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BackgroundThe primary imaging markers for idiopathic Normal Pressure Hydrocephalus (iNPH) emphasize morphological measurements within the ventricular system, with no attention given to alterations in brain parenchyma. This study aimed to investigate the potential effectiveness of combining ventricular morphometry and cortical structural measurements as diagnostic biomarkers for iNPH.MethodsA total of 57 iNPH patients and 55 age-matched healthy controls (HC) were recruited in this study. Firstly, manual measurements of ventricular morphology, including Evans Index (EI), z-Evans Index (z-EI), Cella Media Width (CMW), Callosal Angle (CA), and Callosal Height (CH), were conducted based on MRI scans. Cortical thickness measurements were obtained, and statistical analyses were performed using surface-based morphometric analysis. Secondly, three distinct models were developed using machine learning algorithms, each based on a different input feature: a ventricular morphology model (LVM), a cortical thickness model (CT), and a fusion model (All) incorporating both features. Model performances were assessed using 10-fold cross validation and tested on an independent dataset. Model interpretation utilized Shapley Additive Interpretation (SHAP), providing a visualization of the contribution of each variable in the predictive model. Finally, Spearman correlation coefficients were calculated to evaluate the relationship between imaging biomarkers and clinical symptoms.ResultsiNPH patients exhibited notable differences in cortical thickness compared to HC. This included reduced thickness in the frontal, temporal, and cingulate cortices, along with increased thickness in the supracentral gyrus. The diagnostic performance of the fusion model (All) for iNPH surpassed that of the single-feature models, achieving an average accuracy of 90.43%, sensitivity of 90.00%, specificity of 90.91%, and Matthews correlation coefficient (MCC) of 81.03%. This improvement in accuracy (6.09%), sensitivity (11.67%), and MCC (11.25%) compared to the LVM strategy was significant. Shap analysis revealed the crucial role of cortical thickness in the right isthmus cingulate cortex, emerging as the most influential factor in distinguishing iNPH from HC. Additionally, significant correlations were observed between the typical triad symptoms of iNPH patients and cortical structural alterations.ConclusionThis study emphasizes the significant role of cortical structure changes in the diagnosis of iNPH, providing a novel insights for assisting clinicians in improving the identification and detection of iNPH.

Abstract A muon collider would enable the big jump ahead in energy reach that is needed for a fruitful exploration of fundamental interactions. The challenges of producing muon collisions at high luminosity and 10 TeV centre of mass energy are being investigated by the recently-formed International Muon Collider Collaboration. This Review summarises the status and the recent advances on muon colliders design, physics and detector studies. The aim is to provide a global perspective of the field and to outline directions for future work.

Abstract Intestinal ischemia/reperfusion (I/R) injury is a severe clinical condition without optimal diagnostic markers nor clear molecular etiological insights. Plasma exosomal circular RNAs (circRNAs) are valuable biomarkers and therapeutic targets for various diseases, but their role in intestinal I/R injury remains unknown. Here we screen the expression profile of circRNAs in intestinal tissue exosomes collected from intestinal I/R mice and identify circEZH2_005 as a significantly downregulated exosomal circRNA. In parallel, circEZH2_005 is also reduced in the plasma of clinical cardiac surgery patients who developed postoperative intestinal I/R injury. Exosomal circEZH2_005 displays a significant diagnostic value for intestinal injury induced by I/R. Mechanistically, circEZH2_005 is highly expressed in intestinal crypt cells. CircEZH2_005 upregulation promotes the proliferation of Lgr5+ stem cells by direct interaction with hnRNPA1, and enhanced Gprc5a stability, thereby alleviating I/R-induced intestinal mucosal damage. Hence, exosomal circEZH2_005 may serve as a biomarker for intestinal I/R injury and targeting the circEZH2_005/hnRNPA1/Gprc5a axis may be a potential therapeutic strategy for intestinal I/R injury.

Conventional plasma electrolytic oxidation treatments produce oxide coatings with micron-scale discharge pores, resulting in insulation and wear and corrosion resistance far below that expected of highly dense Al2O3 coatings. The introduction of cathodic polarization during the plasma electrolytic oxidation process, especially when the applied cathode-to-anode current ratio (Rpn) is greater than 1, triggers a unique plasma discharge phenomenon known as “soft sparking”. The soft spark discharge mode significantly improves the densification of the anode ceramic layer and facilitates the formation of the high-temperature α-Al2O3 phase within the coating. Although the soft spark discharge phenomenon has been known for a long time, the growth behavior of the coating under its discharge mode still needs to be studied and improved. In this paper, the growth behavior of the coating before and after soft spark discharge is investigated with the help of the micro-morphology, phase composition and element distribution of a homemade fixture. The results show that the ceramic layer grows mainly along the oxide–electrolyte direction before the soft spark discharge transformation; after the soft spark discharge, the ceramic layer grows along the oxide–substrate direction. It was also unexpectedly found that, under soft spark discharge, the silicon element only exists on the outside of the coating, which is caused by the large size and slow migration of SiO32−, which can only enter the ceramic layer and participate in the reaction through the discharge channel generated by the strong discharge. In addition, it was also found that the relative phase content of α-Al2O3 in the coating increased from 0.487 to 0.634 after 10 min of rotary spark discharge, which is an increase of 30.2% compared with that before the soft spark discharge transition. On the other hand, the relative phase content of α-Al2O3 in the coating decreased from 0.487 to 0.313 after 20 min of transfer spark discharge, which was a 55.6% decrease compared to that before the soft spark discharge transformation.

The correlation between negative pulse and the black electrolyte properties of magnesium alloy micro-arc oxidation and the treated area was investigated by introducing a negative pulse electric field. The physical phase composition, microstructure, elemental distribution, and content of the coating were analyzed using X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). The results showed that the introduction of negative pulses favored the generation of MgO and MgSiO3 contents in the coatings, and an increase in the MgO phase was found in the coatings formed in the failed electrolytes; the microporous size and microcracks of the coatings were gradually and significantly reduced; the average consumption of Cu ions was 0.0453 g/L·dm2, which is only 26% of that in the unipolar condition; the introduction of the negative pulses significantly improved the “anomalous consumption” of Cu ions. The introduction of negative pulse can significantly improve the “abnormal consumption” of copper ions, which is attributed to the change in the electric field by negative pulse, which makes the cathode-enriched Cu ions migrate to the anode and reduces the reduction and precipitation of Cu ions at the cathode.

Alopecia areata (AA) is a chronic inflammatory disease mainly involving Th1 immunoreaction, but Th2 is also involved. A 9-year-old girl presented to our clinic with severe alopecia for 2 months and pruritus-related rashes for 8 years. She was diagnosed with AA and atopic dermatitis (AD), and the Severity of Alopecia Tool (SALT) score was 98. She used a 0.05% halometasone cream (occlusive dressing) topically applied overnight (6 days weekly) for 10 months. After 2 months of treatment, she had regrowth of both black and white hair. However, relapse occurred and she gradually lost all black terminal hair, but white terminal hair remained, with a SALT score of 70. Continuous topical occlusion resulted in white hair regrowth with a SALT score of 20 at the end of month 10. Dupilumab was initially prescribed as a 600-mg subcutaneous injection and maintained at 300 mg every 4 weeks thereafter. Hair repigmentation (10% of whole hair density) started, with black hair shaft appearing at the proximal end in parietal-occipital and occipital areas after three injections at week 12 of dupilumab therapy, with a SALT score of 10. After seven injections at week 28, the percentage of black hair shaft reached up to 90, and she regained her black hair and the pigmented section of hair shaft continued to grow longer at the rate of normal hair growth. Nevertheless, 4 months after termination of dupilumab therapy, the black terminal hair began to fall off, and white vellus hair gradually regrew on the scalp, with a SALT score of 80. Dupilumab induces hair regrowth and repigmentation of white terminal hair without disturbing the anagen phase of hair follicles. Therefore, melanocytes in AA may be a potential target of Th2-related factors. Persistent regrowth of white hair may be used as a signal of Th2 dominance in AA management.

