[Retracted] Antagonist targeting miR­106b­5p attenuates acute renal injury by regulating renal function, apoptosis and autophagy via the upregulation of TCF4.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that the EdU staining assay data shown in Figs. 4C and 5C and the western blotting data shown in Fig. 4E were strikingly similar to data appearing in different form in other research articles written by different authors at different research institutes that had either already been published, or were submitted for publication at around the same time. Owing to the fact that contentious data in the above article had already been submitted for publication elsewhere prior to its submission to International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 48: 169, 2021; DOI: 10.3892/ijmm.2021.5002].

MRI-Based Kinetic Heterogeneity Evaluation in the Accurate Access of Axillary Lymph Node Status in Breast Cancer Using a Hybrid CNN-RNN Model.

BACKGROUND: Accurate evaluation of the axillary lymph node (ALN) status is needed for determining the treatment protocol for breast cancer (BC). The value of magnetic resonance imaging (MRI)-based tumor heterogeneity in assessing ALN metastasis in BC is unclear. PURPOSE: To assess the value of deep learning (DL)-derived kinetic heterogeneity parameters based on BC dynamic contrast-enhanced (DCE)-MRI to infer the ALN status. STUDY TYPE: Retrospective. SUBJECTS: 1256/539/153/115 patients in the training cohort, internal validation cohort, and external validation cohorts I and II, respectively. FIELD STRENGTH/SEQUENCE: 1.5 T/3.0 T, non-contrast T1-weighted spin-echo sequence imaging (T1WI), DCE-T1WI, and diffusion-weighted imaging. ASSESSMENT: Clinical pathological and MRI semantic features were obtained by reviewing histopathology and MRI reports. The segmentation of the tumor lesion on the first phase of T1WI DCE-MRI images was applied to other phases after registration. A DL architecture termed convolutional recurrent neural network (ConvRNN) was developed to generate the KHimage (kinetic heterogeneity of DCE-MRI image) score that indicated the ALN status in patients with BC. The model was trained and optimized on training and internal validation cohorts, tested on two external validation cohorts. We compared ConvRNN model with other 10 models and the subgroup analyses of tumor size, magnetic field strength, and molecular subtype were also evaluated. STATISTICAL TESTS: Chi-squared, Fisher's exact, Student's t, Mann-Whitney U tests, and receiver operating characteristics (ROC) analysis were performed. P < 0.05 was considered significant. RESULTS: The ConvRNN model achieved area under the curve (AUC) of 0.802 in the internal validation cohort and 0.785-0.806 in the external validation cohorts. The ConvRNN model could well evaluate the ALN status of the four molecular subtypes (AUC = 0.685-0.868). The patients with larger tumor sizes (>5 cm) were more susceptible to ALN metastasis with KHimage scores of 0.527-0.827. DATA CONCLUSION: A ConvRNN model outperformed traditional models for determining the ALN status in patients with BC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

[Effect of "Tiaoshen Tongluo" acupuncture on nerve function injury, muscle tension and neurotransmitters through Nrf2/ROS pathway in spastic rats after stroke].

