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Abstract Abnormal cardiac development has been observed in individuals with Cornelia de Lange syndrome (CdLS) due to mutations in genes encoding members of the cohesin complex. However, the precise role of cohesin in heart development remains elusive. In this study, we aimed to elucidate the indispensable role of SMC3, a component of the cohesin complex, in cardiac development and its underlying mechanism. Our investigation revealed that CdLS patients with SMC3 mutations have high rates of congenital heart disease (CHD). We utilized heart-specific Smc3-knockout (SMC3-cKO) mice, which exhibit varying degrees of outflow tract (OFT) abnormalities, to further explore this relationship. Additionally, we identified 16 rare SMC3 variants with potential pathogenicity in individuals with isolated CHD. By employing single-nucleus RNA sequencing and chromosome conformation capture high-throughput genome-wide translocation sequencing, we revealed that Smc3 deletion downregulates the expression of key genes, including Ets2, in OFT cardiac muscle cells by specifically decreasing interactions between super-enhancers (SEs) and promoters. Notably, Ets2-SE-null mice also exhibit delayed OFT development in the heart. Our research revealed a novel role for SMC3 in heart development via the regulation of SE-associated genes, suggesting its potential relevance as a CHD-related gene and providing crucial insights into the molecular basis of cardiac development.

Abstract Eleocharis dulcis (Burm. f.) Trin. ex Hensch., commonly known as Chinese water chestnut, is a traditional aquatic vegetable in China, and now is widely cultivated throughout the world because of its high nutritional value and unique tastes. Here, we report the assembly of a 493.24 Mb telomere-to-telomere (T2T) genome of E. dulcis accomplished by integrating ONT ultra-long reads, PacBio long reads and Hi-C data. The reference genome was anchored onto 111 gap-free chromosomes, containing 48.31% repeat elements and 33,493 predicted protein-coding genes. Whole genome duplication (WGD) and inter-genomic synteny analyses indicated that chromosome breakage and genome duplication in E. dulcis possibly occurred multiple times during genome evolution after its divergence from a common ancestor with Rhynchospora breviuscula at ca. 35.6 Mya. A comparative time-course transcriptome analysis of corm development revealed different patterns of gene expression between cultivated and wild accessions with the highest number of differentially expressed genes (DEGs, 15,870) at the middle swelling stage and some of the DEGs were significantly enriched for starch metabolic process.

Abstract. Background:. Heterotaxy (HTX) is a thoracoabdominal organ anomaly syndrome and commonly accompanied by congenital heart disease (CHD). The aim of this study was to analyze rare copy number variations (CNVs) in a HTX/CHD cohort and to examine the potential mechanisms contributing to HTX/CHD. Methods:. Chromosome microarray analysis was used to identify rare CNVs in a cohort of 120 unrelated HTX/CHD patients, and available samples from parents were used to confirm the inheritance pattern. Potential candidate genes in CNVs region were prioritized via the DECIPHER database, and PNPLA4 was identified as the leading candidate gene. To validate, we generated PNPLA4-overexpressing human induced pluripotent stem cell lines as well as pnpla4-overexpressing zebrafish model, followed by a series of transcriptomic, biochemical and cellular analyses. Results:. Seventeen rare CNVs were identified in 15 of the 120 HTX/CHD patients (12.5%). Xp22.31 duplication was one of the inherited CNVs identified in this HTX/CHD cohort, and PNPLA4 in the Xp22.31 was a candidate gene associated with HTX/CHD. PNPLA4 is expressed in the lateral plate mesoderm, which is known to be critical for left/right embryonic patterning as well as cardiomyocyte differentiation, and in the neural crest cell lineage. Through a series of in vivo and in vitro analyses at the molecular and cellular levels, we revealed that the biological function of PNPLA4 is importantly involved in the primary cilia formation and function via its regulation of energy metabolism and mitochondria-mediated ATP production. Conclusions:. Our findings demonstrated a significant association between CNVs and HTX/CHD. Our data strongly suggested that an increased genetic dose of PNPLA4 due to Xp22.31 duplication is a disease-causing risk factor for HTX/CHD.

Abstract Background Patients with major depressive disorder (MDD) have an increased risk of breast cancer (BC), implying that these two diseases share similar pathological mechanisms. This study aimed to identify the key pathogenic genes that lead to the occurrence of both triple-negative breast cancer (TNBC) and MDD. Methods Public datasets GSE65194 and GSE98793 were analyzed to identify differentially expressed genes (DEGs) shared by both datasets. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify key PPI genes using cytoHubba. Hub DEGs were obtained from the intersection of hub genes from a PPI network with genes in the disease associated modules of the Weighed Gene Co-expression Network Analysis (WGCNA). Independent datasets (TCGA and GSE76826) and RT-qPCR validated hub gene expression. Results A total of 113 overlapping DEGs were identified between TNBC and MDD. The PPI network was constructed, and 35 hub DEGs were identified. Through WGCNA, the blue, brown, and turquoise modules were recognized as highly correlated with TNBC, while the brown, turquoise, and yellow modules were similarly correlated with MDD. Notably, G3BP1, MAF, NCEH1, and TMEM45A emerged as hub DEGs as they appeared both in modules and PPI hub DEGs. Within the GSE65194 and GSE98793 datasets, G3BP1 and MAF exhibited a significant downregulation in TNBC and MDD groups compared to the control, whereas NCEH1 and TMEM45A demonstrated a significant upregulation. These findings were further substantiated by TCGA and GSE76826, as well as through RT-qPCR validation. Conclusions This study identified G3BP1, MAF, NCEH1 and TMEM45A as key pathological genes in both TNBC and MDD.

Multiobjective optimization is a ubiquitous problem that arises naturally in many scientific and industrial areas. Network routing optimization with multiobjective performance demands falls into this problem class, and finding good quality solutions at large scales is generally challenging. In this work, we develop a scheme with which near-term quantum computers can be applied to solve multiobjective combinatorial optimization problems. We study the application of this scheme to the network routing problem in detail, by first mapping it to the multiobjective shortest-path problem. Focusing on an implementation based on the quantum approximate optimization algorithm (QAOA)—the go-to approach for tackling optimization problems on near-term quantum computers—we examine the Pareto plot that results from the scheme and qualitatively analyze its ability to produce Pareto-optimal solutions. We further provide theoretical and numerical scaling analyses of the resource requirements and performance of QAOA and identify key challenges associated with this approach. Finally, through Amazon Braket, we execute small-scale implementations of our scheme on the IonQ Harmony 11-qubit quantum computer.