Abstract Background ADD1 (adducin-1) and TPX2 (targeting protein for Xklp2) are centrosomal proteins and regulate mitotic spindle assembly. Mammalian oocytes that segregate homologous chromosomes in Meiosis I and sister chromatids in Meiosis II with a spindle lacking centrosomes are more prone to chromosome segregation errors than in mitosis. However, the regulatory mechanisms of oocyte spindle assembly and the functions of ADD1 and TPX2 in this process remain elusive. Result We found that the expression levels and localization of ADD1, S726 phosphorylated ADD1 (p-ADD1), and TPX2 proteins exhibited spindle assembly-dependent dynamic changes during mouse oocyte meiosis. Taxol treatment, which stabilizes the microtubule polymer and protects it from disassembly, made the signals of ADD1, p-ADD1, and TPX2 present in the microtubule organizing centers of small asters and spindles. Knockdown of approximately 60% of ADD1 protein levels destabilized interpolar microtubules in the meiotic spindle, resulting in aberrant chromosome alignment, reduced first polar body extrusion, and increased aneuploidy in metaphase II oocytes, but did not affect K-fiber homeostasis and the expression and localization of TPX2. Strikingly, TPX2 deficiency caused increased protein content of ADD1, but decreased expression and detachment of p-ADD1 from the spindle, thereby arresting mouse oocytes at the metaphase I stage with collapsed spindles. Conclusion Phosphorylation of ADD1 at S726 by TPX2 mediates acentriolar spindle assembly and precise chromosome segregation in mouse oocytes.

Hypertrophic cardiomyopathy (HCM) is an inherited heart disease characterized by left ventricular hypertrophy. Although sarcomeric gene mutations can explain many HCM cases, the genetic basis of approximately half of HCM cases remains elusive. Here, we report the case of a 30-year-old woman with HCM after imaging and pathological examinations. We identified a novel mutation in a pathogenic gene from the HCM patient through whole-exome sequencing. A heterozygous missense mutation in exon 1 of the α-tropomyosin (TPM1) gene (NM_000366.5:exon1:c.71A > G) was found based on patient sequencing data. The mutation resulted in glutamine replacing arginine (p.Gln24Arg). This mutation was expected to cause significant and deleterious changes in the structure of the TPM1 protein. Therefore, according to pathogenicity assessment guidelines, the mutation was considered likely pathogenic. We found that most of these mutations are related to cardiomyopathy and majority of them are in exon 1 and are missense mutations. TPM1 mutations are thus a common cause of HCM and other congenital heart defects. Thus, a novel missense variant, p.Gln24Arg, in the TPM1 gene is associated with the autosomal dominant disease HCM. These results expand the knowledge spectrum of TPM1 gene function.

In the past, due to improper sludge treatment technology and the absence of treatment standards, some municipal sludge was simply dewatered and then sent to landfills, occupying a significant amount of land and posing a serious threat of secondary pollution. To free up land in the landfill area for the expansion of a large-scale wastewater treatment plant (WWTP) in Shanghai, in this study, we conducted comprehensive pilot research on the entire chain of landfill sludge reprocessing and resource utilization. Both the combination of polyferric silicate sulfate (PFSS) and polyetheramine (PEA) and the combination of polyaluminum silicate (PAS) and polyetheramine (PEA) were used for sludge conditioning before dewatering, resulting in dewatered sludge with approximately 60% moisture content. The combined process involved coagulation and sedimentation, flocculation, and oxidation to treat the leachate generated during dewatering. The treatment process successfully met the specified water pollutant discharge concentration limits for the leachate, with the concentration of ammonia nitrogen in the effluent as low as 15.6 mg/L. Co-incineration in a power plant and modification were applied to stabilize and harmlessly dispose of the dewatered sludge. The coal-generating system ran stably, and no obvious problems were observed in the blending process. In the modification experiment, adding 5% to 7% of the solidifying agent increased the sludge bearing ratio by 53% and 57%, respectively. This process effectively reduced levels of fecal coliforms and heavy metals in the sludge but had a less noticeable effect on organic matter content. The modified sludge proved suitable for use as backfill material in construction areas without requirements for organic matter. The results of this study provide valuable insights for a completed full-scale landfill sludge reclamation and land resource release project.

BackgroundRight ventricular outflow tract (RVOT) stenting seems to be suggested as a promising treatment option and an alternative to modified Blalock-Taussig shunt (mBTS) in the initial palliation of patients with Fallot-type lesions in recent years. This study sought to assess the effect of RVOT stenting on the growth of the pulmonary artery (PA) in patients with Tetralogy of Fallot (TOF).MethodsRetrospective review analyzing 5 patients with Fallot-type congenital heart disease with small pulmonary arteries who underwent palliative with RVOT stenting and 9 patients underwent modified Blalock-Taussig shunt within 9 years period. Differential left PA (LPA) and right PA (RPA) growth was measured by Cardiovascular Computed Tomography Angiography (CTA).ResultsRVOT stenting improved arterial oxygen saturation from median of 60% (interquartile range [IQR]: 37% to 79%) to 95% (87.5% to 97.5%) (p = 0.028). The LPA diameter Z-score improved from −2.843 (−3.51–2.037) to −0.78 (−2.3305–0.19) (p = 0.03), the RPA diameter Z-score improved from median −2.843 (−3.51–2.037) to −0.477 (−1.1145–0.459) (p = 0.002), the Mc Goon ratio increased from median 1 (0.8–1.105) to 1.32 (1.25–1.98) (p = 0.017). There were no procedural complications and all 5 patients have undergone final repair in the RVOT stent group. In the mBTS group, the LPA diameter Z-score improved from −1.494 (−2.242–0.6135) to −0.396 (−1.488–1.228) (p = 0.15), the RPA diameter Z-score improved from median −1.328 (−2.036–0.838) to 0.088 (−0.486–1.223) (p = 0.007), and there were 5 patients occur different complications and 4 patients was not attained the standards of final surgical repair.ConclusionRVOT stenting, compared with mBTS, seems to better promote pulmonary artery growth, improve arterial oxygen saturations, and have less procedure complications in patients with TOF who being absolute contraindicated for primary repair due to high risks.

A T/C variant in miR-27a is associated with bipolar disorder, potentially by reducing the ability of this microRNA to target important neurodevelopmental genes like NCAM1.

BackgroundHypertrophic cardiomyopathy (HCM) is a grave hazard to human health. Circular RNA (circRNAs) and micro RNA (miRNAs), which are competitive endogenous RNA, have been shown to play a critical role inHCM pathogenicity. However, to a great extent, the biological activities of ceRNA in HCM pathophysiology and prognosis remain to be investigated.Materials and methodsBy analyzing the expression files in the Gene Expression Comprehensive (GEO) database, differentially expressed (DE) circRNAs, miRNAs, and mRNAs in HCM were identified, and the target molecules of circRNAs and miRNAs were predicted. The intersection of the differentially expressed RNA molecules and the expected target was then calculated, and a ceRNA network was subsequently constructed using RNA molecules. Using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, the potential etiology was elucidated. qPCR was used to validate a portion of the hub gene using Angiotensin II to generate a cell hypertrophy model.ResultsThree large-scale HCM sample datasets were extracted from the GEO database. After crossing these molecules with their expected targets, the circRNA-miRNA-mRNA network had two DEcircRNAs, two DEmiRNAs, and thirty DEmRNAs, compared to normal tissues. Functional enrichment analysis of GO and KEGG demonstrated that many of the HCM pathways and mechanisms were associated with calcium channel release, which is also the primary focus of future research. The qPCR results revealed that circRNA, miRNA, and mRNA expression levels were different. They may include novel noninvasive indicators for the early screening and prognostic prediction of HCM.ConclusionIn this study, we hypothesized a circRNA-miRNA-mRNA regulation network that is closely related to the progression and clinical outcomes of HCM and may contain promising biomarkers and treatment targets for HCM.

