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Mollemycin A (MOMA) is a unique glyco-hexadepsipeptide-polyketide that was isolated from a Streptomyces sp. derived from the Australian marine environment. MOMA exhibits remarkable inhibitory activity against both drug-sensitive and multidrug-resistant malaria parasites. Optimizing MOMA through structural modifications or product enhancements is necessary for the development of effective analogues. However, modifying MOMA using chemical approaches is challenging, and the production titer of MOMA in the wild-type strain is low. This study identified and characterized the biosynthetic gene cluster of MOMA for the first time, proposed its complex biosynthetic pathway, and achieved an effective two-pronged enhancement of MOMA production. The fermentation medium was optimized to increase the yield of MOMA from 0.9 mg L−1 to 1.3 mg L−1, a 44% boost. Additionally, a synergistic mutant strain was developed by deleting the momB3 gene and overexpressing momB2, resulting in a 2.6-fold increase from 1.3 mg L−1 to 3.4 mg L−1. These findings pave the way for investigating the biosynthetic mechanism of MOMA, creating opportunities to produce a wide range of MOMA analogues, and developing an efficient strain for the sustainable and economical production of MOMA and its analogues.

Introduction: Tendon-derived stem cells (TDSCs) play a critical role in tendon repair. N5-methylcytosine (m5C) is a key regulator of cellular processes such as differentiation. This study aimed to investigate the impact of m5C on TDSC differentiation and the underlying mechanism. Methods: TDSCs were isolated from rats and identified, and a tendon injury rat model was generated. Tenogenic differentiation in vitro was evaluated using Sirius red staining and quantitative real-time polymerase chain reaction, while that in vivo was assessed using immunohistochemistry and hematoxylin‒eosin staining. m5C methylation was analyzed using methylated RNA immunoprecipitation, dual-luciferase reporter assay, and RNA stability assay. Results: The results showed that m5C levels and NSUN2 expression were increased in TDSCs after tenogenic differentiation. Knockdown of NSUN2 inhibited m5C methylation of KLF2 and decreased its stability, which was recognized by YBX1. Moreover, interfering with KLF2 suppressed tenogenic differentiation of TDSCs, which could be abrogated by KLF2 overexpression. Additionally, TDSCs after NSUN2 overexpression contributed to ameliorating tendon injury in vivo. In conclusion, NSUN2 promotes tenogenic differentiation of TDSCs via m5C methylation of KLF2 and accelerates tendon repair. Conclusions: The findings suggest that overexpression of NSUN2 can stimulate the differentiation ability of TDSCs, which can be used in the treatment of tendinopathy.

To explore the effects of fresh leaves harvested at different picking periods on aroma quality and chemical characteristics of oolong tea, morning leaves and evening leaves of Tieguanyin were selected as materials and turned into morning tea and evening tea according to the traditional technology. The volatile components of fresh leaves and oolong tea were analyzed by the method of gas chromatography-mass spectrometer (GC-MS), in order to compare their differences between morning oolong tea and evening oolong tea. The results showed that total volatile components of evening tea were 28.3% less than that of morning tea. The content and proportion of alcohol compounds were superior, especially isophytol and trans-nerolidol. The characteristics of volatile components in fresh leaves were different from that in oolong tea. The rate of alcohol compounds was close to that of acid compounds in fresh leaves, while in oolong teas the difference was large. Two kinds of fresh leaves had 56 identical components, that were 4 more than the two kinds of oolong tea. However, among 42 common components of fresh leaves and oolong tea, palmitic acid, dihydroactinidiolide, trans-nerolidol and isophytol were obviously affected by the manufacture technology, and their variation amplitudes were large. It can be seen that the distribution characteristics of volatile compounds of evening leaves and morning ones were different, and the aroma quality of evening tea was better than that of morning tea, especially the refreshing aroma.

Abstract Mesenchymal stem cells (MSCs) have demonstrated promising advantages in the therapies of many diseases, while its multi-directional differentiation potential and immunotoxicity are the major concerns hindered their clinical translation. In this study, human umbilical Mesenchymal stem cell (hUC-MSCs) were labeled with a near-infrared fluorescent dye DiR before infused into cynomolgus monkeys, and the amount of hUC-MSCs in the peripheral blood were dynamically estimated from 5 min to 28 days post a single administration at 3 × 106 cells/kg and 2 × 107 cells/kg intravenously. As results, some hUC-MSCs distributed to the whole body within 5 min, while most of the cells accumulate in the lungs along with the systemic blood circulation, and subsequently released into the blood. The toxicity potentials of hUC-MSCs were investigated in another 30 cynomolgus monkeys, and the cells were repeatedly administrated at doses of 3 × 106 cells/kg and 2 × 107 cells/kg for 5 times on a weekly basis, with a recovery period of 1 months. hUC-MSCs showed no obvious toxic effects in cynomolgus monkeys, except xenogeneic immune rejection to human stem cells. Low levels of the hUC-MSC gene were detected in the peripheral blood of a few animals administered 2 × 107 cells/kg at 30 min subsequent to the first and last administration, and there was no significant difference in the copy number of the hUC-MSC gene in the blood samples compared with the first and last administration, indicating that the hUC-MSC was not significantly amplified in vivo, and it its safe in non-human primates. Our study for the first time verified the safety of long-term use of hUC-MSCs in primates. We have pioneered a technology for the real-time detection of hUC-MSCs in peripheral blood and provide dynamicand rapid monitoring of the distribution characteristics of hUC-MSCs in vivo. Here, we provide data supporting the application of such products for clinical treatment and the application of stem cells in major refractory diseases and regenerative medicine.

The objective of this study was to investigate the potential carcinogenic toxicity and mechanisms of PFAS in thyroid, renal, and testicular cancers base on network toxicology and molecular docking techniques. Structural modeling was performed to predict relevant toxicity information, and compounds and cancer-related targets were screened in multiple databases. The interaction of PFAS with three cancers and their key protein targets were explored by combining protein network analysis, enrichment analysis and molecular docking techniques. PFOA, PFOS, and PFHXS exhibited significant carcinogenic and cytotoxic effects. These compounds may induce cancer by mediating active oxygen metabolism and the transduction of phosphatidylinositol 3-kinase/protein kinase B signaling pathway through genes such as ALB, mTOR, MDM2, and ERBB2. Furthermore, the underlying toxic mechanisms may be linked to the pathways in cancer, chemical carcinogenesis through reactive oxygen species/receptor activation, and the FoxO signaling pathway. The results contribute to a comprehensive understanding of the effects of these environmental pollutants on genes, proteins, and metabolic pathways in living organisms. It revealed their toxicity mechanisms in inducing thyroid, renal, and testicular cancers, and provided a solid theoretical foundation for designing new environmental control strategies and drug screening initiatives. Additionally, the integrated application of network toxicology and molecular docking technology can enhance our understanding of the toxicity and mechanisms of unknown environmental pollutants, which is beneficial for protecting the environment and human health.