Superhydrophobic surfaces have been extensively utilized due to their high hydrophobicity and anti-icing properties. Inspired by the shape of a cross flower, research has utilized circular arc curves and Bessel curves to design a cross flower structure model. Using 3D modeling software for modeling and 3D printing technology to prepare biomimetic microstructures in structural design. The structural shape of the microstructure before and after spray coating was detected using ultra depth of field and laser confocal microscopy. Using Ultra-Ever Dry as a low surface energy substance to alter the wettability of microstructure surfaces. Through surface wettability tests, droplet freezing, and droplet impact tests, the cross shaped biomimetic structure designed by the Bessel curve has a maximum droplet freezing time of 4193 s and a minimum droplet impact time of 9.81 ms. The experimental results indicate that the cross shaped biomimetic structure has good hydrophobicity and broad application prospects.

ObjectiveTo assess the exposure and health risks from perchlorates in food and tea among Chinese residents grouped by key and common areas.MethodsPerchlorate content data for food and tea in China were collected from the literature. Combined with data from the Chinese Total Diet Study in 2015 and using the hazard quotient， the estimated dietary exposure to perchlorate in different areas was assessed and compared using several health-based guidance values.ResultsThe highest mean perchlorate content was 175.54 μg/kg in tea. The results of the probability assessment showed that vegetables were critical exposure pathways in the Chinese population， accounting for 79.40% of total daily perchlorate intake. The 99% daily perchlorate intake of Chinese populations was lower than the provisional maximum tolerable daily intake （PMTDI， 10 μg/kg∙BW） set by the Joint FAO/WHO. However， the daily perchlorate intake of 4.96% and 26.57% of the residents in two areas far exceeded the temporary tolerable daily intake （tTDI， 0.7 μg/kg∙BW） set by China. In tea， 95% of daily perchlorate intake was lower than the PMTDI， but the daily perchlorate intakes of 57.47% and 77.94% of the tea drinkers in the two areas exceeded the tTDI.ConclusionThe risk of exposure to perchlorate via dietary intake in the Chinese population is generally low； however， there are key areas where the exposure is significantly higher than those in other areas owing to high local pollution.

Abstract Optical imaging in scattering media is important to many fields but remains challenging. Recent methods have focused on imaging through thin scattering layers or thicker scattering media with prior knowledge of the sample, but this still limits practical applications. Here, we report an imaging method named ‘speckle kinetography’ that enables high-resolution imaging in unknown scattering media with thicknesses up to about 6 transport mean free paths. Speckle kinetography non-invasively records a series of incoherent speckle images accompanied by object motion and the inherently retained object information is extracted through an overlapping speckle correlation algorithm to construct the object’s autocorrelation for imaging. Under single-colour light-emitting diode, white light, and fluorescence illumination, we experimentally demonstrate 1 μm resolution imaging and tracking of objects moving in scattering samples, while reducing the requirements for prior knowledge. We anticipate this method will enable imaging in currently inaccessible scenarios.

ObjectiveCardiac surgery in Congenital Heart Disease-Heterotaxy (CHD-HTX) patients often leads to increased postoperative airway complications. Abnormal respiratory ciliary function, resembling primary ciliary dyskinesia, has been observed. We expanded the sample size by retrospectively reviewing Ciliary Dysfunction (CD) in CHD-HTX patients to verify the increased risk of post-surgical respiratory complications.MethodsWe conducted a retrospective review of 69 CHD-HTX patients undergoing cardiac surgery, assessing abnormal respiratory function using nasal nitric oxide (nNO) levels and nasal ciliary motion observed in video microscopy. Data collected included demographics, surgical details, postoperative complications, length of stay, ICU hours, salvage procedures, intubation duration, and mortality.ResultsThe CD and no-CD cohorts exhibited notable similarities in risk adjustment in Congenital Heart Surgery-1 (RACHS-1) risk categories, age at the time of surgery, and the duration of follow-up evaluations. We observed a trend toward an increased length of post-operative stay in the CD group (15.0 vs. 14.0; P = 0.0017). CHD-HTX patients with CD showed significantly higher rates of respiratory complications (70% vs. 44.4%; P = 0.008). There were no notable variances observed in postoperative hospitalization duration, mechanical ventilation period, or surgical mortality.ConclusionOur findings suggest that CHD-HTX patients with CD may face an elevated risk of respiratory complications. These results offer guidance for perioperative management and serve as a reference for further pathological studies.

Abstract Accurately predicting the brain responses to various stimuli poses a significant challenge in neuroscience. Despite recent breakthroughs in neural encoding using convolutional neural networks (CNNs) in fMRI studies, there remain critical gaps between the computational rules of traditional artificial neurons and real biological neurons. To address this issue, a spiking CNN (SCNN)-based framework is presented in this study to achieve neural encoding in a more biologically plausible manner. The framework utilizes unsupervised SCNN to extract visual features of image stimuli and employs a receptive field-based regression algorithm to predict fMRI responses from the SCNN features. Experimental results on handwritten characters, handwritten digits and natural images demonstrate that the proposed approach can achieve remarkably good encoding performance and can be utilized for “brain reading” tasks such as image reconstruction and identification. This work suggests that SNN can serve as a promising tool for neural encoding.

ObjectiveBased on the reference dose （RfD） of deoxynivalenol （DON）， the applicability of probabilistic RfD was explored.MethodsBased on the uncertainty analysis guidelines established by the World Health Organization， an experimental study of chronic oral exposure to DON in mice was performed to derive RfD. The probability distribution of the reference dose of DON was calculated by the approximate probabilistic method and the complete probabilistic method， respectively. Then， sensitivity analysis was conducted to study the ability of the two probabilistic methods to analyze uncertainty factors.ResultsThe complete probabilistic RfD of DON was 0.42 μg/kg·BW·d， which was higher than the approximate probabilistic reference dose of 0.30 μg/kg·BW·d， and the complete probabilistic method had an uncertainty spanning factor of 42， which was slightly lower than factor of 46 of the approximate probabilistic method， suggested that complete probabilistic RfD had lower conservatism. Sensitivity analysis showed that the complete probabilistic method greatly reduced the uncertainty caused by point of departure （POD）.ConclusionThe complete probability method has advantages over the approximate probabilistic method in analyzing uncertainty， especially in POD aspects. If the data can satisfy the Bayesian analysis of dose-response model， the use of the complete probabilistic method is recommended.

