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Photosynthesis is a process that uses solar energy to fix CO2 in the air and converts it into sugar, and ultimately powers almost all life activities on the earth. C3 photosynthesis is the most common form of photosynthesis in crops. Current efforts of increasing crop yields in response to growing global food requirement are mostly focused on improving C3 photosynthesis. In this review, we summarized the strategies of C3 photosynthesis improvement in terms of Rubisco properties and photorespiratory limitation. Potential engineered targets include Rubisco subunits and their catalytic sites, Rubisco assembly chaperones, and Rubisco activase. In addition, we reviewed multiple photorespiratory bypasses built by strategies of synthetic biology to reduce the release of CO2 and ammonia and minimize energy consumption by photorespiration. The potential strategies are suggested to enhance C3 photosynthesis and boost crop production.

Objective. To explore the effects of different intervention methods on intestinal cleanliness in children undergoing colonoscopy. Methods. 61 children who underwent colonoscopy in our hospital from May 2020 to May 2021 were randomly divided into group A (n = 21), group B (n = 30), and group C (n = 10). The children in the three groups were intervened in different ways before the colonoscopy. Group A received a long-handled Kaiselu +1 cathartic intervention, while group B received a long-handled Kaiselu +2 cathartic intervention, and group C received an enema plus one cathartic intervention. The patients in the three groups were given the same diet before the examination until the examination was completed. The time-related indexes, cleanliness, adverse reactions, tolerance, and adaptability of the three groups under different dietary interventions and cleaning methods were evaluated. Results. The first defecation time in group C was lower than that in group A and group B, the hospital stay was longer than that in group A and group B (p>0.05), and the colonoscopy time in group C was shorter than that in group A and group B (p<0.05). The BBPS score of group C was (2.10 ± 0.32), which was significantly higher than that of group A (1.16 ± 0.19) and group B (1.77 ± 0.18) (p<0.05). The BBPS scores of children with liquid food in the three groups were significantly higher than those of common food, and the BBPS scores of liquid food and common food in group C were significantly higher than those in group A and group B (p<0.05). The incidence of adverse reactions in group C was 20.00%, which was significantly lower than 33.33% in group A and 23.33% in group B (p<0.05). The proportion of grade I in group C was 50.00%, which was significantly higher than 38.10% in group A and 43.33% in group B (p<0.05). Conclusion. Children undergoing colonoscopy take preintestinal preparation under different diets and intervention methods. The cleanliness of liquid food and enema + one-time laxative one day before colonoscopy is the best, which can significantly reduce adverse reactions and increase the acceptability and adaptability of children. It is worthy of clinical application.

Driver gaze zone estimation is an important task in Advanced Driver Assistance Systems (ADAS), which suffers difficulties including head pose, capture direction, glass occlusion, and real-time requirement, etc. Most previous methods combine face modalities and head pose using concat process, which may result in over-fitting due to the unbalanced dimension. Focusing on gaze zone estimation problems, we propose the Head Pose Fusion Assisted supervision & Eye Region Weighted Encoding (HP-ERW) structure, which fuses head pose attribute and face modalities together through spatial attention and Kronecker product mechanisms. Firstly, we introduce a pre-processing module dealing with head pose and face information, with the purpose of extracting input vectors and improving the fusion speed of the HP-ERW structure. Secondly, an Eye Region Weighted Encoding Network (ERW-Net) based on spatial attention is proposed to strengthen the networks perception ability for encoding features. Finally, we propose a dual-channel Head Pose Fusion Network (HP-Net) based on the Kronecker product mechanism, with the purpose of fusing head pose and improving the estimation accuracy. Experiments show that the HP-ERW outperforms compared existing methods on several public datasets. The designed ADAS using the proposed method achieves 23.5 fps real-time application with small memory requirement of 4,884 KB.