BackgroundSepsis-induced myocardial dysfunction (SIMD) has a significant contribution to sepsis-caused death in critically ill patients. In recent years, the number of published articles related to SIMD has increased rapidly. However, there was no literature that systematically analyzed and evaluated these documents. Thus, we aimed to lay a foundation for researchers to quickly understand the research hotspots, evolution processes and development trends in the SIMD field via a bibliometric analysis.MethodsArticles related to SIMD were retrieved and extracted from the Web of Science Core Collection on July 19th, 2022. CiteSpace (version 6.1.R2) and VOSviewer (version 1.6.18) were used for performing visual analysis.ResultsA total of 1,076 articles were included. The number of SIMD-related articles published each year has increased significantly. These publications mainly came from 56 countries, led by China and the USA, and 461 institutions, but without stable and close cooperation. As authors, Li Chuanfu published the most articles, while Rudiger Alain had the most co-citations. Shock was the journal with the most studies, and Critical Care Medicine was the most commonly cited journal. All keywords were grouped into six clusters, some of which represented the current and developing research directions of SIMD as the molecular mechanisms.ConclusionResearch on SIMD is flourishing. It is necessary to strengthen cooperation and exchanges between countries and institutions. The molecular mechanisms of SIMD, especially oxidative stress and regulated cell death, will be critical subjects in the future.

Primary cardiac tumors are extremely uncommon in young children and infants. Cardiac myxoma are typically found in the atria, predominately in the left atrium, with relatively few found on the right side, such as in the right ventricle or pulmonary artery. Numerous significant complications, including sudden death, can result from obstruction of the main pulmonary artery trunk and right ventricular outflow tract. Here, we describe the case of a 14-year-old Chinese girl diagnosed with a right ventricular myxoma located in the right ventricle and extended into the main pulmonary trunk. Complete resection of the myxoma and histological confirmation were performed.

ObjectivesThe abnormal functional connectivity (FC) pattern of default mode network (DMN) may be key markers for early identification of various cognitive disorders. However, the whole-brain FC changes of DMN in delayed neurocognitive recovery (DNR) are still unclear. Our study was aimed at exploring the whole-brain FC patterns of all regions in DMN and the potential features as biomarkers for the prediction of DNR using machine-learning algorithms.MethodsResting-state functional magnetic resonance imaging (fMRI) was conducted before surgery on 74 patients undergoing non-cardiac surgery. Seed-based whole-brain FC with 18 core regions located in the DMN was performed, and FC features that were statistically different between the DNR and non-DNR patients after false discovery correction were extracted. Afterward, based on the extracted FC features, machine-learning algorithms such as support vector machine, logistic regression, decision tree, and random forest were established to recognize DNR. The machine learning experiment procedure mainly included three following steps: feature standardization, parameter adjustment, and performance comparison. Finally, independent testing was conducted to validate the established prediction model. The algorithm performance was evaluated by a permutation test.ResultsWe found significantly decreased DMN connectivity with the brain regions involved in visual processing in DNR patients than in non-DNR patients. The best result was obtained from the random forest algorithm based on the 20 decision trees (estimators). The random forest model achieved the accuracy, sensitivity, and specificity of 84.0, 63.1, and 89.5%, respectively. The area under the receiver operating characteristic curve of the classifier reached 86.4%. The feature that contributed the most to the random forest model was the FC between the left retrosplenial cortex/posterior cingulate cortex and left precuneus.ConclusionThe decreased FC of DMN with regions involved in visual processing might be effective markers for the prediction of DNR and could provide new insights into the neural mechanisms of DNR.Clinical Trial Registration: Chinese Clinical Trial Registry, ChiCTR-DCD-15006096.

Tunnel boring machine (TBM) vibration induced by cutting complex ground contains essential information that can help engineers evaluate the interaction between a cutterhead and the ground itself. In this study, deep recurrent neural networks (RNNs) and convolutional neural networks (CNNs) were used for vibration-based working face ground identification. First, field monitoring was conducted to obtain the TBM vibration data when tunneling in changing geological conditions, including mixed-face, homogeneous, and transmission ground. Next, RNNs and CNNs were utilized to develop vibration-based prediction models, which were then validated using the testing dataset. The accuracy of the long short-term memory (LSTM) and bidirectional LSTM (Bi-LSTM) models was approximately 70% with raw data; however, with instantaneous frequency transmission, the accuracy increased to approximately 80%. Two types of deep CNNs, GoogLeNet and ResNet, were trained and tested with time-frequency scalar diagrams from continuous wavelet transformation. The CNN models, with an accuracy greater than 96%, performed significantly better than the RNN models. The ResNet-18, with an accuracy of 98.28%, performed the best. When the sample length was set as the cutterhead rotation period, the deep CNN and RNN models achieved the highest accuracy while the proposed deep CNN model simultaneously achieved high prediction accuracy and feedback efficiency. The proposed model could promptly identify the ground conditions at the working face without stopping the normal tunneling process, and the TBM working parameters could be adjusted and optimized in a timely manner based on the predicted results.

Aphids are one of the main pests of cotton and have been an important disaster limiting cotton yield. It is important to use satellite multispectral data to monitor the severity of cotton aphids in a timely and accurate manner on regional scale. Based on the combination of derivative of ratio spectra (DRS) and random forest (RF) algorithm, this study researched the quantitative monitoring model of cotton aphid severity based on Sentinel-2 data. First, the cotton area was extracted by using a supervised classification algorithm and the vegetation index threshold method. Then, the DRS algorithm was used to analyze the spectral characteristics of cotton aphids from three scales, and the Pearson correlation analysis algorithm was used to extract the bands significantly related to aphid infestation. Finally, the RF model was trained by ground sampling points and its accuracy was evaluated. The optimal model results were selected by the cross-validation method, and the accuracy was compared with the four classical classification algorithms. The results showed that (1) the canopy spectral reflectance curves at different grades of cotton aphid infestation were significantly different, with a significant positive correlation between cotton aphid grade and spectral reflectance in the visible band range and a negative correlation in the near-infrared band range; (2) The DRS algorithm could effectively remove the interference of the background endmember of satellite multispectral image pixels and enhance the aphid spectral features. The analysis results from three different scales and the evaluation results demonstrate the effectiveness of the algorithm in processing satellite multispectral data; (3) After the DRS processing, Sentinel-2 multispectral images could effectively classify the severity of cotton aphid infestation by the RF model with an overall classification accuracy of 80% and a kappa coefficient of 0.73. Compared with the results of four classical classification algorithms, the proposed algorithm has the best accuracy, which proves the superiority of RF. Based on satellite multispectral data, the DRS and RF can be combined to monitor the severity of cotton aphids on a regional scale, and the accuracy can meet the actual need.

BackgroundRight heart failure results from advanced pulmonary hypertension (PH) and has a poor prognosis. There are few available treatments for right heart failure. Pulmonary artery remodeling, including changes in pulmonary artery endothelial cells to endothelial-mesenchymal cells, and aberrant fibroblast and pulmonary artery smooth muscle cell (PASMC) proliferation, are characteristics of the pathophysiological process of PH. As a result, the clinical situation requires novel PH diagnostic and treatment targets.MethodsMonocrotaline was used to create an animal model of PH, and lung tissue was removed for transcriptome sequencing. The targets with the highest differences were chosen for transfection after possible targets were identified using bioinformatic techniques and confirmed by qPCR to examine their function in hypoxic PASMCs.ResultsAfter sequencing 781 differentially expressed mRNAs, we compared them with the GEO dataset and found 43 differentially expressed genes. We chose the top three scores for further study and verification and discovered that MKI67, a crucial element of the cell cycle that regulates PASMC proliferation, had the greatest effect. After suppressing MKI67 in PASMCs, both cell proliferation and migration decreased.ConclusionSeveral potential targets were chosen for this study, and MKI67 was found to play a regulatory role in cell migration and proliferation. This implies that PH can be diagnosed and treated using MKI67.

