Spectrum-effect relationship between HPLC fingerprints and antioxidant activity of Qi-Fu-Yin based on multiple statistical correlation analysis.

INTRODUCTION: Qi-Fu-Yin has been used to treat Alzheimer's disease (AD) in China. Oxidative stress has been recognized as a factor in AD progress. To date, there is no quality control method to ensure batch-to-batch consistency of Qi-Fu-Yin, and the potential antioxidant compounds in Qi-Fu-Yin remain uncertain. OBJECTIVES: The aim of this study is to identify the potential antioxidant compounds of Qi-Fu-Yin and establish quality control standards for Qi-Fu-Yin. METHODS: High-performance liquid chromatography was used to establish and quantify the fingerprints of Qi-Fu-Yin from various batches. Ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) was used to identify the common peaks. Bivariate correlation analysis, partial least squares regression analysis, and gray correlation analysis were used to establish the spectrum-effect relationship. RESULTS: Forty-nine common peaks were determined through the establishment of fingerprints. Among them, 35 common peaks were preliminarily characterized. The multiple statistical correlation analysis methods identified six compounds as potential antioxidant constituents of Qi-Fu-Yin, and their antioxidant activities were validated in vitro. All six antioxidant compounds derived from two herbs. Therefore, three chemical index compounds derived from other three herbs were added to the quantitative analysis, while for two herbs, no peaks could be included. Eventually, six antioxidant constituents and three index compounds were quantitatively determined to provide a relatively comprehensive quality control for Qi-Fu-Yin. CONCLUSIONS: The study elucidated the antioxidant substance basis of Qi-Fu-Yin and provided a relatively comprehensive approach for the assay of Qi-Fu-Yin, which is a promising advance in the quality control of Qi-Fu-Yin.

Wind Aggregation Enhanced Triboelectric-Electromagnetic Hybrid Generator with Slit Effect.

It is of great significance to establish a low-cost, high-efficiency, self-powered micrometeorological monitoring system for agriculture, animal husbandry, and transportation. However, each additional detection element in the meteorological monitoring system increases the power consumption of the whole system by about 0.7 W. As a renewable energy technology, a triboelectric nanogenerator has the advantages of low price and self-powered sensing. To reduce the power consumption of the micrometeorological monitoring system, this work introduces an innovative solution: the wind-gathering enhanced triboelectric-electromagnetic hybrid generator (WGE-TEHG). Coupling the thin-film vibrating triboelectric nanogenerator (TENG) and electromagnetic generator (EMG), the TENG is used to monitor wind direction and the EMG is used to monitor wind speed and provide energy needed by the system. In particular, the TENG can be used as a self-powered sensor to reduce the power consumption of the sensing system. Besides, the TENG is used to produce slit effect to enhance the output performance of EMG. The experimental results show that the WGE-TEHG can build a self-powered natural environment micrometeorological sensing system. It can monitor the wind direction, wind speed, temperature, and relative humidity. This research has great application value for the self-powered sensing implementation of a hybrid TENG and EMG.

Applying machine learning to assess the morphology of sculpted teeth.

Background/purpose: Producing tooth crowns through dental technology is a basic function of dentistry. The morphology of tooth crowns is the most important parameter for evaluating its acceptability. The procedures were divided into four steps: tooth collection, scanning skills, use of mathematical methods and software, and machine learning calculation. Materials and methods: Dental plaster rods were prepared. The effective data collected were to classify 121 teeth (15th tooth position), 342 teeth (16th tooth position), 69 teeth (21st tooth position), and 89 teeth (43rd tooth position), for a total of 621 teeth. The procedures are divided into four steps: tooth collection, scanning skills, use of mathematical methods and software, and machine learning calculation. Results: The area under the curve (AUC) value was 0, 0.5, and 0.72 in this study. The precision rate and recall rate of micro-averaging/macro-averaging were 0.75/0.73 and 0.75/0.72. If we took a newly carved tooth picture into the program, the current effectiveness of machine learning was about 70%-75% to evaluate the quality of tooth morphology. Through the calculation and analysis of the two different concepts of micro-average/macro-average and AUC, similar values could be obtained. Conclusion: This study established a set of procedures that can judge the quality of hand-carved plaster sticks and teeth, and the accuracy rate is about 70%-75%. It is expected that this process can be used to assist dental technicians in judging the pros and cons of hand-carved plaster sticks and teeth, so as to help dental technicians to learn the tooth morphology more effectively.

