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Music tension is a link between music structures and emotions. As music unfolds, developmental patterns induce various emotional experiences, but the relationship between developmental patterns and tension experience remains unclear. The present study compared two developmental patterns of two successive phrases (tonal shift and melodic shift) with repetition condition to investigate the relationship with tension experience. Professional musicians rated on-line felt tension and EEG responses were recorded while listening to music sequences. Behavioral results showed that tension ratings under tonal and melodic shift conditions were higher than those under repetition conditions. ERP results showed larger potentials at early P300 and late positive component (LPC) time windows under tonal shift condition, and early right anterior negativity (ERAN) and LPC under melodic shift condition. ERSP results showed early beta and late gamma power increased under tonal shift condition, theta power decreased and alpha power increased under melodic shift condition. Our findings suggest that developmental patterns play a vital role in tension experiences; tonal shift affects tension by tonal shift detection and integration, while melodic shift affects tension by attentional processing and working memory integration. From the perspective of Event Structure Processing Model, solid evidence was given to specify the time-span segmentation and reduction. [ABSTRACT FROM AUTHOR]

Sepsis survivors present long-term cognitive deficits. The present study was to investigate the effect of early administration of high-dose vitamin C on cognitive function in septic rats and explore its possible cerebral protective mechanism. Rat sepsis models were established by cecal ligation and puncture (CLP). Ten days after surgery, the Morris water maze test was performed to evaluate the behavior and cognitive function. Histopathologic changes in the hippocampus were evaluated by nissl staining. The inflammatory cytokines, activities of antioxidant enzymes (superoxide dismutase or SOD) and oxidative products (malondialdehyde or MDA) in the serum and hippocampus were tested 24 h after surgery. The activity of matrix metalloproteinase-9 (MMP-9) and expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1(HO-1) in the hippocampus were measured 24 h after surgery. Compared with the sham group in the Morris water maze test, the escape latency of sepsis rats was significantly (P = 0.001) prolonged in the navigation test, whereas the frequency to cross the platform and the time spent in the target quadrant were significantly (P = 0.003) reduced. High-dose vitamin C significantly decreased the escape latency (P = 0.01), but increased the time spent in the target quadrant (P = 0.04) and the frequency to cross the platform (P = 0.19). In the CLP+ saline group, the pyramidal neurons were reduced and distributed sparsely and disorderly, the levels of inflammatory cytokines of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 in the serum and hippocampus were significantly increased (P = 0.000), the blood brain barrier (BBB) permeability in the hippocampus was significantly (P = 0.000) increased, the activities of SOD in the serum and hippocampus were significantly (P = 0.000 and P = 0.03, respectively) diminished while the levels of MDA in the serum and hippocampus were significantly (P = 0.007) increased. High-dose vitamin C mitigated hippocampus histopathologic changes, reduced systemic inflammation and neuroinflammation, attenuated BBB disruption, inhibited oxidative stress in brain tissue, and up-regulated the expression of nuclear and total Nrf2 and HO-1. High-dose vitamin C significantly (P < 0.05) decreased the levels of tumor necrosis factor- (TNF)-α, interleukin-6 (IL-6), MDA in the serum and hippocampus, and the activity of MMP-9 in the hippocampus, but significantly (P < 0.05) increased the levels of SOD, the anti-inflammatory cytokine (IL-10) in the serum and hippocampus, and nuclear and total Nrf2, and HO-1 in the hippocampus. In conclusion, high-dose vitamin C can improve cognition impairment in septic rats, and the possible protective mechanism may be related to inhibition of inflammatory factors, alleviation of oxidative stress, and activation of the Nrf2/HO-1 pathway. [ABSTRACT FROM AUTHOR]

In the post-pandemic era, there is a need for medical professionals with creativity, clinical expertise, and social responsibility. The Chinese government issued a directive to enhance the "Five Characteristics" perceptions of medical students, incorporating moral integrity and adeptness in saving lives and aiding the injured, embracing a compassionate approach to medical practice, possessing the knowledge essential for academic distinction, mastering technical expertise, and the artistry of applying scientific methodologies. The purpose of this study was to investigate the opinions related to ethics and professional behaviors of medical students at one Chinese medical school using a validated 19-item survey instrument and analyze its influencing factors. We conducted a survey in a medical university in Anhui Province, China, and collected 1966 valid questionnaires using the "Five Characteristics Rating Scale". The results indicated high perceptions of "Five Characteristics" among Chinese medical students (85.42 ± 8.727). Lower-grade-year medical students (86.59 ± 7.888) had higher "Five Characteristics" perceptions than upper-grade-year medical students (84.29 ± 9.327, P < 0.05). In addition, medical students experiencing voluntary work during the COVID-19 pandemic showed higher perceptions (86.21 ± 8.357) than those without such experience (85.13 ± 8.842, P < 0.05). Grade year and voluntary work experience during the COVID-19 pandemic were influencing factors of "Five Characteristics" perceptions. Our research offers a theoretical foundation for governments and medical schools to cultivate doctors with high ethical standards and professional expectations. [ABSTRACT FROM AUTHOR]