BackgroundThe Ross procedure is recommended as an optimal aortic valve replacement (AVR) in children and young adults due to several advantages. Nevertheless, multiple reconstructions of the right ventricular outflow tract (RVOT) with new valve conduits have caused some concern regarding the durability of the Ross AVR. Decellularized bovine jugular vein conduit (BJVC) (DP-BJVC) and hand-sewn expanded polytetrafluoroethylene valved conduits (ePTFE VC) are widely employed to reconstruct the RVOT with satisfactory long-term outcomes. However, few studies have compared the safety and efficacy between the two valve conduits. We aimed to evaluate the early outcomes and report our single center experience in the application of these conduits.MethodsTwenty-two pediatric patients (aged < 18 years) who underwent Ross procedures with DP-BJVC and ePTFE VC in our center between 1 June, 2017 and 31 January, 2022 were enrolled. The Kaplan–Meier method was used to evaluate survival, freedom from RVOT reintervention, and freedom from RVOT graft dysfunction. Mixed-effects analysis with the Geisser–Greenhouse correction and Sidak's multiple comparisons test for post-hoc analysis was employed to compare the peak gradient across the conduit at varying follow-ups.ResultsAll patients were followed up in full. The total early survival rate was 90.9%; two patients in the DP-BJVC group died. There was no significant difference in early mortality, cross-clamp time (p = 0.212), in-hospital stay (p = 0.469), and RVOT graft thrombosis or endocarditis between the two groups. There was similarly no significant difference between Kaplan–Meier freedom from RVOT graft dysfunction curve (P = 0.131). The transprosthetic gradient gradually increased over time in both groups and was significantly higher in the DP-BJVC group at follow-up (P < 0.05).ConclusionsBoth conduits show excellent early and midterm outcomes for RVOT reconstruction in the Ross procedure. We suggest that DP-BJVC is more suitable for infants, and ePTFE conduit is more suitable for older children who require larger conduits.

Abstract Secretory carcinoma of the breast (SCB) is a rather rare entity of invasive breast cancer, the clinicopathologic characteristics and survival outcomes remain to be elaborated. A retrospective review was conducted in SEER database. A total of 190 SCB patients identified in SEER were eligible for inclusion in the analysis. Median age at diagnosis was 56 years (range 2–96 years). Both sexes and bilateral breast could be affected. Intriguingly, the incidence of SCB tended towards to decreasing in recent decades. Small tumor burden was observed with a mean tumor size of 2.13 cm. In a subgroup with sufficient details, positive staining of estrogen receptor (ER) and progesterone receptor (PR) was 58% and 40%, respectively. The vast majority of patients were of well to moderate differentiation (86.86%) and negative regional lymph nodes involvement (70.71%). Nearly half of the patients took radiotherapy and chemotherapy. Seniors were inclined to have an inferior breast cancer specific survival (BCSS) than their younger counterparts (P = 0.018). Patients underwent breast conserving surgery (BCS) and radiotherapy had much better BCSS than its mastectomy counterparts (P = 0.014). Collectively, SCB is a clinical indolent invasive breast cancer with excellent prognosis. BCS in conjunction with radiotherapy would be a rational alternative for this distinct entity.

BackgroundMycobacterium senegalense is a non-tuberculous mycobacterium and is found everywhere in the environment. However, M. senegalense infection in human is extremely rare, especially in immunocompetent individuals. It is difficult to detect M. senegalense infection because its symptoms are non-specific, and routine diagnostic tests are less sensitive. It is also resistant to commonly used antibiotics. Here, we report the first case of M. senegalense infection after laparoscopic cholecystectomy in China.Case PresentationA 55-year-old man was admitted because of repeated infections at multiple incision sites for more than 1 year. Although routine diagnostic test results were negative, metagenomic next-generation sequencing (mNGS) identified DNA sequences of M. senegalense in tissue samples from incision sites. The presence of M. senegalense was further confirmed by polymerase chain reaction and capillary electrophoresis. After 60 days of quadruple therapy with clarithromycin, moxifloxacin, rifampicin, and oxycycline, the patient's wound healed.ConclusionWe believe the case findings contribute to the limited amount of knowledge about M. senegalense infection and raises awareness that this infection can result in poor wound healing, even in an immunocompetent host. Owing to a lack of early, precise diagnosis, it is difficult to treat M. senegalense infections. Based on our findings, mNGS is a sensitive diagnostic test for M. senegalense infections.

Abstract Background The outcomes of mitral valve replacement (MVR) in pediatrics especially in the patients weighing less than 10 kg are not always favorable. This study aimed to measure long-term outcomes of MVR in our institution. Methods Nine young children weighing less than 10 kg underwent MVR with mechanical prostheses were enrolled in this retrospectively study. Kaplan–Meier survival analysis was used for the prediction of freedom from death and adverse events. Chi-square test was performed to compare outcomes for patients with different ratios of mechanical prosthesis size and body weight. Fourteen related literatures were also reviewed to support our study. Results All patients received bileaflet mechanical prostheses replacement. The surgical technique varied among the patients with prostheses implanted in the intra-annular (n = 5), supra-annular (n = 1), or with a Dacron conduit segment in the supra-annular position (n = 3). The valve size/weight ratio ranged from 2.11 to 5.00. There were two early death and one late death post-operation. The mean follow-up period was 80.67 ± 63.37 months, the transvalvular gradient was 10.5 ± 1.76 mmHg (range 8 to 12) and the peak gradient of LVOT was 5.00 ± 0.64 mmHg. One (11.1%) patient underwent an immediate revision MVR after initial MVR due to the periprosthetic leak. No patients required surgical reintervention or permanent pacemaker placement during long-term follow-up. Conclusions The tailored surgical strategy utilized for MVR in infants resulted in reliable valve function and excellent survival. Although revision is inevitable due to somatic growth, the bileaflet mechanical prostheses displayed appropriate durability.

Abstract Background Although most cases of atrial septal defect (ASD) are sporadic, familial cases have been reported, which may be caused by mutation of transcription factor GATA binding protein 4 (GATA4). Herein we combined whole-exome sequencing and bioinformatics strategies to identify a novel mutation in GATA4 accounting for the etiology in a Chinese family with ASD. Methods We identified kindred spanning 3 generations in which 3 of 12 (25.0%) individuals had ASD. Punctilious records for the subjects included complete physical examination, transthoracic echocardiography, electrocardiograph and surgical confirming. Whole-exome capture and high-throughput sequencing were performed on the proband III.1. Sanger sequencing was used to validate the candidate variants, and segregation analyses were performed in the family members. Results Direct sequencing of GATA4 from the genomic DNA of family members identified a T-to-C transition at nucleotide 929 in exon 5 that predicted a methionine to threonine substitution at codon 310 (M310T) in the nuclear localization signal (NLS) region. Two affected members (II.2 and III.3) and the proband (III.1) who was recognized as a carrier exhibited this mutation, whereas the other unaffected family members or control individuals did not. More importantly, the mutation GATA4 (c.T929C: p.M310T) has not been reported previously in either familial or sporadic cases of congenital heart defects (CHD). Conclusions We identified for the first time a novel M310T mutation in the GATA4 gene that is located in the NLS region and leads to family ASD with arrhythmias. However, the mechanism by which this pathogenic mutation contributes to the development of heart defect and tachyarrhythmias remains to be ascertained.