BackgroundPrevious clinical evidence has shown a correlation between pulmonary fibrosis (PF) and lung cancer (LC), but their causal relationship remains unknown.MethodsThis study utilized a bidirectional two-sample Mendelian randomization (MR) approach to explore the causal relationship between PF and LC, including its subtypes. Genetic data were obtained from the IEU and FinnGen Genome-Wide Association Studies (GWAS). SNPs with genome-wide significance were selected, and analyses were conducted using Inverse-Variance Weighted (IVW), MR Egger, and Weighted Median methods. The IVW results for various subtypes of lung cancer and PF were used in a meta-analysis to investigate the overall causal effect between PF and lung cancer. Sensitivity analysis was used for both MR and meta-analysis to investigate the robustness of the results.ResultsThe bidirectional MR analysis showed no significant causal relationship between PF and overall, LC or its subtypes, except for SCLC, which had a significant positive association (OR = 1.29, 95% CI 1.07-1.57, p = 0.009). The meta-analysis results indicated no overall causal effect (OR = 1.067, 95% CI: 0.952-1.195, P = 0.265, I² = 57.3%). In the reverse MR analysis, NSCLC and LUSC showed significant associations with PF (OR = 1.12, 95% CI 1.01-1.23, p = 0.028 and OR = 1.04, 95% CI 1.01-1.08, p = 0.012, respectively), while the meta-analysis results indicated no significant causal effect (OR = 1.006, 95% CI: 0.973-1.040, P = 0.734, I² = 55.9%). Sensitivity analyses indicated no evidence of horizontal pleiotropy or significant heterogeneity.ConclusionThis study suggests a potential causal relationship between PF and SCLC, as well as between NSCLC and LUSC with PF. However, the overall causal relationship between PF and LC was not statistically significant, possibly due to individual variability and other influencing factors. Further research using data from diverse populations is needed to validate these findings.

Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive solid malignancy with low 5-year survival and limited treatment options. We conducted an unbiased screening using FDA-approved drug and demonstrated that cetylpyridinium chloride (CPC), a component commonly found in mouthwash and known for its robust bactericidal and antifungal attributes, exhibits anticancer activity against human PDAC cells. CPC inhibited PDAC cell growth and proliferation by inducing paraptosis, rather than apoptosis. Mechanistically, CPC induced paraptosis through the initiation of endoplasmic reticulum stress, leading to the accumulation of misfolded proteins. Subsequently, the endoplasmic reticulum stress to nucleus signaling 1 (ERN1)-mitogen-activated protein kinase kinase kinase 5 (MAP3K5)-p38 mitogen-activated protein kinase (MAPK) signaling pathway was activated, ultimately culminating in the induction of paraptosis. In vivo experiments, including those involving patient-derived xenografts, orthotopic models, and genetically engineered mouse models of PDAC, provided further evidence of CPC’s effectiveness in suppressing the growth of pancreatic tumors.

This paper presents an analysis of various split-ring resonator (SRR) configurations coupled with coplanar waveguides (CPW). Three distinct resonant structures are presented, namely, the S-shaped split-ring resonator (S-SRR), the conventional split-ring resonator (SRR), and a pair of SRR. Among the examined resonant structures, it is observed that the S-SRR exhibits the smallest electrical size with the corresponding resonant frequency of 1.37 GHz, while the conventional SRR has the largest electrical size with the corresponding resonant frequency of 3.34 GHz. On the other hand, the resonant frequency of a dual SRR is 2.37 GHz. However, the transmission coefficient of a dual SRR is -11.43 dB, which is higher than S-SRR (-10.02 dB) and SRR (-8.18 dB). Furthermore, this study extends the analysis between a square dual SRR and a circular dual SRR with retained area. The square SRR demonstrates a lower resonance frequency (2.23 GHz) relative to its circular counterpart (2.37 GHz). The comparison also shows that the transmission coefficient of the square configuration is -13.88 dB, which is higher than its circular counterpart (-11.43 dB). The realization of a barcode application is achieved by loading multiple S-shaped split ring resonators (S-SRRs) with varying geometric parameters adjacently onto the transmission line. By individually rotating each of these S-SRRs, it becomes possible to alter the notch magnitude, thereby positioning it within a specific designated range corresponding to a particular code. In the case of a configuration involving rotations of (0°, 45°, 90°, 0°, 45°, 90°), this approach results in the creation of a barcode denoted as "100 010 000 100 011 000". This methodology enables the encoding of information in the form of distinctive resonant responses, providing a versatile and compact means of realizing barcode applications.

With the commercialization of the fifth generation mobile networks, researchers are now focusing on discovering the potential key techniques of the next generation mobile networks, which are expected to provide more accurate perception, lower latency, and higher network capacity. As the communication equipments increase exponentially, wireless transmission environment becomes more complex, leveraging wireless security challenges more and more severe, such as computationally powerful interception, intelligent malicious jamming, communication behavior monitoring. The physical layer security (PLS) techniques have been widely explored as a complement to traditional encryption schemes by exploiting the randomness characteristics of wireless channels to achieve the security from the physical layer. Additionally, reconfigurable intelligent surface (RIS) is considered as a key enabling technology for the six generation (6G) mobile networks, due to its ability to achieve the reconstruction of wireless channel, which is also regarded as a good match with PLS techniques for improving communication security. This paper presents a comprehensive review of the latest research on the integration of RIS and PLS. First, we introduce the principles of PLS from the development of secure communications and the basics of RIS based on the generalized Snell’s law. Then, we categorize RIS according to different hardware architectures, of which the corresponding scenarios are also presented. Subsequently, we review recent works on RIS-assisted PLS in different communication networks, and classify the security scenarios in which RIS is integrated with various advanced communication technologies. Finally, we discuss the potential future research directions and challenges of RIS-aided PLS communications.

Abstract Mutations in Cullin-3 (Cul3), a conserved gene encoding a ubiquitin ligase, are strongly associated with autism spectrum disorder (ASD). Here, we characterize ASD-related pathologies caused by neuron-specific Cul3 knockdown in Drosophila. We confirmed that neuronal Cul3 knockdown causes short sleep, paralleling sleep disturbances in ASD. Because sleep defects and ASD are linked to metabolic dysregulation, we tested the starvation response of neuronal Cul3 knockdown flies; they starved faster and had lower triacylglyceride levels than controls, suggesting defects in metabolic homeostasis. ASD is also characterized by increased biomarkers of oxidative stress; we found that neuronal Cul3 knockdown increased sensitivity to hyperoxia, an exogenous oxidative stress. Additional hallmarks of ASD are deficits in social interactions and learning. Using a courtship suppression assay that measures social interactions and memory of prior courtship, we found that neuronal Cul3 knockdown reduced courtship and learning compared to controls. Finally, we found that neuronal Cul3 depletion alters the anatomy of the mushroom body, a brain region required for memory and sleep. Taken together, the ASD-related phenotypes of neuronal Cul3 knockdown flies establish these flies as a genetic model to study molecular and cellular mechanisms underlying ASD pathology, including metabolic and oxidative stress dysregulation and neurodevelopment.

