Lesion attention guided neural network for contrast-enhanced mammography-based biomarker status prediction in breast cancer.

BACKGROUND AND OBJECTIVE: Accurate identification of molecular biomarker statuses is crucial in cancer diagnosis, treatment, and prognosis. Studies have demonstrated that medical images could be utilized for non-invasive prediction of biomarker statues. The biomarker status-associated features extracted from medical images are essential in developing medical image-based non-invasive prediction models. Contrast-enhanced mammography (CEM) is a promising imaging technique for breast cancer diagnosis. This study aims to develop a neural network-based method to extract biomarker-related image features from CEM images and evaluate the potential of CEM in non-invasive biomarker status prediction. METHODS: An end-to-end learning convolutional neural network with the whole breast images as inputs was proposed to extract CEM features for biomarker status prediction in breast cancer. The network focused on lesion regions and flexibly extracted image features from lesion and peri­tumor regions by employing supervised learning with a smooth L1-based consistency constraint. An image-level weakly supervised segmentation network based on Vision Transformer with cross attention to contrast images of breasts with lesions against the contralateral breast images was developed for automatic lesion segmentation. Finally, prediction models were developed following further selection of significant features and the implementation of random forest-based classification. Results were reported using the area under the curve (AUC), accuracy, sensitivity, and specificity. RESULTS: A dataset from 1203 breast cancer patients was utilized to develop and evaluate the proposed method. Compared to the method without lesion attention and with only lesion regions as inputs, the proposed method performed better at biomarker status prediction. Specifically, it achieved an AUC of 0.71 (95 % confidence interval [CI]: 0.65, 0.77) for Ki-67 and 0.73 (95 % CI: 0.65, 0.80) for human epidermal growth factor receptor 2 (HER2). CONCLUSIONS: A lesion attention-guided neural network was proposed in this work to extract CEM image features for biomarker status prediction in breast cancer. The promising results demonstrated the potential of CEM in non-invasively predicting the biomarker statuses in breast cancer.

Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

Hepatic Sirt6 activation abrogates acute liver failure.

Acute liver failure (ALF) is a deadly illness due to insufficient detoxification in liver induced by drugs, toxins, and other etiologies, and the effective treatment for ALF is very limited. Among the drug-induced ALF, acetaminophen (APAP) overdose is the most common cause. However, the molecular mechanisms underlying APAP hepatoxicity remain incompletely understood. Sirtuin 6 (Sirt6) is a stress responsive protein deacetylase and plays an important role in regulation of DNA repair, genomic stability, oxidative stress, and inflammation. Here, we report that genetic and pharmacological activation of Sirt6 protects against ALF in mice. We first observed that Sirt6 expression was significantly reduced in the liver tissues of human patients with ALF and mice treated with an overdose of APAP. Then we developed an inducible Sirt6 transgenic mice for Cre-mediated overexpression of the human Sirt6 gene in systemic (Sirt6-Tg) and hepatic-specific (Sirt6-HepTg) manners. Both Sirt6-Tg mice and Sirt6-HepTg mice exhibited the significant protection against APAP hepatoxicity. In contrast, hepatic-specific Sirt6 knockout mice exaggerated APAP-induced liver damages. Mechanistically, Sirt6 attenuated APAP-induced hepatocyte necrosis and apoptosis through downregulation of oxidative stress, inflammation, the stress-activated kinase JNK activation, and apoptotic caspase activation. Moreover, Sirt6 negatively modulated the level and activity of poly (ADP-ribose) polymerase 1 (PARP1) in APAP-treated mouse liver tissues. Importantly, the specific Sirt6 activator MDL-800 exhibited better therapeutic potential for APAP hepatoxicity than the current drug acetylcysteine. Furthermore, in the model of bile duct ligation induced ALF, hepatic Sirt6-KO exacerbated, but Sirt6-HepTg mitigated liver damage. Collectively, our results demonstrate that Sirt6 protects against ALF and suggest that targeting Sirt6 activation could be a new therapeutic strategy to alleviate ALF.

B1 Power Modification for Amide Proton Transfer Imaging in Parotid Glands: A Strategy for Image Quality Accommodation and Evaluation of Tumor Detection Feasibility.