OBJECTIVE: To observe the effect of "Tiaoshen Tongluo" acupuncture (TTA) at "Dingzhongxian" (MS5) and right "Dingpangxian" (MS8) on neurological injury, muscle tension and neurotransmitters through nuclear transcription factor E2 related factor 2 (Nrf2)/reactive oxygen species (ROS) signaling pathway in spastic rats after stroke, so as to explore its mechanisms underlying relief of post-stroke spasm (PSS). METHODS: A total of 90 male SD rats were randomly divided into 6 groups, i.e. sham operation, PSS model, medication, non-acupoint acupuncture, TTA, TTA+ML385 groups, with 15 rats in each group. The PSS model was established by middle cerebral artery occlusion. After modeling, rats of the medication group were treated by gavage of baclofen (0.4 mg/kg), once daily for 7 days. For rats of the non-acupoint acupuncture group, the spot about 10 mm above the iliac crest and below the armpit of the affected side was needled, and for those of the TTA group and TTA+ML385 group, EA stimulation (1 mA, 2 Hz/15 Hz) was applied to MS5 and right MS8 for 10 min, once daily for 7 consecutive days. Intraperitoneal injection of ML385 ［ a specific nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor, 30 mg/kg］ was given to rats of the TTA+ML385 group before TTA was performed. The rats' neurological deficit score (0-4 points) was evaluated by referring to Zea Longa's methods and the muscular spasm degree of the quadriceps femoris of the left hindlimb (0-4 points) assessed by using Ashworth scale (MAS). The muscular tension of the left quadriceps femoris was measured by using a tension sensor, and Hoffman (H)-reflex response and M and H waves of electromyogram of the muscle between the metatarsals of the left foot were measured using an electrophysiological recorder. The cerebral infarction volume was measured after 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of γ-aminobutyric acid (GABA), glycine (Gly), glutamic acid (Glu) and aspartic acid (Asp) of the right cortical infarct area were detected by using high performance capillary electrophoresis, and the contents of 5-hydroxytryptamine (5-HT), dopamine (DA) and norepinephrine (NE) were detected by fluorescence spectrophoto-metry, as well as the level of ROS in the right cerebral cortical infarction tissues was detected by dihydroethidium staining. The expression levels of Nrf2 and heme oxygenase-1 (HO-1) proteins in the infarcted cerebral area were detected using Western blot. RESULTS: Compared with the sham operation group, the neurological deficit score, MAS score, percentage of cerebral infarction volume, Hmax/Mmax ratio, contents of Glu and Asp and ROS level were significantly increased (P<0.001), whereas the muscle tone, stimulation threshold for inducing H-reflex, GABA, Gly, 5-HT, DA and NE contents, cerebral Nrf2 and HO-1 protein expression levels were apparently decreased (P<0.001) in the model group. In comparison with the model group, the neurological deficit score, MAS score, percentage of cerebral infarction volume, Hmax/Mmax ratio, contents of Glu, Asp and ROS levels were decreased (P<0.001), and the muscle tone, stimulation threshold for inducing H-reflex, GABA, Gly, 5-HT, DA and NE contents, Nrf2 and HO-1 protein expressions were increased (P<0.001, P<0.01) in both the medication and TTA groups. No significant differences were found between the non-acupoint group and model group, and between the medication and TTA groups in all the indexes mentioned above (P>0.05). After administration of ML385, the effects of TTA in reducing neurological deficit score, MAS score, Hmax/Mmax, percentage of cerebral infarct volume, Glu, Asp, ROS, and up-regulating H-reflex threshold, GABA, Gly, 5-HT, DA, NE, Nrf2 and HO-1 levels were eliminated (P<0.001，P<0.05,P<0.01). CONCLUSION: TTA can improve neurological behavior and muscle spasm in rats with PSS, which may be associated with its functions in regulating the levels of neurotransmitters in the cortical infarcted area by activating the Nrf2/ROS signaling pathway.

miR171-targeted SCARECROW-LIKE genes CsSCL2 and CsSCL3 regulate somatic embryogenesis in citrus.

Somatic embryogenesis (SE) is a key regeneration pathway in various biotechnology approaches to crop improvement, especially for economically important perennial woody crops like citrus. However, maintenance of SE capability has long been a challenge and becomes a bottleneck in biotechnology-facilitated plant improvement. In the embryogenic callus (EC) of citrus, we identified 2 csi-miR171c-targeted SCARECROW-LIKE genes CsSCL2 and CsSCL3 (CsSCL2/3), which exert positive feedback regulation on csi-miR171c expression. Suppression of CsSCL2 expression by RNA interference (RNAi) enhanced SE in citrus callus. A thioredoxin superfamily protein CsClot was identified as an interactive protein of CsSCL2/3. Overexpression of CsClot disturbed reactive oxygen species (ROS) homeostasis in EC and enhanced SE. Chromatin immunoprecipitation sequencing (ChIP-Seq) and RNA-Seq identified 660 genes directly suppressed by CsSCL2 that were enriched in biological processes including development-related processes, auxin signaling pathway, and cell wall organization. CsSCL2/3 bound to the promoters of regeneration-related genes, such as WUSCHEL-RELATED HOMEOBOX 2 (CsWOX2), CsWOX13, and Lateral Organ Boundaries Domain 40 (LBD40), and repressed their expression. Overall, CsSCL2/3 modulate ROS homeostasis through the interactive protein CsClot and directly suppress the expression of regeneration-related genes, thus regulating SE in citrus. We uncovered a regulatory pathway of miR171c-targeted CsSCL2/3 in SE, which shed light on the mechanism of SE and regeneration capability maintenance in citrus.

miR156 regulates somatic embryogenesis by modulating starch accumulation in citrus.

