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Plants undergo extended morphogenesis. The shoot apical meristem (SAM) allows for reiterative development and the formation of new structures throughout the life of the plant. Intriguingly, the SAM produces morphologically different leaves in an age-dependent manner, a phenomenon known as heteroblasty. In Arabidopsis thaliana, the SAM produces small orbicular leaves in the juvenile phase, but gives rise to large elliptical leaves in the adult phase. Previous studies have established that a developmental decline of microRNA156 (miR156) is necessary and sufficient to trigger this leaf shape switch, although the underlying mechanism is poorly understood. Here we show that the gradual increase in miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE transcription factors with age promotes cell growth anisotropy in the abaxial epidermis at the base of the leaf blade, evident by the formation of elongated giant cells. Time-lapse imaging and developmental genetics further revealed that the establishment of adult leaf shape is tightly associated with the longitudinal cell expansion of giant cells, accompanied by a prolonged cell proliferation phase in their vicinity. Our results thus provide a plausible cellular mechanism for heteroblasty in Arabidopsis, and contribute to our understanding of anisotropic growth in plants.

Cerebral neoplasms like gliomas may cause intracranial pressure increasing, neural tract deviation, infiltration, or destruction in peritumoral areas, leading to neuro-functional deficits. Novel tracking technology, such as DTI, can objectively reveal and visualize three-dimensional white matter trajectories; in combination with intraoperative navigation, it can help achieve maximum resection whilst minimizing neurological deficit. Since the reconstruction of DTI raw data largely relies on the technical engineering and anatomical experience of the operator; it is time-consuming and prone to operator-induced bias. Here, we develop new user-friendly software to automatically segment and reconstruct functionally active areas to facilitate precise surgery. In this pilot trial, we used an in-house developed software (DiffusionGo) specially designed for neurosurgeons, which integrated a reliable diffusion-weighted image (DWI) preprocessing pipeline that embedded several functionalities from software packages of FSL, MRtrix3, and ANTs. The preprocessing pipeline is as follows: 1. DWI denoising, 2. Gibbs-ringing removing, 3. Susceptibility distortion correction (process if opposite polarity data were acquired), 4. Eddy current and motion correction, and 5. Bias correction. Then, this fully automatic multiple assigned criteria algorithms for fiber tracking were used to achieve easy modeling and assist precision surgery. We demonstrated the application with three language-related cases in three different centers, including a left frontal, a left temporal, and a left frontal-temporal glioma, to achieve a favorable surgical outcome with language function preservation or recovery. The DTI tracking result using DiffusionGo showed robust consistency with direct cortical stimulation (DCS) finding. We believe that this fully automatic processing pipeline provides the neurosurgeon with a solution that may reduce time costs and operating errors and improve care quality and surgical procedure quality across different neurosurgical centers.

Advanced oxidation of antibiotic tetracycline (TC) is becoming an accessible and efficient technology. The removal of TC from the complex wastewater needs to be lucubrated. In this study, a TC removal system involving degradation and adsorption was established. TC degradation was accomplished by enhanced advanced oxidation via the addition of sodium persulfate (SP) and biochar into simulated wastewater containing Mn

Background: The flow rate distribution in the flat tubes of a micro-channel evaporator is essential for its heat transfer performance. Due to a large number of flat tubes in a microchannel evaporator, the flow rate distribution is often difficult to determine. Objective: An evaporator test rig was constructed to study the quantification of the refrigerant mass flow rate distribution in a two-pass evaporator without destroying its structure. Methods: A heat transfer performance test rig for a two-pass evaporator was utilized. Subcooled refrigerant R134a was pumped into the inlet header, and infrared thermography was used to obtain the cloud map of the wall temperature distribution on the surface of the evaporator. The flow rate distribution in each flat tube was calculated based on an analysis that combines the heat balance between the air side and the refrigerant side with the effectiveness-Number of Transfer Units (ε- NTU) method. Results: The flow rate distribution was found to be in good agreement with the evaporator wall temperature distribution.The difference between the calculated and measured total mass flow rates was less than 15.9%, which proves that the method is simple and effective. And the unevenness of flow rate distribution in the 1st and 2nd pass is 0.13 and 0.32, respectively. Conclusion: This method is simple and effective, and does not destroy the structure of the microchannel evaporator. However, it is only suitable for cases in which there exists a subcooled zone in a pass, and is not applicable to a pass in which the refrigerant is only in a single-phase or a twophase state.

Multicellular organisms undergo several developmental transitions during their life cycles. In contrast to animals, the plant germline is derived from adult somatic cells. As such, the juvenility of a plant must be reset in each generation. Previous studies have demonstrated that the decline in the levels of miR156/7 with age drives plant maturation. Here we show that the resetting of plant juvenility during each generation is mediated by de novo activation of MIR156/7 in Arabidopsis. Blocking this process leads to a shortened juvenile phase and premature flowering in the offspring. In particular, an Arabidopsis plant devoid of miR156/7 flowers even without formation of rosette leaves in long days. Mechanistically, we find that different MIR156/7 genes are reset at different developmental stages through distinct reprogramming routes. Among these genes, MIR156A, B and C are activated de novo during sexual reproduction and embryogenesis, while MIR157A and C are reset upon seed germination. This redundancy generates a robust reset mechanism that ensures accurate restoration of the juvenile phase in each plant generation.