Flower color can be applied to landscaping and identification of the purity of seeds in hybrid production. However, the molecular basis of white flower trait remains largely unknown in Brassica rapa. In this study, an F2 population was constructed from the cross between 15S1040 (white flower) and 92S105 (yellow flower) for fine mapping of white flower genes in B. rapa. Genetic analysis indicated that white flower trait is controlled by two recessive loci, Brwf1 and Brwf2. Using InDel and SNP markers, Brwf1 was mapped to a 49.6-kb region on chromosome A01 containing 9 annotated genes, and among them, Bra013602 encodes a plastid-lipid associated protein (PAP); Brwf2 was located in a 59.3-kb interval on chromosome A09 harboring 12 annotated genes, in which Bra031539 was annotated as a carotenoid isomerase gene (CRTISO). The amino acid sequences of BrPAP and BrCRTISO were compared between two yellow-flowered and three white-flowered lines and critical amino acid mutations of BrPAP and BrCRTISO were identified between yellow-flowered and white-flowered lines. Therefore, Bra013602 and Bra031539 were predicted as potential candidates for white flower trait. Our results provide a foundation for further identification of Brwf and increase understanding of the molecular mechanisms underlying white flower formation in Chinese cabbage. [ABSTRACT FROM AUTHOR]

Twenty-four hours after CLP-induced sepsis model was established, inflammatory factors, oxidative stress of serum and hippocampus, BBB permeability, Nissl's staining of hippocampus, and Western blot of hippocampus were evaluated. Ten days after CLP-induced sepsis model, behavioral tests of rats were performed. [Extracted from the article]

Type 2 diabetes mellitus (T2DM) is one common chronic disease caused by insulin secretion disorder that often leads to severe outcomes and even death due to complications, among which coronary heart disease (CHD) represents the most common and severe one. Given a huge number of T2DM patients, it is thus increasingly important to identify the ones with high risks of CHD complication but the quantitative method is still not available. Here, we first curated a dataset of 1,273 T2DM patients including 304 and 969 ones with or without CHD, respectively. We then trained an artificial intelligence (AI) model using randomly selected 4/5 of the dataset and use the rest data to validate the performance of the model. The result showed that the model achieved an AUC of 0.77 (fivefold cross-validation) on the training dataset and 0.80 on the testing dataset. To further confirm the performance of the presented model, we recruited 1,253 new T2DM patients as totally independent testing dataset including 200 and 1,053 ones with or without CHD. And the model achieved an AUC of 0.71. In addition, we implemented a model to quantitatively evaluate the risk contribution of each feature, which is thus able to present personalized guidance for specific individuals. Finally, an online web server for the model was built. This study presented an AI model to determine the risk of T2DM patients to develop to CHD, which has potential value in providing early warning personalized guidance of CHD risk for both T2DM patients and clinicians. [ABSTRACT FROM AUTHOR]