Somatic embryogenesis (SE) is a major regeneration approach for in vitro cultured tissues of plants, including citrus. However, SE capability is difficult to maintain, and recalcitrance to SE has become a major obstacle to plant biotechnology. We previously reported that miR156-SPL modules regulate SE in citrus callus. However, the downstream regulatory pathway of the miR156-SPL module in SE remains unclear. In this study, we found that transcription factors CsAGL15 and CsFUS3 bind to the CsMIR156A promoter and activate its expression. Suppression of csi-miR156a function leads to up-regulation of four target genes, SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (CsSPL) genes, and reduction of SE efficiency. In the short tandem target mimic (STTM)-miR156a overexpression callus (MIM156), the number of amyloplasts and starch content were significantly reduced, and genes involved in starch synthesis and transport were down-regulated. csi-miR172d was down-regulated, whereas the target genes, CsTOE1.1 and CsTOE1.2, which inhibit the expression of starch biosynthesis genes, were up-regulated. In our working model, CsAGL15 and CsFUS3 activate csi-miR156a, which represses CsSPLs and further regulates csi-miR172d and CsTOEs, thus altering starch accumulation in callus cells and regulating SE in citrus. This study elucidates the pathway of miR156-SPLs and miR172-TOEs-mediated regulation of SE, and provides new insights into enhancing SE capability in citrus.

Antagonist targeting miR­106b­5p attenuates acute renal injury by regulating renal function, apoptosis and autophagy via the upregulation of TCF4.

Acute renal injury (ARI) is a life­threatening condition and a main contributor to end­stage renal disease, which is mainly caused by ischemia­reperfusion (I/R). miR­106b­5p is a kidney function­related miRNA; however, whether miR­106b­5p regulates the progression of ARI remains unclear. The present study thus aimed to examine the effects of miR­106b­5p antagonist on the regulation of ARI progression. It was found that miR­106b­5p expression was upregulated in the renal tissue of rats with I/R­induced ARI and in NRK­52E rat renal proximal tubular epithelial cells subjected to hypoxia­reoxygenation (H/R). In vitro, H/R induction suppressed the proliferation, and promoted the apoptosis and autophagy of NRK­52E cells, whereas miR­106b­5p antagonist (inhibition of miR­106b­5p) promoted the proliferation, and attenuated the apoptosis and autophagy of NRK­52E cells under the H/R condition. Dual luciferase reporter gene assay validated that transcription factor 4 (TCF4) was a target of miR­106b­5p. It was further found that TCF4 overexpression promoted the proliferation, and inhibited the apoptosis and autophagy of NRK­52E cells subjected to H/R. Moreover, the effects of miR­106b­5p antagonist on NRK­52E cell proliferation, apoptosis and autophagy were mediated through the regulation of TCF4. In vivo, miR­106b­5p antagonist reduced the severity of renal injury, decreased cell proliferation in renal tissues and lowered the serum creatinine (Scr) and blood urea nitrogen (BUN) levels in the blood samples from rats with I/R­induced ARI. On the whole, the findings presented herein demonstrate that miR­106b­5p antagonist attenuates ARI by promoting the proliferation, and suppressing the apoptosis and autophagy of renal cells via upregulating TCF4.

One novel curcumin derivative ZYX01 induces autophagy of human non-small lung cancer cells A549 through AMPK/ULK1/Beclin-1 signaling pathway.

Presently, curcumin derivatives had been paid more attention in view of their high bioavailability or water solubility, which herein possibly replaced the curcumin for their functional applications in future. Here, one novel chemically synthesized curcumin derivative, ZYX01, was used to identify anti-proliferation activity of human non-small lung cancer cells A549 and its anti-proliferative mechanism. Our study showed that ZYX01 could induce autophagic death of A549 cells by morphological observation, MTT assay, acridine orange staining and MDC assay, which possess a dose-and time-dependent manner. ZYX01-treated A549 cells possessed an increase in LC3-II/LC3-I ratio, upregulation of beclin-1 and downregulation of p62 expression. We further confirmed the cellular AMPK/ULK1/Beclin-1 signaling pathway in A549 cells after ZYX01 treatment. The anti-migration effect of ZYX01 in A549 cells was also explored by wound healing assay and transwell experiment. Current results had confirmed that ZYX01 induced A549 cells autophagy through AMPK/ULK1/Beclin-1 pathway and shed light on the future study on the anti-cancer molecular mechanism.