Weed species are detrimental to crop yield. An understanding of how weeds originate and adapt to field environments is needed for successful crop management and reduction of herbicide use. Although early flowering is one of the weed trait syndromes that enable ruderal weeds to overcome frequent disturbances, the underlying genetic basis is poorly understood. Here, we establish Cardamine occulta as a model to study weed ruderality. By genome assembly and QTL mapping, we identify impairment of the vernalization response regulator gene FLC and a subsequent dominant mutation in the blue-light receptor gene CRY2 as genetic drivers for the establishment of short life cycle in ruderal weeds. Population genomics study further suggests that the mutations in these two genes enable individuals to overcome human disturbances through early deposition of seeds into the soil seed bank and quickly dominate local populations, thereby facilitating their spread in East China. Notably, functionally equivalent dominant mutations in CRY2 are shared by another weed species, Rorippa palustris, suggesting a common evolutionary trajectory of early flowering in ruderal weeds in Brassicaceae.

Optimal treatment of patients with high Spetzler-Martin (S-M) grade brain arteriovenous malformations (BAVMs) remains controversial. Few studies have investigated outcomes in such patients treated in a hybrid operating room (hOR).To examine outcomes of one-stop hybrid BAVM treatment in patients with high-grade lesions.We prospectively enrolled patients with high-grade BAVMs (S-M grade ≥3) aged 18-65 years who underwent one-stop hybrid BAVM treatment at our hospital between October 2016 and March 2021. High-grade BAVM patients who underwent surgery from 2010 to 2016 served as historical controls.Forty-one high-grade BAVM patients underwent one-stop hybrid treatment in a hOR. Sixty-one propensity score-matched patients comprised the historical control group. The groups did not significantly differ in patient and BAVM characteristics. Intraoperative angiography in four patients of the hOR group demonstrated residual nidus that required further immediate resection. Main procedural complications included hemorrhage, neurologic deficit, and seizure. In the historical control group, diffuse angioarchitecture and arteriovenous fistula were independent risk factors for incomplete resection.One-stop hybrid BAVM treatment is safe and effective for removal of high-grade BAVMs, especially those with diffuse or complex angioarchitecture. Preoperative embolization can effectively reduce blood flow while preserving motor and language function. The combined application of functional magnetic resonance imaging, electrophysiological monitoring, and awake craniotomy can successfully avoid causing neurological injury.

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Trimetazidine exhibits great therapeutic potential in cardiovascular diseases and mitochondria-mediated cardioprotection by trimetazidine has been widely reported. In this study, to enhance its cardioprotection, the triphenylphosphonium-based modification of trimetazidine was conducted to deliver it specifically to mitochondria. Fifteen triphenylphosphonium (TPP) conjugated trimetazidine analogs were designed and synthesized. Their protective effects were evaluated in vivo using a tert-butyl hydroperoxide (t-BHP) induced zebrafish injury model. Structure-activity relationship correlations revealed the best way to couple the TPP moiety to trimetazidine, and led to a new conjugate (18a) with enhanced therapeutic properties. Compared to trimetazidine, 18a effectively protects against heart injury in the zebrafish model at a much lower concentration. Further study in t-BHP treated zebrafish and H9c2 cells demonstrated that 18a protects against cardiomyocyte death and damage by inhibiting excessive production of ROS, maintaining mitochondrial morphology, and preventing mitochondrial dysfunction. Consequently, 18a can be regarded as a potential therapeutic agent for cardioprotection.

Glioblastoma (GBM) is an aggressive primary brain tumor in adults featured with low overall survival (OS) of around 10-16 months, which is estimated to cause about 200,000 deaths related to the tumors of central nervous systems every year. Therefore, precise therapy on newly diagnosed GBM and increase median OS through concurrent tumor treating fields (TTFields) and chemoradiotherapy (the standard-of-care treatment proposed by NCCN) is of great significance. Though introducing latex-free sponge media was reported beneficial for improving concurrent TTFields and chemoradiotherapy efficacy on GBM, the specific enhancement mechanism and physical/chemical parameters of sponge media has not been studied as far as we know. Herein, different latex-free polyurethane sponges were selected based on SPARE phase II clinical research to investigate their impact on the concurrent TTFields and chemoradiotherapy efficacy on GBM. As computed tomography (CT) imaging of tumor and radiation dose are two vital factors for radiotherapy, the Hounsfield unit (HU) values of sponges were tested under Micro-CT firstly and the results suggest that the sponges with HU value lower than -750 have almost no impact on CT image, and clearer CT image is obtained upon the sponge with lower HU value. Moreover, eight clinical IMRT/VMAT plans were selected randomly and delivered into the bare (as a reference) or each-of-samples-surrounded CIRS head phantom with built-in EBT film to evaluate dosimetry effect. Film-based Gamma Passing Rate (2%/2 mm criteria, 20% threshold) analysis indicates that all the dose distributions upon three sponges (99.55±0.23, 99.54±0.22 and 99.59±0.19, respectively) are in good consistence with that over the reference (99.31%~99.98%). Importantly, the enhancement mechanism of latex-free sponge on concurrent TTFields and radiotherapy efficacy was studied and it corroborated that the introduced sponge could reduce the artifacts of target delineation generated in the presence of transducer array, decrease the position error of transducer array movement/replacement on scalp, lower constrictive injury during TTFields therapy (especially for locating transducer array position upon CT imaging), and reduce the adverse event of TTFields including irritant or allergic contact dermatitis caused by transducer array in the period of radiotherapy. This work corroborates that introducing low-HU-value sponge media into concurrent TTFields and chemoradiotherapy for GBM is a promising strategy to enhance therapy efficacy and thus improve or maintain the quality of patients’ life. Citation Format: Jiajun Zheng, Huanfeng Zhu, Wenjie Guo, Jiahao Guo, Chechen Cao, Li Sun, Geng Xu, Zhi Wang, Baoying Dai, Ning Gu, Xia He. Investigation of sponge property for enhanced concurrent tumor treating fields and radiotherapy for glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2825.