This study investigated the effect of anaerobic treatment on the non-volatile components and angiotensin-converting enzyme (ACE) inhibitory activity in purple-colored leaf tea. Results showed that after 8 h of anaerobic treatment, the γ-aminobutyric acid (GABA) content significantly increased from 0.02 mg/g to 1.72 mg/g (p

Tea grade evaluation is a systematic work with complex and subjective. Grade information from its relevant quality data extracted enables to establish rapid identification method, later of which has guiding meaning to tea production. To establish a rapid identification method of white tea grades, 200 white tea (Bai Mudan) samples with 4 grades were selected as the research objects in this paper, near infrared spectroscopy and gas chromatography-ion mobility spectrometry were used to collect original data. The data dimensions were reduced by principal component analysis or linear discriminant analysis, combed with 7 data mining classifier algorithms to rapidly evaluate the grades of white tea. Results showed that linear discriminant analysis was suitable for dimensionality reduction of the original data from near infrared spectra and gas chromatography-ion mobility spectrometry. After dimensionality reduction of the original data using linear discriminant analysis, classification algorithm including adaptive boosting (Adaboost), k-nearest neighbor (KNN) and multi-layer perceptron (MLP), and random forests (RF), stochastic gradient descent (SGD) and support vector machines (SVM) were used for establishment of white tea grade discriminant models based on near infrared spectroscopy, the correct rate of these models were greater than 94%, and the AUC of the model evaluation index was≥0.95. The discriminant rates of MLP, SGD and SVM models based on gas chromatography-ion mobility spectrometry filtered spectrum data were 91%~93% and the AUC value were 0.94~0.96. The positive judgment rate of models from Adaboost, decision tree (DT), KNN, MLP, SGD and SVM models based on gas chromatography-ion mobility spectrometry labeled substance data was 100%, and the AUC was 1.0, while the model evaluation index of RF model were 96% and 0.98, respectively. With near infrared spectrum and volatile compound characteristic data as important parameters for white tea grade evaluation, 6 and 10 kinds of grade discrimination models were built, which could accurately determine the grade of white tea, and the classifier algorithm was suitable for the modeling of these two types of data.

Increasingly, research indicates that steel fibers can significantly enhance the engineering properties of mortar and concrete; however, few studies have examined their impact on the reinforcement of in-service tunnel linings within sleeve arch structures. In this study, a series of 1:2 scale experiments were conducted using a specialized loading device to compare the reinforcement performance of steel fiber-reinforced concrete sleeve arches and traditional reinforced concrete sleeve arches on prefabricated cracks with depths of 1/3 and 2/3 of the lining thickness. The experimental results were validated using numerical simulations. The results indicate that under the same load, when reinforcing components with 2/3 prefabricated cracks, the maximum compressive strains for steel fiber-reinforced and reinforced concrete sleeve arches were −852 με and −985 με, respectively, and the maximum deflections were 3.57 mm and 5.48 mm. Composite sleeve arches of both materials provide a certain degree of reinforcement to linings with varying damage. The reinforcement performance of steel fiber-reinforced concrete sleeve arches is superior to that of traditional reinforced concrete sleeve arches, with particularly significant reinforcement for linings with 2/3 prefabricated cracks. Numerical simulations have shown that the stress in reinforced concrete at the concentrated stress regions is 16.15%, 6.01%, 12.68%, 36.62%, and 4.82% higher than that in steel fiber-reinforced concrete, respectively, thereby validating the reliability of the experimental results. Therefore, this study recommends the application of steel fiber materials in sleeve arches to achieve superior maintenance and reinforcement, addressing cracking issues in in-service tunnel linings and thereby improving the safety and durability of these structures.

Background: Linezolid has been reported to protect against chronic bone and joint infection. In this study, linezolid was loaded into the 3D printed poly (lactic-co-glycolic acid) (PLGA) scaffold with nano-hydroxyapatite (HA) to explore the effect of this composite scaffold on infected bone defect (IBD). Methods: PLGA scaffolds were produced using the 3D printing method. Drug release of linezolid was analyzed by elution and high-performance liquid chromatography assay. PLGA, PLGA-HA, and linezolid-loaded PLGA-HA scaffolds, were implanted into the defect site of a rabbit radius defect model. Micro-CT, H&E, and Masson staining, and immunohistochemistry were performed to analyze bone infection and bone healing. Evaluation of viable bacteria was performed. The cytocompatibility of 3D-printed composite scaffolds in vitro was detected using human bone marrow mesenchymal stem cells (BMSCs). Long-term safety of the scaffolds in rabbits was evaluated. Results: The linezolid-loaded PLGA-HA scaffolds exhibited a sustained release of linezolid and showed significant antibacterial effects. In the IBD rabbit models implanted with the scaffolds, the linezolid-loaded PLGA-HA scaffolds promoted bone healing and attenuated bone infection. The PLGA-HA scaffolds carrying linezolid upregulated the expression of osteogenic genes including collagen I, runt-related transcription factor 2, and osteocalcin. The linezolid-loaded PLGA-HA scaffolds promoted the proliferation and osteogenesis of BMSCs in vitro via the PI3K/AKT pathway. Moreover, the rabbits implanted with the linezolid-loaded scaffolds showed normal biochemical profiles and normal histology, which suggested the safety of the linezolid-loaded scaffolds. Conclusion: Overall, the linezolid-loaded PLGA-HA scaffolds fabricated by 3D printing exerts significant bone repair and anti-infection effects.

Fermentation is a vital process occurred under the premise of rolling affecting black tea quality. Theoretically, re-rolling during fermentation will remodel the biochemical conditions of tea leaves, and thus influence black tea quality. Herein, we studied the effect of re-rolling on black tea taste and liquor color. Sensory evaluation showed that re-rolling significantly weakened the astringency taste and improved the redness and luminance of liquor. With re-rolling, the color attributes of a* and L* and the contents of theaflavins and thearubigins were significantly improved. Metabolomics analysis showed that the contents of 110 non-volatile compounds were significantly different among black teas with different rolling treatments. In summary, re-rolling accelerated the oxidation of polyphenols into pigments, the hydrolysis of proteins into amino acids, and the metabolism of alkaloids, organic acids, glycosidically-bound volatiles, and lipids during the fermentation period. Our study provided a novel and simple way to improve black tea quality.