Rhythm affects the speech perception of events unfolding over time. However, it is not clear to what extent the rhythm could affect the processes of sentence speech production. In this event-related potential (ERP) study, we examined whether a particular rhythmic pattern could affect the planning of speech production before articulation. We recorded electrophysiological (EEG) and behavioural (reaction time) data while participants read aloud a target speech in Chinese. Target speeches were sentences or phrases consisting four characters, with regular (e.g., the 2 + 2 pattern; numbers in the brackets represent the number of syllables) or irregular (e.g., 1 + 3) rhythmic patterns, which were preceded by congruent or incongruent musical rhythmic patterns formed by simple pure tones with different temporal intervals. Behavioural and ERP findings indicated a rhythmic priming effect in comparing congruent and incongruent conditions in the regular target speeches, but not in the irregular ones. An early component (N100) that was elicited in response to target speeches that were rhythmically mismatched to primes was linked to the detection of hierarchical linguistic units, which did not conform to expectations. A later negative component (N400) was thought to reflect the violation of expectation on rhythmic pattern in speech production. These findings suggest that rhythmic pattern constrains grammatical and prosodic encoding during speech production, and support the hypothesis that speakers form a grammatical or a prosodic abstract frame before articulation. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is commonly present in critically ill patients with sepsis. Early prediction of short-term reversibility of AKI is beneficial to risk stratification and clinical treatment decision. The study sought to use machine learning methods to discriminate between transient and persistent sepsis-associated AKI. Septic patients who developed AKI within the first 48 h after ICU admission were identified from the Medical Information Mart for Intensive Care III database. AKI was classified as transient or persistent according to the Acute Disease Quality Initiative workgroup consensus. Five prediction models using logistic regression, random forest, support vector machine, artificial neural network and extreme gradient boosting were constructed, and their performance was evaluated by out-of-sample testing. A simplified risk prediction model was also derived based on logistic regression and features selected by machine learning algorithms. A total of 5984 septic patients with AKI were included, 3805 (63.6%) of whom developed persistent AKI. The artificial neural network and logistic regression models achieved the highest area under the receiver operating characteristic curve (AUC) among the five machine learning models (0.76, 95% confidence interval [CI] 0.74–0.78). The simplified 14-variable model showed adequate discrimination, with the AUC being 0.76 (95% CI 0.73–0.78). At the optimal cutoff of 0.63, the sensitivity and specificity of the simplified model were 63% and 76% respectively. In conclusion, a machine learning-based simplified prediction model including routine clinical variables could be used to differentiate between transient and persistent AKI in critically ill septic patients. An easy-to-use risk calculator can promote its widespread application in daily clinical practice. [ABSTRACT FROM AUTHOR]

Inflammatory cells in atherosclerotic plaque exclusively originate from hematopoietic stem/progenitor cells (HSPCs). In this study, we investigated whether circulating HSPCs frequency related to coronary stenosis in patients with coronary heart disease (CHD). Coronary angiography was performed in 468 participants who were recruited at Cardiology Centre in LuHe Hospital from March 2016 to May 2017. Among these subjects, 344 underwent echocardiography. Mononuclear cells isolated from peripheral blood were stained with an antibody cocktail containing anti-human CD34, anti-human lineage, anti-human CD38, and anti-human CD45RA. Lineage−CD38−CD45RAdimCD34+HSPCs were quantified by flow cytometry. CHD was defined as coronary stenosis ≥50% and the extent of CHD was further categorised by coronary stenosis ≥70%. A p < 0.0031 was regarded statistically significant by the Bonferroni correction. Circulating HSPCs frequency was 1.8-fold higher in CHD patients than non-CHD participants (p = 0.047). Multivariate-adjusted logistic analysis demonstrated that HSPCs was the only marker that was associated with the odds ratio of having mild vs. severe coronary stenosis (2.08 (95% CI, 1.35-3.21), p = 0.0009). Left ventricular ejection fraction was inversely correlated with HSPCs frequency and CRP in CHD patients (p < 0.05 for both). In conclusion, HSPCs frequency in circulation is intimately related to coronary stenoses in CHD patients. [ABSTRACT FROM AUTHOR]

Propaquizafop is a fatty acid synthetic herbicide used to control annual and perennial grasses. To understand the potential environmental risks of propaquizafop to crops and food safety, the adsorption, mobility, and degradation of propaquizafop in five different soils were studied. At an initial concentration of 5 mg L−1 propaquizafop, its adsorption equilibrium was reached within 24 h, and the adsorption rates were between 46.98 and 57.76%. The Elovich kinetic model provided the best fit for the kinetic model, with R2 values between 0.9882 and 0.9940. For the isothermal adsorption tests, the Freundlich model was used to better fit the adsorption characteristics of propaquizafop in different soils, with R2 values between 0.9748 and 0.9885. Increasing the concentration of Ca2+ was beneficial for propaquizafop adsorption. In the soil thin-layer chromatography tests, the Rf of propaquizafop in the five soil samples ranged from 0.076 to 0.123. The results of the soil column leaching tests showed that propaquizafop did not migrate in the five soil columns; it was not detected in the leachate of each soil column, and propaquizafop in the soil columns only existed in the 0–5 cm soil layer. The results of soil thin-layer chromatography and soil column leaching tests showed that propaquizafop is a pesticide with a weak migration ability. Under the same environmental conditions, the degradation rate of propaquizafop in different soils followed the order LF fluvo–aquic soil (T1/2 = 1.41 d) > CS red loam (T1/2 = 2.76 d) > SX paddy soil (T1/2 = 3.52 d) > CC black soil (T1/2 = 5.74 d) > BS ginseng soil (T1/2 = 7.75 d). Considering the effects of soil moisture, incubation temperature, and microorganisms on propaquizafop degradation in the soil, temperature was found to have the greatest influence on its degradation rate. [ABSTRACT FROM AUTHOR]

