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Glioma stem cells (GSC) are a subpopulation of tumor cells with special abilities to proliferate and differentiate in gliomas. They are one of the main causes of tumor recurrence, especially under hypoxic conditions. Although long noncoding RNAs (lncRNA) are known to be involved in numerous biological processes and are implied in the occurrence of certain diseases, their role in tumor development and progression remains poorly understood. Here we explored the mechanisms by which lncRNA derived from hypoxic GSCs (H-GSC) cause glioma progression. Isolation and identification of the Linc01060 gene, the exosomes containing them, and the proteins from tumor cells regulating the gene allowed for studying the effects of Linc01060 on proliferation and glycometabolism. H-GSC exerted their effects by transferring exosomes to glioma cells, resulting in a significant increase in Linc01060 levels. Mechanistically, Linc01060 directly interacted with the transcription factor myeloid zinc finger 1 (MZF1) and enhanced its stability. Linc01060 facilitated nuclear translocation of MZF1 and promoted MZF1-mediated c-Myc transcriptional activities. In addition, c-Myc enhanced the accumulation of the hypoxia-inducible factor-1 alpha (HIF1α) at the posttranscriptional level. HIF1α bound the hormone response elements of the Linc01060 promoter, upregulating the transcription of Linc01060 gene. Clinically, Linc01060 was upregulated in glioma and was significantly correlated with tumor grade and poor clinical prognosis. Overall, these data show that secretion of Linc01060-containing exosomes from H-GSCs activates prooncogenic signaling pathways in glioma cells to promote disease progression.Significance:These findings suggest that inhibition of Linc01060-containing exosomes or targeting the Linc01060/MZF1/c-Myc/HIF1α axis may be an effective therapeutic strategy in glioma.

Supplementary Figures 1-12

Table S3: all the antibodies used and sequences of probes for Linc01060 RNA FISH.

Supplementary Tables 7: Univariate and multivariate for clinicopathological features associated with various prognostic parameters of 70 glioma patients by Cox-regression analysis.

SUMOylation is an essential protein modification process that regulates numerous crucial cellular and biochemical processes in phytopathogenic fungi, and thus plays important roles in multiple biological functions. The present study characterizes the SUMOylation pathway components, including SMT3 (SUMO), AOS1 (an E1 enzyme), UBC9 (an E2 enzyme), and MMS21 (an E3 ligase), in Fusarium oxysporum f. sp. niveum (Fon), the causative agent of watermelon Fusarium wilt, in terms of the phylogenetic relationship, gene/protein structures, and basic biological functions. The SUMOylation components FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are predominantly located in the nucleus. FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are highly expressed in the germinating macroconidia, but their expression is downregulated gradually in infected watermelon roots with the disease progression. The disruption of FonUBA2 and FonSIZ1 seems to be lethal in Fon. The deletion mutant strains for FonSMT3, FonAOS1, FonUBC9, and FonMMS21 are viable, but exhibit significant defects in vegetative growth, asexual reproduction, conidial morphology, spore germination, responses to metal ions and DNA-damaging agents, and apoptosis. The disruption of FonSMT3, FonAOS1, FonUBC9, and FonMMS21 enhances sensitivity to cell wall-perturbing agents, but confers tolerance to digestion by cell wall-degrading enzymes. Furthermore, the disruption of FonSMT3, FonAOS1, and FonUBC9 negatively regulates autophagy in Fon. Overall, these results demonstrate that the SUMOylation pathway plays vital roles in regulating multiple basic biological processes in Fon, and, thus, can serve as a potential target for developing a disease management approach to control Fusarium wilt in watermelon.

A systematic review and meta-analysis.The objective of this study was to compare the safety of microscopic anterior cervical discectomy and fusion (MI-ACDF) and posterior percutaneous endoscopic keyhole foraminotomy (PPEKF) in patients diagnosed with single-level unilateral cervical radiculopathy.After conservative treatment, the symptoms will be relieved in about 90% of cervical radiculopathy patients. For the other one tenth of patients, surgical treatment is needed. The overall complication rate of MI-ACDF and PPEKF ranges from 0% to 25%, and the reoperation rate ranges from 0% to 20%.Electronic retrieval of studies from PubMed, Embase, and Cochrane Library was performed to identify comparative or single-arm studies on MI-ACDF and PPEKF. A total of 24 studies were included in our meta-analysis by screening according to the inclusion and exclusion criteria. After data extraction and quality assessment of the included studies, a meta-analysis was performed by using the R software. The pooled incidences of efficient rate, total complication rate, and reoperation rate were calculated.A total of 24 studies with 1345 patients (MI-ACDF: 644, PPEKF: 701) were identified. There was no significantly statistical difference in pooled patient effective rate (MI-ACDF: 94.3% vs. PPEKF: 93.3%, P=0.625), total complication rate (MI-ACDF: 7.1% vs. PPEKF: 4.7%, P=0.198), and reoperation rate (MI-ACDF: 1.8% vs. PPEKF: 1.1%, P=0.312). However, the common complications of the 2 procedures were different. The most common complications of MI-ACDF were dysphagia and vertebral body sinking, whereas the most common complication of PPEKF was nerve root palsy.Both MI-ACDF and PPEKF can provide a relatively safe and reliable treatment for single-level unilateral cervical radiculopathy. The 2 techniques are not significantly different in terms of effective rate, total complication rate, and reoperation rate.