Abstract Background Full-cohort and sibling-comparison designs have yielded inconsistent results about the impacts of caesarean delivery on offspring health outcomes, with the effect estimates from the latter being more likely directed towards the null value. We hypothesized that the seemingly conservative results obtained from the sibling-comparison design might be attributed to inadequate adjustment for non-shared confounders between siblings, particularly maternal age at delivery. Methods A systematic review and meta-analysis was first conducted. PubMed, Embase, and the Web of Science were searched from database inception to April 6, 2022. Included studies (1) examined the association of caesarean delivery, whether elective or emergency, with offspring health outcomes; (2) simultaneously conducted full-cohort and sibling-comparison analyses; and (3) reported adjusted effect estimates with 95% confidence intervals (95% CIs). No language restrictions were applied. Data were extracted by 2 reviewers independently. Three-level meta-analytic models were used to calculate the pooled odds ratios (ORs) and 95% CIs for caesarean versus vaginal delivery on multiple offspring health outcomes separately for full-cohort and sibling-comparison designs. Subgroup analyses were performed based on the method of adjustment for maternal age at delivery. A simulation study was then conducted. The simulated datasets were generated with some key parameters derived from the meta-analysis. Results Eighteen studies involving 21,854,828 individuals were included. The outcomes assessed included mental and behavioral disorders; endocrine, nutritional and metabolic diseases; asthma; cardiorespiratory fitness; and multiple sclerosis. The overall pooled OR for estimates from the full-cohort design was 1.14 (95% CI: 1.11 to 1.17), higher than that for estimates from the sibling-comparison design (OR = 1.08; 95% CI: 1.02 to 1.14). Stratified analyses showed that estimates from the sibling-comparison design varied considerably across studies using different methods to adjust for maternal age at delivery in multivariate analyses, while those from the full-cohort design were rather stable: in studies that did not adjust maternal age at delivery, the pooled OR of full-cohort vs. sibling-comparison design was 1.10 (95% CI: 0.99 to 1.22) vs. 1.06 (95% CI: 0.85 to 1.31), in studies adjusting it as a categorical variable, 1.15 (95% CI: 1.11 to 1.19) vs. 1.07 (95% CI: 1.00 to 1.15), and in studies adjusting it as a continuous variable, 1.12 (95% CI: 1.05 to 1.19) vs. 1.12 (95% CI: 0.98 to 1.29). The severe underestimation bias related to the inadequate adjustment of maternal age at delivery in sibling-comparison analyses was fully replicated in the simulation study. Conclusions Sibling-comparison analyses may underestimate the association of caesarean delivery with multiple offspring health outcomes due to inadequate adjustment of non-shared confounders, such as maternal age at delivery. Thus, we should be cautious when interpreting the seemingly conservative results of sibling-comparison analyses in delivery-related studies.

Gas chromatography–ion mobility spectrometry (GC-IMS) is a smart method that has been applied to determine the volatile compounds in Chinese teas, but its use in comparing the volatile compounds of different types of tea has not been mentioned. In this study, the volatile compounds found in four types of samples (green, yellow, white, and black teas) made with fresh leaves of Camellia sinensis (L.) Kuntze ‘Zhongcha 111’ were analyzed using GC-IMS. The results showed that 93 volatile compounds were identified from our tea samples and that the average volume of aldehydes was higher than that for other compounds, especially in white tea. The different samples were successfully categorized using multivariate statistical analysis. Using partial least squares discriminant analysis (PLS-DA), we found 15 key compounds, including four differential components: (E)-2-hexenal, 2-furanmethanethio, 2-hexanol, and 1-octene. There were 29 common components, and their total content reached 386.0 μg/g. Moreover, the 3-methyl-2-butenal and dimethyl disulfide detected in the four samples were also differential compounds, varying according to the manufacturing technology. Thus, this study demonstrates that different types of teas can be discriminated easily using GC-IMS and that this is helpful to shorten the time for improving tea quality and developing new products.

In the context of the rapid development of the Internet of Vehicles, virtual reality, automatic driving and the industrial Internet, the terminal devices in the network show explosive growth. As a result, more and more information is generated from the edge of the network, which makes the data throughput increase dramatically in the mobile communication network. As the key technology of the fifth-generation mobile communication network, mobile edge caching technology which caches popular data to the edge server deployed at the edge of the network avoids the data transmission delay of the backhaul link and the occurrence of network congestion. With the growing scale of the network, distributing hot data from cloud servers to edge servers will generate huge energy consumption. To realize the green and sustainable development of the communication industry and reduce the energy consumption of distribution of data that needs to be cached in edge servers, we make the first attempt to propose and solve the problem of edge caching data distribution with minimum energy consumption (ECDDMEC) in this paper. First, we model and formulate the problem as a constrained optimization problem and then prove its NP-hardness. Subsequently, we design a greedy algorithm with computational complexity of O(n2) to solve the problem approximately. Experimental results show that compared with the distribution strategy of each edge server directly requesting data from the cloud server, the strategy obtained by the algorithm can significantly reduce the energy consumption of data distribution.

As multiprocessor systems continue to grow in processor scale, the incidence of faults also increases. As a result, fault diagnosis is becoming a key mechanism for maintaining the normal operation of multiprocessor systems. To explore more effective diagnostic methods, Somani et al. introduced a generalized pessimistic diagnostic strategy, named t/k-diagnosis, in which all faulty nodes are isolated in a set of nodes and at most k fault-free nodes are misdiagnosed, provided that the quantity of faults is limited by t. By imposing certain conditions or restrictions, the t/k-diagnosability of some regular networks under the Preparata, Metze, and Chien (PMC) model has been determined. However, the t/k-diagnosability of many networks under the comparison model remains unidentified. In this paper, we provide new insights into the study of t/k-diagnosability under the comparison model. After introducing some new notions, such as the 0-test unit, 0-test set and 0-test subgraph, under the comparison model, we study the relationship in a system G between the 0-test subgraphs and the components of G−F, where F is the set of faulty nodes, and we obtain some important correlation properties. Based on these results, we study t/k-diagnosability under the comparison model. As a result, the t/k-diagnosability of some regular interconnection networks can be efficiently determined.

Abstract Inhibitors of enzymes that inactivate amine neurotransmitters (dopamine, serotonin), such as catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO), are thought to increase neurotransmitter levels and are widely used to treat Parkinson's disease and psychiatric disorders, yet the role of these enzymes in regulating behavior remains unclear. Here, we investigated the genetic loss of a similar enzyme in the model organism Drosophila melanogaster. Because the enzyme Ebony modifies and inactivates amine neurotransmitters, its loss is assumed to increase neurotransmitter levels, increasing behaviors such as aggression and courtship and decreasing sleep. Indeed, ebony mutants have been described since 1960 as "aggressive mutants," though this behavior has not been quantified. Using automated machine learning-based analyses, we quantitatively confirmed that ebony mutants exhibited increased aggressive behaviors such as boxing but also decreased courtship behaviors and increased sleep. Through tissue-specific knockdown, we found that ebony’s role in these behaviors was specific to glia. Unexpectedly, direct measurement of amine neurotransmitters in ebony brains revealed that their levels were not increased but reduced. Thus, increased aggression is the anomalous behavior for this neurotransmitter profile. We further found that ebony mutants exhibited increased aggression only when fighting each other, not when fighting wild-type controls. Moreover, fights between ebony mutants were less likely to end with a clear winner than fights between controls or fights between ebony mutants and controls. In ebony vs. control fights, ebony mutants were more likely to win. Together, these results suggest that ebony mutants exhibit prolonged aggressive behavior only in a specific context, with an equally dominant opponent.