Current imaging approaches used to monitor tumor progression can lack the ability to distinguish true progression from pseudoprogression. Simultaneous metabolic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI) offers new opportunities to overcome this challenge by refining tumor identification and monitoring therapeutic responses to cancer immunotherapy. In the current work, spatial and quantitative analysis of tumor burden were performed using simultaneous [18F]FDG-PET/MRI to monitor therapeutic responses to a novel silicified cancer cell immunotherapy in a mouse model of disseminated serous epithelial ovarian cancer. Tumor progression was validated by bioluminescence imaging of luciferase expressing tumor cells, flow cytometric analysis of immune cells in the tumor microenvironment, and histopathology. While PET demonstrated the presence of metabolically active cancer cells through [18F]FDG uptake, MRI confirmed cancer-related accumulation of ascites and tissue anatomy. This approach provides complementary information on disease status without a confounding signal from treatment-induced inflammation. This work provides a possible roadmap to facilitate accurate monitoring of therapeutic responses to cancer immunotherapies.

Hemorrhagic stroke is a leading cause of death. The causes of intracerebral hemorrhage (ICH)-induced brain damage are thought to include lysis of red blood cells, hemin release and iron overload. These mechanisms, however, have not proven very amenable to therapeutic intervention, and so other mechanistic targets are being sought. Here we report that accumulation of endogenously formed zinc protoporphyrin (ZnPP) also critically contributes to ICH-induced brain damage. ICH caused a significant accumulation of ZnPP in brain tissue surrounding hematoma, as evidenced by fluorescence microscopy of ZnPP, and further confirmed by fluorescence spectroscopy and supercritical fluid chromatography-mass spectrometry. ZnPP formation was dependent upon both ICH-induced hypoxia and an increase in free zinc accumulation. Notably, inhibiting ferrochelatase, which catalyzes insertion of zinc into protoporphyrin, greatly decreased ICH-induced endogenous ZnPP generation. Moreover, a significant decrease in brain damage was observed upon ferrochelatase inhibition, suggesting that endogenous ZnPP contributes to the damage in ICH. Our findings reveal a novel mechanism of ICH-induced brain damage through ferrochelatase-mediated formation of ZnPP in ICH tissue. Since ferrochelatase can be readily inhibited by small molecules, such as protein kinase inhibitors, this may provide a promising new and druggable target for ICH therapy.

We previously showed that newly formed vessels in ischemic rat brain have high blood-brain barrier (BBB) permeability at 3 weeks after stroke due to a lack of major endothelial tight junction proteins (TJPs), which may exacerbate edema in stroke patients. Atorvastatin was suggested a dose-dependent pro-angiogenic effect and ameliorating BBB permeability beyond its cholesterol-lowering effects. This study examined our hypothesis that, during vascular remodeling after stroke, treatment with atorvastatin could facilitate BBB maturation in remodeling vasculature in ischemic brain. Adult spontaneously hypertensive rats underwent middle cerebral artery occlusion with reperfusion (MCAO/RP). Atorvastatin, at dose of 3 mg/kg, was delivered daily starting at 14 days after MCAO/RP onset for 7 days. The rats were studied at multiple time points up to 8 weeks with multimodal-MRI, behavior tests, immunohistochemistry, and biochemistry. The delayed treatment of atorvastatin significantly reduced infarct size and BBB permeability, restored cerebral blood flow, and improved the neurological outcome at 8 weeks after MCAO/RP. Postmortem studies showed that atorvastatin promoted angiogenesis and stabilized the newly formed vessels in peri-infarct areas. Importantly, atorvastatin facilitated maturation of BBB properties in the new vessels by promoting endothelial tight junction (TJ) formation. Further in vivo and in vitro studies demonstrated that proliferating peri-vascular pericytes expressing neural-glial antigen 2 (NG2) mediated the role of atorvastatin on BBB maturation through regulating endothelial TJ strand formations. Our results suggested a therapeutic potential of atorvastatin in facilitating a full BBB integrity and functional stroke recovery, and an essential role for pericyte-mediated endothelial TJ formation in remodeling vasculature.

