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Mulberry leaves are excellent for health care, confirmed as a ‘drug homologous food’ by the Ministry of Health, China. The bitter taste of mulberry leaves is one of the main problems that hinders the development of the mulberry food industry. The bitter, unique taste of mulberry leaves is difficult to eliminate by post-processing. In this study, the bitter metabolites in mulberry leaves were identified as flavonoids, phenolic acids, alkaloids, coumarins and L-amino acids by a combined analysis of the metabolome and transcriptome of mulberry leaves. The analysis of the differential metabolites showed that the bitter metabolites were diverse and the sugar metabolites were down-regulated, indicating that the bitter taste of mulberry leaves was a comprehensive reflection of various bitter-related metabolites. Multi-omics analysis showed that the main metabolic pathway related to bitter taste in mulberry leaves was galactose metabolism, indicating that soluble sugar was one of the main factors of bitter taste difference in mulberry leaves. Bitter metabolites play a great role in the medicinal and functional food of mulberry leaves, but the saccharides in mulberry leaves have a great influence on the bitter taste of mulberry. Therefore, we propose to retain bitter metabolites with drug activity in mulberry leaves and increase the content of sugars to improve the bitter taste of mulberry leaves as strategies for mulberry leaf food processing and mulberry breeding for vegetable use.

Accurate and rapid diagnosis of malignant pleural and peritoneal effusions is critical due to potential association with advanced disease stages or progression. Traditional cytodiagnosis suffers from low efficiency and has difficulties in finding malignant tumor cells (MTCs) from a mass of exfoliated cells. Hence, a polymer microfluidic chip with a slanted spiral channel was employed for high-throughput and label-free enrichment of MTCs and MTC clusters from clinical malignant pleural and peritoneal effusions. The slanted spiral channel with trapezoidal cross-sections was fabricated by assembling two patterned polymer films of different thicknesses within one flow channel layer. After systematically exploring the effects of the particle size, effusion concentration, and flow rate on separation performance of the device, we realized the enrichment of MTCs from abundant blood cells in 2-fold diluted effusions. The results indicated that approximately 85% of the spiked tumor cells (A549 and MCF-7 cell lines) were recovered with high purities of over 37% at a high throughput of 2000 μL min

Chromatin loops (or chromatin interactions) are important elements of chromatin structures. Disruption of chromatin loops is associated with many diseases, such as cancer and polydactyly. A few methods, including ChIA-PET, HiChIP and PLAC-Seq, have been proposed to detect high-resolution, specific protein-mediated chromatin loops. With rapid progress in 3D genomic research, ChIA-PET, HiChIP and PLAC-Seq datasets continue to accumulate, and effective collection and processing for these datasets are urgently needed. Here, we developed a comprehensive, multispecies and specific protein-mediated chromatin loop database (ChromLoops, https://3dgenomics.hzau.edu.cn/chromloops), which integrated 1030 ChIA-PET, HiChIP and PLAC-Seq datasets from 13 species, and documented 1 491 416 813 high-quality chromatin loops. We annotated genes and regions overlapping with chromatin loop anchors with rich functional annotations, such as regulatory elements (enhancers, super-enhancers and silencers), variations (common SNPs, somatic SNPs and eQTLs), and transcription factor binding sites. Moreover, we identified genes with high-frequency chromatin interactions in the collected species. In particular, we identified genes with high-frequency interactions in cancer samples. We hope that ChromLoops will provide a new platform for studying chromatin interaction regulation in relation to biological processes and disease.

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A polymer-film inertial microfluidic jigsaw (PIMJ) sorter with trapezoidal spiral channels using the jigsaw puzzle method was proposed to realize precise and high-throughput rare cell separation. The PIMJ sorter was fabricated by assembling laser-patterned polymer-film layers of different thicknesses. After illustrating the conceptual design and fabrication process, the effects of the cross-sectional dimension, particle size, and operational flow rate on particle focusing were systematically explored under a broad flow rate range. Then, the separation performances of the PIMJ sorter were characterized using the binary particle mixture and the blood samples spiked with four types of tumor cells. The results indicated that the complete separation of the binary particles with a minimum size difference of 2 μm was successfully realized at a high throughput up to 3000 μL/min. A high recovery ratio of 90.57%-94.14% and a high purity of 48.67%-79.05% were achieved for the separation of rare tumor cells from white blood cells (WBCs). Finally, the PIMJ sorter was successfully employed for separating rare circulating tumor cells (CTCs) from the metastatic breast and lung cancer patients with a capture ratio of 7–226 CTCs per 5 mL sample. The results proved the high sensitivity and high reliability of the PIMJ sorter. The PIMJ sorter is expected to be a potential device for precise CTC separation towards the clinical applications.