BACKGROUND: In the application of APTw protocols for evaluating tumors and parotid glands, inhomogeneity and hyperintensity artifacts have remained an obstacle. This study aimed to improve APTw imaging quality and evaluate the feasibility of difference B1 values to detect parotid tumors. METHODS: A total of 31 patients received three APTw sequences to acquire 32 lesions and 30 parotid glands (one patient had lesions on both sides). Patients received T2WI and 3D turbo-spin-echo (TSE) APTw imaging on a 3.0 T scanner for three sequences (B1 = 2 µT, 1 µT, and 0.7 µT in APTw 1, 2, and 3, respectively). APTw image quality was evaluated using four-point Likert scales in terms of integrity and hyperintensity artifacts. Image quality was compared between the three sequences. An evaluable group and a trustable group were obtained for APTmean value comparison. RESULTS: Tumors in both APT2 and APT3 had fewer hyperintensity artifacts than in APT1. With B1 values decreasing, tumors had less integrity in APTw imaging. APTmean values of tumors were higher than parotid glands in traditional APT1 sequence though not significant, while the APTmean subtraction value was significantly different. CONCLUSIONS: Applying a lower B1 value could remove hyperintensity but could also compromise its integrity. Combing different APTw sequences might increase the feasibility of tumor detection.

The contribution of semantic distance knowledge to size constancy in perception and grasping when visual cues are limited.

To achieve a stable perception of object size in spite of variations in viewing distance, our visual system needs to combine retinal image information and distance cues. Previous research has shown that, not only retinal cues, but also extraretinal sensory signals can provide reliable information about depth and that different neural networks (perception versus action) can exhibit preferences in the use of these different sources of information during size-distance computations. Semantic knowledge of distance, a purely cognitive signal, can also provide distance information. Do the perception and action systems show differences in their ability to use this information in calculating object size and distance? To address this question, we presented 'glow-in-the-dark' objects of different physical sizes at different real distances in a completely dark room. Participants viewed the objects monocularly through a 1-mm pinhole. They either estimated the size and distance of the objects or attempted to grasp them. Semantic knowledge was manipulated by providing an auditory cue about the actual distance of the object: "20 cm", "30 cm", and "40 cm". We found that semantic knowledge of distance contributed to some extent to size constancy operations during perceptual estimation and grasping, but size constancy was never fully restored. Importantly, the contribution of knowledge about distance to size constancy was equivalent between perception and action. Overall, our study reveals similarities and differences between the perception and action systems in the use of semantic distance knowledge and suggests that this cognitive signal is useful but not a reliable depth cue for size constancy under restricted viewing conditions.

The impact of goal-directed fluid therapy on postoperative pulmonary complications in patients undergoing thoracic surgery: a systematic review and meta-analysis.

BACKGROUND: Pulmonary complications after thoracic surgery are common and associated with significant morbidity and high cost of care. Goal-directed fluid therapy (GDFT) could reduce the incidence of postoperative pulmonary complications (PPCs) and facilitate recovery in patients undergoing major abdominal surgery. However, whether GDFT could reduce the incidence of PPCs in patients undergoing thoracic surgery was unclear. The present meta-analysis was designed to assess the impact of Goal-directed Fluid Therapy on PPCs in patients undergoing thoracic surgery. METHODS: Randomized controlled trials (RCTs) comparing GDFT with other conventional fluid management strategies in adult patients undergoing thoracic surgery were identified. Databases searched included PubMed, Web of Science, Embase, and Cochrane Library databases. Review Manager 5.4 (The Cochrane Collaboration, Oxford, UK) software was used for statistical analysis. Heterogeneity was analyzed using I2 statistics, and a standardized mean difference with 95% CI and P value was used to calculate the treatment effect for outcome variables. The primary study outcomes were the incidence of PPCs. Secondary outcomes were the total volume infused, the length of hospitalization, the incidence of cardiac complications, and the incidence of renal dysfunction. Subgroup analysis was planned to verify the definite role of GDFT. RESULTS: A total of 6 RCTs consisting of 680 patients were included in this meta-analysis, which revealed that GDFT did not reduce the incidence of PPCs in patients undergoing thoracic surgery (RR, 0.57; 95% CI 0.29-1.14). However, GDFT decreased the total intra-operative fluid input (MD, - 244.40 ml; 95% CI - 397.06 to - 91.74). There was no statistical difference in the duration of hospitalization (MD; - 1.31, 95% CI - 3.00 to 0.38), incidence of renal dysfunction (RR, 0.62; 95% CI 0.29-1.35), and incidence of cardiac complications (RR, 0.62; 95% CI 0.27-1.40). CONCLUSIONS: The results of this meta-analysis indicate that GDFT did not reduce the postoperative incidence of pulmonary complications in individuals undergoing thoracic surgery. However, considering the small number of contributing studies, these results should be interpreted with caution.