Microglial/macrophage activation plays a dual role in response to brain injury after a stroke, promoting early neuroinflammation and benefit for neurovascular recovery. Therefore, the dynamics of stroke-induced cerebral microglial/macrophage activation are of substantial interest. This study used novel anti-Iba-1-targeted superparamagnetic iron–platinum (FePt) nanoparticles in conjunction with magnetic resonance imaging (MRI) to measure the spatiotemporal changes of the microglial/macrophage activation in living rat brain for four weeks post-stroke. Ischemic lesion areas were identified and measured using T2-weighted MR images. After injection of the FePt-nanoparticles, T2*-weighted MR images showed that the nanoparticles were seen solely in brain regions that coincided with areas of active microglia/macrophages detected by post-mortem immunohistochemistry. Good agreement in morphological and distributive dynamic changes was also observed between the Fe+-cells and the Iba-1+-microglia/macrophages. The spatiotemporal changes of nanoparticle detected by T2*-weighted images paralleled the changes of microglial/macrophage activation and phenotypes measured by post-mortem immunohistochemistry over the four weeks post-stroke. Maximum microglial/macrophage activation occurred seven days post-stroke for both measures, and the diminished activation found after two weeks continued to four weeks. Our results suggest that nanoparticle-enhanced MRI may constitute a novel approach for monitoring the dynamic development of neuroinflammation in living animals during the progression and treatment of stroke.

Tauopathies, including frontotemporal dementia (FTD) and Alzheimer’s disease (AD) are progressive neurodegenerative diseases clinically characterized by cognitive decline and could be caused by the aggregation of hyperphosphorylated pathological tau (pTau) as neurofibrillary tangles (NFTs) inside neurons. There is currently no FDA-approved treatment that cures, slows or prevents tauopathies. Current immunotherapy strategies targeting pTau have generated encouraging data but may pose concerns about scalability, affordability, and efficacy. Here, we engineered a virus-like particle (VLP)-based vaccine in which tau peptide, phosphorylated at threonine 181, was linked at high valency to Qß bacteriophage VLPs (pT181-Qß). We demonstrate that vaccination with pT181-Qß is sufficient to induce a robust and long-lived anti-pT181 antibody response in the sera and the brains of both Non-Tg and rTg4510 mice. Only sera from pT181-Qß vaccinated mice are reactive to classical somatodendritic pTau in human FTD and AD post-mortem brain sections. Finally, we demonstrate that pT181-Qß vaccination reduces both soluble and insoluble species of hyperphosphorylated pTau in the hippocampus and cortex, avoids a Th1-mediated pro-inflammatory cell response, prevents hippocampal and corpus callosum atrophy and rescues cognitive dysfunction in a 4-month-old rTg4510 mouse model of FTD. These studies provide a valid scientific premise for the development of VLP-based immunotherapy to target pTau and potentially prevent Alzheimer’s diseases and related tauopathies., Tauopathies: Active vaccination of mouse tauopathy Tauopathies such as fronto-temporal dementia or Alzheimer’s disease are characterized by the accumulation of phosphorylated Tau (pTau) protein into pathogenic neurofibrillary tangles (NFT). Kiran Bhaskar and colleagues at the University of New Mexico investigate the efficacy of an active vaccine approach in the treatment of rTg4510 mice—an aggressive model of tauopathy. Mice receive 3 intramuscular doses of a disease-relevant pTau peptide (pT181) multivalently conjugated to an immunostimulatory bacteriophage virus-like particle (pT181-Qß). Vaccination induces high titers of anti-pTau—stable to at least 20 weeks—that is also able to bind human disease samples, but importantly does not react to unphosphorylated physiological Tau protein. Antibody can enter the brain and bind both soluble and intraneuronal pTau. Vaccination of mice reduces brain NFT, pathology, indicators of neuroinflammation and improves cognitive function in two different models of memory.

Photon counting x-ray detectors (PCDs) with energy discrimination capabilities provide spectral information, can eliminate electronic and Swank noise, and image multiple contrast agents simultaneously with high resolution. However, with high flux on the detectors, pulse pileup leads to count loss and spectral distortion. Accurate description of the output count rate and spectrum behavior of a PCD is crucial to the development of further applications, e.g., material decomposition. In this work, a fully analytical model of the pulse pileup spectrum and count statistics for a nonparalyzable detector with nonzero pulse length is proposed, which accounts for seminonparalyzable behavior, i.e., retriggering of counts by pulses incident during the dead time. We use a triangle to approximate a realistic pulse shape and recursively compute the output spectrum of different pulse pileup orders. A count-rate and spectrum dependent expression of count statistics is further derived based on renewal theory. Our analytical model can then be used to predict material decomposition noise using the Cramer–Rao lower bound (CRLB). We compared our model predictions with Monte Carlo simulations. The results show that our model can accurately predict the count loss and spectral distortion resulting from pulse pileup and can be used in predicting material decomposition noise over a large range of count rates.