Ethylene promotes ripening in fruits as well as the biosynthesis of anthocyanins in plants. However, the question of which ethylene response factors (ERFs) interact with the genes along the anthocyanin biosynthesis pathway is yet to be answered. Herein, we conduct an integrated analysis of transcriptomes and metabolome on fruits of two mulberry genotypes ('Zijin', ZJ, and 'Dashi', DS, with high and low anthocyanin abundance, respectively) at different post-flowering stages. In total, 1035 upregulated genes were identified in ZJ and DS, including

The mechanism by which synaptic plasticity mediates the occurrence of depression is unknown. Low-density lipoprotein receptor-related protein 1 (LRP1) affects axon growth and neurogenesis in the brain, but its role in depressive-like behaviors is poorly understood.Adeno-associated virus-mediated small interfering RNA was injected into the bilateral hippocampus 14 days before chronic unpredicted mild stress (CUMS). Behavior performance was assessed for depressive-like behaviors. Western blot was conducted to detect levels of LRP1, neurogenesis-related proteins, synaptic markers, microtubule system molecules and Akt/GSK-3β signaling-related proteins. Immunohistochemical staining was performed for LRP1 protein, immunofluorescence staining was conducted to determine the Sox2 protein, Nissl's staining and transmission electron microscope staining were used to observe hippocampal morphological features.The expression of hippocampal LRP1 was positively correlated with depressive-like behaviors. Treatment with iAAV-LRP1 exerted protective effects on depressive-like behaviors. LRP1 Knockdown relieved the inhibition of synaptic plasticity induced by CUMS. Expression of Sox2, GluR2 and SYP was significantly increased in iAAV-LRP1 CUMS rats. LRP1 knockdown reduced the p-tau (Ser262 and Thr404) and Acet-tubule levels in depressed rats. Finally, we found that LRP1 knockdown activated the PI3K/Akt pathway and inhibited GSK-3β signal transduction.More neurogenesis markers would be considered, and stereotactic injection into hippocampal DG region could be performed to investigate the effects of LRP1.These findings indicated that hippocampal LRP1 deficiency in stressed rats plays an important protective role in depressive-like behavior by increasing synaptic plasticity mediated by microtubule dynamic and activating Akt/GSK-3β signaling pathway. Therefore, LRP1 may represent a potential therapeutic target for depression.

DNA methylation is known to be the most stable epigenetic modification and has been extensively studied in relation to cell differentiation, development, X chromosome inactivation and disease. Allele-specific DNA methylation (ASM) is a well-established mechanism for genomic imprinting and regulates imprinted gene expression. Previous studies have confirmed that certain special regions with ASM are susceptible and closely related to human carcinogenesis and plant development. In addition, recent studies have proven ASM to be an effective tumour marker. However, research on the functions of ASM in diseases and development is still extremely scarce. Here, we collected 4400 BS-Seq datasets and 1598 corresponding RNA-Seq datasets from 47 species, including human and mouse, to establish a comprehensive ASM database. We obtained the data on DNA methylation level, ASM and allele-specific expressed genes (ASEGs) and further analysed the ASM/ASEG distribution patterns of these species. In-depth ASM distribution analysis and differential methylation analysis conducted in nine cancer types showed results consistent with the reported changes in ASM in key tumour genes and revealed several potential ASM tumour-related genes. Finally, integrating these results, we constructed the first well-resourced and comprehensive ASM database for 47 species (ASMdb, www.dna-asmdb.com).