Novel quantitative immunohistochemistry method using histone H3, family 3B as the internal reference standard for measuring human epidermal growth factor receptor 2 expression in breast cancer.

BACKGROUND: Immunohistochemistry (IHC) is an essential technique in surgical and clinical pathology for detecting diagnostic, prognostic, and predictive biomarkers for personalized cancer therapy. However, the lack of standardization and reference controls results in poor reproducibility, and a reliable tool for IHC quantification is urgently required. The objective of this study was to describe a novel approach in which H3F3B (histone H3, family 3B) can be used as an internal reference standard to quantify protein expression levels using IHC. METHODS: The authors enrolled 89 patients who had human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). They used a novel IHC-based assay to measure protein expression using H3F3B as the internal reference standard. H3F3B was uniformly expressed at the protein level in all tumor regions in cancer tissues. HER2 expression levels were measured with the H-score using HALO software. RESULTS: Kaplan-Meier analysis indicated that, among patients who had HER2-positive BC in The Cancer Genome Atlas data set and the authors' data set, the subgroup with low HER2 expression had a significantly better prognosis than the subgroup with high HER2 expression. Furthermore, the authors observed that HER2 expression levels were precisely evaluated using the proposed method, which can classify patients who are at higher risk of HER2-positive BC to receive trastuzumab-based adjuvant therapy. Dual-color IHC with H3F3B is an excellent tool for internal and external quality control of HER2 expression assays. CONCLUSIONS: The proposed IHC-based quantification method accurately assesses HER2 expression levels and provides insights for predicting clinical prognosis in patients with HER2-positive BC who receive trastuzumab-based adjuvant therapy.

Molecular understanding of the critical role of alkali metal cations in initiating CO2 electroreduction on Cu(100) surface.

Molecular understanding of the solid-liquid interface is challenging but essential to elucidate the role of the environment on the kinetics of electrochemical reactions. Alkali metal cations (M+), as a vital component at the interface, are found to be necessary for the initiation of carbon dioxide reduction reaction (CO2RR) on coinage metals, and the activity and selectivity of CO2RR could be further enhanced with the cation changing from Li+ to Cs+, while the underlying mechanisms are not well understood. Herein, using ab initio molecular dynamics simulations with explicit solvation and enhanced sampling methods, we systematically investigate the role of M+ in CO2RR on Cu surface. A monotonically decreasing CO2 activation barrier is obtained from Li+ to Cs+, which is attributed to the different coordination abilities of M+ with *CO2. Furthermore, we show that the competing hydrogen evolution reaction must be considered simultaneously to understand the crucial role of alkali metal cations in CO2RR on Cu surfaces, where H+ is repelled from the interface and constrained by M+. Our results provide significant insights into the design of electrochemical environments and highlight the importance of explicitly including the solvation and competing reactions in theoretical simulations of CO2RR.

Bionic Fish-Shaped Triboelectric-Electromagnetic Hybrid Generator via a Two-Stage Swing Mechanism for Water Flow Energy Harvesting and Condition Monitoring.

The water flow energy of rivers is an important renewable and clean energy that plays a vital role in human life but is challenging to harvest at low flow velocity. This work proposes a bionic fish-shaped triboelectric-electromagnetic hybrid generator (BF-TEHG) via a two-stage swing mechanism for harvesting water flow energy. It is designed to simulate the shape of fish, effectively improving its ability to utilize low-velocity water flow energy and enabling it to operate at a minimum flow rate of 0.24 m/s. Furthermore, the impact of motion parameters on electrical performance is studied. The triboelectric and electromagnetic power-generation units can generate peak powers of 0.55 and 0.34 mW in the simulated river environments with a flow velocity of 0.98 m/s. In applications, after being immersed in water for 40 days, the BF-TEHG maintains its electrical performance without reduction, indicating excellent water immersion durability. Therefore, this work proposes an efficient strategy to harvest low-velocity water flow energy and provides an acceptable candidate for monitoring water flow conditions.