Significance Tuberous sclerosis complex (TSC) is caused by mutations in TSC1 or TSC2 gene and affects multiple organs, including the kidney, where it presents with angiomyolipomata and cysts that can result in kidney failure. The factors promoting cyst formation and tumor growth in TSC are incompletely understood. Current studies demonstrate that kidney cyst epithelia in TSC mouse models and in humans with TSC are composed of hyperproliferating intercalated cells, along with activation of H+-ATPase and carbonic anhydrase 2. Interfering with intercalated cell proliferation completely inhibited and inactivating carbonic anhydrase 2 significantly protected against cyst formation in TSC. Targeting the acid base and/or electrolyte transporters of intercalated cells may provide a therapeutic approach for the treatment of kidney cysts in TSC., Tuberous sclerosis complex (TSC) is caused by mutations in either TSC1 or TSC2 genes and affects multiple organs, including kidney, lung, and brain. In the kidney, TSC presents with the enlargement of benign tumors (angiomyolipomata) and cysts, which eventually leads to kidney failure. The factors promoting cyst formation and tumor growth in TSC are incompletely understood. Here, we report that mice with principal cell-specific inactivation of Tsc1 develop numerous cortical cysts, which are overwhelmingly composed of hyperproliferating A-intercalated (A-IC) cells. RNA sequencing and confirmatory expression studies demonstrated robust expression of Forkhead Transcription Factor 1 (Foxi1) and its downstream targets, apical H+-ATPase and cytoplasmic carbonic anhydrase 2 (CAII), in cyst epithelia in Tsc1 knockout (KO) mice but not in Pkd1 mutant mice. In addition, the electrogenic 2Cl−/H+ exchanger (CLC-5) is significantly up-regulated and shows remarkable colocalization with H+-ATPase on the apical membrane of cyst epithelia in Tsc1 KO mice. Deletion of Foxi1, which is vital to intercalated cells viability and H+-ATPase expression, completely abrogated the cyst burden in Tsc1 KO mice, as indicated by MRI images and histological analysis in kidneys of Foxi1/Tsc1 double-knockout (dKO) mice. Deletion of CAII, which is critical to H+-ATPase activation, caused significant reduction in cyst burden and increased life expectancy in CAII/Tsc1 dKO mice vs. Tsc1 KO mice. We propose that intercalated cells and their acid/base/electrolyte transport machinery (H+-ATPase/CAII/CLC-5) are critical to cystogenesis, and their inhibition or inactivation is associated with significant protection against cyst generation and/or enlargement in TSC.

We propose Spherical Hierarchical modeling of 3D point cloud. Inspired by Shape Context, we design a receptive field on each 3D point by placing a spherical coordinate on it. We sample points using the furthest point method and creating overlapping balls of points. We divide the space into radial, polar angular, and azimuthal angular bins on which we form a Spherical Hierarchy for each ball. We apply 1x1 CNN convolution on points to start the initial feature extraction. Repeated 3D CNN and max-pooling over the Spherical bins propagate contextual information until all the information is condensed in the center bin. Extensive experiments on five datasets strongly evidence that our method outperforms current models on various Point Cloud Learning tasks, including 2D/3D shape classification, 3D part segmentation, and 3D semantic segmentation.

3D points distribute in a continuous 3D space irregularly, thus directly adapting 2D image convolution to 3D points is not an easy job. Previous works often artificially divide the space into regular grids, yet it could be suboptimal to learn geometry. In this paper, we propose SPCNN, namely, Space Probing Convolutional Neural Network, which naturally generalizes image CNN to deal with point clouds. The key idea of SPCNN is learning to probe the 3D space in an adaptive manner. Specifically, we define a pool of learnable convolutional weights, and let each point in the local region learn to choose a suitable convolutional weight from the pool. This is achieved by constructing a geometry guided index-mapping function that implicitly establishes a correspondence between convolutional weights and some local regions in the neighborhood (Fig. 1). In this way, the index-mapping function learns to adaptively partition nearby space for local geometry pattern recognition. With this convolution as a basic operator, SPCNN, a hierarchical architecture can be developed for effective point cloud analysis. Extensive experiments on challenging benchmarks across three tasks demonstrate that SPCNN achieves the state-of-the-art or has competitive performance.