Animal models of heart failure with preserved ejection fraction (HFpEF): from metabolic pathobiology to drug discovery.

Heart failure (HF) with preserved ejection fraction (HFpEF) is currently a preeminent challenge for cardiovascular medicine. It has a poor prognosis, increasing mortality, and is escalating in prevalence worldwide. Despite accounting for over 50% of all HF patients, the mechanistic underpinnings driving HFpEF are poorly understood, thus impeding the discovery and development of mechanism-based therapies. HFpEF is a disease syndrome driven by diverse comorbidities, including hypertension, diabetes and obesity, pulmonary hypertension, aging, and atrial fibrillation. There is a lack of high-fidelity animal models that faithfully recapitulate the HFpEF phenotype, owing primarily to the disease heterogeneity, which has hampered our understanding of the complex pathophysiology of HFpEF. This review provides an updated overview of the currently available animal models of HFpEF and discusses their characteristics from the perspective of energy metabolism. Interventional strategies for efficiently utilizing energy substrates in preclinical HFpEF models are also discussed.

Atmospheric plasma treatment: an alternative of HF etching in lithium disilicate glass-ceramic cementation.

Objectives: This study aimed to investigate whether the atmospheric pressure plasma jet (APPJ) could modify the surface of lithium disilicate glass ceramics (LDC) instead of hydrofluoric acid (HF) in LDC resin cementation. Methods: Two hundred and thirty-two LDC blocks were randomly divided into seven groups: Group 1 (16 specimens) was the blank control group (without HF or APPJ treatment); Group 2 (36 specimens) was etched by HF; Groups 3-7 (36 specimens each) were treated with APPJ, and the relative air humidity (RAH) of the discharge was 22.8%, 43.6%, 59.4%, 75.2%, and 94.0%, respectively. Three LDC blocks in each group were characterized via X-ray photoemission spectroscopy (XPS) analyses, 3 blocks via contact angle measurements, and other 10 blocks via surface roughness measurements. The residual LDC blocks in groups 2-7 were cemented to composite cylinders. Testing the cemented specimens' shear bond strength (SBS) before and after thermocycling (6,500 cycles of 5°C and 55°C) revealed fracture patterns. Data were analyzed by ANOVA (post hoc: Bonferroni) (α = 0.05). Results: After APPJ treatment, the water contact angle values of APPJ treated blocks dropped from 31.37° to 5.66°, while that of HF etched ones dropped to 18.33°. The O/C ratio increased after HF etching or APPJ treatment according to the calculated results, except for the APPJ-treated samples at a RAH of 22.8%. The surface roughness of LDC blocks showed no statistic difference before and after APPJ treatment, but experienced significant difference after HF etching. The O/Si and O/C ratios varied after HF etching or APPJ treatment. No significant difference in SBS values could be found among groups 2-7 before or after artificial aging (p > 0.05). All specimens showed mixed failure patterns. Conclusion: The APPJ treatment method reported in this study is a promising novel strategy for surface modification of the LDC. With acceptable bonding strength, it might be an alternative to HF in LDC-resin cementation.

Lactobacillus sp. participated in the adaptation of Rongchang piglets to cold stress.

Rongchang piglets were easily induced to cold stress and diarrhoea in the winter when raised in an open hog house. However, they also gradually recovered under mid-cold stress. Other studies have suggested gut microbiome might be involved in the host energy metabolism to relieve stress. To study how to adapt Rongchang piglets to cold stress by gut microbiome, thirty Rongchang piglets were randomly divided into a mild cold stress group and a control group for 30 consecutive days. The findings revealed that the piglets had low growth performance and a high diarrhoea rate and mortality rate during the first half of the cold treatment, but subsequently stabilised. The level of cortisol (COR) also displayed a similar trend. In the mild cold stress group, the relative abundance of Muribaculaceae significantly increased on day 15, and the predominant bacterial on day 30 was Lactobacillus sp. Our results indicated that the Rongchang piglet's production performance and health were impaired at the start of the mild cold stress. However, as time passed, the body could progressively adapt to the low temperature, and Lactobacillus sp. participated in this process. This study provides new insight into how to alleviate health damage caused by cold stress.