Identifying the early predictive biomarkers or compounds represents a pivotal task for guiding a targeted agricultural practice. Despite the various available tools, it remains challenging to define the ideal compound combination and thereby elaborate an effective predictive model fitting that. Hence, we employed a stepwise feature selection approach followed by a maximum relevance and minimum redundancy (MRMR) on the untargeted metabolism in four mulberry genotypes at different fruit developmental stages (FDSs). Thus, we revealed that 7 out of 226 differentially abundant metabolites (DAMs) explained up to 80% variance of anthocyanin based on linear regression model and stepwise feature selection approach accompanied by an MRMR across the genotypes over the FDSs. Among them, the phosphoenolpyruvate, d-mannose and shikimate show the top 3 attribution indexes to the accumulation of anthocyanin in the fruits of these genotypes across the four FDSs. The obtained results were further validated by assessing the regulatory genes expression levels and the targeted metabolism approach. Taken together, our findings provide valuable evidences on the fact that the anthocyanin biosynthesis is somehow involved in the coordination between the carbon metabolism and secondary metabolic pathway. Our report highlights as well the importance of using the feature selection approach for the predictive biomarker identification issued from the untargeted metabolomics data.

Photosynthesis is one of the most important factors in mulberry growth and production. To study the photosynthetic regulatory network of mulberry we sequenced the transcriptomes of two high-yielding (E1 and E2) and one low-yielding (H32) mulberry genotypes at two-time points (10:00 and 12:00). Re-annotation of the mulberry genome based on the transcriptome sequencing data identified 22,664 high-quality protein-coding genes with a BUSCO-assessed completeness of 93.4%. A total of 6587 differentially expressed genes (DEGs) were obtained in the transcriptome analysis. Functional annotation and enrichment revealed 142 out of 6587 genes involved in the photosynthetic pathway and chloroplast development. Moreover, 3 out of 142 genes were further examined using the VIGS technique; the leaves of MaCLA1- and MaTHIC-silenced plants were markedly yellowed or even white, and the leaves of MaPKP2-silenced plants showed a wrinkled appearance. The expression levels of the ensiled plants were reduced, and the levels of chlorophyll b and total chlorophyll were lower than those of the control plants. Co-expression analysis showed that MaCLA1 was co-expressed with CHUP1 and YSL3; MaTHIC was co-expressed with MaHSP70, MaFLN1, and MaEMB2794; MaPKP2 was mainly co-expressed with GH9B7, GH3.1, and EDA9. Protein interaction network prediction revealed that MaCLA1 was associated with RPE, TRA2, GPS1, and DXR proteins; MaTHIC was associated with TH1, PUR5, BIO2, and THI1; MaPKP2 was associated with ENOC, LOS2, and PGI1. This study offers a useful resource for further investigation of the molecular mechanisms involved in mulberry photosynthesis and preliminary insight into the regulatory network of photosynthesis.

Research shows that stress, a common problem in dense cities, can be relieved in the natural environment. As great significance has been attached to the urban environment and public health in the society, this paper aims to study the relation and interaction between the perceived sensory dimension of urban park green space, attention restoration and state empathy. Therefore, we conducted an on-site questionnaire survey in four typical parks in Chengdu in terms of age, sex, daily stress, frequency of access in parks and other basic information of the respondents. The main part consists of perceived dimension, state empathy and attention restoration. The software SPSS24.0 is applied to the test of the validity and reliability of the PSD Scale, and then the important correlation between the perceived sensory dimensions in the parks and visitors' attention restoration is analyzed through multiple linear regression. Finally, the moderation effect of state empathy is tested by PROCESS. The findings show that (1) only seven dimensions in the PSD Scale are effective; (2) Serene and Refuge in the perceived sensory dimensions have significant effect on the restorative components of attention. (3) Except the dimensions of Rich in Species and Refuge, empathy enhanced the moderation effect in the interaction between the other five dimensions the Perceived Restorative Scale(PRS), especially in the interaction between the dimension Social and PRS. However, this study needs to be further explored to provide scientific basis and design strategy guidance for the research on the restoration potential of urban park green space in high-density urban areas.