The blood-brain barrier (BBB) poses a significant challenge for drug delivery to the brain. The limitations of our knowledge about the nature of BBB explains the slow progress in the therapy of brain diseases and absence of methods for drug delivery to the brain in clinical practice. Here we show that the BBB opens for high molecular weight compounds after exposure to loud sound (100 dB 370 Hz) in rats. The role of stress induced by loud sound and the systemic and molecular mechanisms behind it are discussed in the framework of the BBB opening as an informative platform for a novel fundamental knowledge about the nature of BBB and for the development of a non-invasive brain drug delivery technology.

Music plays a more important role in our life than just being an entertainment. For example, it can be used as an anti-anxiety therapy of human and animals. However, the unsafe listening of loud music triggers hearing loss in millions of young people and professional musicians (rock, jazz and symphony orchestra) owing to exposure to damaging sound levels using personal audio devices or at noisy entertainment venues including nightclubs, discotheques, bars and concerts. Therefore, it is important to understand how loud music affects us. In this pioneering study on healthy mice, we discover that loud rock music below the safety threshold causes opening of the blood-brain barrier (OBBB), which plays a vital role in protecting the brain from viruses, bacteria and toxins. We clearly demonstrate that listening to loud music during 2 h in an intermittent adaptive regime is accompanied by delayed (1 h after music exposure) and short-lasting to (during 1–4 h) OBBB to low and high molecular weight compounds without cochlear and brain impairments. We present the systemic and molecular mechanisms responsible for music-induced OBBB. Finally, a revision of our traditional knowledge about the BBB nature and the novel strategies in optimizing of sound-mediated methods for brain drug delivery are discussed.

We previously showed that newly formed vessels in ischemic rat brain have high blood-brain barrier (BBB) permeability at 3 weeks after stroke due to a lack of major endothelial tight junction proteins (TJPs), which may exacerbate edema in stroke patients. Atorvastatin was suggested a dose-dependent pro-angiogenic effect and ameliorating BBB permeability beyond its cholesterol-lowering effects. This study examined our hypothesis that, during vascular remodeling after stroke, treatment with atorvastatin could facilitate BBB maturation in remodeling vasculature in ischemic brain. Adult spontaneously hypertensive rats underwent middle cerebral artery occlusion with reperfusion (MCAO/RP). Atorvastatin, at dose of 3 mg/kg, was delivered daily starting at 14 days after MCAO/RP onset for 7 days. The rats were studied at multiple time points up to 8 weeks with multimodal-MRI, behavior tests, immunohistochemistry, and biochemistry. The delayed treatment of atorvastatin significantly reduced infarct size and BBB permeability, restored cerebral blood flow, and improved the neurological outcome at 8 weeks after MCAO/RP. Postmortem studies showed that atorvastatin promoted angiogenesis and stabilized the newly formed vessels in peri-infarct areas. Importantly, atorvastatin facilitated maturation of BBB properties in the new vessels by promoting endothelial tight junction (TJ) formation. Further in vivo and in vitro studies demonstrated that proliferating peri-vascular pericytes expressing neural-glial antigen 2 (NG2) mediated the role of atorvastatin on BBB maturation through regulating endothelial TJ strand formations. Our results suggested a therapeutic potential of atorvastatin in facilitating a full BBB integrity and functional stroke recovery, and an essential role for pericyte-mediated endothelial TJ formation in remodeling vasculature.