The risk factors of postoperative cognitive dysfunction in patients undergoing carotid endarterectomy: an updated meta-analysis.

OBJECTIVE: The purpose of the current meta-analysis was to determine the incidence and risk factors to provide a scientific basis for prevention and treatment of postoperative cognitive dysfunction (POCD) after carotid endarterectomy (CEA). METHODS: Relevant articles published before October 2022 were searched from Pubmed/MEDLINE, Cochrane and Embase databases. The outcomes were the incidence and risk factors for POCD. A random-effects model was applied to estimate the overall odds ratios (ORs) and mean differences (MDs) for all risk factors through STATA 14.0 and RevMan 5.4. The quality of eligible studies was evaluated by Newcastle-Ottawa Scale (NOS) as previously described. RESULTS: A total of 22 articles involving 3459 CEA patients were finally identified. The weighted mean incidence of POCD was 19% (95% confidence intervals (95% CI) 0.16-0.24, P < 0.001). Of the 16 identified risk factors, hyperperfusion (OR: 0.54, 95% CI 0.41-0.71) and degree of internal carotid artery (ICA) stenosis (OR: 5.06, 95% CI 0.86-9.27) were the potential risk factors of POCD, whereas patients taking statins preoperative had a lower risk of POCD (OR: 0.54, 95% CI 0.41-0.71). Subgroup analysis revealed that the risk of POCD at 1 month after CEA was higher in patients with diabetes (OR: 1.70, 95% CI 1.07-2.71). CONCLUSION: The risk factors of POCD were hyperperfusion and degree of ICA stenosis, while diabetes could significantly increase the incidence of POCD at 1 month after surgery. Additionally, preoperative statin use could be a protective factor for POCD following CEA.

HAKE: A Knowledge Engine Foundation for Human Activity Understanding.

Human activity understanding is of widespread interest in artificial intelligence and spans diverse applications like health care and behavior analysis. Although there have been advances with deep learning, it remains challenging. The object recognition-like solutions usually try to map pixels to semantics directly, but activity patterns are much different from object patterns, thus hindering another success. In this article, we propose a novel paradigm to reformulate this task in two-stage: first mapping pixels to an intermediate space spanned by atomic activity primitives, then programming detected primitives with interpretable logic rules to infer semantics. To afford a representative primitive space, we build a knowledge base including 26+ M primitive labels and logic rules from human priors or automatic discovering. Our framework, Human Activity Knowledge Engine (HAKE), exhibits superior generalization ability and performance upon canonical methods on challenging benchmarks. Code and data are available at http://hake-mvig.cn/.

Altered cfDNA fragmentation profile in hypomethylated regions as diagnostic markers in breast cancer.

BACKGROUND: Breast cancer, the most common malignancy in women worldwide, has been proven to have both altered plasma cell-free DNA (cfDNA) methylation and fragmentation profiles. Nevertheless, simultaneously detecting both of them for breast cancer diagnosis has never been reported. Moreover, although fragmentation pattern of cfDNA is determined by nuclease digestion of chromatin, structure of which may be affected by DNA methylation, whether cfDNA methylation and fragmentation are biologically related or not still remains unclear. METHODS: Improved cfMeDIP-seq were utilized to characterize both cfDNA methylation and fragmentation profiles in 49 plasma samples from both healthy individuals and patients with breast cancer. The feasibility of using cfDNA fragmentation profile in hypo- and hypermethylated regions as diagnostic markers for breast cancer was evaluated. RESULTS: Mean size of cfDNA fragments (100-220 bp) mapped to hypomethylated regions decreased more in patients with breast cancer (4.60 bp, 172.33 to 167.73 bp) than in healthy individuals (2.87 bp, 174.54 to 171.67 bp). Furthermore, proportion of short cfDNA fragments (100-150 bp) in hypomethylated regions when compared with it in hypermethylated regions was found to increase more in patients with breast cancer in two independent discovery cohort. The feasibility of using abnormality of short cfDNA fragments ratio in hypomethylated genomic regions for breast cancer diagnosis in validation cohort was evaluated. 7 out of 11 patients were detected as having breast cancer (63.6% sensitivity), whereas no healthy individuals were mis-detected (100% specificity). CONCLUSION: We identified enriched short cfDNA fragments after 5mC-immunoprecipitation (IP) in patients with breast cancer, and demonstrated the enriched short cfDNA fragments might originated from hypomethylated genomic regions. Furthermore, we proved the feasibility of using differentially methylated regions (DMRs)-dependent cfDNA fragmentation profile for breast cancer diagnosis.