Jet ampleness of line bundles generalizes very ampleness by requiring the existence of enough global sections to separate not just points and tangent vectors, but also their higher order analogues called jets. We give sharp bounds guaranteeing that a line bundle on a projective toric variety is $k$-jet ample in terms of its intersection numbers with the invariant curves, in terms of the lattice lengths of the edges of its polytope, in terms of the higher concavity of its piecewise linear function and in terms of its Seshadri constant. For example, the tensor power $k+n-2$ of an ample line bundle on a projective toric variety of dimension $n \geq 2$ always generates all $k$-jets, but might not generate all $(k+1)$-jets. As an application, we prove the $k$-jet generalizations of Fujita's conjectures on toric varieties with arbitrary singularities., 24 pages; added a section on Seshadri constants

Urban deciduous forests are an important ecological resource and seasonal landscape in the urban environment. However, in the abundant literature on how urban green space promotes human health and well-being, research on urban seasonal deciduous forests is limited. This study aimed to investigate the physiological and psychological recovery potential provided of urban deciduous forest space for youths and the spatial preferences of youths regarding such spaces. We recruited 120 participants to study the restorative potential of two typical urban deciduous forest landscape spaces (experimental groups) and one urban road environment (control group). The results showed that after 15 min of observation, the blood pressure (especially the diastolic blood pressure (p < 0.01)) and pulse of the deciduous forest trail setting (DFTS) group effectively decreased, and the restorative mood significantly increased. Regarding change in emotional parameters, the DFTS group scored higher on “interest” and significantly higher than the other two groups on positive emotion. The correlation results show that density and level are the key factors affecting spatial preferences regarding complex deciduous forests. An increase in density reduces the mood of re-laxation, and an increase in level decreases fatigue and interest. We suggest (1) constructing foot-paths in urban deciduous forests to reduce their spatial density as to improve the relaxation effect and (2) increasing landscape diversity according to the forest space to facilitate user participation and interest. This study provides a scientific basis for the environmental restoration of deciduous landscapes and for urban forestry management decision-makers based on space type construction.

Microfluidic technologies for cell separation were reported frequently in recent years. However, a compact microfluidic instrument enabling thoroughly automated cell separation is still rarely reported until today due to the difficult hybrid between the macrosized fluidic control system and the microsized microfluidic device. In this work, we propose a novel and automated microfluidic instrument to realize size-based separation of cancer cells in a label-free and high-throughput manner. Briefly, the instrument is equipped with a fully integrated microfluidic device and a set of robust fluid-driven and control units, and the instrument functions of precise fluid infusion and high-throughput cell separation are guaranteed by a flow regulatory chip and two cell separation chips which are the key components of the microfluidic device. With optimized control programs, the instrument is successfully applied to automatically sort human breast adenocarcinoma cell line MCF-7 from 5 mL of diluted human blood with a high recovery ratio of ∼85% within a rapid processing time of ∼23 min. We envision that our microfluidic instrument will be potentially useful in many biomedical applications, especially cell separation, enrichment, and concentration for the purpose of cell culture and analysis.

In this paper, we present a characterization of a big Q-divisor D on a smooth projective surface S with D2 > 0 and H1(OS(−D)) = 0, which generalizes a result of Sakai [Sak90] for D integral. As applications of this result for Q-divisors, we prove results on base-pointfreeness and very-ampleness of the adjoint linear system |KS + D|. These results can be viewed as refinements of previous results on smooth surfaces of Ein-Lazarsfeld [EL93] and Ma¸sek [Ma¸s99].

This study assessed the relationships between maternal systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) and risk for autism spectrum disorders (ASDs) in offspring. Seven observational studies, including 25,005 ASD cases and 4,543,321 participants, were included for meta-analysis. Pooled results by using random-effects models suggested that maternal RA was associated with an increased risk for ASDs [odds ratio (OR) 1.39, 95% confidence interval (CI) 1.16-1.67], while maternal SLE was associated with an increased risk for ASDs only in western population (OR 1.91, 95% CI 1.02-3.57). Further study is warranted to confirm these results.