The concept design evaluation phase of the new product launch is extremely important. However, current evaluation information relies mainly on the a priori knowledge of decision makers and is subjective and ambiguous. For this reason, a conceptual design solution decision model based on Pythagorean fuzzy sets in a big data environment is proposed. Firstly, we use the ability of big data to mine and analyze information to construct a new standard for product concept design evaluation in the big data environment. Secondly, the Pythagorean fuzzy set (PFS), Analytic Hierarchy Process (AHP), and Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) are integrated into a decision model. AHP, extended by the Pythagorean fuzzy set, is used to determine the weights of new conceptual design criteria in a big data environment. The Pythagorean fuzzy TOPSIS is used to prioritize alternative conceptual design solutions. The feasibility of the approach is proven with a practical case, the generalizability of the method is confirmed with two descriptive digital cases, and the reliability, validity, and superiority of the process are demonstrated with sensitivity analysis, comparative analysis, and computational complexity analysis. [ABSTRACT FROM AUTHOR]

Jagged canonical Notch ligand 1 (JAG1) regulates the progression of many cancers by the Notch signaling pathway, but its role in breast cancer (BC) remains unclear. In this research, JAG1 protein expression in BC tissues was detected by immunohistochemistry. The association between JAG1 and clinical significance was analyzed. The effect of JAG1 on malignant behaviors of BC cells was demonstrated by in vitro experiments. JAG1 expression in BC tissues was higher than that in para-carcinoma tissues. High JAG1 expression was significantly linked to advanced lymph node metastasis, distant metastasis, and the TNM stage. JAG1 was an independent prognostic factor for BC patients. JAG1 knockdown inhibited the proliferation, motility, migration, and invasion of BC cells, and weakened adhesion and penetration abilities to the blood–brain barrier, whereas JAG1 overexpression had the opposite effects. JAG1 has the potential to be a prognostic marker and therapeutic target for BC patients. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is common among hospitalized children and is associated with a poor prognosis. The study sought to develop machine learning-based models for predicting adverse outcomes among hospitalized AKI children. We performed a retrospective study of hospitalized AKI patients aged 1 month to 18 years in the Second Xiangya Hospital of Central South University in China from 2015 to 2020. The primary outcomes included major adverse kidney events within 30 days (MAKE30) (death, new renal replacement therapy, and persistent renal dysfunction) and 90-day adverse outcomes (chronic dialysis and death). The state-of-the-art machine learning algorithm, eXtreme Gradient Boosting (XGBoost), and the traditional logistic regression were used to establish prediction models for MAKE30 and 90-day adverse outcomes. The models' performance was evaluated by split-set test. A total of 1394 pediatric AKI patients were included in the study. The incidence of MAKE30 and 90-day adverse outcomes was 24.1% and 8.1%, respectively. In the test set, the area under the receiver operating characteristic curve (AUC) of the XGBoost model was 0.810 (95% CI 0.763–0.857) for MAKE30 and 0.851 (95% CI 0.785–0.916) for 90-day adverse outcomes, The AUC of the logistic regression model was 0.786 (95% CI 0.731–0.841) for MAKE30 and 0.759 (95% CI 0.654–0.864) for 90-day adverse outcomes. A web-based risk calculator can facilitate the application of the XGBoost models in daily clinical practice. In conclusion, XGBoost showed good performance in predicting MAKE30 and 90-day adverse outcomes, which provided clinicians with useful tools for prognostic assessment in hospitalized AKI children. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) correlates with increased health-care costs and poor outcomes in older adults. However, there is no good scoring system to predict mortality within 30-day, 1-year after AKI in older adults. We performed a retrospective analysis screening data of 53,944 hospitalized elderly patients (age > 65 years) from multi-centers in China. 944 patients with AKI (acute kidney disease) were included and followed up for 1 year. Multivariable regression analysis was used for developing scoring models in the test group (a randomly 70% of all the patients). The established models have been verified in the validation group (a randomly 30% of all the patients). Model 1 that consisted of the risk factors for death within 30 days after AKI had accurate discrimination (The area under the receiver operating characteristic curves, AUROC: 0.90 (95% CI 0.875–0.932)) in the test group, and performed well in the validation groups (AUROC: 0.907 (95% CI 0.865–0.949)). The scoring formula of all-cause death within 1 year (model 2) is a seven-variable model including AKI type, solid tumor, renal replacement therapy, acute myocardial infarction, mechanical ventilation, the number of organ failures, and proteinuria. The area under the receiver operating characteristic (AUROC) curves of model 2 was > 0.80 both in the test and validation groups. Our newly established risk models can well predict the risk of all-cause death in older hospitalized AKI patients within 30 days or 1 year. [ABSTRACT FROM AUTHOR]