The effects of irreversible electroporation triggering anti-tumor immunity and the value of its combination with immunotherapy.

Recently, interventional ablation techniques have gained prominence in tumor treatment guidelines and complement traditional approaches, such as surgery, chemotherapy, and radiotherapy. Conventional ablation techniques, such as microwave, radiofrequency, and cryoablation, have been used; however, they have certain limitations, including the risk of damaging surrounding normal tissues and the heat sink effect caused by tumor blood flow.1 Irreversible electroporation (IRE), an ablation technology independent of thermal energy, is a promising alternative.2 Clinical studies have demonstrated IRE's efficacy in treating tumors, such as pancreatic and liver tumors.3 Recent research has shown that IRE can elicit specific anti-tumor immune responses in the body.5 IRE also plays a crucial role in eliminating residual tumor cells postoperatively and preventing tumor recurrence.

Vehicle-Mounted Pavement Health Monitoring System Based on a Spring-Guide-Assisted Triboelectric Sensor.

The present pavement health monitoring is limited by a professional staff patrol. Herein, a vehicle-mounted pavement health monitoring system (VPHMS) based on a spring-guide-assisted triboelectric sensor (S-TES) is proposed, which uses the vibration generated by vehicles passing through uneven pavements to monitor the pavement damage. The VPHMS consists of S-TES, the integration module, and the terminal display module. The designed S-TES has high stability and can achieve a high linear vibration amplitude measurement within 90 mm. Moreover, the integration module is used to process signals and transmit wireless data transmission. The terminal display module is used to receive signals and display the measurement results on the screen. When a vehicle equipped with VPHMS is driven over uneven pavements, the system can accurately monitor the potholes and upheavals on the pavement in real time. This work has significant application value in fields such as pavement health monitoring and intelligent transportation.

HLF promotes ovarian cancer progression and chemoresistance via regulating Hippo signaling pathway.

Hepatic leukemia factor (HLF) is aberrantly expressed in human malignancies. However, the role of HLF in the regulation of ovarian cancer (OC) remains unknown. Herein, we reported that HLF expression was upregulated in OC tissues and ovarian cancer stem cells (CSCs). Functional studies have revealed that HLF regulates OC cell stemness, proliferation, and metastasis. Mechanistically, HLF transcriptionally activated Yes-associated protein 1 (YAP1) expression and subsequently modulated the Hippo signaling pathway. Moreover, we found that miR-520e directly targeted HLF 3'-UTR in OC cells. miR-520e expression was negatively correlated with HLF and YAP1 expression in OC tissues. The combined immunohistochemical (IHC) panels exhibited a better prognostic value for OC patients than any of these components alone. Importantly, the HLF/YAP1 axis determines the response of OC cells to carboplatin treatment and HLF depletion or the YAP1 inhibitor verteporfin abrogated carboplatin resistance. Analysis of patient-derived xenografts (PDXs) further suggested that HLF might predict carboplatin benefits in OC patients. In conclusion, these findings suggest a crucial role of the miR-520e/HLF/YAP1 axis in OC progression and chemoresistance, suggesting potential therapeutic targets for OC.

Profiling extracellular vesicle surface proteins with 10 µL peripheral plasma within 4 h.

Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non-EV components in clinical samples. Herein, we present a MEmbrane-Specific Separation and two-step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin-coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2-positive breast cancer, triple-negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.

Plant resistance against whitefly and its engineering.

Plants face constant threats from insect herbivores, which limit plant distribution and abundance in nature and crop productivity in agricultural ecosystems. In recent decades, the whitefly Bemisia tabaci, a group of phloem-feeding insects, has emerged as pests of global significance. In this article, we summarize current knowledge on plant defenses against whitefly and approaches to engineer plant resistance to whitefly. Physically, plants deploy trichome and acylsugar-based strategies to restrain nutrient extraction by whitefly. Chemically, toxic secondary metabolites such as terpenoids confer resistance against whitefly in plants. Moreover, the jasmonate (JA) signaling pathway seems to be the major regulator of whitefly resistance in many plants. We next review advances in interfering with whitefly-plant interface by engineering of plant resistance using conventional and biotechnology-based breeding. These breeding programs have yielded many plant lines with high resistance against whitefly, which hold promises for whitefly control in the field. Finally, we conclude with an outlook on several issues of particular relevance to the nature and engineering of plant resistance against whitefly.

