A1 in rats. Matrine or oxymatrine could activate human CAR and induce the CYP2B reporter construct in CV-1 cells. These results reveal that matrine and oxymatrine can induce the activity and expression of CYP2B1/2 in rats, and the underlying mechanism may be related to the activation of CAR. [ABSTRACT FROM AUTHOR]

Hybridization-based and sequencing-based technologies have found a widespread application in gene expression profiling analysis but much ambiguity exists regarding their reliability. This study developed a framework based on three parameters: detection ability, repeatability, and accuracy to evaluate the reliability of gene expression profiling technologies. The fraction of coverage of detected transcript category, the degree of variance for the number of differentially expressed genes (DEGs), the consistency of DEG category, and suspected false discovery rate (sFDR) were first introduced as statistical indices. In order to validate the availability of these indices, based on the same RNA extract, the analysis was performed by comparing gene expression differences between wild-type and transgenic rice using deep sequencing and microarray. The results suggested that the parameters were available and showed advances in the determination of gene expression differences. Based on relative self-comparison design, suspected false positive genes were easily identified from all DEGs detected, which was difficult for quantitative real-time polymerase chain reaction (qRT-PCR) validation when the count of DEGs was enormous. In addition, sFDRs had advantages in the accuracy evaluation for previous datasets. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [ABSTRACT FROM AUTHOR]

Using X-ray fluorescent computed tomography (XFCT), the in vivo and ex vivo cerebral distribution of a stable-iodine-labeled cerebral perfusion agent, iodoamphetamine analog (127I-IMP), has been recorded in the brains of mice. In vivo cerebral perfusion in the cortex, hippocampus and thalamus was depicted at 0.5 mm in-plane spatial resolution. Ex vivo XFCT images at 0.25 mm in-plane spatial resolution allowed the visualisation of the detailed structures of these regions. The quality of the XFCT image of the hippocampus was comparable with the 125I-IMP autoradiogram. These results highlight the sensitivity of XFCT and its considerable potential to evaluate cerebral perfusion in small animals without using radioactive agents. [ABSTRACT FROM AUTHOR]

Aim: Low-molecular-weight heparin (LMWH) is a negatively charged glycoprotein and has a very similar structure to that of cell surface heparin sulfate (HS). Thus, LMWH, an analog of HS, may inhibit positively charged respiratory syncytial virus (RSV) infection through cooperative electrostatic association. Methods: In this study, rats were respectively treated with 400 IU/kg LMWH before, during or after being inoculated with 6 × 106 plaque-forming unit (PFU) RSV. RSV and normal control groups were respectively inoculated by RSV and virus-free Dulbecco's modified Eagle's medium (DMEM). HeLa cells in vitro were pretreated with LMWH, elastase (ELA), heparinase (HpaIII) and protamine before being inoculated with 6 × 101 PFU RSV. RSV infectivity was determined by in situ hybridization and plaque assay. Results: After inoculation, the urinary protein excretion and serum parameters in LMWH-treated rats were significantly lower than those in the RSV group. No abnormalities of glomerular structure were observed in LMWH-treated groups whereas swelling and slight hypercellularity in minority glomeruli and foot process effacement were observed in the RSV group. RSV RNA of LMWH-treated rats had weaker expression than that of the RSV group. In vitro, RSV infection in RSV + LMWH, HpaIII + ELAI, protamine + ELAI, ELAI, HpaIII and protamine treatment cells were significantly lower than that of the RSV control, and that in RSV + LMWH was the least. There were no significant differences in RSV infection between ELAI + LMWH and RSV control. Conclusion: Our study confirmed that there is a correlation between RSV and proteinuria in rats. LMWH can alleviate proteinuria in rats through inhibiting RSV from binding with HS which plays an important role in the onset of RSV infection. [ABSTRACT FROM AUTHOR]

Fluorescent X-ray computed tomography (FXCT) enables visualization of myocardial fatty acid metabolism by using non-radio-iodinated I-5-(p-iodophenyl)-3-(R,S)-methylpentadecanoice acid (BMIPP). In this experiment, age- dependent myocardial metabolic impairment was successfully imaged and analyzed quantitatively in J2N-k cardiomyopathic hamster using FXCT. [ABSTRACT FROM AUTHOR]