The leaf veins of higher plants contain a highly specialized vascular system comprised of xylem and phloem cells that transport water, organic compounds and mineral nutrients. The development of the vascular system is controlled by phytohormones that interact with complex transcriptional regulatory networks. Before the emergence of true leaves, the cotyledons of young seedlings perform photosynthesis that provides energy for the sustainable growth and survival of seedlings. However, the mechanisms underlying the early development of leaf veins in cotyledons are still not fully understood, in part due to the complex cellular composition of this tissue. To better understand the development of leaf veins, we analyzed 14 117 single cells from 3-day-old cotyledons using single-cell RNA sequencing. Based on gene expression patterns, we identified 10 clusters of cells and traced their developmental trajectories. We discovered multiple new marker genes and developmental features of leaf veins. The transcription factor networks of some cell types indicated potential roles of CYCLING DOF FACTOR 5 (CDF5) and REPRESSOR OF GA (RGA) in the early development and function of the leaf veins in cotyledons. These new findings lay a foundation for understanding the early developmental dynamics of cotyledon veins. The mechanisms underlying the early development of leaf veins in cotyledons are still not fully understood. In this study, we comprehensively characterized the early differentiation and development of leaf veins in 3-day-old cotyledons based on single-cell transcriptome analysis. We identified the cell types and novel marker genes of leaf veins and characterized the novel regulators of leaf vein.

As the major source of edible protein and oil, the global demand for soybean (Glycine max (L.) Merr.) is increasing. Plant height is closely related to yield; therefore, understanding the genetic basis of plant height will help to improve soybean plant type and increase seed yield. In this study, quantitative trait loci (QTLs) and nucleotides (QTNs) for soybean plant height were detected by linkage analysis and association analysis. A high-density map containing 2225 bin markers was constructed by using 108 342 SNPs of a recombinant inbred line population (named RIL3613) of 120 lines for linkage analysis. In total, 39 QTLs were detected, including 16 QTLs that were repeatedly detected in multiple environments. Association analysis was performed by using 63 306 SNPs from a germplasm population of 455 natural soybean accessions. In total, 62 QTNs were detected, and 26 QTNs were repeatedly detected by multiple methods. Fourteen QTNs were distributed in the intervals of six multiple-environment QTLs by comparing the results of association analysis and linkage analysis. With pathway analysis, six candidate genes were identified as being associated with plant height. These results contribute to analysis of the genetic basis of plant height and will promote marker-assisted selection for breeding ideal plant shape.

Background: In humans, methane (CH4) is exclusively produced by the intestinal microbiota and has been implicated in several conditions including cardiovascular disease. After microbial production of CH4 in the gut, it steadily crosses into the systemic circulation and reaches the lungs where it can be detected in the exhaled breath, as a surrogate measure for intestinal CH4 production. Recent reports have shown an association between CH4 and vagal dysfunction as well as the inhibition of CH4 activity on ileal contractions with atropine, suggesting its action on the parasympathetic nervous system. Given these findings, we hypothesized that CH4 may be affecting resting heart rate (HR) based on the potential effect of CH4 on the vagus nerve. Objectives: Given its possible role in the parasympathetic nervous system, we aimed to study the relationship between breath CH4 and resting HR in humans. Additionally, we performed a longitudinal study analyzing the change in HR and its association with breath CH4 over time. Methods: First, we reviewed 1,126 subjects and compared HR in subjects with detectable and undetectable breath CH4. Second, we performed a post hoc analysis of a randomized control trial to compare the change in HR for those who had an increase in breath CH4 versus those that had a decrease in breath CH4 over 14 weeks. Last, we assessed whether a larger decrease in CH4 is associated with a larger increase in HR over time. Results: In the retrospective cohort, subjects with detectable CH4 had a lower HR compared to those with undetectable CH4 (73.0 ± 0.83 vs. 76.0 ± 0.44 beats/min, p = 0.01). In the post hoc analysis, a decrease in CH4 over time was associated with an increase in HR (median ∆ = 6.5 ± 8.32 beats/min, p = 0.0006). Last, we demonstrated a biological gradient whereby a larger drop in CH4 was associated with a greater increase in HR (R = −0.31, p = 0.03). Conclusion: Our findings suggest a potential role for the microbiome (and specifically CH4 from methanogens) to regulate HR. Considering these findings, mechanistic studies are warranted to further investigate this potential novel microbiome-neurocardiac axis.