Iron is one of the most important strategic materials in national production, and the demand for iron ore is huge in the world. High quality iron ore reserves have been almost exhausted, and it is necessary to develop a technology that utilizes low-grade iron ore. Limonite is a representative low-grade iron ore due to its complex mineral and elemental composition. In this paper, the union process was employed to separate the iron elements in low-grade limonite. Firstly, a rough iron concentrate was obtained under 1.0 T of magnetic field intensity and −0.074 mm > 94.84% of grinding fineness; then, the rough iron concentrate was magnetization roasted under a temperature of 700 °C, 60 min of retention time, 3 wt% of biochar consumption, and 0.15 T of magnetic field intensity. The grade of iron concentrate was 59.57% and the recovery of iron was 90.72%. Finally, the red iron pigment was produced via a high temperature hydrothermal method in order to increase the additional value of this ultra-low-grade limonite. The optimal parameters were 10.0 g/L of solution acidity, a 200 °C reaction temperature, 5 h of reaction time, and a 6:1 solid-to-liquid ratio. The reaction mechanism was also discussed.

Step detection is very important for the foot-mounted Pedestrian Dead Reckoning (PDR) system. To deal with the false detection caused by variant stepping modes and occasional disturbance, a novel robust step detection algorithm is proposed. The proposed algorithm detects the number of steps and zero-velocity phase using data from inertial sensors mounted on the user’s foot. It includes two parts: a novel anti-fault detection algorithm and a novel zero-velocity detection method, which are used to reduce the over-detection and miss-detection of steps, respectively. Field tests show that the proposed approach is robust under varying motion speeds in different step modes for different persons and the average accuracy of the proposed algorithm is 99.94% in all motion modes, which significantly exceeds conventional estimation approaches in terms of step detection accuracy.

OBJECTIVES Given the increasing importance of patient’s perspective in adverse events reporting, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE™) has been proposed as new PRO measures in oncology; however, its implementation has not yet been evaluated in glioma patients, and standardized selection process of priority symptom terms has not been applied. METHODS A total of 16 experts (13 neurosurgeons, 2 radiotherapists, 1 psychiatrist) from 14 medical centers in China were invited to participate in a consensus-seeking 2-round online Delphi survey. Participants rated the level of their agreement with each symptom term likely to occur during adult diffuse gliomas treatment on a 5-point Likert scale. Terms not reaching consensus over the first round were modified in the second rounds. Consensus was defined as content validity index (CVI) > 0.78，coefficient of variation (CV)< 0.35 and average Likert score > 3.00. RESULTS Experts reached a consensus on 21 PRO-CTCAE™ symptom terms in the first Delphi round, and 10 terms in the second round. Likert scale scoring among all experts showed significant consistency (Round 1: Kendall’s W= 0.415，p＜0.001; Round 2: Kendall’s W = 0.351，P＜0.001). The 31 terms (38.75%) screened out of all 78 terms covered neurological symptoms(n=7), psychiatric symptoms(n=6), dermatological symptoms(n=6), gastrointestinal symptoms(n=5) and other common postoperative systemic symptoms of glioma patients. CONCLUSIONS We identified a customized PRO-CTCAE™ questionnaire containing a core set of priority symptom terms for the adult diffuse glioma through a 2-round Delphi survey. Next, a prospective, multi-center, real-word study would be performed to assess the validity, reliability and responsiveness of the customized PRO-CTCAE™ for adult diffuse glioma patients in Chinese population (VERONICA).