IntroductionEmbryonic chromosomal abnormalities represent a major causative factor in early pregnancy loss, highlighting the importance of understanding their role in spontaneous abortion. This study investigates the potential correlation between chromosomal abnormalities and spontaneous abortion using copy number variation sequencing (CNV-seq), a Next-Generation Sequencing (NGS) technology.MethodsWe analyzed Copy Number Variations (CNVs) in 395 aborted fetal specimens from spontaneous abortion patients by CNV-seq. And collected correlated data, including maternal age, gestational week, and Body Mass Index (BMI), and analyzed their relationship with the CNVs.ResultsOut of the 395 cases, 67.09% of the fetuses had chromosomal abnormalities, including numerical abnormalities, structural abnormalities, and mosaicisms. Maternal age was found to be an important risk factor for fetal chromosomal abnormalities, with the proportion of autosomal trisomy in abnormal karyotypes increasing with maternal age, while polyploidy decreased. The proportion of abnormal karyotypes with mosaic decreased as gestational age increased, while the frequency of polyploidy and sex chromosome monosomy increased. Gene enrichment analysis identified potential miscarriage candidate genes and functions, as well as pathogenic genes and pathways associated with unexplained miscarriage among women aged below or over 35 years old. Based on our study, it can be inferred that there is an association between BMI values and the risk of recurrent miscarriage caused by chromosomal abnormalities.DiscussionOverall, these findings provide important insights into the understanding of spontaneous abortion and have implications for the development of personalized interventions for patients with abnormal karyotypes.

The high water content of the surrounding rock in loess tunnels will lead to the deterioration of rock strength, causing deformation and damage to the initial support structure and thereby affecting safety during construction and operation. This article first analyzes the strength characteristics of loess under different water contents through indoor physical and mechanical tests. Secondly, based on numerical simulation results, the ecological environment, and design requirements, the water content threshold is determined. Finally, a reinforcement scheme combining surface precipitation measures and curtain grouting measures is proposed, and the reinforcement effect is analyzed based on on-site monitoring data. The results show that as the water content of loess increases, the cohesion, internal friction angle, and elastic modulus of the surrounding rock all decrease, leading to an increase in the sensitivity of the surrounding rock to excavation disturbances and a deterioration in strength. During the construction process, it shows an increase in the vault settlement and sidewalls’ convergence. During the process of increasing the distance between the monitoring section and the palm face, the settlement and convergence of the tunnel show a rapid growth stage, slow growth stage, and stable stage. The water content threshold is determined to be 22%. The reinforcement scheme of combining surface precipitation measures with curtain grouting measures not only meets the requirements of the ecological environment but also makes the settlement and convergence values lower than the yellow warning deformation values required by the design.

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.

Ferroptosis is cell death caused by lipid peroxidation and plasma membrane rupture. Here, the authors report an additional role for the lipid flippase SLC47A1 as a regulator of lipid remodeling and survival during ferroptosis, thereby providing a metabolic target for overcoming drug resistance.

The chemical diversity of terpenoids is typically established by terpene synthase-catalyzed cyclization and diversified by post-tailoring modifications. Fungal bifunctional terpene synthase (BFTS) associated P450 enzymes have shown significant catalytic potentials through the development of various new terpenoids with different biological activities. This study discovered the BFTS and its related gene cluster from the plant endophytic fungus Didymosphaeria variabile 17020. Heterologous expression of the BFTS in Saccharomyces cerevisiae resulted in the characterization of a major product diterpene variediene (1), along with two new minor products neovariediene and neoflexibilene. Further heterologous expression of the BFTS and one cytochrome P450 enzyme VndE (CYP6138B1) in Aspergillus oryzae NSAR1 led to the identification of seven norditerpenoids (19 carbons) with a structurally unique 5/5 bicyclic ring system. Interestingly, in vivo experiments suggested that the cyclized terpene variediene (1) was modified by VndE along with the endogenous enzymes from the host cell A. oryzae through serial chemical conversions, followed by multi-site hydroxylation via A. oryzae endogenous enzymes. Our work revealed that the two-enzymes biosynthetic system and host cell machinery could produce structurally unique terpenoids.

Carbamoyltransferases are a class of enzymes catalyzing carbamoylation of primary and secondary metabolites. Here, the authors show the molecular structure of the ansamycin-modifying carbamoyltransferase GdmN and repurpose the enzyme for the iterative carbamoylation of ansamitocins.

BackgroundJianghua Kucha (JHKC) is a special tea germplasm with enriched specialized secondary metabolites, including theacrine, non-epimeric flavanols and methylated flavanols. Moreover, primary metabolites provide precursors and energy for the production of secondary metabolites. However, the accumulation patterns of primary and secondary metabolites in different tissues of JHKC are unclear.MethodsThe changes of primary and secondary metabolites and related metabolic pathways (primary and secondary metabolism) in different JHKC tissues (the bud, 1st-4th leaves, and new stem) were investigated via metabolomics analysis with ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS).ResultsSignificant differences were observed in 68 primary and 51 secondary metabolites mainly related with the pathways of starch and sucrose, amino acids, caffeine, and flavanols metabolism and TCA cycle. The bud exhibited higher levels of glucose-6-phosphate, citric acid, most amino acids, theobromine, catechin-gallate, epicatechin-gallate, procyanidins, and theasinensins; the 1st leaf showed higher levels of caffeine and epigallocatechin-3-gallate; and the 4th leaf contained higher levels of most monosaccharides, theacrine, and epigallocatechin-3-O-(3”-O-methyl)-gallate. In addition, primary metabolites and important secondary metabolites had certain correlations.ConclusionThis study provides comprehensive insight into primary and secondary metabolites in JHKC and offers guidelines for efficiently utilizing specialized metabolites of JHKC in the future.

Renewable electricity products, for example, from wind and photovoltaic energy, need large-scale and economic energy storage systems to guarantee the requirements of our daily lives. Sodium-ion batteries are considered more economical than lithium-ion batteries in this area. Na3V2(PO4)2F3, NaVPO4F, and Na3(VO)2(PO4)2F are one type of material that may be used for Na-ion batteries. In order to better understand the synthesis of these materials, the phase formation in a NaH2PO4–VOSO4–NaF–H2O system under hydrothermal conditions was studied and is reported herein. This research focused on the influences of the sodium fluoride content and hydrothermal crystallization time on phase formation and phase purity. The phase transformation between Na(VO)2(PO4)2(H2O)4 and Na3V2O2x(PO4)2F3-2x was also studied. Na3V2O2x(PO4)2F3-2x with a high degree of crystallinity can be obtained in as short as 2 h via hydrothermal synthesis using a conventional oven at 170 °C without agitation. All compounds obtained in this research were studied mainly using powder X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectrometry, and Fourier-transform infrared spectroscopy.