Mothers' depressive symptoms and children's behavioral adjustment: The role of negative parental emotional states.

The contribution of fathers and family dynamics to the deleterious effects of mothers' depressive symptoms on children's behavioral adjustment has been evaluated in this study. Using longitudinal data spanning from toddlerhood to grade school (N = 1,311), this study examined whether negative emotional states in both parents related to mothers' cumulative depressive symptoms during the early years of children were associated with children's later internalizing and externalizing problems in grade school. A random intercept cross-lagged panel model was used to segregate between- and within-individual effects. The results demonstrated that, independent of fathers' depressive symptoms, high levels of maternal cumulative depressive symptoms were positively associated with negative emotional states in both parents over time, which then independently mediated the longitudinal associations between mothers' depressive symptoms and children's subsequent behavioral maladjustment, particularly internalizing problems, at the between-individual trait level. The findings highlight the interdependence of family members from a longitudinal perspective and support the unique contributions of both parents' negative emotional states to better understand children's behavioral adjustment in the context of maternal depressive symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Hot Topic Recognition of Health Rumors Based on Anti-Rumor Articles on the WeChat Official Account Platform: Topic Modeling.

BACKGROUND: Social networks have become one of the main channels for obtaining health information. However, they have also become a source of health-related misinformation, which seriously threatens the public's physical and mental health. Governance of health-related misinformation can be implemented through topic identification of rumors on social networks. However, little attention has been paid to studying the types and routes of dissemination of health rumors on the internet, especially rumors regarding health-related information in Chinese social media. OBJECTIVE: This study aims to explore the types of health-related misinformation favored by WeChat public platform users and their prevalence trends and to analyze the modeling results of the text by using the Latent Dirichlet Allocation model. METHODS: We used a web crawler tool to capture health rumor-dispelling articles on WeChat rumor-dispelling public accounts. We collected information from health-debunking articles posted between January 1, 2016, and August 31, 2022. Following word segmentation of the collected text, a document topic generation model called Latent Dirichlet Allocation was used to identify and generalize the most common topics. The proportion distribution of the themes was calculated, and the negative impact of various health rumors in different periods was analyzed. Additionally, the prevalence of health rumors was analyzed by the number of health rumors generated at each time point. RESULTS: We collected 9366 rumor-refuting articles from January 1, 2016, to August 31, 2022, from WeChat official accounts. Through topic modeling, we divided the health rumors into 8 topics, that is, rumors on prevention and treatment of infectious diseases (1284/9366, 13.71%), disease therapy and its effects (1037/9366, 11.07%), food safety (1243/9366, 13.27%), cancer and its causes (946/9366, 10.10%), regimen and disease (1540/9366, 16.44%), transmission (914/9366, 9.76%), healthy diet (1068/9366, 11.40%), and nutrition and health (1334/9366, 14.24%). Furthermore, we summarized the 8 topics under 4 themes, that is, public health, disease, diet and health, and spread of rumors. CONCLUSIONS: Our study shows that topic modeling can provide analysis and insights into health rumor governance. The rumor development trends showed that most rumors were on public health, disease, and diet and health problems. Governments still need to implement relevant and comprehensive rumor management strategies based on the rumors prevalent in their countries and formulate appropriate policies. Apart from regulating the content disseminated on social media platforms, the national quality of health education should also be improved. Governance of social networks should be clearly implemented, as these rapidly developed platforms come with privacy issues. Both disseminators and receivers of information should ensure a realistic attitude and disseminate health information correctly. In addition, we recommend that sentiment analysis-related studies be conducted to verify the impact of health rumor-related topics.

SIRT4 protects against intestinal fibrosis by facilitating GLS1 degradation.