Fusarium oxysporum f. sp. niveum ( Fon ), the causal agent of watermelon Fusarium wilt, is one of the most serious threats for the sustainable development of the watermelon industry worldwide. However, little is known about the underlying molecular mechanism of pathogenicity in Fon .

Sino-Tibetan is the second largest language family in the world. Recent linguistic and genetic studies have traced its origin to Neolithic millet farmers in the Yellow River region of China around 8,000 y ago and also suggested that initial divergence among branches of Sino-Tibetan coincided with expansion of the Neolithic Yangshao culture to the west and southwest during the sixth millennium BP. However, archaeological investigations to date have been insufficient to understand the lifeways of these migrant Proto Sino-Tibetan speakers. Here, we present the results of the interdisciplinary research on the material culture and ritual activities related to the initial southwestward migration of Yangshao populations, based on evidence from microfossil remains on ceramics at three sites in Gansu and Sichuan, regional archaeological contexts, and ethnographic accounts of modern Gyalrong Tibetans. The first Yangshao migrants may have integrated with indigenous hunter-gatherers in the NW Sichuan highlands, and adopted broad-spectrum subsistence strategies, consisting of both millet farming and foraging for local wild resources. Meanwhile, the migrants appear to have retained important ritual traditions previously established in their Yellow River homelands. They prepared qu starter with Monascus mold and rice for brewing alcoholic beverages, which may have been consumed in communal drinking festivals associated with the performance of ritual dancing. Such ritual activities, which to some extent have survived in the skorbro-zajiu ceremonies in SW China, may have then played a central role in maintaining and reinforcing cultural identities, social values, and connections with the homelands of the Proto Sino-Tibetan migrants.

This paper constructed a biobjective model based on the total cost and time satisfaction to provide a desirable solution to the distribution and inventory cooperation of agricultural means supply chain. The model simulated how the distribution center and retailers collaborate to meet the needs of the order customer in the random lead time and out-of-stock loss costs. By the features of the model, the biobjective genetic algorithm was improved based on elitism selection, aiming to improve the quality of noninferior solution in biobjective model. Finally, the influence degree of the lead time of delivery, unit inventory cost, and unit transport cost on the total cost of the system was quantified through the analysis of examples and sensitivity of model parameters. This research has provided valuable new insights into the distribution and inventory coordination of supply chain.

There is increasing evidence that the early rice farming communities of southern China emerged from societies heavily dependent on acorns. Recent archaeological investigations have recovered large quantities of acorn remains from multiple archaeological sites (10,000–6000 cal. BP) in the Lower Yangtze River Valley, suggesting that acorns were a staple food for preagricultural societies. However, most previous studies have focused on taxonomical identification, leaving us a poor understanding of acorn processing technology. This research addresses this shortcoming by conducting a systematic microbotanical residue analysis (starch and phytolith) of pottery and grinding stones from the Shangshan culture (10,000–8200 cal. BP). The results show that the artifacts analyzed were predominantly used for processing acorns, and to a lesser extent, USOs and cereals. Combining the microbotanical data and an ethnographic study, we reconstruct a 10,000-year-old acorn processing technology. We suggest that intensive acorn processing provided an impetus for the increased production of pottery and grinding stones in early Holocene China.

Mountain summits are vital topographic feature points, which are essential for understanding landform processes and their impacts on the environment and ecosystem. Traditional summit detection methods operate on handcrafted features extracted from digital elevation model (DEM) data and apply parametric detection algorithms to locate mountain summits. However, these methods may no longer be effective to achieve desirable recognition results in small summits and suffer from the objective criterion lacking problem. Thus, to address these problems, we propose an improved Faster region-convolutional neural network (R-CNN) to accurately detect the mountain summits from DEM data. Based on Faster R-CNN, the improved network adopts a residual convolution block to replace the traditional part and adds a feature pyramid network (FPN) to fuse the features with adjacent layers to better address the mountain summit detection task. The residual convolution is employed to capture the deep correlation between visual and physical morphological features. The FPN is utilized to integrate the location and semantic information in the extracted feature maps to effectively represent the mountain summit area. The experimental results demonstrate that the proposed network could achieve the highest recall and precision without manually designed summit features and accurately identify small summits.

Gummy stem blight (GSB), which is caused by three related species of Stagonosporopsis, is a worldwide devastating disease of cucurbit crops including watermelon. Previously S. cucurbitacearum was reported to be the major fungal cause of watermelon GSB in Southern China, where it causes a significant decrease in watermelon yield. Here, we present the draft whole genome sequence, gene prediction and annotation of S. cucurbitacearum strain DBTL4, isolated from diseased watermelon plants. To our knowledge, this is the first publicly available genome sequence of this species, and knowledge of this genome sequence will help further understand the pathogenic mechanism of S. cucurbitacearum to cucurbit plants. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .

Subsequent microvascular decompression (MVD) might be affected by the previous two-isocentre gamma knife radiosurgery (GKS) due to the tissue changes caused by its higher dose radiation and larger treatment volume. This study aimed to evaluate the safety and efficacy of MVD as a second step treatment after two-isocentre GKS. Between December 2016 and May 2019, data from 19 consecutive trigeminal neuralgia (TN) patients who experienced MVD after failed two-isocentre GKS were collected. The clinical characteristics, intraoperative findings, surgical outcomes and complications were reviewed and compared with 158 patients who underwent MVD as an initial treatment. Fifteen patients (78.9%) achieved complete pain relief (Barrow Neurological Institute, BNI class I) immediately after surgery and nine patients (47.4%) maintained complete pain relief at the last follow-up, which was similar to patients who underwent initial MVD. The median follow-up period was 36 months. The incidence of new or worsened facial numbness showed no statistical significance between the groups. During surgery, trigeminal nerve atrophy was noted in 9 patients (47.4%), thickened arachnoid in 3 patients (15.8%), atherosclerotic plaque in 3 patients (15.8%) and neurovascular adhesion in 1 patient (5.3%). MVD remains an effective and safe rescue therapy for patients who elect the minimally invasive treatment with two-isocentre GKS for the first time, without an increased risk of facial numbness.

Retinal progenitor cell (RPC) transplantation has been proposed as a potential strategy for the treatment of retinal degeneration, which is a leading cause of vision loss. However, a major obstacle is the poor proliferation of RPCs. Accumulating evidence suggests that the chiral features of the extracellular microenvironment are closely related to cell proliferation. Inspired by this, L/D-phenylalanine-derived molecules (LP and DP) are employed to construct a biomimetic chiral microenvironment for enhancing RPC proliferation. LP and DP self-assemble into left-handed and right-handed helical fibrous networks, respectively. It is found that DP nanofibrous films show an excellent ability in promoting RPC proliferation

The widely available crop oil is an effective alternative to the increasingly scarce marine fish oil. However, simple alternative strategies have led to declining growth and the edible value of farmed fish. It is worthwhile to explore the effects of micro supplements in diets to improve the tolerance of fish to different dietary lipid sources, which finally optimizes the feeding strategies. This study aimed to investigate the regulation of L-carnitine and dietary oil conditions on nutrient composition, lipid metabolism, and glucose regulation of Rhynchocypris lagowskii. Four diets were prepared according to fish oil, fish oil supplemented with L-carnitine, corn oil, and corn oil supplemented with L-carnitine, and FO, LCFO, CO, and LCCO were labeled, respectively. R. lagowskii was fed experimental diets for 8 weeks, and the glucose tolerance test was performed. The CO diet significantly resulted in higher crude lipid content in muscle but a lower level of serum lipid parameters of R. lagowskii than the FO diet. However, dietary L-carnitine supplementation significantly reduced the crude lipid content in the hepatopancreas and muscle of the fish fed with the CO diet yet increased the serum lipid parameters. Additionally, the crude lipid content of muscle was reduced in the fish fed with an FO diet supplemented with L-carnitine. Compared with the FO diet, the CO diet significantly reduced the ratio of n3/n6 polyunsaturated fatty acid in the hepatopancreas and muscle of R.lagowskii. Dietary L-carnitine supplementation significantly reduced the contents of total saturated fatty acids and total monounsaturated fatty acids in hepatopancreas under both dietary lipid sources. The CO diet significantly up-regulated the expression of genes related to lipid uptake and adipogenesis in hepatopancreas, including lipoprotein lipase (lpl), acetyl-coenzyme A carboxylase alpha (accα), and sterol regulatory element binding protein-1 (srebp1), compared with the FO diet. While dietary L-carnitine supplementation significantly down-regulated the expressions of lpl, accα, srebp1, and fatty acid synthase in hepatopancreas and muscle of fish under both dietary lipid sources, along with up-regulated expression of carnitine palmitoyltransferase 1 in hepatopancreas. Moreover, the fish fed with a CO diet significantly increased the expression of glucose uptake and clearance and significantly down-regulated the expressions of glucose regulation-related genes, including glucose transporter 1, glycogen synthase 1, and phosphofructokinase in hepatopancreas and muscle, resulting in slower glucose uptake and clearance than fish fed with FO diet. Nevertheless, dietary L-carnitine supplementation up-regulated the expression of gluconeogenesis-related genes, including glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the hepatopancreas of R. lagowskii under both dietary lipid sources. In conclusion, a higher dietary n6 PUFA resulted in lipid deposition, decreased serum lipid parameters, and limited serum glucose utilization of R. lagowskii. While the regulatory effect of L-carnitine on lipid metabolism and glucose utilization of R. lagowskii varies with dietary lipid sources and tissues.