In the brain, AMPA receptors mediate fast excitatory neurotransmission, the dysfunction of which leads to neuropsychiatric disorders. Synaptic function of AMPA receptors is tightly controlled by a protein group called transmembrane AMPAR regulatory proteins (TARPs). TARP γ-8 (also known as CACNG8) preferentially expresses in the hippocampus, cortex and subcortical regions that are critical for emotion generation indicating its association with psychiatric disorders. Here, we identified rs10420324 (T/G), a SNP located in the human CACNG8 gene, regulated reporter gene expression in vitro and TARP γ-8 expression in the human brain. A guanine at the locus (rs10420324G) suppressed transcription likely through modulation of a local G-quadruplex DNA structure. Consistent with these observations, the frequency of rs10420324G was higher in patients with anti-social personality disorder (ASPD) than in controls, indicating that rs10420324G in CACNG8 is more voluntary for ASPD. We then characterized the behavior of TARP γ-8 knockout and heterozygous mice and found that consistent with ASPD patients who often exhibit impulsivity, aggression, risk taking, irresponsibility and callousness, a decreased γ-8 expression in mice displayed similar behaviors. Furthermore, we found that a decrease in TARP γ-8 expression impaired synaptic AMPAR functions in layer 2–3 pyramidal neurons of the prefrontal cortex, a brain region that inhibition leads to aggression, thus explaining, at least partially, the neuronal basis for the behavioral abnormality. Taken together, our study indicates that TARP γ-8 expression level is associated with ASPD, and that the TARP γ-8 knockout mouse is a valuable animal model for studying this psychiatric disease. [ABSTRACT FROM AUTHOR]

Loess covers approximately 6.6% of China and forms thick extensive deposits in the northern and northwestern parts of the country. Natural erosional processes and human modification of thick loess deposits have produced abundant, potentially unstable steep slopes in this region. Slope deformation monitoring aimed at evaluating the mechanical behavior of a loess slope has shown a cyclic pattern of contraction and expansion. Such cyclic strain change on the slope materials can damage the loess and contribute to slope instability. The site showing this behavior is a 70-m high loess slope near Yan'an city in Shanxi Province, northwest China. A Ground-Based Synthetic Aperture Radar (GB-SAR) sensor and a displacement meter were used to monitor this cyclic deformation of the slope over a one-year period from September 2018 to August 2019. It is postulated that this cyclic behavior corresponds to thermal and moisture fluctuations, following energy conservation laws. To investigate the validity of this mechanism, physical models of soil temperature and moisture measured by hygrothermographs were used to simulate the observed cyclic deformations. We found good correlations between the models based on the proposed mechanism and the exhibited daily and annual cyclic contraction and expansion. The slope absorbed energy from the time of maximum contraction to the time of maximum expansion, and released energy from the time of maximum expansion to the time of maximum contraction. Recoverable cyclic deformations suggest stresses in the loess are within the elastic range, and non-recoverable cyclic deformations suggest damage of the loess material (breakage of bonds between soil grains), which could lead to instability. Based on these observations and the models, we developed a quantitative relationship between weather cycles and thermal deformation of the slope. Given the current climate change projections of temperature increases of up to 3.5 °C by 2100, the model estimates the loess slope to expand about 0.35 mm in average, which would be in addition to the current cyclic "breathing" behavior experienced by the slope. [ABSTRACT FROM AUTHOR]

The optimized strategy to further increase the success rate of ablation for ventricular arrhythmias (VAs) from the right ventricular outflow tract (RVOT) is challenging. Recent studies have shown that the pulmonary sinus cusp (PSC) region may be the origin of certain RVOT VAs. We evaluated the efficacy of preferential ablation below the pulmonary valve (PV) and alternated radiofrequency delivery in the PSC using remote magnetic navigation (RMN). Sixty-five (65) consecutive patients experiencing VAs with RVOT-like appearance were included in this study. Mapping and ablation were preferentially performed below the PV. Ablation in the PSC would only be attempted when intensified ablation below the PV could not eliminate VAs. Finally, if ablation in the RVOT region failed, the aortic sinus cusp (ASC) would be mapped. Sixty-one (61) of 65 (93.8%) patients achieved procedural success. Except 7 cases of which the VAs were ablated in the ASC, the rest 54 VAs were thought to be originate from the RVOT region. Fifty (50) of 54 VAs were successfully ablated below the PV, and in the presence of a local special signal in the bipolar electrogram a more aggressive ablation was required. Subsequent ablation in the PSC with assistance of the RMN system achieved success in the remaining 4 patients. No complications occurred in this study. Our strategy of using RMN-guided ablation below the PV for VAs of RVOT origin was proved to be effective. PSC mapping and ablation using a magnetic catheter may provide the optimal strategy for treating these types of arrhythmias. [ABSTRACT FROM AUTHOR]