The use of ionic liquid [emim][Tf2N] as an additive in polyethersulphone (PES) and nano-sized silico-aluminophosphate-34 (SAPO-34) mixed matrix membrane was studied through the incorporation of different amounts of [emim][Tf2N] in the membrane composition, as presented in this work, varying from 10 to 40 wt%. Through gas permeation tests using CO2 and N2, the membrane composition containing 20 wt% [emim][Tf2N] led to the highest increase in CO2 permeability and CO2/N2 selectivity. The use of low concentrations of additive (10–20 wt%) promoted a state called antiplasticization; in this state, the permeability was even more regulated by the kinetic diameter of the species which, in this work, permitted achieving a higher CO2/N2 selectivity while increasing the CO2 permeability until an optimal condition. [emim][Tf2N] also promoted a better dispersion of SAPO-34 particles and an increase in the flexibility of the polymeric matrix when compared to a film with the same composition without [emim][Tf2N]. Moreover, the characterizations corroborated that the inclusion of [emim][Tf2N] increased the zeolite dispersion and improved the polymer/zeolite compatibility and membrane flexibility, characterized by a decrease in glass transition temperature, which helped in the fabrication process while presenting a similar thermal resistance and hydrophilicity as neat PES membrane, without affecting the membrane structure, as indicated by FTIR and a contact angle analysis.

To investigate the differences of aroma characteristics between Jingui green tea (JGT) and Jingui flowers, Jingui (JG) and Dangui (DG) flowers were analyzed the aroma quality and volatile compounds by the method of sense evaluation and GC-MS, respectively. JG flowers were selected to scent green tea and the aroma quality and chemical characteristics of Jingui green tea were further researched. The results showed that JG showed a more excellent aroma quality than that of DG, and its total content of volatile components was 22.7% higher than DG, so JG flowers was used to make flower tea and acted as a control like green tea (GT). Comparing the aroma characteristics of JGT, JG and GT, the fragrance and floral characteristics of JGT were slightly inferior to those of JG and higher than that of GT. JGT absorbed 8 ingredients such as linalool, α-ylangene, megastigma-4,6(E),8(E)-triene, cis-pyranoid linalool oxide 1, α-ionone, 2,6,6-tetramethyl-1-cyclohexene-1-propanol, γ-decalactone and 4-hydroxy-β-ionone from JG and 6 new components such as 3,4-dimethylaniline, trans-Z-α-bisabolene epoxide, geranyl isovalerate, 1,2,3,4-tetrahydro-1,1,6-trimethyl-naphthalene, dihydro-beta-ionone and phytol acetate formed during green tea scenting, and kept 10 common volatile components with green tea (control), but its volatile components was still 60.4% lower than that of JG. In summary, JGT obtained the parts of aroma components from JG and GT, and formed its unique components by scenting technology, so it was beneficial for technology optimization and quality improvement of flower tea.

C-C motif ligand 2 (CCL2), also known as monocytic chemotactic protein 1 (MCP-1), is an integral chemotactic factor which recruits macrophages for the immune response. Together with its receptors (e.g., CCR2, ACKR1, and ACKR2), they exert noticeable influences on various diseases of different systems. At the maternal-fetal interface, CCL2 is detected to be expressed in trophoblasts, decidual tissue, the myometrium, and others. Meanwhile, existing reports have determined a series of physiological regulators of CCL2, which functions in maintaining normal recruitment of immunocytes, tissue remodeling, and angiogenesis. However, abnormal levels of CCL2 have also been reported to be associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and preterm labor. In this review, we concentrate on CCL2 expression at the maternal-fetal interface, as well as its precise regulatory mechanisms and classic signaling pathways, to reveal the multidimensional aspects of CCL2 in pregnancy.

Phosphate rock has great potential value in the application of cut-off walls for heavy metal contaminated sites. The effects of initial concentration of Pb2+, contact time, temperature and pH on the adsorption performance of phosphate rock modified soil-bentonite (PSB) were analyzed by Batch tests, and the microstructure and physicochemical properties of the adsorbent were characterized and analyzed by scanning electron microscopy (SEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). The results showed that the incorporation of phosphate rock improves the adsorption performance of the mixed material for Pb2+ in an acidic environment, and the maximum adsorption amount of PSB can be 154% greater than that of soil-bentonite (SB). Kinetic analysis showed that intraparticle diffusion and liquid film diffusion both participate in control of the adsorption process, and the Langmuir model fitted the isothermal adsorption data better. The adsorption process of PSB to Pb2+ is an exothermic reaction process, and a low temperature environment is beneficial to the adsorption of Pb2+. Studies on the microscopic mechanism show that PO43− reacts with Pb2+ in solution to form phosphate precipitation, and –OH and PO43− are on the surface or interlayer of the adsorbent participate in the adsorption process of Pb2+. HIGHLIGHTS Proposes a new modified material to be used for a cut-off wall.; The adsorption mechanism is investigated by kinetic, thermodynamic and microscopic analyses.;

This paper studies the short-circuit safe operating area (SCSOA) of the conventional field-stop (FS) IGBT and the superjunction (SJ) FS IGBT, based on 1200 V-rated samples, with the help of numerical electrothermal simulations. The results show that the peak electric field influences the distribution of the temperature inside devices and plays a crucial role in determining their SCSOAs. When the doping concentration of the collector, $\text{N}_{\mathrm{ C}}$ , is low, the peak electric field exits near the collector. Both types of IGBTs have a long short-circuit time, $\text{T}_{\mathrm{ SC}}$ , which can exceed $15~{\mathrm {\mu }}\text{s}$ . $\text{T}_{\mathrm{ SC}}$ decreases with the increase of $\text{N}_{\mathrm{ C}}$ because the peak electric field transfers to near the channel. The introduction of the SJ structure weakens the peak electric field and increases $\text{T}_{\mathrm{ SC}}$ . The difference is at least 4 $\mu \text{s}$ and up to 6.87 $\mu \text{s}$ , when $\text{N}_{\mathrm{ C}}$ ranges from 2.0 $\times \,\,10^{17}$ cm $^{-3}$ to 1.1 $\times \,\,10^{18}$ cm $^{-3}$ . Besides, $\text{T}_{\mathrm{ SC}}$ of the SJ IGBT can be increased by using highly-doped pillars.

A hybrid junction termination structure consisting of a variation lateral doping (VLD) region and a spiral polysilicon resistive field plate (PRFP) is proposed in this brief. Surface electric fields of the VLD region are modulated by the PRFP and distribute more uniformly. Compared with the conventional VLD structure with the same size, its measured breakdown voltage increases by 11%. The breakdown voltage still has a positive temperature coefficient. And, the leakage current changes very little from −40 to 150 °C. Besides, it is more immune to the deviation of the VLD dosage. The deviation range of the VLD dosage increase from −20% - +20% to −50% - +60% when the breakdown voltage keeps above 90% of the maximum value. No extra masks or process steps are needed in power devices with a MOS gate structure, because the gate layer can be used to implement the spiral PRFP. At last, the hybrid termination is not detrimental to the switching characteristic of the device.