Background Attention-deficit/hyperactivity disorder (ADHD) is the most common psychiatric disorder in childhood. Studies explored the association of maternal exposure to pesticides during pregnancy with a risk of offspring developing ADHD, but have reported inconclusive results. Here, we will perform a systematic review and meta-analysis of observational studies to assess a possible association between them. Methods This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. PubMed, Embase, Web of Science, the Cochrane Library, and the PsycINFO will be searched from inception to May 2021. Observational studies investigating the association of maternal exposure to pesticides during pregnancy with a risk of offspring developing ADHD will be considered. The Newcastle-Ottawa Scales or the scale of the Agency for Healthcare Research and Quality will be used to assess the methodological quality of the included studies according to their study design. A fixed or random-effect model will be used to synthesize data depend on the heterogeneity test. STATA version 12.0 will be used to conduct the meta-analysis. Results This study will provide a high-quality evaluation of association between maternal exposure to pesticides during pregnancy and risk for ADHD in offspring. Conclusion This study will present evidence on whether maternal exposure to pesticides during pregnancy is a risk factor for ADHD in offspring.

Control of surface wettability is very important and useful for many industrial applications, and can be realized by controlling surface chemistry and microstructure simultaneously. Here, we present a facile laser-based surface texturing method to achieve switchable wettability control on titanium surface. The experimental results indicate that the laser-treated surfaces became superhydrophilic immediately upon laser texturing. Using alternate low-temperature heat treatment and UV irradiation, the wettability of the laser-treated surface could be efficiently switched between superhydrophilicity and superhydrophobicity for many times. Surface morphology and chemistry analyses confirm that the reversible wettability transition should be attributed to the combined effect of the dual-scale surface structure and controllable surface chemistry. Using the laser-based wettability control method, a water collection device was fabricated and demonstrated by a superhydrophobic-superhydrophilic hybrid surface pattern. The developed method could enable a practical throughput for large-area processing, and endow various industrial applications.

Accurate isolation and detection of disseminated tumor cells from the malignant pleural effusion (MPE) is of significant clinical importance. Cytology is a routine diagnostic tool for the analysis of MPE. However, its sensitivity is limited by the existence of a significant number of contaminating blood cells and relatively small and even rare number of target tumor cells in the effusion. To address this limitation, we proposed and developed multiplexed inertial microfluidic devices for fast and efficient isolation and purification of tumor cells from a large volume (> 50 mL) of pleural effusion sample in a label-free way. The rare tumor cells were separated from blood cells relying on the mechanism of size-based differential inertial focusing. The inertial focusing and separation performance of the single serpentine channel was characterized using polystyrene beads and cancer cells lines (A549 and MCF-7) spiked in blood. Subsequently, the multiplexed devices were developed by parallelizing serpentine channels in both planar and vertical directions (e.g., 8 and 24 parallel channel) and the separation was evaluated by the spiked tumor cells (recovery ratio ∼ 80 % for the 8-channel device). Finally, we validated the performance of the multiplexed device using the clinical pleural effusion samples. Malignant tumor cells (MTCs) with a concentration of 49–4806 counts/mL were detected in all 5 pleural effusion samples, with an average purity of ∼30 %. We envision that the multiplexed device is a promising disposable tool towards the clinical applications, given the superiorities of simple structure, high throughput, low cost and good efficiency.

Let $X$ be a smooth projective variety of dimension $5$ and $L$ be an ample line bundle on $X$ such that $L^5>7^5$ and $L^d\cdot Z\geq 7^d$ for any subvariety $Z$ of dimension $1\leq d\leq 4$. We show that $\mathcal{O}_X(K_X+L)$ is globally generated., Final version to appear in manuscripta mathematica. We notice that mistakes were introduced by the journal to some fractions in the form "expression/expression" which should be read as "(expression)/(expression)"