The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored. We developed a suitable experimental model that mimics naturally infected livers using portal injection of protoscoleces. Opposite to Echinococcus multilocularis infection which is dose-dependent, fully mature hydatid cysts can be established in the liver whatever the injection dose; although most of the infection sites were seen at the establishment phase as inflammatory granulomas associated with fibrosis, they never matured into cysts. At the establishment phase, a strong immune response was composed of T and B cells, with T1-type, T2-type cells and cytokines and IL-10-secreting CD8+ T cells in the liver. At the established phase, results suggested a local production of antibodies by B cells, and an involvement of NK and NKT cells. Infection outcome and local immune response in the liver, were different in the mouse models of Echinococcus granulosus sensu stricto and Echinococcus multilocularis respectively; however, only early specificities at the microenvironment level might explain the major differences found between the lesions induced by the two species. Our quantitative experimental model appears fully appropriate to further study this microenvironment and its relationship with each cestode species. [ABSTRACT FROM AUTHOR]

Cancers are driven by a variety of somatic gene mutations and identifying these mutations enables the development of novel target drugs. We have sought to identify abnormalities in Wnt pathway-related genes that are sensitive to Wnt inhibitor treatment. We examined Patient Derived Xenograft (PDX) RNA samples and found new R-Spondin 2 (RSPO2) transcript fusions with the EMC2, PVT1 or HNF4G genes. These fusion events were identified in about 1.4% of the digestive system cancer samples. We then examined the oncogenic effects of the RSPO2-EMC2 fusion gene and confirmed that it can drive oncogenesis, sustain tumor growth and promote metastasis. Finally, we used a Wnt pathway Porcupine inhibitor CGX1321 to treat PDX mouse models containing RSPO2 fusion genes. All the RSPO2 fusion tumors responded to the treatment and stopped progression. Our data show that Wnt pathway inhibition could provide an effective treatment for cancers containing RSPO2 fusion. The RSPO2 fusion will serve as a good biomarker for screening patients to support clinical treatment of digestive system cancers using Wnt pathway inhibitors. [ABSTRACT FROM AUTHOR]

Double-shell cobalt monoxide (CoO) hollow particles were successfully synthesized by a facile and effective one-pot solution-based synthetic route. The inner architecture and outer structure of the double-shell CoO hollow particles could be readily created through controlling experimental parameters. A possible formation mechanism was proposed based on the experimental results. The current synthetic strategy has good prospects for the future production of other transition-metal oxides particles with hollow interior. Furthermore, double-shell cobalt oxide (Co3O4) hollow particles could also be obtained through calcinating corresponding CoO hollow particles. The magnetic measurements revealed double-shell CoO and Co3O4 hollow particles exhibit ferromagnetic and antiferromagnetic behaviour, respectively. [ABSTRACT FROM AUTHOR]

Acute kidney disease (AKD) is a state between acute kidney injury (AKI) and chronic kidney disease (CKD), but the prognosis of AKD is unclear and there are no risk-prediction tools to identify high-risk patients. 2,556 AKI patients were selected from 277,898 inpatients of three affiliated hospitals of Central South University from January 2015 to December 2015. The primary point was whether AKI patients developed AKD. The endpoint was death or end stage renal disease (ESRD) 90 days after AKI diagnosis. Multivariable Cox regression was used for 90-day mortality and two prediction models were established by using multivariable logistic regression. Our study found that the incidence of AKD was 53.17% (1,359/2,556), while the mortality rate and incidence of ESRD in AKD cohort was 19.13% (260/1,359) and 3.02% (41/1,359), respectively. Furthermore, adjusted hazard ratio of mortality for AKD versus no AKD was 1.980 (95% CI 1.427–2.747). In scoring model 1, age, gender, hepatorenal syndromes, organic kidney diseases, oliguria or anuria, respiratory failure, blood urea nitrogen (BUN) and acute kidney injury stage were independently associated with AKI progression into AKD. In addition, oliguria or anuria, respiratory failure, shock, central nervous system failure, malignancy, RDW-CV ≥ 13.7% were independent risk factors for death or ESRD in AKD patients in scoring model 2 (goodness-of fit, P1 = 0.930, P2 = 0.105; AUROC1 = 0.879 (95% CI 0.862–0.896), AUROC2 = 0.845 (95% CI 0.813–0.877), respectively). Thus, our study demonstrated AKD was independently associated with increased 90-day mortality in hospitalized AKI patients. A new prediction model system was able to predict AKD following AKI and 90-day prognosis of AKD patients to identify high-risk patients. [ABSTRACT FROM AUTHOR]