Intestinal fibrosis is a prevalent complication of Crohn's disease (CD), characterized by excessive deposition of extracellular matrix (ECM), and no approved drugs are currently available for its treatment. Sirtuin 4 (SIRT4), a potent anti-fibrosis factor in mitochondria, has an unclear role in intestinal fibrosis. In this study, fibroblasts isolated from biopsies of stenotic ileal mucosa in CD patients were analyzed to identify the most down-regulated protein among SIRT1-7, and SIRT4 was found to be the most affected. Moreover, in vivo and in vitro models of intestinal fibrosis, SIRT4 expression was significantly decreased in a TGF-ß dependent manner, and its decrease was negatively associated with disease severity. SIRT4 impeded ECM deposition by inhibiting glutaminolysis, but not glycolysis, and α-ketoglutarate (α-KG) was identified as the key metabolite. Specifically, SIRT4 hinders SIRT5's stabilizing interaction with glutaminase 1 (GLS1), thereby facilitating the degradation of GLS1. KDM6, rather than KDM4, is a potential mediator for α-KG-induced transcription of ECM components, and SIRT4 enhances the enrichment of H3K27me3 on their promotors and enhancers. These findings indicate that the activation of TGF-ß signals decreases the expression of SIRT4 in intestinal fibrosis, and SIRT4 can facilitate GLS1 degradation, thereby resisting glutaminolysis and alleviating intestinal fibrosis, providing a novel therapeutic target for intestinal fibrosis.

Facile fabrication of PMIA composite separator with bi-functional sodium-alginate coating layer for synergistically increasing performance of lithium-ion batteries.

Lack of safety and unenough electrochemical performance have been known as a fundamental obstacle limiting the extensive application of lithium-ion batteries (LIBs). It is really preferable but challenging to fabricate thermal-response separator with shutdown function for high-performance LIBs. Herein, a thermal-response sodium-alginate modified PMIA (Na-Alg/PMIA) composite separator with shutdown function was designed and prepared by non-solvent phase induced separation (NIPs). PMIA and Na-Alg are combined by hydrogen bonding. While Na-Alg increases polar groups and makes Li+ easy to be transported, a small amount of Na+ can provide Li+ active sites, accelerate Li+ deposition coating and effectively inhibit the formation of Li dendrites. The as-prepared Na-Alg/PMIA composite separators can close pores at 200 °C and maintain dimensional integrity without obvious thermal shrinkage. In addition, the Na-Alg/PMIA composite separators has excellent wettability and ionic conductivity, resulting in high specific capacity and retention during the charge-discharge cycles. After 50 cycles, the capacity retention of cells with the Na-Alg/PMIA-20 composite separator is 84.3 %. At 2 C, cells with the Na-Alg/PMIA-20 composite separators still held 101.1 mAh g-1. This facile yet effective method improves the electrochemical performance while ensuring the safety of the LIBs, which provides ideas for the commercial application of PMIA separators.

Syntaxin of plants71 plays essential roles in plant development and stress response via regulating pH homeostasis.

SYP71, a plant-specific Qc-SNARE with multiple subcellular localization, is essential for symbiotic nitrogen fixation in nodules in Lotus, and is implicated in plant resistance to pathogenesis in rice, wheat and soybean. Arabidopsis SYP71 is proposed to participate in multiple membrane fusion steps during secretion. To date, the molecular mechanism underlying SYP71 regulation on plant development remains elusive. In this study, we clarified that AtSYP71 is essential for plant development and stress response, using techniques of cell biology, molecular biology, biochemistry, genetics, and transcriptomics. AtSYP71-knockout mutant atsyp71-1 was lethal at early development stage due to the failure of root elongation and albinism of the leaves. AtSYP71-knockdown mutants, atsyp71-2 and atsyp71-3, had short roots, delayed early development, and altered stress response. The cell wall structure and components changed significantly in atsyp71-2 due to disrupted cell wall biosynthesis and dynamics. Reactive oxygen species homeostasis and pH homeostasis were also collapsed in atsyp71-2. All these defects were likely resulted from blocked secretion pathway in the mutants. Strikingly, change of pH value significantly affected ROS homeostasis in atsyp71-2, suggesting interconnection between ROS and pH homeostasis. Furthermore, we identified AtSYP71 partners and propose that AtSYP71 forms distinct SNARE complexes to mediate multiple membrane fusion steps in secretory pathway. Our findings suggest that AtSYP71 plays an essential role in plant development and stress response via regulating pH homeostasis through secretory pathway.