Abstract The high inter-individual heterogeneity in individuals with depression limits neuroimaging studies with case-control approaches to identify promising biomarkers for individualized clinical decision-making. We put forward a framework integrating the normative model and non-negative matrix factorization (NMF) to quantitatively assess altered gray matter morphology in depression from a dimensional perspective. The proposed framework parses altered gray matter morphology into overlapping latent disease factors, and assigns patients distinct factor compositions, thus preserving inter-individual variability. We identified four robust disease factors with distinct clinical symptoms and cognitive processes in depression. In addition, we showed the quantitative relationship between the group-level gray matter morphological differences and disease factors. Furthermore, this framework significantly predicted factor compositions of patients in an independent dataset. The framework provides an approach to resolve neuroanatomical heterogeneity in depression.

Zirconia (ZrO2) is a ceramic material with high-temperature resistance and good insulating properties. Herein, for the first time, the surface of ZrO2 was modified with docosanoic acid (DCA) to improve its self-cleaning and hydrophobic properties. This surface modification transformed the surface of ZrO2 from hydrophilic to superhydrophobic. A two-step spraying method was used to prepare the superhydrophobic surface of ZrO2 by sequentially applying a primer and a topcoat. The primer was a solution configured using an epoxy resin as the adhesive and polyamide as the curing agent, while the topcoat was a modified ZrO2 solution. The superhydrophobic surface of ZrO2 exhibited a contact angle of 154° and a sliding angle of 4°. Scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and other analytical techniques were used to characterize the prepared zirconia particles and their surfaces. Moreover, results from surface self-cleaning and droplet freezing tests showed that DCA-modified ZrO2 can be well combined, and its coatings show good self-cleaning and anti-icing properties on TA2 bases.

Abstract Introduction The aim was to develop and validate a nomogram for the prediction of brain metastases (BM) in small cell lung cancer (SCLC), to explore the risk factors and assist clinical decision‐making. Methods We reviewed the clinical data of SCLC patients between 2015 and 2021. Patients between 2015 and 2019 were included to develop, whereas patients between 2020 and 2021 were used for external validation. Clinical indices were analysed by using the least absolute shrinkage and selection operator (LASSO) logistic regression analyses. The final nomogram was constructed and validated by bootstrap resampling. Results A total of 631 SCLC patients between 2015 and 2019 were included to construct model. Gender, T stage, N stage, Eastern Cooperative Oncology Group (ECOG), haemoglobin (HGB), the absolute value of lymphocyte (LYMPH #), platelet (PLT), retinol‐binding protein (RBP), carcinoembryonic antigen (CEA) and neuron‐specific enolase (NSE) were identified as risk factors and included into the model. The C‐indices were 0.830 and 0.788 in the internal validation by 1000 bootstrap resamples. The calibration plot revealed excellent agreement between the predicted and the actual probability. Decision curve analysis (DCA) showed better net benefits with a wider range of threshold probability (net clinical benefit was 1%–58%). The model was further externally validated in patients between 2020 and 2021 with a C‐index of 0.818. Conclusions We developed and validated a nomogram to predict the risk of BM in SCLC patients, which could help clinicians to rationally schedule follow‐ups and promptly implement interventions.

BackgroundAs a severe morbidity during pregnancy, the etiology of spontaneous pregnancy loss (SPL) remains largely unknown. Serum glycated hemoglobin (HbA1c) level is an established predictor of SPL risk among women with diabetes, but little is known about whether such an association exists among pregnant women without diabetes when glycemic levels are within the normal range. ObjectiveThis study aimed to quantify the association between maternal HbA1c levels in early pregnancy and subsequent SPL risk in a cohort of pregnant women without diabetes. MethodsThis prospective cohort study involved 10,773 pregnant women without diabetes enrolled at their first antenatal care visit at a hospital’s early pregnancy clinic from March 2016 to December 2018 in Shanghai, China. HbA1c and fasting blood glucose (FBG) levels were examined at enrollment. Participants with diabetes before or pregnancy or those diagnosed with gestational diabetes were excluded. Diagnosis of SPL, defined as fetal death occurring before 28 gestational weeks, was derived from medical records and confirmed via telephone interviews. We used generalized linear models to quantify the associations of continuous and dichotomized maternal HbA1c levels with SPL risk and reported crude and adjusted risk ratios (RRs) and 95% CIs. A restricted cubic spline (RCS) regression model was used to assess the potential nonlinear dose-response relationship. Adjusted covariates included maternal age, education level, preconception BMI, gestational weeks, gravidity, history of adverse pregnancy outcomes, family history of diabetes, folic acid supplementation, and smoking and drinking during the periconception period. ResultsIn total, 273 (2.5%) SPL cases occurred. Every 0.5% increase in HbA1c levels was linearly associated with a 23% increase in SPL risk (adjusted RR [aRR] 1.23; 95% CI 1.01-1.50). The RCS model revealed that this association was linear (P=.77 for the nonlinearity test). Analyses based on dichotomized HbA1c levels showed a significantly increased risk of SPL when HbA1c levels were ≥5.9% (aRR 1.67; 95% CI 0.67-3.67), and the significance threshold was ≥5.6% (aRR 1.60; 95% CI 1.01-2.54). Sensitivity analyses showed similar results when including the participants with missing SPL records or HbA1c data. Linear associations of HbA1c levels remained significant even in the subgroups without overweight, alcohol consumption, and a family history of diabetes and adverse pregnancy outcomes. Every 1 mmol/L increment in maternal FBG levels was associated with a >2-fold higher risk of SPL (aRR 2.12; 95% CI 1.61-2.80; P

ABSTRACT Conventional von Neumann architecture is insufficient in establishing artificial intelligence (AI) in terms of energy efficiency, computing in memory and dynamic learning. Delightedly, rapid developments in neuromorphic computing provide a new paradigm to solve this dilemma. Furthermore, neuromorphic devices that can realize synaptic plasticity and neuromorphic function have extraordinary significance for neuromorphic system. A three-terminal neuromorphic transistor is one of the typical representatives. In addition, human body has five senses, including vision, touch, auditory sense, olfactory sense and gustatory sense, providing abundant information for brain. Inspired by the human perception system, developments in artificial perception system will give new vitality to intelligent robots. This review discusses the operation mechanism, function and application of neuromorphic transistors. The latest progresses in artificial perception systems based on neuromorphic transistors are provided. Finally, the opportunities and challenges of artificial perception systems are summarized.