Background Recent studies have demonstrated that glioma-associated mesenchymal stem cells (GA-MSCs) are implicated in the regulation of glioma malignant progression. However, the prognostic value of GA-MSCs has not been comprehensively explored in glioma. Methods We extracted GA-MSCs from glioma tissues, established intracranial xenograft models in nude mice, and obtained GA-MSC-related genes (GA-MSCRGs) by using microarrays. The transcriptome data and clinical information of glioma patients were obtained from the CGGA and TCGA databases. We screened 8 prognostic GA-MSCRGs to construct a prognostic index by using the multivariate Cox regression method. The validity of the GA-MSCRGPI was verified in the training (CGGA693) and validation (TCGA and CGGA325) cohorts. The expression patterns of these 8 GA-MSCRGs were validated in 78 glioma tissue specimens by using a qRT‒PCR assay. Results GA-MSCs were successfully isolated from glioma tissues. Based on intracranial xenograft models and transcriptome microarray screening, 8 genes (MCM7, CDK6, ORC1, CCL20, TNFRSF12A, POLA1, TRAF1 and TIAM1) were selected for the construction of a GA-MSC-related gene prognostic index (GA-MSCRGPI). In both the training and validation cohorts, high GA-MSCRGPI patients showed an inferior survival outcome compared with low GA-MSCRGPI patients. A nomogram was established based on independent prognostic indicators (age, WHO grade and GA-MSCRGPI) and exhibited a strong forecasting ability for overall survival (OS). Moreover, we found that the GA-MSCRGPI could evaluate the prognosis of glioma patients undergoing chemoradiotherapy. The high GA-MSCRGPI group exhibited higher immune, stromal and ESTIMATE scores; lower tumor purity; higher infiltration of Tregs and M2-type macrophages; fewer activated NK cells; and higher expression of immune checkpoints. Tumor Immune Dysfunction and Exclusion (TIDE) showed that the high GA-MSCRGPI group had more responders to ICI therapy. The results of the genetic mutation profile and tumor mutation burden (TMB) in different GA-MSCRGPI subgroups further supplement GA-MSCRGPI-related mechanisms. Finally, the expression patterns of 8 selected GA-MSCRGs in GA-MSCRGPI were correlated with glioma WHO grades to a certain extent. Conclusion The constructed GA-MSCRGPI could predict prognosis and guide individualized therapy in glioma patients.

Glioma represents the most prevalent malignant primary brain cancer, and its treatment remains a tremendous challenge. Novel and efficient molecular targets are therefore required for improving diagnosis, survival prediction, and treatment outcomes. Additionally, some studies have shown that immunity is highly associated with glioma progression. Our study aimed to investigate the clinicopathological features, prognostic significance, and immunotherapeutic targetability of ELK3, a member of the erythroblast transformation-specific transcription factor family, in glioma using bioinformatics analyses. ELK3 transcript levels in glioma tissues were evaluated using the Gene Expression Omnibus and The Cancer Genome Atlas databases. Clinical and transcriptomic data of The Cancer Genome Atlas glioma patients were analyzed to identify the molecular and clinical characterizations of ELK3. The prognostic significance of ELK3 was assessed using Cox regression and Kaplan-Meier analysis. The biological pathways related to ELK3 expression were identified by gene set enrichment analysis. The relationships between ELK3 and inflammatory responses, immune cell infiltration, and immune checkpoints were explored using canonical correlation analysis and gene set variation analysis. ELK3 was upregulated in gliomas, and its high expression was correlated with advanced clinicopathologic features and unfavorable prognosis. Gene set enrichment analysis revealed that several immune-related pathways were tightly linked to high ELK3 expression. gene set variation analysis and correlograms demonstrated that ELK3 was robustly associated with inflammatory and immune responses. Correlation analyses indicated that ELK3 was positively associated with infiltrating immune cells and synergistic with several immune checkpoints. ELK3 may serve as a novel marker of poor prognosis and a potential immunotherapeutic target in glioma.