Liver-cell protective pyridones from the fungi Tolypocladium album dws120.

Five previously undescribed pyridone derivatives, tolypyridones I-M, were identified from the solid rice medium fermented by Tolypocladium album dws120, along with two known compounds tolypyridone A (or trichodin A) and pyridoxatin. Their planar structures and partial relative configurations have been determined by careful interpretation of their spectroscopic data. The full assignment of the relative and absolute configurations of tolypyridones I-M was achieved by gauge-independent atomic orbital 13C NMR calculation, quantitative nuclear Overhauser effects based interatomic distance calculation, and electronic circular dichroism calculation. In addition, we have fully determined the configuration of tolypyridone A by X-ray diffraction analysis. In bioassay, tolypyridones I was able to restore cell viability and inhibit the release of alanine aminotransferase and aspartate aminotransferase for ethanol-induced LO2 cells, suggesting its potential as a liver protective agent.

Correlation between 18F-FDG PET/MR parameters with the expression level of epidermal growth factor receptor and the diagnostic value of PET/MR in head and neck squamous cell carcinoma.

Objective: To investigate the correlation between parameters of PET/MR and the expression level of epidermal growth factor receptor (EGFR) in head and neck squamous cell carcinoma (HNSCC) and to evaluate diagnostic efficacy of independent and combined PET/MR parameters for the expression level of EGFR. Materials and methods: 21 patients who had undergone PET/MR and been proven HNSCC pathologically were included in this retrospective study. The PET/MR sequences included 18-flurodeoxyglucose (18F-FDG) PET, T1, T2-weighted imaging, DWI, ADC and DCE. Parameters including ADCmean from DWI, Ktrans, Ve, Kep from DCE, and SUVmean, SUVmax from PET were obtained. Immunohistochemical method was used to detect the expression level of EGFR. The associations between parameters of PET/MR and EGFR expression level were analyzed by Spearman's analysis. Logistic regression was utilized to establish the diagnostic model of EGFR expression level with PET/MR parameters. The efficacy of the independent and combined diagnostic model for EGFR expression level in HNSCC was analyzed by ROC curve. P value ≤ 0.05 was considered statistically significant. Results: (1) Expression level of EGFR was correlated to SUVmean with correlation coefficient of 0.47 (p = 0.05). (2) There was significant difference of SUVmean between the EGFR high- and low-expression groups (p = 0.02). (3) Combination of PET/MR improved the diagnostic efficacy for expression level of EGFR, with AUC = 0.93. Conclusion: There were different degrees of correlation between PET/MR parameters and EGFR expression level in HNSCC. Combination of PET/MR might improve diagnostic efficacy of EGFR expression level.

Optimization of the Brewing Conditions of Shanlan Rice Wine and Sterilization by Thermal and Intense Pulse Light.

This study aimed to optimize the brewing conditions of Shanlan rice wine (SRW) and select a suitable sterilization method. The response surface method experiment was used to optimize the brewing process of SRW. LC-MS/MS (liquid chromatography-tandem mass spectrometry) and GC-MS (gas chromatography-mass spectrometry) were used to analyze the physicochemical components, free amino acids, and flavor metabolites of the thermal-sterilized SRW and the SRW sterilized by intense pulsed light (IPL), respectively. Results showed that the optimum fermentation conditions of SRW were as follows: fermentation temperature, 24.5 °C; Qiuqu amount (the traditional yeast used to produce SRW), 0.78%; water content, 119%. Compared with the physicochemical properties of the control, those of the SRWs separately treated with two sterilization methods were slightly affected. The 60 s pulse treatment reduced the content of bitter amino acids, maintained sweet amino acids and umami amino acids in SRW, and balanced the taste of SRW. After pasteurization, the ester content in wine decreased by 90%, and the alcohol content decreased to different degrees. IPL sterilization slightly affected the ester content and increased the alcohol content. Further analysis of the main flavor metabolites showed that 60 s pulse enhanced the important flavor-producing substances of SRW. In conclusion, 60 s pulse is suitable for sterilizing this wine.