Purpose Lung cancer is the leading cause of cancer-related mortality. STEAP1 and STEAP2 are overexpressed in various cancers. The purpose of this study was to evaluate the expression and prognostic value of STEAP1 and STEAP2 in patients with lung cancer. Methods The mRNA expression and protein expression of STEAP1 and STEAP2 and their prognostic characteristics were examined using Oncomine, GEPIA, and Kaplan-Meier (KM) plotters. The correlation analysis of STEAP1 and STEAP2 gene and protein levels was conducted using GeneMANIA and STRING. KEGG pathway analysis was used to explore the related signal pathways of STEAP 1 and STEAP2. Immunohistochemical methods were used to compare the expression of STEAP2 in normal lung and non-small cell lung cancer (NSCLC) tissues. Real-time quantitative polymerase chain reaction, western blotting, and immunocytochemistry were used to evaluate the expression of STEAP1 and STEAP2 in three lung cancer cell lines and normal lung epithelial cell lines. Results Analysis of the Oncomine database and GEPIA showed that STEAP1 was upregulated and STEAP2 was downregulated in lung cancer tissue, and both expressions were related to the clinical stage of lung cancer. Immunohistochemical analysis showed that STEAP1 protein expression was significantly upregulated in lung cancer compared to that in adjacent tissues. The expression of STEAP1 was positively correlated with the migration and invasion abilities of lung cancer cells. Compared with paracancer tissues, the expression of STEAP2 protein in lung cancer was significantly downregulated and was correlated with the histological grade of squamous cell carcinoma, pathological classification of adenocarcinoma, tumor, lymph node, and metastasis clinical stage, and lymph node metastasis. The expression of STEAP2 was negatively correlated with the migration and invasion abilities of lung cancer cells. The KM curve showed that the downregulation of STEAP1 expression and upregulation of STEAP2 expression were related to a good lung cancer prognosis. Conclusion STEAP1 and STEAP2 are expected to be potential diagnostic and prognostic markers for lung cancer, which may provide more accurate prognostic indicators for lung cancer.

Background Transcription factors (TFs) play central roles in regulating gene expression. With the rapid growth in the use of high-throughput sequencing methods, there is a need to develop a comprehensive data processing and analyzing framework for inferring influential TFs based on ChIP-seq/ATAC-seq datasets. Results Here, we introduce FindIT2 (Find Influential TFs and Targets), an R/Bioconductor package for annotating and processing high-throughput multi-omics data. FindIT2 supports a complete framework for annotating ChIP-seq/ATAC-seq peaks, identifying TF targets by the combination of ChIP-seq and RNA-seq datasets, and inferring influential TFs based on different types of data input. Moreover, benefited from the annotation framework based on Bioconductor, FindIT2 can be applied to any species with genomic annotations, which is particularly useful for the non-model species that are less well-studied. Conclusion FindIT2 provides a user-friendly and flexible framework to generate results at different levels according to the richness of the annotation information of user’s species. FindIT2 is compatible with all the operating systems and is released under Artistic-2.0 License. The source code and documents are freely available through Bioconductor (https://bioconductor.org/packages/devel/bioc/html/FindIT2.html).

To better solve the filtering problem of transfer alignment with an inaccurate measurement noise covariance matrix, a novel computationally efficient version of existing variational adaptive Kalman filter is proposed in this paper, in which an equivalent variational iteration process of the measurement noise covariance matrix is derived. The proposed filter is identical to the existing variational adaptive Kalman filter, but the total computational complexity of algorithm implementation is significantly reduced, which facilitates the application of variational adaptive Kalman filter to transfer alignment. Simulation and experiment results of transfer alignment demonstrate that the computational complexity of the proposed filter is reduced by 55.4% as compared with existing variational adaptive Kalman filter.

A series of mitochondria-targeted triphenylphosphonium conjugated C-3 modified betulin were synthesized and evaluated against tumor cells. As a result, a new derivative 13 i, the conjugate of 3-O-(3'-acetylphenylacetate)-betulin with triphenylphosphonium, was identified as the one with the best anti-tumor effect. Conjugate 13 i significantly inhibited HCT116 cells with IC

Increasing evidence shows that the early onset of puberty in female offspring may be caused by maternal prenatal exposure to bisphenol A (BPA) during pregnancy; however, the critical time window of maternal prenatal BPA exposure remains unknown. Here, we identify the critical time window of gestational BPA exposure that induces early onset of puberty in female offspring. Pregnant CD-1 mice were gavaged with BPA (8 mg/kg) daily during the early gestational stage (GD1-GD6), middle gestational stage (GD7-GD12) or late gestational stage (GD13-GD18). We show that maternal BPA exposure during the early and middle gestational stages could advance the vaginal opening time and increase the serum levels of kisspeptin-10 and GnRH in the female offspring at PND 34. Mechanistically, maternal BPA exposure during early and middle gestation could significantly increase CpG island methylation in the Eed gene promoters but reduce the mRNA expression of Eed in the hypothalamus tissues of the female offspring. In conclusion, the critical period of maternal BPA exposure-induced early onset of puberty in female offspring is early and middle gestation; this BPA-induced early onset of puberty might be partly attributed to epigenetic programming of the Eed gene in the hypothalamus. This study provides important insights regarding the relationship and the mechanisms between BPA and offspring pubertal development.

The placement of left ventricular (LV) pacing lead at the latest activation sites with viable myocardium confers better cardiac resynchronization therapy (CRT) response ([1–3][1]). However, placing LV lead at the appropriate site remains a challenge for achieving an adequate CRT response. This

DNA methylation affects gene expression and maintains genome integrity. The DNA-dependent RNA polymerase IV (Pol IV), together with the RNA-dependent RNA polymerase RDR2, produces double-stranded small interfering RNA precursors essential for establishing and maintaining DNA methylation in plants. We determined the cryo–electron microscopy structures of the Pol IV–RDR2 holoenzyme and the backtracked transcription elongation complex. These structures reveal that Pol IV and RDR2 form a complex with their active sites connected by an interpolymerase channel, through which the Pol IV–generated transcript is handed over to the RDR2 active site after being backtracked, where it is used as the template for double-stranded RNA (dsRNA) synthesis. Our results describe a ‘backtracking-triggered RNA channeling’ mechanism underlying dsRNA synthesis and also shed light on the evolutionary trajectory of eukaryotic RNA polymerases.