Formation and Effect of Residual Lithium Compounds on Li-Rich Cathode Material Li1.35[Ni0.35Mn0.65]O2.

Li-rich cathode materials are regarded as ideal cathode materials, owing to their excellent electrochemical capacity. However, residual lithium compounds, which are formed on the surface of the materials by reacting with moisture and carbon dioxide in ambient atmosphere, can impair the surface structure, injure the capacity, and impede the electrode fabrication using Li-rich materials. Exposure to air atmosphere causes the formation of residual lithium compounds; the formation of such compounds is believed to be related to humidity, temperature, and time during handling and storage. In this study, we demonstrated for the first time an artificial strategy for controlling time, temperature, and humidity to accelerate exposure. The formation and effect of residual lithium compounds on Li-rich cathode material Li1.35[Ni0.35Mn0.65]O2 were systematically investigated. The residual lithium compounds formed possessed primarily an amorphous structure and were partially coated on the surface. These compounds include LiOH, Li2O, and Li2CO3. Li2CO3 is the major component in residual lithium compounds. The presence of residual lithium compounds on the material surface led to a high discharge capacity loss and large discharge voltage fading. Understanding the formation and suppressing the effect of residual lithium compounds will help prevent their unfavorable effects and improve the electrochemical performance.

Multiple Linkage Modification of Lithium-Rich Layered Oxide Li1.2Mn0.54Ni0.13Co0.13O2 for Lithium Ion Battery.

A multiple linkage modification (MLM) method was investigated to comprehensively improve the properties of lithium-rich layered oxides. MLM Li1.2Mn0.54Ni0.13Co0.13O2 was successfully synthesized via continuous and appropriate heat treatment. The synthesized Li1.2Mn0.54Ni0.13Co0.13O2 particles were coated with a Li2ZrO3 layer and doped with Zr4+ by using a Zr compound as the MLM reagent. The Li2ZrO3 coating layer could protect materials from the corrosion of hydrogen fluoride, and the structure of the base materials was stabilized due to Zr4+ doping. In addition, the formation of Li2ZrO3 captured inactive residual lithium on the surface and absorbed lithium of host materials, thereby leading to the reduction in the Li/M ratio of materials and promoting the first-cycle Coulombic efficiency. The MLM material delivered the highest initial cycle Coulombic efficiency (∼85%), the best cycle and rate performance among bare and ZrO2-coated particles. These results indicate that MLM is an important technique for improving the performance of electrode materials.

Comparative Investigation of 0.5Li2MnO3·0.5LiNi0.5Co0.2Mn0.3O2 Cathode Materials Synthesized by Using Different Lithium Sources.

Lithium-rich manganese-based cathode materials has been attracted enormous interests as one of the most promising candidates of cathode materials for next-generation lithium ion batteries because of its high theoretic capacity and low cost. In this study, 0.5Li2MnO3·0.5LiNi0.5Co0.2Mn0.3O2 materials are synthesized through a solid-state reaction by using different lithium sources, and the synthesis process and the reaction mechanism are investigated in detail. The morphology, structure, and electrochemical performances of the material synthesized by using LiOH·H2O, Li2CO3, and CH3COOLi·2H2O have been analyzed by using Thermo gravimetric analysis (TGA), X-ray diffraction (XRD), Scanning electron microscope (SEM), Transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), and electrochemical measurements. The 0.5Li2MnO3·0.5LiNi0.5Co0.2Mn0.3O2 material prepared by using LiOH·H2O displays uniform morphology with nano particle and stable layer structure so that it suppresses the first cycle irreversible reaction and structure transfer, and it delivers the best electrochemical performance. The results indicate that LiOH·H2O is the best choice for the synthesis of the 0.5Li2MnO3·0.5LiNi0.5Co0.2Mn0.3O2 material.

Construction and immunogenicity analysis of Lactobacillus plantarum expressing a porcine epidemic diarrhea virus S gene fused to a DC-targeting peptide.