Eleocharis dulcis is a perennial herbaceous plant in the family Cyperaceae, which is native to China and India where it grows well in moist-to-wet soils. It is commonly used as a fruit or a vegetable. From August 2009 to December 2010, symptoms were observed on E. dulcis stems in Tuanfeng County, Hubei, China, with the crop area affected estimated to be more than 1,300 ha per year. Corm yield was reduced by 20% on average with as much as 60% yield losses in some fields. Lesions were initially small, red-brown, and oval or circular that enlarged to produce apical necrosis and extending until the stems withered, usually within 2 months. To obtain isolates, diseased tissue was disinfested for 1 min in 0.1% mercuric chloride solution, rinsed with sterilized water, and plated on potato dextrose agar. Isolates with similar morphological characteristics were consistently recovered. Three isolates, CTF-3, CTF-10, and CTF-11, were used to further evaluate characteristics of the pathogen. After 7 days, white colonies were 76 to 80 mm across on oatmeal agar (OA) with sparse aerial hyphae and a slight salmon color in the conidial masses. Pycnidia produced on OA were globose to subglobose, usually with one slightly ostiolar papilla, olivaceous to olivaceous black, and 93 to 245 μm in diameter. Conidia were hyaline, unicellular, ellipsoidal, mostly with two polar guttules, and 3.6 to 6.2 × 2.0 to 3.3 μm. Chlamydospores were absent. Growth of the isolates on malt extract agar (MEA) was slower than on OA, and the colony diameters at 7 days were 60 to 65 mm. The reactions with 1M NaOH were both positive on OA and MEA where the cultures initially changed to yellow green and gradually turned to red. The pathogen was identified as Phoma bellidis Neerg. based on descriptions in Boerema et al. (2). Pathogenicity tests were performed with the three isolates in the laboratory by spraying conidial suspensions (1 × 106 conidia/ml) containing 0.1% Tween 20 until runoff (30 ml per plant) onto stem surfaces of 50-day-old, 60 cm tall plants. For each isolate, there were 50 stems from five replicate plants that had multiple stems per plant. Control plants were treated with sterilized water containing 0.1% Tween 20 only. Plants were incubated with a 16-h photoperiod at 28°C and 90% relative humidity in an artificial climate chamber. Five days after inoculation, typical red-brown spots were observed on all inoculated stems but no symptoms were seen on water-treated control plants. Koch's postulates were fulfilled by reisolation of P. bellidis from diseased stems. The pathogenicity tests were repeated twice more with the same results. P. bellidis has only been reported previously on Bellis spp. from England, Denmark, Italy, the Netherlands, and Switzerland (1,2). Furthermore, there are only a few fungal diseases known to be associated with E. dulcis, and none so far that involve species of Phoma (3,4). To our knowledge, this is the first report of P. bellidis infecting E. dulcis worldwide. References: (1) M. M. Aveskamp et al. Stud. Mycol. 65:27, 2010. (2) G. H. Boerema et al. Phoma Identification Manual: Differentiation of Specific and Infra-Specific Taxa in Culture. CABI Publishing, Wallingford, UK, 2004. (3) P. L. Lentz. Am. Midl. Nat. 67:184, 1962. (4) L. Pan et al. J. Changjiang Vegetables (in Chinese) 14:10, 2010.

Kempf proved that the theta divisor of a smooth projective curve C has rational singularities. In this paper we estimate the dimensions of the jet schemes of the theta divisor and show that all these schemes are irreducible. In particular, we recover Kempf's theorem in this way. For general projective smooth curves, our method also gives a formula for the log canonical threshold of the pair .

This work presents the fabrication of a microfluidic autoregulatory valve which is composed of several layers of thin polymer films (i.e., polyvinyl chloride (PVC), polyethylene terephthalate (PET) double-sided tape, and polydimethylsiloxane (PDMS)). Briefly, pulsed UV laser is employed to cut the microstructures of through grooves or holes in the thermoplastic polymer films, and then the polymer-film valves are precisely assembled through laminating the PDMS membranes to the thermoplastic polymer films through the roll-lamination method. The effective bonding between the PVC film and the PDMS membrane is realized using the planar seal method, and the valve is sandwiched and compressed by a home-made housing to achieve the good seal effect. Then, the flow performances of the prototype valve are examined, and constant flow autoregulation is realized under the static or dynamic test pressures. The long-term response of the valve is also studied and minimum flow-rate decrements are found over a long actuation time. The fabrication method proposed in this work is successful for the low-cost and fast prototyping of the polymer-film valve. We believe our method will also be broadly applicable for fabrication of other low-cost and disposable polymer-film microfluidic devices.