Concrete is susceptible to cracking owing to drying shrinkage, freeze-thaw cycles, delayed ettringite formation, reinforcement corrosion, creep and fatigue, etc. Continuous inspection and maintenance of concrete infrastructure require onerous labor and high costs. If the damaging cracks can heal by themselves without any human interference or intervention, that could be of great attraction. In this study, a novel self-healing approach is investigated, in which fungi are applied to heal cracks in concrete by promoting calcium carbonate precipitation. The goal of this investigation is to discover the most appropriate species of fungi for the application of biogenic crack repair. Our results showed that, despite the significant pH increase owing to the leaching of calcium hydroxide from concrete, Aspergillus nidulans (MAD1445), a pH regulatory mutant, could grow on concrete plates and promote calcium carbonate precipitation. [ABSTRACT FROM AUTHOR]

High-throughput sequencing was employed to investigate the expression of miRNAs and their target genes in superior and inferior seeds of Aikang 58. Small RNA sequencing revealed 620 conserved and 64 novel miRNAs in superior grains, and 623 conserved and 66 novel miRNAs in inferior grains. Among these, 97 known miRNAs, and eight novel miRNAs showed differential expression between the superior and inferior seeds. Degradome sequencing revealed at least 140 candidate target genes associated with 35 miRNA families during the development of superior and inferior seeds. GO and KEGG pathway analysis showed that the differentially expressed miRNAs, both conserved and novel, were likely involved in hormone production, carbohydrate metabolic pathways, and cell division. We validated eight known and four novel grain development-related miRNAs and their target genes by quantitative real-time polymerase chain reaction to ensure the reliability of small RNA and degradome-seq results. Of these, miR160 and miR165/166 were knocked down in Arabidopsis using short-tandem target mimic (STTM160 and STTM165/166) technology, which confirmed their roles in seed development. Specifically, STTM160 showed significantly smaller grain size, lower grain weight, shorter siliques length, shorter plant height, and more serrated leaves, whereas STTM165/166 showed decreased seed number, disabled siliques, and curled upward leaves. [ABSTRACT FROM AUTHOR]

Chinese tongue sole is a marine fish with ZW sex determination. Genome sequencing suggested that the Z-linked dmrt1 is a putative male determination gene, but direct genetic evidence is still lacking. Here we show that TALEN of dmrt1 efficiently induced mutations of this gene. The ZZ dmrt1 mutant fish developed ovary-like testis, and the spermatogenesis was disrupted. The female-related genes foxl2 and cyp19a1a were significantly increased in the gonad of the ZZ dmrt1 mutant. Conversely, the male-related genes Sox9a and Amh were significantly decreased. The dmrt1 deficient ZZ fish grew much faster than ZZ male control. Notably, we obtained an intersex ZW fish with a testis on one side and an ovary on the other side. This fish was chimeric for a dmrt1 mutation in the ovary, and wild-type dmrt1 in the testis. Our data provide the first functional evidence that dmrt1 is a male determining gene in tongue sole. [ABSTRACT FROM AUTHOR]

Many cytotoxic chemotherapeutics elicit a proinflammatory response which is often associated with chemotherapy-induced behavioral alterations. The immune system is under circadian influence; time-of-day may alter inflammatory responses to chemotherapeutics. We tested this hypothesis by administering cyclophosphamide and doxorubicin (Cyclo/Dox), a common treatment for breast cancer, to female BALB/c mice near the beginning of the light or dark phase. Mice were injected intravenously with Cyclo/Dox or the vehicle two hours after lights on (zeitgeber time (ZT2), or two hours after lights off (ZT14). Tissue was collected 1, 3, 9, and 24 hours later. Mice injected with Cyclo/Dox at ZT2 lost more body mass than mice injected at ZT14. Cyclo/Dox injected at ZT2 increased the expression of several pro-inflammatory genes within the spleen; this was not evident among mice treated at ZT14. Transcription of enzymes within the liver responsible for converting Cyclo/Dox into their toxic metabolites increased among mice injected at ZT2; furthermore, transcription of these enzymes correlated with splenic pro-inflammatory gene expression when treatment occurred at ZT2 but not ZT14. The pattern was reversed in the brain; pro-inflammatory gene expression increased among mice injected at ZT14. These data suggest that inflammatory responses to chemotherapy depend on time-of-day and are tissue specific. [ABSTRACT FROM AUTHOR]