Porcine epidemic diarrhea virus (PEDV) is one of the most important causative pathogens of swine diarrhea, which is widely prevalent throughout the world and is responsible for significant economic losses in the commercial pig industry, both domestic and abroad. The spike (S) protein in the PEDV capsid structure can carry the major B lymphocyte epitope, which induces production of neutralizing antibodies and provides immunoprotective effects. Moreover, the conserved region encoded by the S gene can be considered a target for establishing a new diagnostic method and is a new candidate for vaccine design. In this study, use of anchorin pgsA' allowed the fusion protein of S-DCpep to express on the surface of recombinant Lactobacillus plantarum (NC8-pSIP409-pgsA'-S-DCpep) NC8 strain. Mice were immunized by lavage administration of the recombinant NC8-pSIP409-pgsA'-S-DCpep, which was observed to induce DC activation and high production of sIgA and IgG antibodies in experimental animals, while also eliciting production of significantly more IgA+B220+ B cells. More importantly, secretion of cytokines IFN-γ, IL-4 and IL-17 in mice that were vaccinated with NC8-pSIP409-pgsA'-S-DCpep was remarkably increased. The results of our study suggest that NC8-pSIP409-pgsA'-S-DCpep potently triggers cellular and humoral immune responses. The obtained experimental results can provide a theoretical basis that lays the foundation for production of a novel oral vaccine against PED.

Characteristics, Management, and Outcomes of Acute Heart Failure in the Emergency Department: A Multicenter Registry Study with 1-year Follow-up in a Chinese Cohort in Beijing.

BACKGROUND: The emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF. METHODS: This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables. RESULTS: The median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively. CONCLUSIONS: Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.

A Wide-Swath Spaceborne TOPS SAR Image Formation Algorithm Based on Chirp Scaling and Chirp-Z Transform.

Based on the terrain observation by progressive scans (TOPS) mode, an efficient full-aperture image formation algorithm for focusing wide-swath spaceborne TOPS data is proposed. First, to overcome the Doppler frequency spectrum aliasing caused by azimuth antenna steering, the range-independent derotation operation is adopted, and the signal properties after derotation are derived in detail. Then, the azimuth deramp operation is performed to resolve image folding in azimuth. The traditional dermap function will introduce a time shift, resulting in appearance of ghost targets and azimuth resolution reduction at the scene edge, especially in the wide-swath coverage case. To avoid this, a novel solution is provided using a modified range-dependent deramp function combined with the chirp-z transform. Moreover, range scaling and azimuth scaling are performed to provide the same azimuth and range sampling interval for all sub-swaths, instead of the interpolation operation for the sub-swath image mosaic. Simulation results are provided to validate the proposed algorithm.

A Novel General Imaging Formation Algorithm for GNSS-Based Bistatic SAR.

Global Navigation Satellite System (GNSS)-based bistatic Synthetic Aperture Radar (SAR) recently plays a more and more significant role in remote sensing applications for its low-cost and real-time global coverage capability. In this paper, a general imaging formation algorithm was proposed for accurately and efficiently focusing GNSS-based bistatic SAR data, which avoids the interpolation processing in traditional back projection algorithms (BPAs). A two-dimensional point target spectrum model was firstly presented, and the bulk range cell migration correction (RCMC) was consequently derived for reducing range cell migration (RCM) and coarse focusing. As the bulk RCMC seriously changes the range history of the radar signal, a modified and much more efficient hybrid correlation operation was introduced for compensating residual phase errors. Simulation results were presented based on a general geometric topology with non-parallel trajectories and unequal velocities for both transmitter and receiver platforms, showing a satisfactory performance by the proposed method.

ABCA4 sequence variants in Chinese patients with age-related macular degeneration or Stargardt's disease.

ABCA4 gene sequence alterations cause Stargardt's disease (STGD) and may cause some age-related macular degeneration (AMD). We sought to shed light on these associations among Hong Kong Chinese by genotyping 140 AMD, 18 STGD and 95 normal control subjects for 15 ABCA4 exons which were reported to often contain AMD- or STGD-associated mutations. Sequence alterations R212H, T1428M, V1433I, T1572M, I2166M, IVS6-5T>G and IVS33+1G>T were found in AMD patients. T1428M and R2040X occurred in STGD patients. Control subjects displayed all the above missense alterations but no splicing or nonsense changes. Therefore, ABCA4 splicing mutations may be associated with a small proportion of AMD cases.