Abstract Background Previous studies have revealed that mutations of Spalt Like Transcription Factor 1 (SALL1) are responsible for Townes-Brocks syndrome (TBS), a rare genetic disorder that is characterized by an imperforate anus, dysplastic ears, thumb malformations and other abnormalities, such as hearing loss, foot malformations, renal impairment with or without renal malformations, genitourinary malformations, and congenital heart disease. In addition, the protein tyrosine phosphatase receptor type Q (PTPRQ) gene has been identified in nonsyndromic hearing loss patients with autosomal recessive or autosomal dominant inherited patterns. Methods A Chinese family with TBS and hearing loss was enrolled in this study. The proband was a two-month-old girl who suffered from congenital anal atresia with rectal perineal fistula, ventricular septal defect, patent ductus arteriosus, pulmonary hypertension (PH), and finger deformities. The proband’s father also had external ear deformity with deafness, toe deformities and PH, although his anus was normal. Further investigation found that the proband’s mother presented nonsyndromic hearing loss, and the proband’s mother’s parents were consanguine married. Whole-exome sequencing and Sanger sequencing were applied to detect the genetic lesions of TBS and nonsyndromic hearing loss. Results Via whole-exome sequencing and Sanger sequencing of the proband and her mother, we identified a novel heterozygous mutation (ENST00000251020: c.1428_1429insT, p. K478QfsX38) of SALL1 in the proband and her father who presented TBS phenotypes, and we also detected a new homozygous mutation [ENST00000266688: c.1057_1057delC, p. L353SfsX8)] of PTPRQ in the proband’s mother and uncle, who suffered from nonsyndromic hearing loss. Both mutations were located in the conserved sites of the respective protein and were predicted to be deleterious by informatics analysis. Conclusions This study confirmed the diagnosis of TBS at the molecular level and expanded the spectrum of SALL1 mutations and PTPRQ mutations. Our study may contribute to the clinical management and genetic counselling of TBS and hearing loss.

We describe stimulated Brillouin scattering process in a fiber system with light field phase modulated by lowpass filtered and amplified pseudo random bit sequence (PRBS) using localized nonfluctuating source model. The effective Brillouin gain spectra and the ratio of normalized Stimulated Brillouin Scattering (SBS) threshold to RMS optical linewidth is used to characterize the SBS suppression capability of the PRBS phase modulation. The normalized effective Brillouin gain spectra for different modulation parameters are calculated to exhibit the Brillouin gain broadening process. Based on the theoretical model, we find that the SBS threshold reaches a maximum for the ratio of cutoff frequency to clock rate rc = 0.53 and RMS modulation depth krms = 0.55 π for PRBS9. An effective Brillouin gain spectrum measurement setup is established, and the theoretical predictions are verified by the experiment.

With the large-scale access of distributed resources to distribution network operation, there are more and more prosumers on the user side. It forms the basis of load prediction and demand-side management to identify different power consumption patterns and establish a typical load characteristic database according to the load data of prosumers. Therefore, a method to build a prosumer load characteristic database based on a deep convolutional autoencoder is proposed. First, the autoencoder network was used to extract the features of the load data collected to reduce the data dimension. Then, the density weight canopy algorithm was used to precluster the data after dimensionality reduction to obtain the initial clustering center and the optimal clustering number K value. The pre-clustering results were combined with the k-means algorithm for clustering, and the typical load characteristic database of prosumers was obtained. Finally, the comparison between the clustering index and the traditional k-means clustering algorithm and the improved k-means direct clustering algorithm proves that the method can effectively improve the accuracy of clustering results.

BackgroundPediatric primary cardiac tumors (PCTs) are rare. Its clinical features and prognoses are not well defined. The management of asymptomatic patients with cardiac fibromas remains controversial.ObjectiveWe aimed to examine our experience in surgical resection of pediatric PCT, with specific focuses on the management of large fibromas.MethodsThis study included all the children who underwent surgical resection of PCT in our institution between December 2008 and June 2021. The last follow-up was performed between June 1st and August 26th, 2021. Kaplan–Meier method was used to estimate the postoperative survival, freedom from reoperation, event-free survival, and also related risk factors. The tumor volume and volume index (volume divided by body surface area) were measured for cardiac fibromas.ResultsOf the 39 patients with median operative age of 9.5 [interquartile range (IQR): 1.2–16.5] years, 35 (89.7%) had benign tumors (fibromas for 15, myxomas for 13, and others for 7). The length and volume of fibromas were independent of age and symptoms (Ps > 0.05). The fibroma volume index was negatively correlated with age (P = 0.039), with a mean value of 105 ± 70 ml/m2. Of the 15 patients with fibromas, 5 were asymptomatic, 4 received partial resection, 4 required transmural resection, and 4 presented postoperative left ventricular (LV) dysfunction (ejection fraction

BackgroundsArrhythmic right ventricular cardiomyopathy (ARVC) is a cardiomyopathy with a genetic predisposition that can lead to a sudden cardiac death and heart failure. According to the 2010 Task Force Criteria, genetic diagnosis is one of the most important methods, but, so far, only a few genes related to ARVC have been identified.MethodsIn this study, the pathogenic gene of a patient with ARVC was examined using whole-exome sequencing. The plasmids of TNNI3K were constructed, and the effects of the TNNI3K variant was investigated by a real-time polymerase chain reaction (PCR) and western blot.ResultsA novel variant (c.1538T > C) of TNNI3K was identified, with phenotypes of dominant right ventricular (RV) disease preliminarily fulfilling the diagnosis of ARVC. A comprehensive assessment revealed that the variant was pathogenic. We found that this variant would lead to a decrease in the level of TNNI3K mRNA and protein, as well as a decrease in the expression of the RYR2 gene, which further proves that TNNI3K plays an important role in cardiomyopathy and expands the spectrum of the TNNI3K variants.ConclusionIn this study, we reported a TNNI3K variant in ARVC for the first time, and the results not only contribute to the diagnosis of ARVC, but also provide a reference for genetic counseling and promote the understanding of the genetic mechanism of cardiomyopathy.

Lipid-rich porcine oocytes are extremely sensitive to cryopreservation compared to other low-lipid oocytes. Vitrification has outperformed slowing freezing in oocyte cryopreservation and is expected to improve further by minimizing cellular osmotic and/or oxidative stresses. In this study, we compared the effects of loading porcine cumulus-oocyte complexes with glycine (an organic osmolyte) or glycine plus melatonin (an endogenous antioxidant) during vitrification, thawing and subsequent maturation to mitigate osmotic injuries or osmotic and oxidative damages on the developmental potential of porcine oocytes. Our data demonstrated that glycine treatment significantly increased the vitrification efficiency of porcine oocytes to levels comparable to those observed with glycine plus melatonin treatment. It was manifested as the thawed oocyte viability, oocyte nuclear maturation, contents of reactive oxygen species, translocation of cortical granules and apoptotic occurrence in mature oocytes, levels of ATP and transcripts of glycolytic genes in cumulus cells (markers of oocyte quality), oocyte fertilization and blastocyst development. However, the latter was more likely than the former to increase ATP contents and normal mitochondrial distribution in mature oocytes. Taken together, our results suggest that mitigating osmotic and oxidative stresses induced by vitrification and thawing can further enhance the developmental competency of vitrified porcine oocytes at the germinal vesicle stage.