Pan-fried green tea (PGT) is an easily acceptable tea drink for general consumers. In this study, volatile profiles and characteristic aroma of 22 representative Chinese PGT samples were extracted using stir bar sorptive extraction (SBSE) and analysed by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O) analysis, and odour activity value (OAV) calculations. In total, 88 volatile compounds were identified. Alcohols (45%), esters (19%), and ketones (16%) were the dominant volatiles, and geraniol (484.8 μg/kg) was the most abundant volatile component in PGT, followed by trans-β-ionone and linalool. In addition, the differences of aroma characteristics among PGT and other three types of green tea, namely baked green tea, steamed green tea, and sun-dried green tea, were also observed using partial least squares discriminant analysis (PLS-DA) and heatmap analysis, and it was found that β-myrcene, methyl salicylate, (E)-nerolidol, geraniol, methyl jasmonate were generally present at higher content in PGT. This is the first comprehensive report describing the volatile profiles of Chinese PGT, and the findings from this study can advance our understanding of PGT aroma quality, and provide important theoretical basis for processing and quality control of green tea products.

Background and objectives: To help house officers adjust quickly to their new responsibilities, a departmental handbook is provided. As this had not been updated recently and was underutilised, a quality improvement project was undertaken to improve this resource. Methods: The handbook was updated and new material added based on feedback from house officers and senior medical staff. Subsequently, house officers were surveyed on their utilization rate of the new handbook and its usefulness in various clinical scenarios. An open-book clinical quiz was administered to gauge their clinical competency. Results: There was a 26.8% increase in the proportion of house officers who used the handbook more than once every 2–3 days compared to pre-intervention. There was a significant improvement in quiz scores from 26.7/40 to 31.1/40 between the pre-intervention ( n =19) and post-intervention ( n =37) groups ( p

Breast cancer is the most common cause of cancer death in women. Early screening and treatment can effectively improve the success rate of treatment. Ultrasound imaging technology, as the preferred modality for breast cancer screening, provides an essential reference for early diagnosis. Existing computer-aided ultrasound imaging diagnostic techniques mainly rely on the selected key frames for breast cancer lesion diagnosis. In this paper, we first collected and annotated a dataset of ultrasound video sequences of 268 cases of breast lesions. Moreover, we propose a contrastive learning–guided multi-meta attention network (CLMAN) by combining a deformed feature extraction module and a multi-meta attention module to address breast lesion diagnosis in ultrasound sequence. The proposed feature extraction module can autonomously acquire key information of the feature map in the spatial dimension, whereas the designed multi-meta attention module is dedicated to effective information aggregation in the temporal dimension. In addition, we utilize a contrast learning strategy to alleviate the problem of high imaging variability within ultrasound lesion videos. The experimental results on our collected dataset show that our CLMAN significantly outperforms existing advanced methods for video classification.

Abstract The problems caused by the interaction between slopes and hydrologic environment in traffic civil engineering are very serious in the granite residual soil area of China, especially in Guangdong Province. Against the background of two heavy rainfall events occurring during a short period due to a typhoon making landfall twice or even two typhoons consecutively making landfall, laboratory model tests were carried out on the hydrological effects of the granite residual soil slope considering three vegetation types under artificial rainfall. The variation in slope surface runoff, soil moisture content and rain seepage over time was recorded during the tests. The results indicate that surface vegetation first effectively reduces the splash erosion impact of rainwater on slopes and then influences the slope hydrological effect through rainwater forms adjustment. (1) The exposed slope has weak resistance to two consecutive heavy rains, the degree of slope scouring and soil erosion damage will increase greatly during the second rainfall. (2) The multiple hindrances of the stem leaf of Zoysia japonica plays a leading role in regulating the hydrological effect of slope, the root system has little effect on the permeability and water storage capacity of slope soil, but improves the erosion resistance of it. (3) Both the stem leaf and root system of Nephrolepis cordifolia have important roles on the hydrological effect. The stem leaf can stabilize the infiltration of rainwater, and successfully inhibit the surface runoff under continuous secondary heavy rainfall. The root system significantly enhances the water storage capacity of the slope, and greatly increases the permeability of the slope soil in the second rainfall, which is totally different from that of the exposed and Zoysia japonica slopes. (4) Zoysia is a suitable vegetation species in terms of slope protection because of its comprehensive slope protection effect. Nephrolepis cordifolia should be cautiously planted as slope protection vegetation. Only on slopes with no stability issues should Nephrolepis cordifolia be considered to preserve soil and water.

A novel split-gate SiC MOSFET with an embedded MOS-channel diode for enhanced third-quadrant and switching performances is proposed and studied using TCAD simulations in this paper. During the freewheeling period, the MOS-channel diode with a low potential barrier constrains the reverse current flow through it. Therefore, the suggested device not only has a low diode cut-in voltage but also entirely suppresses the intrinsic body diode, which will cause bipolar deterioration. In order to clarify the barrier-lowering effect of the MOS-channel diode, an analytical model is proposed. The calibrated simulation results demonstrate that the diode cut-in voltage of the proposed device is decreased from the conventional voltage of 2.7 V to 1.2 V. In addition, due to the split-gate structure, the gate-to-drain charge (QGD) of the proposed device is 20 nC/cm2, and the reverse-transfer capacitance (CGD) is 14 pF/cm2, which are lower than the QGD of 230 nC/cm2 and the CGD of 105 pF/cm2 for the conventional one. Therefore, a better high-frequency figure-of-merit and lower switching loss are obtained.

Abstract The purpose of this study was to develop a dynamic model to predict the risk of spontaneous preterm birth at

To identify an apoptosis-related gene (ARG) prediction model for oral squamous cell carcinoma (OSCC), we analyzed and validated the data from TCGA and GEO, respectively. Kaplan–Meier survival analysis and ROC curves showed a good prognostic ability of the model both in the internal training set and in the external testing set. Furthermore, we built a nomogram using these ARGs to forecast the survival probability of OSCC patients. Moreover, we evaluated the rate of immune cells infiltrating in the tumor samples and found obvious, different patterns between the high and low risk groups. GO and KEGG analyses demonstrated multiple molecular biological processes and signaling pathways connecting with this prognostic model in OSCC. The expression of these risk genes in clinical specimens was higher in the non-survival patients than in the well-survival patients by immunohistochemical staining analysis. In conclusion, we established a signature made up of six risk apoptosis-related genes to predict the survival rate of OSCC. These genes could also be targets for the treatment of OSCC.