IntroductionNoncardiac anomalies (NCAs) in patients with congenital heart defects (CHDs) are crucial for perioperative management and etiology studies. This study aimed to investigate NCAs in Chinese children with CHDs.MethodsMedical records for CHD-diagnosed children hospitalized from 1 January 2015 to 31 December 2019 were collected and subjected to retrospective analyses to excavate potential association rules between CHDs and noncardiac malformations.ResultsA total of 3,788 CHD patients were included in this study. The main phenotypes of CHD were Ventricular Septal Defect (VSD, 33.69%), Atrial Septal Defect (ASD, 12.72%), and Tetralogy of Fallot (TOF, 5.54%). A total of 887 (23.42%) cases showed noncardiac anomalies, which were mainly associated with the central nervous system (34.61%), nose/ear/mandibular/face (19.39%), genitourinary system (15.78%), and musculoskeletal system (15.56%). Compared to other CHD subtypes, septal defects had a lower percentage of associated NCAs (P = 3.7 × 10−9) while AVSD had a higher percentage (P = 0.0018).DisscussionNCAs are prevalent among CHD-diagnosed children in China, and the spectrums of NCAs in different CHD subcategories were different.

Background: To explore the prognosis and risk factors of postoperative hepatic dysfunction in patients with acute type A aortic dissection. Methods: A total of 156 patients who underwent surgery for acute type A aortic dissection in our hospital from May 2014 to May 2018 were retrospectively enrolled. The patients were divided into 2 groups based on postoperative liver function. The postop-erative model for end-stage liver disease score was used to define hepatic dysfunction. There were 35 patients with postoperative hepatic dysfunction (group hepatic dysfunction, model for end-stage liver disease score ≥ 15) and 121 patients without postoperative hepatic dysfunction (group non-hepatic dysfunction, model for end-stage liver disease score < 15). Univariate and multiple analyses (logistic regression) were used to identify the predictive risk factors. Results: In-hospital mortality rate was 8.3%. Multiple logistic analysis showed that preoperative alanine aminotransferase (P

“Dietary fiber” (DF) refers to a type of carbohydrate that cannot be digested fully. DF is not an essential nutrient, but it plays an important part in enhancing digestive capacity and maintaining intestinal health. Therefore, DF supplementation in the daily diet is highly recommended. Inulin is a soluble DF, and commonly added to foods. Recently, several studies have found that dietary supplementation of inulin can improve metabolic function and regulate intestinal immunity. Inulin is fermented in the colon by the gut microbiota and a series of metabolites is generated. Among these metabolites, short-chain fatty acids provide energy to intestinal epithelial cells and participate in regulating the differentiation of immune cells. Inulin and its intestinal metabolites contribute to host immunity. This review summarizes the effect of inulin and its metabolites on intestinal immunity, and the underlying mechanisms of inulin in preventing diseases such as type 2 diabetes mellitus, inflammatory bowel disease, chronic kidney disease, and certain cancer types.

In order to study the change rules of mineral composition, micro-structure evolution characteristics and their relationship with dynamic properties of granite after high temperature treatment, the high temperature tests on Beishan granite in Gansu Province, China, were carried out at 20−1 000 ℃. Microscopic images of granite after high temperature treatment were obtained by slicing technique and polarizing microscope. The evolution of mineral composition, mineral content and micro-structure characteristic parameters of granite with temperature were studied through mineral composition analysis, micro-cracks characteristic identification and parameters calculation. Subsequently, dynamic impact compression tests of high temperature treated granite were carried out by split Hopkinson pressure bar (SHPB) system, to analyze the effects of temperature, impact rate and micro-structure characteristics on dynamic peak stress. On this basis, the quantitative relationship between micro-structure characteristics and macroscopic dynamic properties was established. The results show that high temperature has a significant effect on the mineral composition, micro-structure and impact compressive strength of granite, and 600 ℃ is taken as the threshold temperature. The loading rate also significantly affects the impact compressive strength, and the larger the loading rate is, the less the influence of temperature on the macroscopic dynamic properties is. The evolution process of the micro-structure of granite after high temperature treatment is the internal mechanism for the change of its macroscopic dynamic properties with temperature. The microcrack characteristics have a significant correlation with the dynamic peak stress, and the average crack width is the main factor affecting the dynamic peak stress of granite.

Major depressive disorder is a serious disease that impacts human health worldwide. Traditional antidepressant medications are limited by the delayed onset of therapeutic effects and the unacceptable side effects. Recently, the rapid antidepressant effect of ketamine, which decreases depressive symptoms within hours, has been a very attractive finding in the field, but the underlying mechanisms mediating this rapid response remain unclear. Besides, the clinical application of ketamine still carries risks, such as addiction and deleterious side effects. In May 2022, Rawat et al. reported that the acute activation of adult-born immature granule neurons (ABINs) in the dentate gyrus played a key role in the rapid antidepressant effects of ketamine. This commentary reviews the important findings of this research and looks forward to the future work.

ObjectiveTo construct disease models of dietary inorganic arsenic-induced cancer and cardiovascular disease in China.MethodsThe different health hazard endpoints due to dietary inorganic arsenic should be identified. Based on the epidemiological data of related diseases in the Chinese population， the risk assessment method and counterfactual analysis method were used to calculate the attributable morbidity and mortality of cancer and cardiovascular disease caused by dietary inorganic arsenic exposure. Combined with disability weight and disease course characteristics， a disease model of cancer and cardiovascular disease caused by dietary inorganic arsenic exposure was established.ResultsLifetime persistent dietary exposure to 1.41 μg/（kg∙d） of inorganic arsenic in the population resulted in 0.135%， 0.010% and 0.034% of skin， bladder， and lung cancer incidence with 0.015%， 0.004% and 0.138% of mortality， respectively. The incidence and mortality of cardiovascular diseases caused by 1 μg/（kg∙d） of dietary inorganic arsenic exposure were 0.082% and 0.025%， respectively.ConclusionThe disease model can be used to calculate the burden of disease caused by food contaminants and quantify the health hazards caused by food contaminants.

Pigeon pea is a perennial leguminous plant that is widely cultivated as a forage and pharmaceutical plant in subtropical and tropical areas, especially in artificial grasslands. Higher seed shattering is one of the most important factors in potentially increasing the seed yield of pigeon pea. Advance technology is necessary to increase the seed yield of pigeon pea. Through 2 consecutive years of field observations, we found that fertile tiller number was the key component of the seed yield of pigeon pea due to the direct effect of fertile tiller number per plant (0.364) on pigeon pea seed yield was the highest. Multiplex morphology, histology, and cytological and hydrolytic enzyme activity analysis showed that shatter-susceptible and shatter-resistant pigeon peas possessed an abscission layer at the same time (10 DAF); however, abscission layer cells dissolved earlier in shattering-susceptible pigeon pea (15 DAF), which led to the tearing of the abscission layer. The number of vascular bundle cells and vascular bundle area were the most significant negative factors (p< 0.01) affecting seed shattering. Cellulase and polygalacturonase were involved in the dehiscence process. In addition, we inferred that larger vascular bundle tissues and cells in the ventral suture of seed pods could effectively resist the dehiscence pressure of the abscission layer. This study provides foundation for further molecular studies to increase the seed yield of pigeon pea.

Repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (L-DLPFC) is commonly used for the clinical treatment of major depressive disorder (MDD). The neuroimaging biomarkers and mechanisms of rTMS are still not completely understood. This study aimed to explore the functional neuroimaging changes induced by rTMS in adolescents with MDD. A total of ten sessions of rTMS were administrated to the L-DLPFC in thirteen adolescents with MDD once a day for two weeks. All of them were scanned using resting-state functional magnetic resonance imaging at baseline and after rTMS treatment. The regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF), and the subgenual anterior cingulate cortex (sgACC)-based functional connectivity (FC) were computed as neuroimaging indicators. The correlation between changes in the sgACC-based FC and the improvement in depressive symptoms was also analyzed. After rTMS treatment, ReHo and ALFF were significantly increased in the L-DLPFC, the left medial prefrontal cortex, bilateral medial orbital frontal cortex, and the left ACC. ReHo and ALFF decreased mainly in the left middle occipital gyrus, the right middle cingulate cortex (MCC), bilateral calcarine, the left cuneus, and the left superior occipital gyrus. Furthermore, the FCs between the left sgACC and the L-DLPFC, the right IFGoper, the left MCC, the left precuneus, bilateral post-central gyrus, the left supplementary motor area, and the left superior marginal gyrus were enhanced after rTMS treatment. Moreover, the changes in the left sgACC-left MCC FC were associated with an improvement in depressive symptoms in early improvers. This study showed that rTMS treatment in adolescents with MDD causes changes in brain activities and sgACC-based FC, which may provide basic neural biomarkers for rTMS clinical trials.

ObjectiveTo estimate the global prevalence and concentration of deoxynivalenol （DON）， aflatoxins （AFs）， zearalenone （ZEN）， nivalenol （NIV）， T-2 toxin （T2）， HT-2 toxin （HT2）， ochratoxin A （OTA）， fumonisins （FBs）， alternariol （AOH）， alternariol monomethyl ether （AME）， tentoxin （TEN） and tenuazonic acid （TeA） in wheat and wheat-based products via Meta-analysis.MethodsThe databases include PubMed， Web of Science， CNKI and WANFANG database.ResultsA total of 69 eligible studies were included in this study， related to 22，308 samples. The global pooled prevalence of mycotoxins in wheat and wheat-based products was 58% （95%CI： 51%-66%）， which mainly were TeA （99%）， TEN （88%）， DON （85%）， AFs （57%）， ZEN （42%）， T2 （39%）， AOH （30%）， AME （29%）， NIV （28%）， HT2 （25%）， OTA （21%） and FBs （16%）. The global pooled concentration of mycotoxins in wheat and wheat-based products was 32.80 μg/kg （95%CI： 24.96-43.10 μg/kg）. DON showed the highest concentration （317.53 μg/kg）， followed by TeA （117.37 μg/kg）， FBs （45.09 μg/kg）. The co-occurrence rate of DON-ZEN was 11.0%, 14.0% and 26.7%, TeA-TEN was 16.2%, TeA-TEN-AME was 14.3% and TeA-TEN-AOH-AME was 19.5%, respectively.ConclusionWheat and wheat-based products showed different characteristics of mycotoxin contamination in different countries or regions, and the co-occurrence rate of more than one mycotoxin in wheat and wheat-based products was high, which should be paid attention to in the combined exposure assessment.

ObjectiveThe advantages and disadvantages of three statistical models commonly used in food contaminant exposure assessment， namely the observed individual means （OIM） model， the beta-abinomial and normal （BBN） model and the non-parametric model were compared by an example of the estimation of long-term exposure to cadmium via rice.MethodsRice， cadmium and diet were used as Chinese and English keywords to search the literature on cadmium concentration in rice in China National Knowledge Infrastructure， Wanfang Data Knowledge Service Platform and PubMed database. Long-term levels of exposure to cadmium via rice for the total population and age groups in China were estimated by combining partial consumption frequency data obtained from the Chinese nutrition survey.ResultsIn the total population， the OIM model showed that the 2.5th to 97.5th percentile （P2.5、P97.5） of the exposure to heavy metal Cd in rice was 0.081-0.576 μg/（kg·BW·d）， the non-parametric model result was 0.081-0.573 μg/（kg·BW·d）， and the BBN model result was 0.104-0.611 μg/（kg·BW·d）. The average results of the OIM model， non-parametric model and BBN model in different populations were close. The average values of the three models in the total population were 0.278， 0.277 and 0.278 μg/（kg·BW·d）， respectively.ConclusionWith large sample data， non-parametric models have similar assessment results to the OIM model， while BBN models can allow for a more conservative assessment of exposure by subtracting differences in consumption frequency within individuals， and better evaluate the long-term exposure level of pollutants.

PurposeTo confirm the ability of native T1 and T2 values in detecting and monitoring early myocardial injuries of chest radiotherapy in neoplasm patients.Materials and methodsFifteen participants received non-anthracycline chemotherapy and chest radiotherapy, and 30 age/gender-matched controls were enrolled in this prospective study. Cardiac magnetic resonance scans were performed within 2 days, 3 months, and 6 months after chest radiotherapy. Myocardial native T1 and T2 values were measured in irradiated and nonirradiated areas. Meanwhile, the parameters of left ventricular function and left ventricular myocardial strain were obtained.ResultsThere were no significant differences in left ventricular function, native T1, T2, and strain between patients and controls before chest radiotherapy. In 15 participants who were followed up for 6 months, there was a significant change only in left ventricular ejection fraction (LVEF) among baseline and the first follow-up (P = 0.021), while the adjusted P-value was higher than 0.05 after Bonferroni correction, as well as other parameters. Native T1 values were elevated at 3 and 6 months in irradiated areas compared with baseline (1,288.72 ± 66.59 ms vs. 1,212.51 ± 45.41 ms; 1,348.01 ± 54.16 ms vs. 1,212.51 ± 45.41 ms; P 0.05). There were no significant differences in strain changes during the follow-up period (all P > 0.05).ConclusionNative T1 and T2 values elevated at 3 months after chest radiotherapy, whereas LVEF showed no significant change during the 6-month follow-up.