Micro-Droplets Parameters Monitoring in a Microfluidic Chip via Liquid-Solid Triboelectric Nanogenerator.

The monitoring of micro-droplets parameters is significant to the development of droplet microfluidics. However, existing monitoring methods have drawbacks such as high cost, interference with droplet movement, and even the potential for cross-contamination. Herein, a micro-droplets monitoring method (MDMM) based on liquid-solid triboelectric nanogenerator (LS-TENG) is proposed, which can realize non-invasive and self-powered monitoring of micro-droplets in a microfluidic chip. The droplet frequency is monitored by voltage pulse frequency and a mathematical model is established to monitor the droplet length and velocity. Furthermore, this work constructs micro-droplets sensor (MDS) based on the MDMM to carry out the experiment. The coefficients of determination (R2 ) of the fitting curves of the micro-droplets frequency, length, and velocity monitoring are 0.998, 0.997, and 0.995, respectively. To prove the universal applicability of the MDMM, the micro-droplets generated by different liquid media and channel structures are monitored. Eventually, a micro-droplet monitoring system is built, which can realize the counting of micro-droplets and the monitoring of droplet frequency and length. This work provides a novel approach for monitoring micro-droplets parameters, which holds the potential to advance developments in the field of microfluidics.

Click-iG: Simultaneous Enrichment and Profiling of Intact N-linked, O-GalNAc, and O-GlcNAcylated Glycopeptides.

Proteins are ubiquitously modified with glycans of varied chemical structures through distinct glycosidic linkages, making the landscape of protein glycosylation challenging to map. Profiling of intact glycopeptides with mass spectrometry (MS) has recently emerged as a powerful tool for revealing matched information of the glycosylation sites and attached glycans (i.e., intact glycosites), but is largely limited to individual glycosylation types. Herein, we describe Click-iG, which integrates metabolic labeling of glycans with clickable unnatural sugars, an optimized MS method, and a tailored version of pGlyco3 software to enable simultaneous enrichment and profiling of three types of intact glycopeptides: N-linked, mucin-type O-linked, and O-GlcNAcylated glycopeptides. We demonstrate the utility of Click-iG by the identification of thousands of intact glycosites in cell lines and living mice. From the mouse lung, heart, and spleen, a total of 2053 intact N-glycosites, 262 intact O-GalNAc glycosites, and 1947 O-GlcNAcylation sites were identified. Click-iG-enabled comprehensive coverage of the protein glycosylation landscape lays the foundation for interrogating crosstalk between different glycosylation pathways.

Investigations into wetting and spreading behaviors of impacting metal droplet under ultrasonic vibration control.

Ultrasonic-assisted metal droplet deposition (UAMDD) is currently considered a promising technology in droplet-based 3D printing due to its capability to change the wetting and spreading behaviors at the droplet-substrate interface. However, the involved contact dynamics during impacting droplet deposition, particularly the complex physical interaction and metallurgical reaction of induced wetting-spreading-solidification by the external energy, remain unclear to date, which hinders the quantitative prediction and regulation of the microstructures and bonding property of the UAMDD bumps. Here, the wettability of the impacting metal droplet ejected by a piezoelectric micro-jet device (PMJD) on non-wetting and wetting ultrasonic vibration substrates is studied, and the corresponding spreading diameter, contact angle, and bonding strength are also discussed. For the non-wetting substrate, the wettability of the droplet can be significantly increased due to the extrusion of the vibration substrate and the momentum transfer layer at the droplet-substrate interface. And the wettability of the droplet on a wetting substrate is increased at a lower vibration amplitude, which is driven by the momentum transfer layer and the capillary waves at the liquid-vapor interface. Moreover, the effects of the ultrasonic amplitude on the droplet spreading are studied under the resonant frequency of 18.2-18.4 kHz. Compared to deposit droplets on a static substrate, such UAMDD has 31% and 2.1% increments in the spreading diameters for the non-wetting and wetting systems, and the corresponding adhesion tangential forces are increased by 3.85 and 5.59 times.