Significance Why the developmental transitions of multicellular organisms are unidirectional and how the rate of these transitions is determined are biological mysteries. Earlier reports have shown that both animals and plants utilize microRNA (miRNA) as a timer in regulating their developmental transitions. However, how age temporally regulates the abundance of these miRNAs is poorly understood. In plants, the progressive decline in miR156 triggers the appearance of adult traits. Here, we show that cell division in the apical meristem is a trigger for miR156 decline. The transcriptional decline in MIR156C along with cell division in the apical meristem contributes to plant maturation. This simple model explains why the developmental transitions of a plant are unidirectional and inevitable under normal growth conditions.

ObjectiveTumor metabolism has always been the focus of cancer research. SLC16A1, as a key factor in catalysis of monocarboxylate transport across the plasma membrane, has been found to be associated with the occurrence and metastasis of a variety of cancers, but its prognostic significance and mechanism in different tumors are still unclear.MethodsBased on the gene expression matrix and clinical information of human cancer tissues acquired from TCGA and GTEX databases, the differential expression of SLC16A1 in different tumors and normal tissues was analyzed. To confirm the association between its expression, the mutation of MMRS gene, and the expression level of DNMTs. Univariate Cox regression was applied to analyze the association between SLC16A1 expression and patient prognosis. The effect of SLC16A1 expression on patient survival was examined by Kaplan Meier analysis. GSEA was used to identify related signaling pathways.ResultsThe expression of SLC16A1 was differentially expressed in most tumors, especially in the urinary tract where it is commonly highly expressed, and differential expression of SLC16A1 in different clinical stages. SLC16A1 expression was significantly positively correlated with MMRS gene mutation and DNMTS expression. Moreover, high SLC16A1 expression was associated with poorer overall survival (OS) and progression-free survival (PFS) in urological cancers. In particular, the results of the enrichment analysis showed that SLC16A1 was associated with processes such as cell adhesion and many signaling pathways affecting cell cycle were significantly enriched in the group with high-expressed SLC16A1.ConclusionSLC16A1 expression was upregulated in urological cancer. SLC16A1 may promote tumor development by regulating the epigenetic process of urological cancer and demonstrated a great potential as a prognostic biomarker of urological cancer patients.

The crack closure phenomenon significantly influences low cycle fatigue (LCF) crack growth. The crack closure theory deems that a crack can grow only when the applied load is greater than the fatigue crack opening and closing loads. The revised crack closure theory proposed in this paper provides a new understanding of crack growth: It is no longer the range of stress intensity factor ΔK that controls the crack growth rate, but the effective stress intensity factor ΔKeff. Therefore, it is of great importance to study the crack closure phenomenon of LCF. A combination of experiments and the finite element method (FEM) was used to study the effect of overload on the crack closure effect, and the study was carried out using compact tensile (CT) specimens made of AH32 steel. The FEM was used to obtain the stress changes near the crack tip and the opening displacement changes in the crack trailing area after a single tensile overload, to study the intrinsic mechanism of overload on crack closure, and to obtain the LCF crack opening and closing loads by the nodal displacement method. The effect of overload on crack morphology was observed by using high-magnification electron microscopy in combination with testing.

Age and wounding are two major determinants for regeneration. In plants, the root regeneration is triggered by wound-induced auxin biosynthesis. As plants age, the root regenerative capacity gradually decreases. How wounding leads to the auxin burst and how age and wound signals collaboratively regulate root regenerative capacity are poorly understood. Here, we show that the increased levels of three closely-related miR156-targeted Arabidopsis (Arabidopsis thaliana) SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, SPL2, SPL10, and SPL11, suppress root regeneration with age by inhibiting wound-induced auxin biosynthesis. Mechanistically, we find that a subset of APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors including ABSCISIC ACID REPRESSOR1 and ERF109 is rapidly induced by wounding and serves as a proxy for wound signal to induce auxin biosynthesis. In older plants, SPL2/10/11 directly bind to the promoters of AP2/ERFs and attenuates their induction, thereby dampening auxin accumulation at the wound. Our results thus identify AP2/ERFs as a hub for integration of age and wound signal for root regeneration.