Although trastuzumab is an effective treatment in early stage HER2+ breast cancer the majority of advanced HER2+ breast cancers develop trastuzumab resistance, especially in the 40% of breast cancers with loss of PTEN. However, HER2+ breast cancer patients continue to receive trastuzumab regardless PTEN status and the consequence of therapy in these patients is unknown. We demonstrate that continued use of trastuzumab in HER2+ cells with loss of PTEN induces the epithelial-mesenchymal transition (EMT) and transform HER2+ to a triple negative breast cancer. These transformed cells exhibited mesenchymal morphology and gene expression markers, while parent HER2+ cells showed epithelial morphology and markers. The transformed cells exhibited loss of dependence on ERBB family signaling (such as HER2, HER3, HER4, BTC, HRG, EGF) and reduced estrogen and progesterone receptors. Continued use of trastuzumab in HER2+ PTEN− cells increased the frequency of cancer stem cells (CSCs) and metastasis potential. Strikingly, parental HER2+ cells and transformed resistant cells respond to treatment differently. Transformed resistant cells were sensitive to chemical probe (sulforaphane) through inhibition of IL-6/STAT3/NF-κB positive feedback loop whereas parental HER2+ cells did not respond. This data suggests that trastuzumab resistance in HER2+ PTEN− breast cancer induces EMT and subtype switching, which requires unique treatment options. [ABSTRACT FROM AUTHOR]

The inflammatory mediator high-mobility group box 1 (HMGB1) plays a critical role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, the regulation of HMGB1 in NAFLD, particularly through sirtuin 1 (SIRT1), remains unclear. In this study, we investigated the role of SIRT1-mediated inhibition of HMGB1 release in NAFLD and the effect of salvianolic acid B (SalB), which is a water-soluble phenolic acid extracted from Radix Salvia miltiorrhiza, on NAFLD through SIRT1/HMGB1 signaling. In vivo, SalB treatment significantly attenuated high-fat diet (HFD)-induced liver damage, hepatic steatosis, and inflammation. Importantly, SalB significantly inhibited HMGB1 nuclear translocation and release, accompanied by SIRT1 elevation. In HepG2 cells, palmitic acid (PA)-induced pro-inflammatory cytokines release were blocked by HMGB1 small interfering RNA (siRNA) transfection. Moreover, pharmacological SIRT1 inhibition by Ex527 induced HMGB1 translocation and release, whereas SIRT1 activation by resveratrol or SalB reversed this trend. SIRT1 siRNA abrogated the SalB-mediated inhibition of HMGB1 acetylation and release, suggesting that SalB-mediated protection occurs by SIRT1 targeting HMGB1 for deacetylation. We are the first to demonstrate that the SIRT1/HMGB1 pathway is a key therapeutic target for controlling NAFLD inflammation and that SalB confers protection against HFD- and PA-induced hepatic steatosis and inflammation through SIRT1-mediated HMGB1 deacetylation. [ABSTRACT FROM AUTHOR]

The order Magnaporthales (Ascomycota, Fungi) includes devastating pathogens of cereals, such as the rice blast fungus Pyricularia (Magnaporthe) oryzae, which is a model in host-pathogen interaction studies. Magnaporthales also includes saprotrophic species associated with grass roots and submerged wood. Despite its scientific and economic importance, the phylogenetic position of Magnaporthales within Sordariomycetes and the interrelationships of its constituent taxa, remain controversial. In this study, we generated novel transcriptome data from 21 taxa that represent key Magnaporthales lineages of different infection and nutrition modes and phenotypes. Phylogenomic analysis of >200 conserved genes allowed the reconstruction of a robust Sordariomycetes tree of life that placed the monophyletic group of Magnaporthales sister to Ophiostomatales. Among Magnaporthales, three major clades were recognized: 1) an early diverging clade A comprised of saprotrophs associated with submerged woods; 2) clade B that includes the rice blast fungus and other pathogens that cause blast diseases of monocot plants. These species infect the above-ground tissues of host plants using the penetration structure, appressorium; and 3) clade C comprised primarily of root-associated species that penetrate the root tissue with hyphopodia. The well-supported phylogenies provide a robust framework for elucidating evolution of pathogenesis, nutrition modes, and phenotypic characters in Magnaporthales. [ABSTRACT FROM AUTHOR]