The blood-brain barrier (BBB) is an essential structure of the central nervous system (CNS), and its existence makes the local internal environment of the CNS a relatively independent structure distinct from other internal environments of the human body to ensure normal physiological and high stability of activities of the CNS. Changes in BBB structure and function are fundamental to the pathophysiology of many diseases. The occurrence and development of glioma are often accompanied by a series of changes in the structure and function of the internal environment, the most significant of which is remodelling of the BBB. The remodelling of the BBB usually leads to changes in the permeability of local microvessels, which provide certain favourable conditions for the occurrence and development of glioma. Meanwhile, the newly generated abnormal blood vessels and the remaining intact regions of the BBB also hinder the effects of drug treatments. Changes in permeability and structural function often lead to the creation of abnormally functioning vascular regions, which pose further treatment challenges. At present, therapeutic methods for glioma have not achieved satisfactory effects in clinical practice, and emerging therapeutic methods have not yet been widely used in clinical practice. In this review, we summarize the knowledge of remodelling of the BBB in the glioma environment, the type of changes that occur, and current BBB treatment methods and prospects for the treatment of glioma.

Low luminescence efficiency of rare-earth ions doped upconversion (UC) nanomaterials is still a major limitation for their applications. Here, based on bismuth oxychloride nanosheets that show efficient photocarriers separation due to combining spontaneous polarization and layered semiconductor, we report a new carbon heterovalent doping strategy for efficient UC luminescence enhancement by suppressing the intermediate excited states of Er3+ ions. The first-principles calculations and photoelectrochemical characterizations provide evidences that the replacement of C ions for Cl strengthen the spontaneous polarization and inter electric field (IEF) of bismuth oxychloride nanosheets, which further improve the photocarriers separation efficiency. Under 808 or 980 nm excitation, the emission intensity of 4I13/2 energy level of Er3+ ions (1550 nm) increase slightly with C doping, but the its decay time and the visible UC emission are improved tremendously at the same time. We show that the recombination rate of intermediate excited state electrons of Er3+ ions with the ground state is inhibited by the enhanced IEF, which promotes the energy reabsorption transition to upper energy levels, thus enhancing the visible UC emission. This work not only may provide a new insight into the method for engineering of UC emissions but also deepen the understanding for layered semiconducting material to modify the transition of Lanthanide ions.

Retinal degeneration is a main class of ocular diseases. So far, retinal progenitor cell (RPC) transplantation has been the most potential therapy for it, in which promoting RPCs neuronal differentiation remains an unmet challenge. To address this issue, innovatively designed L/d-phenylalanine based chiral nanofibers (LPG and DPG) are employed and it finds that chirality of fibers can efficiently regulate RPCs differentiation. qPCR, western blot, and immunofluorescence analysis show that right-handed helical DPG nanofibers significantly promote RPCs neuronal differentiation, whereas left-handed LPG nanofibers decrease this effect. These effects are mainly ascribed to the stereoselective interaction between chiral helical nanofibers and retinol-binding protein 4 (RBP4, a key protein in the retinoic acid (RA) metabolic pathway). The findings of chirality-dependent neuronal differentiation provide new strategies for treatment of neurodegenerative diseases via optimizing differentiation of transplanted stem cells on chiral nanofibers., Graphical abstract L/d-phenylalanine-based enantiomers are employed as building blocks to fabricate chiral nanofibers. Right-handed helical nanofibers significantly promote RPC neuronal differentiation, migration and synapse formation, which are mainly ascribed to activation of the RA metabolic pathway. This provides a feasible strategy to address retinal degeneration if chiral structure of extracellular microenvironment is considered.Image 1, Highlights • This is the first attempt to utilize chiral structure to induce retinal progenitor cell neuronal differentiation. • Right-handed nanofibers promote cell neuronal differentiation, whereas left-handed fibers decrease this effect. • The different cell differentiations are attributed to the stereoselective interaction between chiral fibers and proteins. • It provides new strategies for treatment of neurodegenerative diseases via optimizing chiral structures of biomaterials.

Although toluene is a typical in-vehicle pollutant, the impacts of in-vehicle toluene exposure on cognitive functions remain unestablished. Therefore, this study aimed to investigate the effects of short-term toluene exposure in vehicles on working memory based on neural oscillations. In total, 24 healthy adults were recruited. Each subject was exposed to four different concentrations of toluene and divided into 0 ppb, 17.5 ppb, 35 ppb, and 70 ppb groups for self-control studies. After 4 h of exposure to each concentration of toluene, a behavioral test of visual working memory was performed while 19-channel electroencephalogram (EEG) signals were collected. Meanwhile, the power spectral density (PSD) and spatial distribution of working memory encoding, maintenance, and extraction periods were calculated by short-time Fourier transform to clarify the characteristic frequency bands, major brain regions, and characteristic channels of each period. To compare the changes in the characteristic patterns of neural oscillations under the effect of different concentrations of toluene. There was no significant difference in working memory reaction time and correct rate between the groups at different toluene concentrations (p 0.05). The characteristic frequency band of the working memory neural oscillations in each group was the theta frequency band; the PSD of the theta frequency band was predominantly concentrated in the frontal area, and the characteristic channel was the Fz channel. The whole brain (F = 3.817, p 0.05; F = 4.758, p 0.01; F = 3.694, p 0.05), the frontal area (F = 2.505, p 0.05; F = 2.839, p 0.05; F = 6.068, p 0.05), the Fz channel (F = 3.522, p 0.05; F = 3.745, p 0.05; F = 6.526, p 0.05), and the PSD of working memory in the theta frequency band was significantly increased in the 70 ppb group compared with the other three groups during the coding, maintenance, and retrieval phases of working memory. When the in-vehicle toluene exposure concentration was 70 ppb, the PSD of the characteristic frequency bands of working memory was significantly increased in the whole brain, major brain regions, and characteristic channels.