The combined effects of human exposure to chemical mixtures have attracted the attention of government agencies in many countries. Many institutions have carried out a lot of research on the cumulative exposure assessment of the combined effects of chemical mixtures. This article outlines the principles and standards for grouping chemicals with a common action mechanism in the cumulative exposure risk assessment of chemicals, and based on the types of combined effects of chemicals and their judgment method, expounds the Hazard Index method, Cumulative Risk Index method, Relative Potency Factor method, Point of Departure method, combined Margin of Exposure method, reaction addition method based on independent reaction, and hazard index correction method based on interaction, etc. In addition, in the exposure assessment of compound mixtures, the accuracy of physiologically-based toxicokinetic model method and conventional assessment method are analyzed, and a new direction for exploration is proposed for more accurate and scientific assessments in China in the future.

Vibriosis and parasitic leech infestations cause the death of various farmed fish, such as groupers, hybrid groupers, sea bass, etc., in Malaysia and other Southeast Asian countries. In the absence of natural control agents, aquaculture operators rely on toxic chemicals to control Vibrio infections and parasitic leeches, which can have a negative impact on the environment and health. In the present study, we investigated the antivibrio and antiparasitic activities of the aqueous extract of giant sword fern (GSF) (Nephrolepis biserrata, Nephrolepidaceae, locally known as “Paku Pedang”) against four Vibrio spp. and the parasitic leech Zeylanicobdella arugamensis, as well as its metabolic composition using the ultra-high-performance liquid chromatography–high-resolution mass spectrometry system (UHPLC-HRMS). The data show that the aqueous extract of GSF at a concentration of 100 mg/mL exhibits potent bactericidal activity against V. parahaemolyticus with a zone of inhibition of 19.5 mm. In addition, the extract showed dose-dependent activity against leeches, resulting in the complete killing of the parasitic leeches within a short period of 11–43 min when tested at concentrations ranging from 100 to 25 mg/mL. The UHPLC-HRMS analysis detected 118 metabolites in the aqueous extract of GSF. Flavonoids were the primary metabolites, followed by phenolic, aromatic, fatty acyl, terpenoid, vitamin and steroidal compounds. Notably, several of these metabolites possess antibacterial and antiparasitic properties, including cinnamaldehyde, cinnamic acid, apigenin, quercetin, cynaroside, luteolin, naringenin, wogonin, 6-gingerol, nicotinamide, abscisic acid, daidzein, salvianolic acid B, etc. Overall, our study shows the significant antibacterial and antiparasitic potential of the GSF aqueous extract, which demonstrates the presence of valuable secondary metabolites. Consequently, the aqueous extract is a promising natural alternative for the effective control of Vibrio infections and the treatment of parasitic leeches in aquaculture systems.

Using petiole material as explants and directly inducing the formation of microtubers without going through the callus stage is an essential way to rapidly expand scarce medical plants such as Pinellia ternata. However, the early molecular mechanism underlying the formation of the microtuber is largely elusive. Here, we conducted cytology and dynamic transcriptome analyses of inchoate microtubers in Pinellia explants and identified 1092 differentially expressed genes after their cultivation in vitro for 0, 5, and 15 days. Compared with 0 day, the number and size of the microtuber cells were larger at 5 and 15 days of culture. Detailed categorization revealed that the differentially expressed genes were mainly related to responses to stimulus, biological regulation, organelles, membranes, transcription factor activity, and protein binding. Further analysis revealed that the microtuber at different incubation days exhibited quite a difference in both hormone signaling pathway transduction and the regulation pattern of transcription factors. Therefore, this study contributes to a better understanding of the early molecular regulation during the formation of the microtuber and provides new insights for the study of the rapid expansion of P. ternata and other medical plants.

ObjectiveTo evaluate the exposure level and health risk of inorganic arsenic ingested by rice in Chinese residents.MethodsThe data of inorganic arsenic content in rice published in PubMed, CNKI and other databases from 2001 to 2020 were systematically retrieved. Combined with the monitoring data of nutrition and health status of Chinese residents in 2012, the inorganic arsenic intake level of Chinese residents through rice was estimated by semi parametric Monte Carlo simulation. Target hazard quotient method and lifetime cancer risk method were used to evaluate the health risk caused by inorganic arsenic in rice.ResultsThe content of inorganic arsenic in rice ranged from 0.038 to 0.1 mg/kg. The average level of inorganic arsenic exposure of Chinese residents through rice was higher in the south than in the north(p

The emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has affected billions of lives globally, and the world hopes to end this epidemic by effective vaccination. In this review, we depict the latest panorama of global COVID-19 vaccine research and development based on different technology platforms, and summarize key characteristics and available evidence on vaccines authorized for emergency use, in order to provide insights into improve coordination in the COVID-19 outbreak response for related stakeholders.

Nonalcoholic steatohepatitis (NASH) is the progressive form of nonalcoholic fatty liver disease (NAFLD), and the dysregulation of lipid metabolism and oxidative stress are the typical features. Subsequent dyslipidemia and oxygen radical production may render the formation of modified lipids. Macrophage scavenger receptor 1 (MSR1) is responsible for the uptake of modified lipoprotein and is one of the key molecules in atherosclerosis. However, the unrestricted uptake of modified lipoproteins by MSR1 and the formation of cholesterol-rich foamy macrophages also can be observed in NASH patients and mouse models. In this review, we highlight the dysregulation of lipid metabolism and oxidative stress in NASH, the alteration of MSR1 expression in physiological and pathological conditions, the formation of modified lipoproteins, and the role of MSR1 on macrophage foaming and NASH development and progression.

A dose-escalation, randomized, double-blind, placebo-controlled phase 1 clinical trial enrolled 145 eligible participants aged 18–55 years in March 2015 in Liuzhou, China. Stratified by age and sex, the participants were randomly assigned to receive either 30, 60, or 90 μg of the HPV-6/11 vaccine (n = 41/40/40) or the parallel placebo vaccine (n = 8/8/8) with a 0/1/6-month dose-escalation schedule. Participants were actively followed-up to record local and systemic AEs occurring within 30 days after each vaccination, and SAEs occurred in 7 months. Blood and urine samples of each participant were collected before and 2 days after the first and third vaccination to determine changes in routine blood, serum biochemical, and urine indexes. Serum HPV-6/11-specific IgG and neutralizing antibody levels at month 7 were analyzed. A total of 79 adverse events were reported, and no SAEs occurred. The incidences of total adverse reactions in the 30 μg, 60 μg, and 90 μg HPV vaccine groups and the control group were 31.7%, 50.0%, 42.5%, and 62.5%, respectively. All but one of the adverse reactions was mild or moderate with grade 1 or 2. No vaccine-related changes with clinical significance were found in paired blood and urine indexes before and after vaccinations. All the participants in the per-protocol set seroconverted at month 7 for both IgG and neutralizing antibodies. The candidate novel Escherichia-coli-produced bivalent HPV-6/11 vaccine has been preliminarily proven to be well tolerated and with robust immunogenicity in a phase 1 clinical study, supporting further trials with larger sample size. The study has been registered at ClinicalTrials.gov (NCT02405520)