Abstract Background During the past few decades, drug delivery system (DDS) has attracted many interests because it could enhance the therapeutic effects of drugs and reduce their side effects. The advent of nanotechnology has promoted the development of nanosized DDSs, which could promote drug cellular uptake as well as prolong the half-life in blood circulation. Novel polymer micelles formed by self-assembly of amphiphilic polymers in aqueous solution have emerged as meaningful nanosystems for controlled drug release due to the reversible destabilization of hydrophobic domains under different conditions. Results The amphiphilic polymers presented here were composed of cholesterol groups end capped and poly (poly (ethylene glycol) methyl ether methacrylate) (poly (OEGMA)) as tailed segments by the synthesis of cholesterol-based initiator, followed by atom transfer radical polymerization (ATRP) with OEGMA monomer. FT-IR and NMR confirmed the successfully synthesis of products including initiator and polymers as well as the Mw of the polymers were from 33,233 to 89,088 g/mol and their corresponding PDI were from 1.25 to 1.55 by GPC. The average diameter of assembled polymer micelles was in hundreds nanometers demonstrated by DLS, AFM and SEM. The behavior of the amphiphilic polymers as micelles was investigated using pyrene probing to explore their critical micelle concentration (CMC) ranging from 2.53 × 10−4 to 4.33 × 10−4 mg/ml, decided by the balance between cholesterol and poly (OEGMA). Besides, the CMC of amphiphilic polymers, the quercetin (QC) feeding ratio and polarity of solvents determined the QC loading ratio maximized reaching 29.2% certified by UV spectrum, together with the corresponding size and stability changes by DLS and Zeta potential, and thermodynamic changes by TGA and DSC. More significantly, cholesterol end-capped polymer micelles were used as nanosized systems for controlled drug release, not only alleviated the cytotoxicity of QC from 8.6 to 49.9% live cells and also achieved the QC release in control under different conditions, such as the presence of cyclodextrin (CD) and change of pH in aqueous solution. Conclusions The results observed in this study offered a strong foundation for the design of favorable polymer micelles as nanosized systems for controlled drug release, and the molecular weight adjustable amphiphilic polymer micelles held potential for use as controlled drug release system in practical application.

Pericardial synovial sarcomas are sporadic tumors. Herein, we report a case of primary pericardial synovial sarcoma originating from the right pericardium. Missed diagnosis delayed surgical treatment. Eventually, the tumor occupied the almost entire pericardial cavity. The pericardial tumor was surgically removed as soon as possible after admission. In this paper, we aim to provide details that can help further understand the differing symptoms and presentations of pericardial synovial sarcoma and highlight the importance of consideration of this disease in similar cases where the etiology of pericardial effusion is unknown.

Background: The dihydrofolate reductase (DHFR) gene is imperative in development, therefore it is essential to explore its effects on heart development. Thus, here a dhfr zebrafish knock-in (KI) strain was constructed.Methods: CRISPR/Cas9 technology was used to establish the dhfr KI zebrafish strain. This strain was hybridized with TgG fluorescent strain zebrafish to observe the phenotypes of heart shape, size, and circularization direction. Wild-type (WT) and KI zebrafish were then dissected and histologically stained to observe pathological changes. Western blot analysis was used to verify the increased expressions of zebrafish genes after KI. Hybridization experiments were used to confirm the presence of abnormal gonadal dysplasia.Results: The zebrafish dhfr KI strain was successfully constructed through CRISPR/Cas9 technology. At 6 days post fertilization (dpf), microscopic examinations of KI (homozygous) specimens revealed pericardial effusions, heart compressions, and curled tails. Compared with WT, the Hematoxylin and Eosin (H&E) tissue sections of KI-homozygous zebrafish showed defects such as reduced atria and ventricles. Western blot analysis indicated that the expression of the DHFR protein increased in both heterozygotes and homozygotes of dhfr KI zebrafish. Hybridization experiments revealed that dhfr KI may affect gonadal function.Conclusion: The DHFR gene plays an important regulatory role in the process of heart development, and copy number variations (CNVs) of this gene may constitute a new pathogenic mechanism of congenital heart disease (CHD).

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer affecting humans. However, appropriate biomarkers for diagnosis and prognosis have not yet been established. Here, we evaluated the gene expression profiles of patients with NSCLC to identify novel biomarkers. Methods: Three datasets were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes were analyzed. Venn diagram software was applied to screen differentially expressed genes, and gene ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Cytoscape was used to analyze protein-protein interactions (PPI) and Kaplan–Meier Plotter was used to evaluate the survival rates. Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), and The Human Protein Atlas (THPA) were used to analyze protein expression. Quantitative real-time polymerase (qPCR) chain reaction was used to verify gene expression. Results: We identified 595 differentially expressed genes shared by the three datasets. The PPI network of these differentially expressed genes had 202 nodes and 743 edges. Survival analysis identified 10 hub genes with the highest connectivity, 9 of which ( CDC20 , CCNB2 , BUB1 , CCNB1 , CCNA2 , KIF11 , TOP2A , NDC80 , and ASPM ) were related to poor overall survival in patients with NSCLC. In cell experiments, CCNB1 , CCNB2 , CCNA2 , and TOP2A expression levels were upregulated, and among different types of NSCLC, these four genes showed highest expression in large cell lung cancer. The highest prognostic value was detected for patients who had successfully undergone surgery and for those who had not received chemotherapy. Notably, CCNB1 and CCNA2 showed good prognostic value for patients who had not received radiotherapy. Conclusion : CCNB1 , CCNB2 , CCNA2 , and TOP2A expression levels were upregulated in patients with NSCLC. These genes may be meaningful diagnostic biomarkers and could facilitate the development of targeted therapies.

As peripheral blood contains fluctuated levels of circulating cell-free mitochondrial DNA (ccf mtDNA), we aimed to evaluate ccf mtDNA as a biomarker for diagnosis and prognosis of epithelial ovarian cancer (EOC). In the present study, we recruited 165 EOC patients and 60 healthy women. Quantitative RT-PCR was applied to amplify 79-bp and 230-bp fragments of the mitochondrial 16 s RNA gene in sera of these participants. MtDNA integrity was defined as the ratio of long to short mtDNA fragments. We observed that the levels of mtDNA79 and mtDNA230 were significantly increased (P = .0001), whereas the mtDNA integrity (P = .0001) was decreased in EOC patients compared with those in healthy controls. MtDNA79 showed a sensitivity of 90.3% and a specificity of 81.7% (AUC = 0.900) to discriminate EOC from healthy controls. Moreover, the amounts of mtDNA79 (P = .0001, P = .012, P = .039) and mtDNA230 (P = .0001, P = .042) continuously raised from healthy controls over FIGO I-II to FIGO III and IV, with highest levels of mtDNA79 (P = .0001) and mtDNA230 (P = .0001) in FIGO III and IV. Increasing levels of mtDNA79 (P = .003, P = .0001) and mtDNA230 (P = .041, P = .0001) were also associated with lymph node metastasis and CA125 values. The higher levels of mtDNA79 (P = .0001; HR 3.2, 95%CI:1.6–6.3) and mtDNA230 (borderline P = .048, HR 0.9, 95%CI:0.9–1.0) also correlated with poor patients' overall survival, of which mtDNA79 could act as an independent factor for overall survival. Our data show a significant association of increasing levels of ccf mtDNA with EOC progress and poor prognosis.