In this paper, the low cycle fatigue failure and ratcheting behavior, as well as their interaction of AH32 steel were experimentally investigated under uniaxial cyclic loading. The effects of mean stress, stress amplitude and stress ratio on the low cycle fatigue life and ratcheting strain were discussed. It was found that the ratcheting strain increased while the fatigue life decreased with the increase of mean stress and stress amplitude, and the increasing stress ratio would result in smaller ratcheting and larger fatigue life. Two kinds of failure modes, i.e. low cycle fatigue failure due to crack propagates and ratcheting failure due to large plastic strain will take place respectively. Based on the experimental results, considered the effect of ratcheting on fatigue life, a model with the maximum stress and ratcheting strain rate was proposed. Comparison with the experimental result showed that the new model provided a good prediction for AH32 steel. Keywords: Low cycle fatigue, Ratcheting, Cyclic loading, AH32 steel

Cells of eukaryotic multicellular organisms have inherent heterogeneity. Recent advances in single-cell gene expression studies enable us to explore transcriptional regulation in dynamic development processes and highly heterogeneous cell populations. In this study, using a high-throughput single-cell RNA-sequencing assay, we found that the cells in Arabidopsis root are highly heterogeneous in their transcriptomes. A total of 24 putative cell clusters and the cluster-specific marker genes were identified. The spatial distribution and temporal ordering of the individual cells at different developmental stages illustrate their hierarchical structures and enable the reconstruction of continuous differentiation trajectory of root development. Moreover, we found that each root cell cluster exhibits distinct patterns of ion assimilation and hormonal responses. Collectively, our study reveals a high degree of heterogeneity of root cells and identifies the expression signatures of intermediate states during root cell differentiation at single-cell resolution. We also established a web server (http://wanglab.sippe.ac.cn/rootatlas/) to facilitate the use of the datasets generated in this study.

The present study aims to investigate the risk factors for urosepsis and the diagnostic and prognostic values of the bone morphogenetic protein endothelial cell precursor-derived regulator (BMPER) in patients with urosepsis following ureteroscopic lithotripsy. A total of 305 patients with unilateral ureteral obstruction caused by calculi were included in the study. Patients were divided into three groups, namely, high, medium, and low perfusion pressure groups. The serum C-reactive protein, procalcitonin, lactate (LAC), and BMPER were measured after operation. A logistic regression model was used to assess the risk factors for postoperative urosepsis. The relationships of BMPER with laboratory parameters were explored with a multiple linear regression model. Receiver operating characteristic (ROC) curves were used to diagnosis urosepsis. The cumulative incidence of the adverse events after operation was calculated and compared by log-rank test. Forty-five patients (14.8%) had an episode of urosepsis after operation. Irrigation pressure was an independent risk factor for urosepsis. LAC and sequential organ failure assessment (SOFA) were associated with BMPER after operation. The area under curve value of BMPER for urosepsis was 0.829 (95% confidence interval [CI], 0.773 to 0.884). Uroseptic patients with higher BMPER concentration exhibited more adverse outcome. BMPER possesses valuable discriminative capacity for urosepsis and is a strong predictor of adverse outcome in patients with urosepsis.

Context: Ursolic acid (UA; 3β-hydroxy-urs-12-en-28-oic acid), one of the pentacyclic triterpenoids found in various plants and herbs, possesses some beneficial effects under pathological conditions, including combating hepatic fibrosis. Objective: This study investigates the effects of UA on renal tubulointerstitial fibrosis in vivo and in vitro. Materials and methods: In vivo, 24 male C57BL6 mice were divided into four groups. Eighteen mice were subjected to unilateral ureteral obstruction (UUO) and the remaining six sham-operated mice served as control. UUO mice received either vehicle or UA (50 or 100 mg/kg) by gastric gavage for 6 days. In vitro, HK-2 cells were treated with 10 or 50 μM UA and 10 ng/mL recombinant human transforming growth factor-β1 (TGF-β1). The molecular mechanisms of fibrosis were investigated. Results: UUO induced marked interstitial collagen I and fibronectin deposition and epithelial-mesenchymal transition (EMT), as evidenced by increased α-smooth muscle actin (α-SMA) and decreased E-cadherin. However, UA treatment significantly reduced collagen I and fibronectin accumulation in the fibrotic kidney. UA treatment also decreased α-SMA and preserved E-cadherin in vivo. In vitro, TGF-β1-treated HK-2 cells demonstrated elevated α-SMA, snail1, slug, TGF-β1, and p-smad3, as well as diminished E-cadherin. UA pretreatment prevented E-cadherin loss and diminished α-SMA expression in HK-2 cells. UA downregulated mRNA expression of snail1 and slug. UA also lowered TGF-β1 protein expression and p-Smad3 in HK-2 cells. Conclusions: UA attenuated renal tubulointerstitial fibrosis by inhibiting EMT, and such inhibition may be achieved by decreasing profibrotic factors. UA may be a novel therapeutic agent for renal fibrosis.

The present work aims to investigate the fatigue crack growth behavior of AH-32 steel with the experimental application of CTOD. A series of fatigue crack growth experiments on AH32 steel were conducted by a constant amplitude loading with a single/two tensile overload. The fatigue crack growth behavior of AH32 steel with overload was explored in a detailed manner. The retardation effect of the overload with different overload ratio and overload spacing were quantified by crack growth rate. Moreover, a different relationship between d a / d N and CTOD for all tests was obtained. In a parallel study, the elastic-plastic numerical model was developed to investigate the crack closure effect expressed in the form of crack opening load and CTOD. Experimental results show that the CTOD is able to characterize and correlate the fatigue crack growth at large scale yielding. This work is intended to contribute to a better understanding of the different mechanisms driving fatigue crack growth.