Stylosanthes spp. (stylo) are annual or perennial legume forages that are widely grown as forage and cover crops in tropical and subtropical regions. However, the seed yield of stylo is very low due to serious seed shattering. In the present study, we found that, although seed shattering was common among the stylo accessions, the shattering rates were genetically different. Therefore, we first synthesized the morphological, histological characteristic, physiochemical, and transcriptome analyses to determine the seed shattering mechanism in stylo. In general, the stylo germplasm with shorter lobules and thicker stems had a lower seed shattering rate and a higher seed weight. The seed and seed stalk joint is the abscission zone in stylo. Multiplex histology and hydrolytic enzyme activity analysis showed that the tearing of the abscission zone occurs due to the intense enzymatic degradation of polygalacturonase and cellulase in the seed shattering-susceptible accession TF0275. cDNA libraries from the abscission zone tissues of TF0041 and TF0275 at 14, 21, and 28 days after flowering were constructed and sequenced. A total of 47,606 unigenes were annotated and 18,606 differentially expressed genes (DEGs) were detected, including 9,140 upregulated and 9,446 downregulated unigenes. Furthermore, the 26 candidate DEGs involved in lignin biosynthesis, cellulase synthesis, and plant hormone signal transduction were found at all three developmental stages. This study provides valuable insights for future mechanistic studies of seed shattering in stylo.

ObjectiveAs one of the common mycotoxins in the food, deoxynivalenol (DON) poses multiple health risks. Limited information is available on DON exposure in Chinese pregnant women who they are vulnerable to various pollutants exposure hazards. The purpose of this study was to detect urine DON concentrations and estimate dietary DON intake in Chinese pregnant women, and provide evidence for assessing the risk of dietary DON exposure for pregnant women.MethodsThe study involved 103 pregnant women from the Tongji birth cohort study in Wuhan, China. Urine samples were collected and dietary investigation was conducted using food-frequency questionnaire (FFQ). The level of DON in urine was determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).ResultsAmong 103 pregnant women, total DON was detected in 95 urine samples (92.23%, 95/103), free DON was detected in 76 samples (73.79%, 76/103). The mean total DON levels were 19.12 ng/mg creatinine for both trimesters, 15.17 ng/mg creatinine for the first trimester and 20.91 ng/mg creatinine for the second trimester. The dietary DON intake for pregnant women was 0.45-0.89 μg/(kg b. w.·d). The dietary DON intake of 11.65%-22.33% pregnant women exceeded current guidance regarding the provisional maximum tolerable daily intake (PMTDI) for DON. The diet of pregnant women was mainly rice and its products, and its intake was positively correlated with the concentration of DON.ConclusionIn this study, the detection rate of DON in the urine samples of pregnant women in Wuhan was high, but the level of DON was low. Future attention should be paid to the exposure level of pregnant women to DON and the potential health risks to both mother and fetus.

Lithocholic acid (LCA) is a monohydroxy bile acid produced by intestinal flora, which has been found to be associated with a variety of hepatic and intestinal diseases. LCA is previously considered to be toxic, however, recent studies revealed that LCA and its derivatives may exert anti-inflammatory and anti-tumor effects under certain conditions. LCA goes through enterohepatic circulation along with other bile acids, here, we mainly discuss the effects of LCA on the gut-liver axis, including the regulation of gut microbiota, intestinal barrier, and relevant nuclear receptors (VDR, PXR) and G protein-coupled receptor five in related diseases. In addition, we also find that some natural ingredients are involved in regulating the detoxification and excretion of LCA, and the interaction with LCA also mediates its own biological activity.

Abstract Background Congenital heart disease (CHD) is the most common birth defect and has high heritability. Although some susceptibility genes have been identified, the genetic basis underlying the majority of CHD cases is still undefined. Methods A total of 1320 unrelated CHD patients were enrolled in our study. Exome‐wide association analysis between 37 tetralogy of Fallot (TOF) patients and 208 Han Chinese controls from the 1000 Genomes Project was performed to identify the novel candidate gene WD repeat‐containing protein 62 (WDR62). WDR62 variants were searched in another expanded set of 200 TOF patients by Sanger sequencing. Rescue experiments in zebrafish were conducted to observe the effects of WDR62 variants. The roles of WDR62 in heart development were examined in mouse models with Wdr62 deficiency. WDR62 variants were investigated in an additional 1083 CHD patients with similar heart phenotypes to knockout mice by multiplex PCR‐targeting sequencing. The cellular phenotypes of WDR62 deficiency and variants were tested in cardiomyocytes, and the molecular mechanisms were preliminarily explored by RNA‐seq and co‐immunoprecipitation. Results Seven WDR62 coding variants were identified in the 237 TOF patients and all were indicated to be loss of function variants. A total of 25 coding and 22 non‐coding WDR62 variants were identified in 80 (6%) of the 1320 CHD cases sequenced, with a higher proportion of WDR62 variation (8%) found in the ventricular septal defect (VSD) cohort. WDR62 deficiency resulted in a series of heart defects affecting the outflow tract and right ventricle in mouse models, including VSD as the major abnormality. Cell cycle arrest and an increased number of cells with multipolar spindles that inhibited proliferation were observed in cardiomyocytes with variants or knockdown of WDR62. WDR62 deficiency weakened the association between WDR62 and the cell cycle‐regulated kinase AURKA on spindle poles, reduced the phosphorylation of AURKA, and decreased expression of target genes related to cell cycle and spindle assembly shared by WDR62 and AURKA. Conclusions WDR62 was identified as a novel susceptibility gene for CHD with high variant frequency. WDR62 was shown to participate in the cardiac development by affecting spindle assembly and cell cycle pathway in cardiomyocytes.

Hair color fade is an important issue for consumers who use permanent hair colorants and is caused by both washing and UV exposure. The mechanism of light-induced fading was explored using a solution model system and shows that both UV and visible light contribute to color fade and a significant amount of fade is via radical pathways. It was demonstrated that this fade can be reduced by incorporation into a conditioner of a Grape Seed Extract (GSE) that has antioxidant activity. The efficacy of performance was linked to phytochemistry of the extract, specifically catechins and procyanidins and illustrated the importance of extract choice. Levels of these phytochemicals varied between different samples of GSE tested and this correlated well with measured antioxidant performance as measured by ORAC and FRAP. Light-induced fading of hair treated with a permanent hair color was measured with a selection of the GSE extracts. Benefits in protection were measured as a reduction in color lightness changes vs the starting hair color before light exposure.