We consider a fluid stirred by the locomotions of squirmers through it and generalize the stochastic hydrodynamic model proposed by Thiffeault and Childress, Phys. Lett. A (2010) and Lin et al., J. Fluid Mech. (2011) to the case in which the swimmers move in anisotropically random directions. A non-diagonal effective diffusivity tensor is derived with which the diffusive preference of a passive particle along any given direction can be computed to provide more details of the phenomena beyond scalar statistics. We further identify a fraction from the orthogonal decomposition of the drift-induced particle displacement to distinguish the underlying nonlinear mixing mechanism for different types of swimmers. Numerical simulations verify the analytical results with explicit examples of prescribed, anisotropic stirring motions. We also connect our formulation to several measures used in clinical medical research such as diffusion tensor imaging where anisotropic diffusion has a significant consequence.

Microbial communities of soil aggregate-size fractions were explored with molecular and networking assays for topsoil samples from a clayey rice paddy under long-term fertilization treatments. The treatments included no fertilizer (NF) as control, chemical fertilizer only (CF), chemical fertilizer with swine manure (CFM), and chemical fertilizer with rice straw return (CFS). Following a wet-sieving protocol, water-stable aggregates were separated into size fractions of large macroaggregates (L-MacA, >2,000 μm), macroaggregates (MacA, 2,000–250 μm), microaggregates (MicA, 250–53 μm), fine microaggregates (F-MicA, 53–2 μm), and fine clay (F-Clay,

Abstract Colorectal cancer (CRC) is a common hereditary tumor that is often fatal. Its pathogenesis involves multiple genes, including circular RNAs (circRNAs). Notably, circRNAs constitute a new class of noncoding RNAs (ncRNAs) with a covalently closed loop structure and have been characterized as stable, conserved molecules that are abundantly expressed in tissue/development-specific patterns in eukaryotes. Based on accumulating evidence, circRNAs are aberrantly expressed in CRC tissues, cells, exosomes, and blood from patients with CRC. Moreover, numerous circRNAs have been identified as either oncogenes or tumor suppressors that mediate tumorigenesis, metastasis and chemoradiation resistance in CRC. Although the regulatory mechanisms of circRNA biogenesis and functions remain fairly elusive, interesting results have been obtained in studies investigating CRC. In particular, the expression of circRNAs in CRC is comprehensively modulated by multiple factors, such as splicing factors, transcription factors, specific enzymes and cis-acting elements. More importantly, circRNAs exert pivotal effects on CRC through various mechanisms, including acting as miRNA sponges or decoys, interacting with RNA binding proteins, and even translating functional peptides. Finally, circRNAs may serve as promising diagnostic and prognostic biomarkers and potential therapeutic targets in the clinical practice of CRC. In this review, we discuss the dysregulation, functions and clinical significance of circRNAs in CRC and further discuss the molecular mechanisms by which circRNAs exert their functions and how their expression is regulated. Based on this review, we hope to reveal the functions of circRNAs in the initiation and progression of cancer and highlight the future perspectives on strategies targeting circRNAs in cancer research.

A power MOSFET with P-base Schottky diode and built-in channel diode is proposed and numerically investigated in this article. The P-base Schottky diode formed by the P-base Schottky contact is in reverse series with the P-base/N-drift junction diode. Besides, by coupling the gate of the dummy MOSFET to the source, a built-in channel diode is introduced, which provides a unipolar reverse conduction current path and drastically reduces the gate-to-drain charge. When the proposed MOSFET serves as the freewheeling diode, the reverse-biased P-base Schottky diode inactivates the P-base/N-drift junction diode, so that the reverse current will be carried out by the built-in channel diode. As a result, in comparison with the planar gate power MOSFET, the reverse recovery charge and the gate-to-drain charge could be reduced by 96.9 % and 75.4%, respectively.

In this study, we used a 6-methyl-2,3-pyridine dicarboxylate ligand to develop the frameworks. Two novel compounds, [Zn2(L)2(H2O)4] (1) and [Cd(L)(H2O)] (2) (where L = 6-methyl-pyridine-2,3-dicarboxylate) were produced. The compounds were characterized by elemental analysis, powder X-ray diffraction, Fourier-transform infrared spectroscopy and single crystal X-ray crystallography. We successfully tuned the framework dimensionality by varying the size of the metal ions from small Zn to large Cd ions. Single crystal X-ray investigations of compound 1 show a good dimeric motif, while compound 2 shows a 2D network. In compound 1, the dimeric units are further bonded by strong hydrogen bonds and create a 3D network whereas compound 2 produces a 2D layer that in turn connects via short contacts to form a 3D network in the crystallographic space.

Circular RNAs (circRNAs) have been shown to be closely linked to the tumorigenesis and treatment response of hematological malignancies. However, the biological functions and clinical implications of circRNAs in acute myeloid leukemia (AML) remain largely unknown. CircRNA microarray datasets were analyzed to screen differentially expressed circRNAs in AML patients. It was found that circZBTB46 was significantly upregulated in AML patients and AML cells. Moreover, the expression of circZBTB46 was associated with the stages of AML patients and showed high sensitivity and specificity for diagnosing AML. Silencing of circZBTB46 inhibited AML cell proliferation and induced cell cycle arrest. Importantly, the depletion of circZBTB46 notably increased ferroptosis and enhanced RSL3-induced ferroptosis in AML cells. Mechanistically, circZBTB46 upregulated the expression of stearoyl-CoA desaturase 1 (SCD) possibly by acting as a miRNA sponge. Finally, the circZBTB46 knockdown repressed the tumor growth of AML in vivo. In conclusion, circZBTB46 protects AML cells from ferroptosis and promotes the proliferation by upregulating SCD, thus suggesting that circZBTB46 may be a potential therapeutic target for AML.

Bacterial heterodimeric tryptophan-containing diketopiperazines (HTDKPs) are bioactive natural products that are difficult to access chemically. Here, the authors identify a family of three related HTDKP-forming cytochrome P450s and engineer key amino acid residues to produce distinct diketopiperazines frameworks.

Jianghua Kucha (JHKC) is a special tea germplasm with high bitterness growing in China; however, the chemical characteristics of JHKC are not completely understood. In this study, 61 differential metabolites were identified between 11 wild JHKC individuals and 3 control cultivars of Fudingdabai, Yunkang 10, and Zhuyeqi using comprehensive nontargeted and targeted metabolomics approach. The JHKC accessions mainly possessed significantly higher levels of purine alkaloids of theacrine (12.06 ± 5.23 mg/g) and 1,3,7-trimethyluric acid, non-epi-form flavanols (catechin, gallocatechin, catechin gallate, and gallocatechin gallate), and methylated flavanols of epigallocatechin-3-O-(3″-O-methyl)-gallate (4.79 ± 1.45 mg/g) and epicatechin-3-O-(3″-O-methyl)-gallate (1.02 ± 0.34 mg/g), as well as significantly lower levels of flavonol glycosides, which indicated that caffeine metabolism, flavonoid biosynthesis, and flavonol and flavone biosynthesis are mostly differential metabolic pathways. Our study demonstrated that JHKC germplasm is a promising resource for breeding novel tea cultivars with high contents of theacrine, non-epi-form flavanols, and methylated flavanols.