The widely cultivated medicinal and ornamental plant sage (Salvia officinalis L.) is an evergreen shrub of the Lamiaceae family, native to the Mediterranean. We assembled a high-quality sage genome of 480 Mb on seven chromosomes, and identified a biosynthetic gene cluster (BGC) encoding two pairs of diterpene synthases (diTPSs) that, together with the cytochromes P450 (CYPs) genes located inside and outside the cluster, form two expression cascades responsible for the shoot and root diterpenoids, respectively, thus extending BGC functionality from co-regulation to orchestrating metabolite production in different organs. Phylogenomic analysis indicates that the Salvia clades diverged in the early Miocene. In East Asia, most Salvia species are herbaceous and accumulate diterpenoids in storage roots. Notably, in Chinese sage S. miltiorrhiza, the diterpene BGC has contracted and the shoot cascade has been lost. Our data provide genomic insights of micro-evolution of growth type-associated patterning of specialized metabolite production in plants.

Summary Open or accessible regions of the genome are the primary positions of binding sites for transcription factors and chromatin regulators. Transposase-accessible chromatin sequencing (ATAC-seq) can probe chromatin accessibility in the intact nucleus. Here, we describe a protocol to generate ATAC-seq libraries from fresh Arabidopsis thaliana tissues and establish an easy-to-use bioinformatic analysis pipeline. Our method could be applied to other plants and other tissues and allows for the reliable detection of changes in chromatin accessibility throughout plant growth and development. For complete details on the use and execution of this protocol, please refer to Wang et al. (2020)., Graphical Abstract, Highlights • A protocol to generate ATAC-seq libraries from fresh plant tissues • An easy-to-use bioinformatic analysis pipeline for ATAC-seq • Identification of differentially accessible peaks by ATAC-seq, Open or accessible regions of the genome are the primary positions of binding sites for transcription factors and chromatin regulators. Transposase-accessible chromatin sequencing (ATAC-seq) can probe chromatin accessibility in the intact nucleus. Here, we describe a protocol to generate ATAC-seq libraries from fresh Arabidopsis thaliana tissues and establish an easy-to-use bioinformatic analysis pipeline. Our method could be applied to other plants and other tissues and allows for the reliable detection of changes in chromatin accessibility throughout plant growth and development.

This paper proposes a single-stage three-phase quasi-Z-source inverter with strong boost ability and three new kinds of simple boost modified space vector modulation (SVM) strategies. Compared with the traditional quasi-Z-source inverter, the quasi-Z-source inverter with the simple boost modified SVM strategy has the advantages of maximizing the use of zero vector action time, small impedance network volume, low switching loss and voltage stress, and strong boosting ability. The performance parameters of the inverter with different modulation strategies were deeply investigated and compared, including the switching losses of the inverter bridge and the impedance network diode, the loss of the energy storage inductor. The experimental results of the 1.2kVA 96VDC/220V50Hz AC inverter prototype verified the feasibility of the inverter and the correctness of the theoretical analysis, determined a simple boost modified SVM strategy with optimal performance, which lay the key technical foundations on new energy power generation systems such as photovoltaic, wind.

OBJECTIVE: To observe the curative effects of four kinds of plant extracts nasal spray mixture (myrtle oil, hyaluronic acid, fucoidan, anthocyanin) on 161 patients with nasal mucosa dryness, hemorrhae and erosion. METHODS: ① Diagnosis: patients with nasal dryness, erosive and hemorrhae nasal septum mucosa confirmed by patients' complaints and nasal endoscopic test; ② Evaluation: the severity of subjective symptoms was evaluated by VAS score method from 0 to 10 points; the degree of mucosal lesions was divided into 0-8 points by nasal endoscopic test. ③ Intranasal Intranasal administration: 2 times per-day with 2 sprays on each side of the nasal cavity, and no less than 6-8 weeks. In the patients which with allergic rhinitis were also given conventional oral administration of montelukast at the same time. ④ Follow up and curative effect evaluation: VAS and nasal endoscopic test scores that before and after treatment was statistically processed; the patients' own how feels the treatment were evaluated; finally, doctor made the final evaluation based on the combined results of subjective and objective evaluation results before and after treatment, the patients' satisfaction with treatment effect. RESULTS: ① There were significant differences in VAS scores of 161 patients before and after treatment (P < 0.01).② There were statistically significant differences in nasal endoscopic test scores of 104 patients before and after treatment (P < 0.01). ③ Patients' satisfaction survey showed the satisfied with the compliance, tolerance and treatment effect was 95%. CONCLUSION: The mixed nasal spray of four plant extracts can effectively improve the dryness, hemorrhae and erosion of nasal mucosal.