Chitinases (EC 3.2.1.14) are found in a broad range of organisms, including bacteria, fungi and higher plants, and play different roles depending on their origin. A chitinase from Bacillus cereus NCTU2 (ChiNCTU2) capable of hydrolyzing chitin as a carbon and nitrogen nutrient has been identified as a member of the family 18 glycoside hydrolases. ChiNCTU2 of molecular weight 36 kDa has been crystallized using the hanging-drop vapour-diffusion method. According to the diffraction of chitinase crystals at 1.10 Å resolution, the crystal belongs to space group P21, with unit-cell parameters a = 50.79, b = 48.79, c = 66.87 Å, β = 99.31°. Preliminary analysis indicates there is one chitinase molecule in the asymmetric unit, with a solvent content of 43.4%. [ABSTRACT FROM AUTHOR]

Signaling through tumor necrosis factor receptor 2 (TNF-R2) results in ubiquitination of TRAF2 by the E3 c-IAP1. In this report, we confirm that TRAF2 translocates to a Triton X-100 (TX)-insoluble compartment upon TNF-R2 engagement. Moreover, TRAF2 ubiquitination occurs in this compartment, from which TRAF2 is degraded in a proteasome-dependant manner. Confocal microscopy demonstrated that the TX-insoluble compartment is perinuclear and co-localizes with endoplasmic reticulum (ER) markers. The ER transmembrane Ubc6 bound to c-IAP1 and served as a cognate E2 for c-IAP1's E3 activity in vitro. Furthermore, Ubc6 co-localized with translocated TRAF2/c-IAP1 in the ER-associated compartment in vivo, and a catalytically inactive Ubc6 mutant inhibited TNF-a-induced, TNF-R2-dependent TRAF2 degradation. These results indicate that upon TNF-R2 signaling, translocation of TRAF2 and c-IAP1 to an ER-associated, Ubc6-containing perinuclear compartment is required for the ubiquitination of TRAF2 by c-IAP1. Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus type 1 (HIV-1) protease hydrolysis of the Gag CA-p2 cleavage site is crucial for virion maturation and is optimal at acidic pH. To understand the processing of the CA-p2 site, we have determined the structure of HIV-1 protease complexed with an analog of the CA-p2 site, the reduced peptide inhibitor Arg-Val-Leu-r-Phe-Glu-Ala-Ahx-NH2 [r denotes the reduced peptide bond and Ahx 2-aminohexanoic acid (norleucine), respectively]. The crystal structure was refined to an Rfactor of 0.17 ,at 0.21-nm resolution. The crystals have nearly the same lattice as related complexes in P212121 which have twofold disordered inhibitor, but are in space group P21, and the asymmetric unit contains two dimers of HIV-1 protease related by 180° rotation. An approximate non-crystallographic symmetry has replaced the exact crystal symmetry resulting in well-ordered inhibitor structure. Each protease dimer binds one ordered inhibitor molecule, but in opposite orientations. The interactions of the inhibitor with the two dimers are very similar for the central P2 Val to P2' Glu residues, but show more wariation for the distal P3 Arg and P4' Ahx residues. Importantly, the carboxylate oxygens of Glu at P2' in the inhibitor are within hydrogen-bonding distance of a carboxylate oxygen of Asp30 of the protease suggesting that the two side chains share a proton. This interaction suggests that the enzyme-substrate complex is additionally stabilized at lower pH. The importance of this interaction is emphasized by the absence of polymorphisms of Asp30 in the protease and variants of P2' Glu in the critical CA-p2 cleavage site. [ABSTRACT FROM AUTHOR]

To broaden the scope of phase-contrast X-ray imaging in biomedical applications, the energy of X-rays in a large-area imaging system using a two-crystal X-ray interferometer has been increased from 17.7 keV to 35 keV. The use of higher-energy X-rays makes it possible to observe larger samples having greater variation in density within shorter measurement periods, at higher spatial resolution, and at lower X-ray doses. After optimizing the imaging system for 35 keV X-rays, a 25 mm ⊗ 30 mm interference pattern with 50% visibility was generated at the Photon Factory. The system's capabilities are demonstrated by this pattern and a high-quality three-dimensional image of a rat heart. [ABSTRACT FROM AUTHOR]

A diagram is presented of thiadiazole derivatives from thiomides using molecular oxygen as oxidant.