Circular RNAs (circRNAs) are implicated in the tumorigenesis of human cancers. However, the effects of circRNAs on laryngeal squamous cell carcinoma (LSCC) are largely unknown. Here, we aimed to explore the roles of circ_0023028 in LSCC development. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure circ_0023028, miR-486-3p, and Lin-Isl-Mec (LIM) and SH3 domain protein 1 (LASP1) mRNA. The characteristics of circ_0023028 were determined by RNase R digestion assay and Actinomycin D assay. Cell Counting Kit-8 (CCK-8) assay and colony formation assay were utilized for cell proliferation. Transwell assay was adopted for cell invasion and migration. Flow cytometry analysis was carried out to analyze cell cycle and apoptosis. RNA pull-down assay and dual-luciferase reporter assay were used to explore the association between miR-486-3p and circ_0023028 or LASP1. Western blot assay was adopted to measure LASP1 protein level. Murine xenograft model was executed to investigate the function of circ_0023028 in vivo. High expression of circ_0023028 was observed in LSCC tissues and cells. Circ_0023028 was stable and possessed a loop structure. Circ_0023028 silencing suppressed LSCC cell proliferation, metastasis and cell cycle process and induced apoptosis in vitro and hampered tumor growth in vivo. Further mechanism analysis demonstrated that circ_0023028 could sponge miR-486-3p to regulate LASP1 expression in LSCC cells. The malignant behaviors of LSCC cells mediated by circ_0023028 knockdown were rescued by the inhibition of miR-486-3p. Moreover, miR-486-3p suppressed LSCC cell progression via binding to LASP1. Circ_0023028 knockdown might impede the progression of LSCC by regulating miR-486-3p/LASP1 axis, which could provide a novel insight on the mechanism of LSCC progression.

Supplemental material, sj-pdf-1-jcb-10.1177_0271678X20953913 for Longitudinal monitoring of microglial/macrophage activation in ischemic rat brain using Iba-1-specific nanoparticle-enhanced magnetic resonance imaging by Laurel O Sillerud, Yirong Yang, Lisa Y Yang, Kelsey B Duval, Jeffrey Thompson and Yi Yang in Journal of Cerebral Blood Flow & Metabolism

Background Vagus nerve stimulation (VNS) significantly reduces infarct volume in rat models of cerebral ischemia, but the mechanism of this protective effect remains open. Hypothesis This study tested the hypothesis that non-invasive VNS (nVNS), during transient middle cerebral artery occlusion (MCAO), protects the blood-brain barrier (BBB), leading to reduced infarct size in ischemic brain. Methods Spontaneous hypertensive rats (SHRs) were subjected to a 90 min MCAO. nVNS treated rats received 5 stimulations (duration: 2 min; every 10 min) on the skin overlying the cervical vagus nerve in the neck beginning 30 min after MCAO onset. Control rats received the same stimulations on the quadriceps femoris muscle. Twenty-four hours after MCAO onset, MRI and immunohistochemistry (IHC) were performed for analyses of infarct size and BBB leakage. Results Compared with the control group, anatomic MRI T2-weighted images showed significantly smaller infarct sizes in the nVNS group. Dynamic contrast-enhanced (DCE)-MRI showed a significantly decreased BBB transfer rate (Ki map) in the lesion area in the nVNS group, which was spatially correlated with the attenuation of the infarct size. Furthermore, significantly lower serum IgG leakage, visualized by IHC, was seen in the ischemic hemisphere in nVNS treated rats. nVNS also protected vascular tight junction proteins from disruption in microvessels, and reduced expression of matrix metalloproteinases-2/9 in reactive astrocytes surrounding the compromised vessels in the ischemic hemispheres. Conclusion Our data suggest that the neuroprotective role of a series of nVNS administrations during MCA occlusion, spatially correlates with protection of BBB integrity from damage and reduction of infarct extent induced by ischemic stroke.