Background: Virtual reality (VR) offers significant potential for hands-on learning environments by providing immersive and visually stimulating experiences. Interacting with such environments can bring numerous benefits to learning, including enhanced engagement, knowledge construction, and higher-order thinking. However, many current VR studies in hands-on learning tend to utilise one-way learning materials, limiting participants' ability to interact with and reflect on their actions and learning experiences. Moreover, these studies often neglect to assess learners' capacity to transfer their skills from VR learning to real-world scenarios. Therefore, this study aims to investigate participants' engagement, learning outcomes, higher-order thinking, and their ability to apply acquired skills in real-world contexts. Method and Objective: Participants were immersed in a hands-on learning environment in VR, where they received feedback and engaged in reflection during the learning process. This study recruited 68 university students to participate in the experiment, employing a quasi-experimental design. Participants experienced learning units both with and without reflection on the feedback. The theme of these learning units was related to embedded systems, encompassing topics such as the assembly of embedded components and Python programming. The investigation aimed to assess whether reflection in VR could enhance cognitive levels, engagement, real-world hands-on tasks abilities, and higher-order thinking. Results: The research results indicate that in the VR hands-on learning environment, participants engage in reflection through the provided feedback, effectively enhancing their engagement, cognitive levels, and hands-on task abilities. Simultaneously, it also successfully assists participants in developing problem-solving skills and critical thinking in higher-order thinking. Conclusions: Participants actively engaged in reflection on their own learning tasks and actions within the hands-on learning environment, enabling them to develop a deeper understanding of the learning material and enhance their real-world hands-on tasks abilities, we encourage the integration of reflection strategies in VR learning environments for hands-on learning, as they can yield positive benefits for learners.

Abstract Background Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. Methods In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. Results Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. Conclusion PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.

Background: Gut microbiota mainly function in the biotransformation of primary ginsenosides into bioactive metabolites. Herein, we investigated the effects of three prebiotic fibers by targeting gut microbiota on the metabolism of ginsenoside Rb1 in vivo. Methods: Sprague Dawley rats were administered with ginsenoside Rb1 after a two-week prebiotic intervention of fructooligosaccharide, galactooligosaccharide, and fibersol-2, respectively. Pharmacokinetic analysis of ginsenoside Rb1 and its metabolites was performed, whilst the microbial composition and metabolic function of gut microbiota were examined by 16S rRNA gene amplicon and metagenomic shotgun sequencing. Results: The results showed that peak plasma concentration and area under concentration time curve of ginsenoside Rb1 and its intermediate metabolites, ginsenoside Rd, F2, and compound K (CK), in the prebiotic intervention groups were increased at various degrees compared with those in the control group. Gut microbiota dramatically responded to the prebiotic treatment at both taxonomical and functional levels. The abundance of Prevotella, which possesses potential function to hydrolyze ginsenoside Rb1 into CK, was significantly elevated in the three prebiotic groups (P

RNA binding protein Quaking (QKI) is known for its broad function in pre-mRNA splicing and modification and its association with several neurodevelopmental disorders. Here the authors reveal that QKI-mediated regulation of RNA splicing is indispensable to cardiac development and contractile physiology.

Sponges are aquatic, spineless organisms that belong to the phylum Porifera. They come in three primary classes: Hexactinellidae, Demospongiae, and Calcarea. The Demospongiae class is the most dominant, making up over 90% of sponge species. One of the most widely studied genera within the Demospongiae class is Xestospongia, which is found across Southeast Asian waters. This genus is of particular interest due to the production of numerous primary and secondary metabolites with a wide range of biological potentials. In the current review, the antioxidant, anticancer, anti-inflammatory, antibacterial, antiviral, antiparasitic, and cytotoxic properties of metabolites from several varieties of Southeast Asian Xestospongia spp. were discussed. A total of 40 metabolites of various natures, including alkaloids, fatty acids, steroids, and quinones, were highlighted in X. bergquistia, X. testudinaria, X. muta, X. exigua, X. ashmorica and X. vansoesti. The review aimed to display the bioactivity of Xestospongia metabolites and their potential for use in the pharmaceutical sector. Further research is needed to fully understand their bioactivities.

Abstract Background Cancer-related fatigue (CRF) is a debilitating condition which commonly affects cancer survivors. The management of CRF remains a challenge due to the lack of effective pharmacological interventions. Traditional Chinese medicine (TCM) could be a potential therapeutic option for CRF. The modified Xiang Bei Yang Rong Tang (XBYRT) is a TCM herbal decoction, formulated to improve fatigue symptoms in cancer survivors. This clinical trial aims to evaluate the efficacy and safety of XBYRT in improving CRF and quality of life (QOL) of cancer survivors. Methods This is a single centre, randomized, double-blind, placebo-controlled, parallel trial. Eighty cancer survivors will be recruited and randomized to receive the XBYRT or placebo decoction, in a ratio of 1:1. Participants will consume the XBYRT/placebo decoction daily for 8 weeks and undergo assessments at baseline and 4, 8 and 10 weeks after baseline. The participants will be assessed for patient-reported outcomes (PRO), blood biomarkers and adverse events at each time point. The primary outcome is the overall health and QOL status, at 8 weeks follow-up. The secondary outcomes are the effects of XBYRT on fatigue levels, cancer-related cognitive impairment and QOL, as assessed by PRO. The incidence of adverse events and the effects of the XBYRT decoction on blood biomarkers associated with CRF will also be evaluated. Discussion Efficacy and safety outcomes from this trial will provide important clinical data to guide future large-scale randomized controlled trials, and the evaluation of the objective blood biomarkers can help to delineate the biological mechanisms of CRF. Trial registration number ClinicalTrials.gov NCT04104113 . Registered on 26 September 2019

Influence maximization is a hot research topic in the social computing field and has gained tremendous studies motivated by its wild application scenarios. As the structures of social networks change over time, how to seek seed node sets from dynamic networks has attracted some attention. However, all of the existing studies were based on network topology structure data which have the limitations of high dimensionality and low efficiency. Aiming at this drawback, we first convert each node in the network to a low-dimensional vector representation by network representation learning and then solve the problem of dynamic influence maximization in the low-dimensional latent space. Comprehensive experiments on NetHEPT, Twitter, UCI, and Wikipedia datasets show that our method can achieve influence diffusion performance similar to state-of-the-art approaches in much less time.