Abstract Background Traditional percutaneous device closure of perimembranous ventricular septal defects (PmVSDs) is a minimally invasive technique, but can result in high radiation exposure and can result in potential arterial complications. Here, we aimed to assess the safety and feasibility of device closure of PmVSDs via the femoral vein approach under transesophageal echocardiography (TEE) guidance in children. Methods From January 2014 to December 2017, a total of 46 PmVSD patients (mean age, 6.5 ± 2.3 years [range, 4.2–12.0 years]; mean body weight 22.1 ± 6.6 kg [range, 16.0–38.5 kg]; VSD diameter, 4.1 ± 0.6 mm [range, 3.2–5.0 mm]) underwent attempted transcatheter closure via the femoral vein approach under the guidance of TEE without fluoroscopy. Results The transcatheter occlusion procedure under TEE guidance was successful in 44 (95.7%) patients. Surgery was necessary in 2 (4.3%) patients. The procedure duration was 28.2 ± 8.7 min (range, 12.0–42.0 min). One patient had immediate post-operative trivial residual shunt and three patients had immediate incomplete right bundle branch block (IRBBB) after operation; the new IRBBB in 1 case was noted in the first postoperative month. No residual shunt was noted at 3 months after the procedure, and no intervention related complications were detected at 1–24 months follow-up. Conclusions Percutaneous device closure of PmVSDs under TEE guidance solely by femoral vein approach is effective and safe, avoids radiation exposure, potential arterial complications and a surgical incision.

The relative pose estimation between the chaser and the non-cooperative target is a significant prerequisite for performing on-orbit servicing (OOS) missions. The chaser could design the close-range rendezvous trajectory to approach the non-cooperative target only when the relative pose parameters are obtained effectively and efficiently. In this paper, a pose estimation scheme is designed to obtain the relative pose parameters between the chaser and the non-cooperative target coated with multilayer insulation material (MLI). The scheme utilizes a time-of-flight (TOF) camera to acquire 3D point clouds of the non-cooperative target, and uses the iterative closest point (ICP) method to achieve the point cloud registration between every two frames. Aiming at decreasing the non-systematic errors caused by MLI in the data acquisition of the TOF camera, the corresponding point median filtering approach is adopted to filter out the bad corresponding point pairs generated in the ICP method. A semi-physical experiment is carried out to evaluate the performance of the proposed scheme, the result of which shows that the proposed scheme could notably improve the accuracy of pose estimation of the non-cooperative target, meanwhile the computational efficiency is also ensured.

Objectives To summarise current evidence on the use of pentoxifylline (PTX) to prevent contrast-induced nephropathy (CIN).Methods The PubMed, Embase and CENTRAL databases were searched for randomised controlled trials including patients with and without PTX undergoing contrast media exposure. We analysed the incidence of CIN and serum creatinine changes before and after contrast media exposure. All statistical analyses were conducted with Review Manager V.5.3.Results We finally enrolled in seven randomised controlled trials with a total of 1484 patients in this analysis. All of seven included studies were performed in patients undergoing angioplasty or stenting. The overall rates of CIN were 8.8% and 10.4% in the PTX groups and control groups, respectively. However, no significant reduction in the CIN rate was observed in the patients treated with PTX compared with the control groups (OR 0.81, 95% CI 0.57 to 1.13, I2=0, p=0.21). All studies reported no hospital mortality and the new requirement for dialysis during the trials.Conclusion Perioperative administration of PTX to patients undergoing angioplasty did not significantly reduce the development of CIN but showed some weak tendency of lower serum creatinine increase. Based on the available trials, the evidence does not support the administration of PTX for the prevention of CIN. More trials with larger sample sizes are needed to evaluate the role of PTX in CIN prevention.

IntroductionKidney renal clear cell carcinoma (KIRC) has a high incidence globally, and its pathogenesis remains unclear. Long non-coding RNA (lncRNA), as a molecular sponge, participates in the regulation of competitive endogenous RNA (ceRNA). We aimed to construct a ceRNA network and screened out possible lncRNAs to predict KIRC prognosis.Material and methodsAll KIRC data were downloaded from the TCGA database and screened to find the possible target lncRNA; a ceRNA network was designed. Next, GO functional enrichment and KEGG pathway of differentially expressed mRNA related to lncRNA were performed. We used Kaplan-Meier curve analysis to predict the survival of these RNAs. We used Cox regression analysis to construct a model to predict KIRC prognosis.ResultsIn the KIRC datasets, 1457 lncRNA, 54 miRNA and 2307 mRNA were screened out. The constructed ceRNA network contained 81 lncRNAs, nine miRNAs, and 17 mRNAs differentially expressed in KIRC. Survival analysis of all differentially expressed RNAs showed that 21 lncRNAs, four miRNAs, and two mRNAs were related to the overall survival rate. Cox regression analysis was performed again, and we found that eight lncRNAs were related to prognosis and used to construct predictive models. Three lnRNAs from independent samples were meaningful.ConclusionThe construction of ceRNA network was involved in the process and transfer of KIRC, and three lncRNAs may be potential targets for predicting KIRC prognosis.

Background Use of inpatient brain magnetic resonance imaging (MRI) in patients with acute ischemic stroke is highly institution dependent and has been associated with increased length and cost of hospital stay. We examined whether inpatient brain MRI in patients with acute ischemic stroke is associated with improved clinical outcomes to justify its resource requirements. Methods and Results The National Inpatient Sample database was queried retrospectively to find 94 003 patients who were admitted for acute ischemic stroke and then received inpatient brain MRI between 2012 and 2014. Multivariable regression analysis was performed with respect to a control group to assess for differences in the rates of inpatient mortality and complications, as well as the length and cost of hospital stay based on brain MRI use. Inpatient brain MRI was independently associated with lower rates of inpatient mortality (1.67% versus 3.09%; adjusted odds ratio [OR], 0.60; 95% CI, 0.53–0.68; P

Ruminant methane, which is generated by methanogens through the consumption of hydrogen and supports the normal function of the rumen ecosystem, is a major source of greenhouse gases. Reductive acetogenesis by acetogens is a possible alternative sink that can dispose of hydrogen for acetate production. However, the distribution of rumen methanogens and acetogens along with the relationships among methanogens, acetogens, and their host are poorly understood. Therefore, we investigated the rumen methanogen and acetogen communities of 97 individual animals representing 14 ruminant species within three ruminant families Cervidae (deer), Bovidae (bovid), and Moschidae (musk deer). The results showed that the Methanobrevibacter spp. and acetogens associated with Eubacteriaceae were the most widespread methanogens and acetogens, respectively. However, other methanogens and acetogens exhibited host specificity in the rumen of reindeer and Chinese muntjac deer. Acetogen and methanogen communities were not correlated in these species, and the phylosymbiosis signature between host phylogeny and the composition of both communities was lacking. The abundance of Methanobrevibacter gottschalkii was negatively correlated with the degree of papillation of the rumen wall. Finally, co-occurrence analysis showed that the variation of the predicted methane yields was characterized by the interactive patterns between methanogens, acetogens, and concentrations of rumen metabolites. Our results show that rumen methanogen and acetogen communities have low compositional interdependence and do not exhibit parallel host evolution, which suggests that the strategies for mitigating methane production should be based on a species-specific rumen microbiota analysis.

We have established a thermal distribution model of the multilayer dielectric grating with laser irradiation based on the Beer–Lambert theory and the thermal conduction theory. The temperature change on the surface and inside of the grating is simulated according to the laser irradiation time, laser power, substrate size, and substrate material. The actual thermal behavior of a 50 × 50 × 10 mm3 multilayer dielectric grating with fused silica substrate is measured with 10 kW fiber laser irradiation. The results show a dynamic equilibrium between the energy absorbed in the laser irradiation area and the energy transferred in the thermal transfer area when the maximum temperature of the grating is kept stable. The simulation results are in good agreement with the experimental data, which provides a reference for understanding the thermal dynamics process of the multilayer dielectric grating with high power density laser irradiation.