Children who are born preterm are at risk for encephalopathy of prematurity, a leading cause of cerebral palsy, cognitive delay and behavioral disorders. Current interventions are limited and none have been shown to reverse cognitive and behavioral impairments, a primary determinant of poor quality of life for these children. Moreover, the mechanisms of perinatal brain injury that result in functional deficits and imaging abnormalities in the mature brain are poorly defined, limiting the potential to target interventions to those who may benefit most. To determine whether impairments are reversible after a prenatal insult, we investigated a spectrum of functional deficits and diffusion tensor imaging (DTI) abnormalities in young adult animals. We hypothesized that prenatal transient systemic hypoxia-ischemia (TSHI) would induce multiple functional deficits concomitant with reduced microstructural white and gray matter integrity, and tested whether these abnormalities could be ameliorated using postnatal erythropoietin (EPO), an emerging neurorestorative intervention. On embryonic day 18 uterine arteries were transiently occluded for 60 minutes via laparotomy. Shams underwent anesthesia and laparotomy for 60 min. Pups were born and TSHI pups were randomized to receive EPO or vehicle via intraperitoneal injection on postnatal days 1 to 5. Gait, social interaction, olfaction and open field testing was performed from postnatal day 25–35 before brains underwent ex vivo DTI to measure fractional anisotropy, axial diffusivity and radial diffusivity. Prenatal TSHI injury causes hyperactivity, impaired gait and poor social interaction in young adult rats that mimic the spectrum of deficits observed in children born preterm. Collectively, these data show for the first time in a model of encephalopathy of prematurity that postnatal EPO treatment mitigates impairments in social interaction, in addition to gait deficits. EPO also normalizes TSHI-induced microstructural abnormalities in fractional anisotropy and radial diffusivity in multiple regions, consistent with improved structural integrity and recovery of myelination. Taken together, these results show behavioral and memory deficits from perinatal brain injury are reversible. Furthermore, resolution of DTI abnormalities may predict responsiveness to emerging interventions, and serve as a biomarker of CNS injury and recovery.

MicroRNAs (miRs) are a class of non‑coding small RNAs that have been demonstrated to be involved in the pathogenesis of human cancer. There is even evidence that microRNAs can act as oncogenes or tumor suppressors. Although microRNA expression profiles have been characterized in colorectal carcinoma, their precise physiological functions are largely unknown. It has become clear that the activated KRAS Proto‑Oncogene, GTPase (KRAS) oncogene plays an important role in colorectal carcinogenesis. In the present study, it was found that the level of mature miR‑143 was lower in colorectal carcinoma tissues compared with that observed in normal adjacent tissues. A lack of miR‑143 was detected in human colorectal carcinoma cell lines, SW480, LoVo and HT‑29, compared to the high expression observed in normal colon epithelial cell line NCM460. pcDNA3.1‑pri‑miR‑143 and its mutant were successfully constructed and transfected into colorectal carcinoma cells. Increased accumulation of mature miR‑143 was observed in the pcDNA3.1‑pri‑miR‑143‑transfected cells. In SW480 cells, transfection of pcDNA3.1‑pri‑miR‑143 resulted in a 35 and 47% reduction in cell growth after incubation for 4 and 5 days, respectively, compared with transfection of the pcDNA3.1‑pri‑miR‑143 mutant; while in LoVo cells, transfection of pcDNA3.1‑pri‑miR‑143 resulted in a 33 and 46% reduction in cell growth respectively. In contrast, transfection of pcDNA3.1‑pri‑miR‑143 had no significantly effects on HT‑29 cell growth. We also found that transfection of pcDNA3.1‑pri‑miR‑143 had no effect on levels of KRAS mRNA, but resulted in a 58% decrease in the KRAS protein level in the transfected SW480 cells, while an approximate 54 and 43% KRAS protein reduction in LoVo and HT‑29 cells, respectively, compared with the pcDNA3.1‑pri‑miR‑143 mutant. Two fragments containing the putative complementary site were cloned into the pGL3 vector, constructing the luciferase reporter pGL3‑KRAS‑CS1 and pGL3‑KRAS‑CS2. Cotransfection of pcDNA3.1‑pri‑miR‑143 with pGL3‑KRAS‑CS1 and pGL3‑KRAS‑CS2 respectively resulted in 4.6‑ and 3.3‑fold inhibition of luciferase activity in the SW480 cells, while a 4.0‑ and 3.2‑fold inhibition of luciferase activity in the LoVo cells, 3.7‑ and 3.1‑fold inhibition in the HT‑29 cells. Differences in pGL3‑KRAS‑CS1 and pGL3‑KRAS‑CS2 activity were not significant. Our results revealed that increased accumulation of miR‑143 is likely to modulate levels of KRAS protein expression at the post‑transcriptional level by interacting specifically with the complementary site, and consequently inhibiting proliferation of the transfected cells.