Esophageal cancer is still one of the most common cancers in the world. We review the appropriate treatments at different stages of esophageal cancer and also analyze the advantages and disadvantages of these treatments. The prognosis and recovery of different treatment regimens are further discussed. In particular, post-operative complications are the major causes of high mortality derived from the esophageal cancer. Therefore, we particularly discuss the main complications resulting in high mortality after surgery of esophageal cancer, and summarize their risk factors and treatment options. Background As the common cancer, the complications of esophageal cancer after surgery have been not obtained systematic treatment strategy, focusing on treatment regimens based on the different stages of esophageal cancers. Methods and overview This paper systematically summarizes the appropriate treatment strategies for different stages of esophageal cancers, and their advantages and disadvantages. We particularly focus on the postoperative survival rate of patients and postoperative complications, and discuss the causes of high mortality risk factors after surgery. The risk factors of death and corresponding treatment methods are further summarized in this study. Conclusion Postoperative complications is the main cause responsible for the hard cure of esophageal cancers. The existing literatures indicate that postoperative anastomotic fistula is one of the most important complications leading to death, while it has not received much attention yet. We suggest that anastomotic fistula should be detected and dealt with early by summarizing these literatures. It is, therefore, necessary to develop a set of methods to predict or check anastomotic fistula in advance.

MiR-146a has been shown to negatively regulate innate immune, inflammatory response and antiviral pathway, however, its role in the tolerogenic responses remains largely unknown. This study aimed to investigate the role of miR-146a in the OVA-induced allergic inflammation of dendritic cells (DCs).Bone marrow-derived DCs (BMDCs) were treated with OVA (100 µg/ml) for 24 h. MiR-146a expressions were assessed by quantitative RT-PCR. BMDCs were transfected with miR-146a mimics or inhibitor. Cell surface markers were analyzed by flow cytometry. Cytokine levels were determined by ELISA assay. Mixed lymphocyte culture assay was adopted to assess CD4 + T-cell differentiation. The 3' UTR luciferase reporter assay was utilized to determine the miRNA target sequence.OVA treatment significantly up-regulated miR-146a in BMDCs in a dose- and time-dependent manner. In the OVA-treated DCs, overexpression of miR-146a (mimics transfection) down-regulated the surface markers (CD80, CD86) and increased production of anti-inflammatory cytokines TGF-β1 and IL-10 but decreased pro-inflammatory cytokine IL-12. MiR-146a overexpression promoted immature DC to induce regulatory T cells (Treg) differentiation. By contrast, transfection of miR-146a inhibitor into DC exhibited the opposite trends. Notch1 was a direct target of miR-146a, and Notch1 knock-down induced similar effects as miR-146a mimics transfection in BMDCs. Moreover, the effect of miR-146a inhibitor on OVA-induced DC was attenuated by Notch1 knock-down.miRNA-146a promoted tolerogenic properties of DCs, at least partially, through targeting Notch1 signaling.

Backgroud: Lipopolysaccharide (LPS) exposure can induce Leydig cell dysfunction. This study aims to investigate whether adrenomedullin (ADM) rescues the steroidogenic functions of Leydig cells by suppressing TGF-β1 via PI3K/Akt/ GSK-3β/β-catenin signaling. Methods: Rats were given LPS and injected with an adeno-associated virus vector that expressed ADM (Ad-ADM). Plasma concentrations of testosterone and estradiol were measured. Testes were collected and analyzed by gene expression profiling, western blot and immunofluorescence staining. Primary Leydig cells were treated with various concentrations of LPS and ADM. Cell viability and proliferation and medium concentrations of testosterone and estradiol were detected. Gene expression and protein l evels were detected for steroidogenic enzymes, TGF-β1, PI3K, Akt, GSK-3β and β-catenin. Role of ADM in the regulation of TGF-β1 promoter was confirmed by ChIP and Co-IP. Finding: ADM reversed the decreased number of Leydig cells and plasma concentrations of testosterone and estradiol by rescuing the expression of SF-1, 17β-HSD, LRH1, CYP19, StAR, P450scc, 3β-HSD and CYP17. ADM inhibited the LPS-induced cytotoxicity and reversed the cell proliferation by rescuing the expression of Ki-67. ADM also rescued the expression of SF-1, 17β-HSD, LRH1, CYP19, StAR, P450scc, 3β-HSD and CYP17 and the medium concentrations of testosterone and estradiol in LPS-induced Leydig cells. ADM ameliorated LPS-induced TGF-β1 expression in LPS-exposed Leydig cells. ADM enhanced the phosphorylation of PI3K, Akt and GSK-3β but reduced the activation of β-catenin which interacted with TCF4 and then bound to TGF-β1 gene promoter. Interpretation: ADM may rescue the steroidogenic functions of Leydig cells by suppressing TGF-β1 via the PI3K/Akt/GSK-3β/β-catenin signaling. Funding Statement: This study was supported by the National Science Foundation of China, Beijing, China (Grant Nos.: 81402100, 81401190), Natural Science Foundation of Hunan Province, China (Grant Nos.: 2019JJ40269, 2020JJ4542), Foundation for “Young Medical Talents” of Jiangsu Province, China (Grant No.: QNRC2016840), and Key Guidance Project of University of South China, China (Grant No.: USCKF201902K01). Declaration of Interests: The authors declare no competing financial interests with regard to the publication of this paper. Ethics Approval Statement: Procedures involving rats were approved by the Local Ethics Committee for the Care and Use of Laboratory Animals of University of South China and were conducted in accordance with the national guidelines and protocols of the National Institutes of Health.

Additional file 7: Figure S3. Meta-analysis on antral follicle count in non-RCTs: the ultra-long protocol versus long protocol (A), and the ultra-long protocol versus short protocol (B).