Yuan Zhang,1,* Hongli Yue,1,* Yirui Qin,1 Jiajing Wang,1 Chenyang Zhao,1 Miao Cheng,1 Bo Han,2 Ruquan Han,1 Weihua Cui1,* 1Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ruquan Han; Weihua Cui, Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613701285393 ; Tel +8613701285393, Fax +861059976658, Email ruquan.han@ccmu.edu.cn; weihuacui@ccmu.edu.cnPurpose: Patients undergoing intraspinal tumor resection usually experience severe postoperative pain. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Recently, an increasing number of studies have found that gabapentin can relieve hyperalgesia, postoperative pain, and postoperative inflammation. However, there have been no reports on the use of gabapentin combined with sufentanil preoperatively for acute pain following intraspinal tumor resection.Study Design and Methods: This is a protocol for a randomized, placebo-controlled, and double-blinded trial. One-hundred and sixty-eight participants with chronic pain related to the intraspinal tumor will be randomized into the gabapentin and placebo groups in a 1:1 ratio. In the gabapentin group, patients will be given 300 mg gabapentin orally 36 h, 24 h, and 12 h before surgery; the placebo group will receive a placebo orally at the same time points preoperatively. To estimate the efficacy and safety endpoints, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the consumption of sufentanil within 48 h postoperatively. The secondary outcomes include the visual analog scale pain score and Von Frey mechanical pain threshold 36 h and 24 h before and 24 h and 48 h after surgery, the incidence of postoperative nausea, vomiting, and drowsiness, the length of hospital stay and medical expenses.Discussion: This trial is to evaluate the efficacy and safety of gabapentin combined with sufentanil for postoperative analgesia in patients who complain of pain before intraspinal tumor resection. The findings will provide a new strategy for multimode perioperative analgesia management in these patients.Keywords: gabapentin, intraspinal tumor resection, multimode perioperative analgesia, opiates

Epidermal cells are the main avenue for signal and material exchange between plants and the environment. Leaf epidermal cells primarily include pavement cells (PCs), guard cells, and trichomes cells (TCs), which differentiate from protodermal cells or meristemoids. The development and distribution of different epidermal cells are tightly regulated by a complex transcriptional regulatory network mediated by phytohormones, including jasmonic acid (JA), and transcription factors. Understanding how the fate of leaf epidermal cells is determined, however, is still largely unknown due to the diversity of cell types and the complexity of its regulation. Here, we characterized the transcriptional profiles of epidermal cells in 3-day-old true leaves of Arabidopsis thaliana using single-cell RNA-sequencing. We identified two genes encoding BASIC LEUCINE-ZIPPER (bZIP) transcription factors, namely the bZIP25 and bZIP53, which are highly expressed in PCs and early-stage meristemoid cells. Densities of PCs and TCs were found to increase and decrease, respectively, in bzip25 and bzip53 mutants, compared with wild-type plants. This trend was more pronounced in the presence of JA, suggesting that these transcription factors regulate the development of TCs and PCs in response to JA.IN A NUTSHELLBackgroundLeaf epidermal cells, comprised of trichome cells (TCs), guard cells (GCs), and pavement cells (PCs), are responsible for exchanging materials and information between plants and the surrounding aerial environment. Many genes have been identified in Arabidopsis thaliana and confirmed to be involved in the initiation and differentiation of TCs and PCs. The fate determination of TCs and PCs is tightly regulated by positive and negative regulators at the cellular level. The precise underlying molecular mechanisms responsible for the fate determination of TCs and PCs, however, are still unclear at this time.QuestionWhat are the transcriptomic profiles of different leaf epidermal cell types? Can we dissect the genes that are specifically expressed in certain epidermal cell types? What kinds of transcription factors are involved in regulating the fate determination of TCs and PCs?FindingsWe performed single cell RNA-seq to investigate the transcriptomic profiles of different leaf epidermal cell types and identified differentially expressed genes in each cell type. We found that genes that are involved in jasmonic acid signaling are highly expressed in early-stage meristemoid (EM) cells which can act as the precursor of PCs and perhaps of TCs. To investigate the regulatory mechanisms underlying EM development, we identified the transcription factors (TFs) in EM cells and found that two bZIP TF genes, bZIP25 and bZIP53, are highly expressed in EMs. Further analyses of these two genes using both loss-of-function and gain-of-function approaches indicated that bZIP25 and bZIP53 are functionally involved in promoting trichome formation but inhibit pavement cell development in response to jasmonic acid.Next stepsBesides of bZIP25 and bZIP53, we also identified other key genes, for example FES1B, in leaf epidermal cells. Our next step will be to explore the regulation of other key genes involved in the fate determination of different cell types in leaf epidermis.