Abstract Background Ankylosing spondylitis (AS) is a debilitating autoimmune disease affecting tens of millions of people in the world. The genetics of AS is unclear. Analysis of rare AS pedigrees might facilitate our understanding of AS pathogenesis. Methods We used genome-wide linkage analysis and whole-exome sequencing in combination with variant co-segregation verification and haplotype analysis to study an AS pedigree and a sporadic AS patient. Results We identified a missense variant in the ankyrin repeat and death domain containing 1B gene ANKDD1B from a Han Chinese pedigree with dominantly inherited AS. This variant (p.L87V) co-segregates with all male patients of the pedigree. In females, the penetrance of the symptoms is incomplete with one identified patient out of 5 carriers, consistent with the reduced frequency of AS in females of the general population. We further identified a distinct missense variant affecting a conserved amino acid (p.R102L) of ANKDD1B in a male from 30 sporadic early onset AS patients. Both variants are absent in 500 normal controls. We determined the haplotypes of four major known AS risk loci, including HLA-B*27, 2p15, ERAP1 and IL23R, and found that only HLA-B*27 is strongly associated with patients in our cohort. Conclusions Together these results suggest that ANKDD1B variants might be associated with AS and genetic analyses of more AS patients are warranted to verify this association.

Sika deer (Cervus Nippon) and wapiti (Cervus elaphus) are closely related species and their hybridization can result in significant allele-shift of their gene pool. Additive genetic effects and putative heterotic effects of their hybridization on growth performance could confer considerable economic advantage in deer farming. Here, we used double-digest restriction site-associated DNA sequencing technology (ddRAD-seq) and detected ∼320,000 genome-wide SNPs from 30 captive individuals: 7 sika deer, 6 wapiti and 17 F1 hybrids (reciprocal cross). By screening observed heterozygosity of each SNP across four taxonomic groups, we report for the first time a resource of 2,015 putative diagnostic SNP markers (species-specific SNPs for sika deer and wapiti), which can be used to design tools for assessing or monitoring the degree of hybridization between sika deer and wapiti. These ddRAD-seq data and SNP datasets are also valuable resources for genome-wide studies, including trait discovery for breeders of domestic deer.

Wheat take-all, caused by two variants of the fungus Gaeumannomyces gramnis (Sacc.) Arx & D. Olivier, was common in spring wheat areas in northwest and north China and occurred in winter wheat areas in north China. The yield of common disease areas was reduced by more than 20% and the yield of severe cases was reduced by more than 50%. Large-scale rapid and accurate estimation of the incidence of wheat take-all plays an important role in guiding field control and agricultural yield estimation. In this study, a portable ground spectrometer was used to collect the spectral reflectance in the 350–1050 nm band range of wheat canopy after take-all infection in the wheat grain filling stage and combined with the ground disease survey data.Then a winter wheat take-all disease index estimation model was proposed based on the spectral band division interval and selected band combination. According to the normalized difference spectral index (NDSI) and the determinative coefficient of the disease index formed by any two band combinations, the spectral index band combinations corresponding to the spectral index with high correlation in each region were screened by dividing spectral intervals. Partial least-squares regression was used to establish a binary and ternary disease index calibration model. The results showed that the model based on spectral indices of ternary variables had the highest coefficient of determination. Finally, the optimal regression model of wheat take-all disease condition index composed of NDSI(R590,R598), NDSI(R534,R742) and NDSI(R810,R834) was established: Y = 134.577 − 70.301 NDSI(R590,R598) − 223.533 NDSI(R534,R742) + 51.584 NDSI(R810,R834) (R2 = 0.743, RMSEP = 0.094, df = 15), which was the most suitable model for winter wheat take-all estimation. The construction of this model can provide new method and technical support for future evaluation and monitoring of wheat take-all disease on the field.

Sika deer are an economically valuable species owing to their use in traditional Chinese medicine, particularly their velvet antlers. Sika deer in northeast China are mostly farmed in enclosure. Therefore, genetic management of farmed sika deer would benefit from detailed knowledge of their genetic diversity. In this study, we generated over 1.45 billion high-quality paired-end reads (288 Gbp) across 42 unrelated individuals using double-digest restriction site-associated DNA sequencing (ddRAD-seq). A total of 96,188 (29.63%) putative biallelic SNP loci were identified with an average sequencing depth of 23×. Based on the analysis, we found that the majority of the loci had a deficit of heterozygotes (FIS >0) and low values of Hobs, which could be due to inbreeding and Wahlund effects. We also developed a collection of high-quality SNP probes that will likely be useful in a variety of applications in genotyping for cervid species in the future.

Abstract Inflammatory factors regulated by NF-κB play a significant role in PAH and myocardial hypertrophy. LXR activation may inhibit myocardial hypertrophy via suppressing inflammatory pathways; it is unknown whether LXR is also involved in PAH-induced myocardial hypertrophy or remodeling. To further explore the protective effect of LXR in PAH-induced cardiac hypertrophy and remodeling, a PAH model was developed, and T0901317, an agonist of LXR, was used to examine the effect of LXR activation. PAH rats demonstrated obvious cardiac hypertrophy and remodeling in the right ventricle, but significant improvement of cardiac hypertrophy and remodeling was observed in PAH rats treated with T0901317. Through RT-PCR, Western blot and ELISA examination, NF-κB, IL-6, TNF-α, and iNOS were found to be significantly reduced in PAH rats treated with T0901317 compared to PAH rats treated with DMSO. Apoptosis was also significantly reduced in PAH rats treated with T0901317. Thus, LXR activation may inhibit PAH-induced cardiac hypertrophy and remodeling by inhibiting NF-κB-mediated inflammatory pathways.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most lethal malignancies in China and is an exceptionally drug-resistant tumor with a 5-year survival rate less than 15%. Cisplatin is the most commonly used conventional chemotherapeutic drug for the treatment of ESCC, but some patients have a poor response to cisplatin-based chemotherapy. New strategies that could enhance chemosensitivity to cisplatin are needed. Methods We used reverse transcription-RCR (RT-PCR), immunoblot, immunohistochemical (IHC) staining, anchorage-dependent and -independent growth assays, co-immunoprecipitation (Co-IP) assay, RNA interference and in vivo tumor growth assay to study the expression of MCL-1 in ESCCs and the response of ESCC cells to cisplatin. Results The present study showed that MCL-1 expression was significantly increased in ESCC tissues compared to normal adjacent tissues and was associated with depth of invasion and lymph node metastasis. Knockdown of MCL-1 produced significant chemosensitization to cisplatin in association with caspase-3 activation and PARP cleavage in KYSE150 and KYSE510 cells. The selective MCL-1 inhibitor UMI-77 caused dissociation of MCL-1 from the proapoptotic protein BAX and BAK, and enhanced KYSE150 and KYSE510 cells to cisplatin-induced apoptosis accompanied by caspase-3 activation and PARP cleavage. Conclusions The current study suggests that MCL-1 contributes to the development of ESCC and is a promising therapeutic target for chemosensitization of ESCC cells to cisplatin. This might provide a scientific basis for developing effective approaches to treat the subset of ESCCs patients with MCL-1 overexpression.

The hair follicle dermal papilla is critical for hair generation and de novo regeneration. When cultured in vitro, dermal papilla cells from different species demonstrate two distinguishable growth patterns under the conventional culture condition: a self-aggregative three dimensional spheroidal (3D) cell pattern and a two dimensional (2D) monolayer cell pattern, correlating with different hair inducing properties. Whether the loss of self-aggregative behavior relates to species-specific differences or the improper culture condition remains unclear. Can the fixed 2D patterned dermal papilla cells recover the self-aggregative behavior and 3D pattern also remains undetected. Here, we successfully constructed the two growth patterns using sika deer (Cervus nippon) dermal papilla cells and proved it was the culture condition that determined the dermal papilla growth pattern. The two growth patterns could transit mutually as the culture condition was exchanged. The fixed 2D patterned sika deer dermal papilla cells could recover the self-aggregative behavior and transit back to 3D pattern, accompanied by the restoration of hair inducing capability when the culture condition was changed. In addition, the global gene expressions during the transition from 2D pattern to 3D pattern were compared to detect the potential regulating genes and pathways involved in the recovery of 3D pattern and hair inducing capability.