Total resection of meningiomas involving the major dural sinuses (MIMDS) is still challenging for neurosurgeons. Gamma knife radiosurgery (GKRS) was shown to have a high probability of tumor control. The current study evaluated the clinical outcomes of patients who underwent subtotal resection alone or in combination with postoperative GKRS for the treatment of WHO grade I MIMDS. From January 2006 to December 2016, 204 patients with MIMDS underwent Simpson IV subtotal resection in Wuhan Union Hospital. In 151 patients, no additional treatment was performed, while the tumor remnant was treated with GKRS in 53 patients. All patients were monitored with regular MR follow-ups. We retrospectively reviewed the clinical data, radiological characteristics, and outcomes of these 204 patients. Progression-free survival (PFS) was determined by Kaplan-Meier analysis. Related factors were determined by univariate Cox regression analyses. The mean follow-up period was 75.5 months. The tumor recurrence/progression rates were 13.9% in the microsurgery group and 3.8% in the combined therapy group (p = 0.045). The 5- and 10- year progression-free survival (PFS) rates were 92.3 and 80.7%, respectively, in the microsurgery group and 100.0 and 88.5% in the combined therapy group. Treatment approach was found to be an independent prognostic factor for tumor recurrence/progression in the univariable analyses (p=0.04). Compared with microsurgery alone, targeted Simpson grade IV resection combined with early gamma knife treatment resulted in longer progression-free survival without increased complications for WHO grade I MIMDS.

Bacterial spot, which is caused by several Xanthomonas species, is an economically important disease in tomato (Solanum lycopersicum). Great efforts have been made for the identification of resistant sources and the genetic analysis of resistance. However, the development of resistant commercial varieties is slow due to the existence of multiple species of the pathogen and a poor understanding of the resistance mechanism in tomato. The current study revealed that the Rx4 gene encodes a nucleotide-binding leucine-rich repeat protein in the wild tomato species Solanum pimpinellifolium and specifically recognizes and confers a hypersensitive response (HR) to Xanthomonas euvesicatoria pv. perforans race T3 expressing the AvrXv3 avirulence protein. Complementation of the Rx4 gene in the susceptible tomato line Ohio 88119 using a transgenic approach resulted in HR, whereas knockout of the gene through CRISPR/Cas9 editing in resistant lines Hawaii 7981 and PI 128216 led to non-HR to race T3. Transcription of Rx4 was not induced by the presence of race T3. Furthermore, the Rx4 protein did not show physical interaction with AvrXv3 but interacted with SGT1-1 and RAR1. Virus-induced gene silencing of SGT1-1 and RAR1 in the resistant line PI128216 suppressed the HR to race T3. Taken together, our study confirms Rx4 is the gene conferring the HR to bacterial spot race T3 and reveals the potential roles of SGT1-1 and RAR1 as signals in the Rx4-mediated HR. This discovery represents a step forward in our understanding of the mechanism of resistance to bacterial spot in tomato and may have important implications for understanding plant-bacterial interactions.

Soybean is one main source of dietary protein; therefore, improving protein content is an important objective in breeding programs. There is a significant negative correlation between protein and oil content, which influenced mapping quantitative trait locus (QTL) and quantitative trait nucleotides for these two traits. In this study, a linkage map was created with 2232 single-nucleotide polymorphism markers for the four-way recombinant inbred line (FW-RIL) population derived from the cross (Kenfeng 14 × Kenfeng 15) × (Heinong 48 × Kenfeng 19), and then conditional and unconditional QTL analyses were carried out by inclusive complete interval mapping based on the phenotypic data of protein and oil content collected in 10 different environments. As shown in the results of linkage analysis, a total of 85 QTL have been detected. We have performed association analysis using 109,676 markers after quality filtering for FW-RIL, and the results have shown that a total of 60 QTNs were detected. We have performed association analysis using 63,306 markers after quality filtering for resource population, and the results have shown that a total of 123 QTNs were detected. We have combined linkage and association analysis, and there are six QTNs verified by FW-RIL and resource population. We have performed pathway analysis on the genes in these six QTN attenuation regions, and the result shows that a total of four candidate genes are related to the synthesis or metabolism of soybean protein. These findings will facilitate marker-assisted selection and molecular breeding of soybean.