Temporal Dynamic of the Ratio between Monopartite Begomoviruses and Their Associated Betasatellites in Plants, and Its Modulation by the Viral Gene ßC1.

The begomovirus-betasatellite complex constantly threatens crops in Asia. However, the quantitative relationship between begomoviruses and betasatellites remains largely unknown. The quantities of tobacco curly shoot virus (TbCSV) and its betasatellite (TbCSB) and their ratio varied significantly in initial infection, and thereafter, the ratio tended to become constant. The TbCSB/TbCSV ratio in agrobacteria inoculum significantly affected that in plants in the initial infection but not thereafter. Null-mutation of ßC1 that encodes a multifunctional protein important for pathogenesis in TbCSB significantly reduced the TbCSB/TbCSV ratio in plants. Viral inoculum plants with higher TbCSB/TbCSV ratios promoted whitefly transmission of the virus. The expression of AV1 encoded by TbCSV, ßC1 encoded by TbCSB and the ßC1/AV1 ratio varied significantly in the initial infection and thereafter the ratio tended to become constant. Additionally, the temporal dynamics of the ratio between another begomovirus and its betasatellite was similar to that of TbCSV and was positively regulated by ßC1. These results indicate that the ratio between monopartite begomoviruses and betasatellites tend to become constant as infection progresses, and is modulated by ßC1, but a higher betasatellite/begomovirus ratio in virally inoculated plants promotes virus transmission by whiteflies. Our findings provide novel insights into the association between begomoviruses and betasatellites.

N6-Methyladenosine-Mediated Up-Regulation of FZD10 Regulates Liver Cancer Stem Cells' Properties and Lenvatinib Resistance Through WNT/ß-Catenin and Hippo Signaling Pathways.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, but there is a deficiency of early diagnosis biomarkers and therapeutic targets. Drug resistance accounts for most HCC-related deaths, yet the mechanisms underlying drug resistance remain poorly understood. METHODS: Expression of Frizzled-10 (FZD10) in liver cancer stem cells (CSCs) was identified by means of RNA sequencing and validated by means of real-time polymerase chain reaction and immunohistochemistry. In vitro and in vivo experiments were used to assess the effect of FZD10 on liver CSC expansion and lenvatinib resistance. RNA sequencing, RNA binding protein immunoprecipitation, and luciferase report assays were applied to explore the mechanism underlying FZD10-mediated liver CSCs expansion and lenvatinib resistance. RESULTS: Activation of FZD10 in liver CSCs was mediated by METTL3-dependent N6-methyladenosine methylation of FZD10 messenger RNA. Functional studies revealed that FZD10 promotes self-renewal, tumorigenicity, and metastasis of liver CSCs via activating ß-catenin and YAP1. The FZD10-ß-catenin/YAP1 axis is activated in liver CSCs and predicts poor prognosis. Moreover, FZD10-ß-catenin/c-Jun axis transcriptionally activates METTL3 expression, forming a positive feedback loop. Importantly, the FZD10/ß-catenin/c-Jun/MEK/ERK axis determines the responses of hepatoma cells to lenvatinib treatment. Analysis of patient cohort, patient-derived tumor organoids, and patient-derived xenografts further suggest that FZD10 might predict lenvatinib clinical benefit in patients with HCC. Furthermore, treatment of lenvatinib-resistant HCC with adeno-associated virus targeting FZD10 or a ß-catenin inhibitor restored lenvatinib response. CONCLUSIONS: Elevated FZD10 expression promotes expansion of liver CSCs and lenvatinib resistance, indicating that FZD10 expression is a novel prognostic biomarker and therapeutic target for human HCC.

Ultrathin ALD Aluminum Oxide Thin Films Suppress the Thermal Shrinkage of Battery Separator Membranes.

Thermal runaway is a major safety concern in the applications of Li-ion batteries, especially in the electric vehicle (EV) market. A key component to mitigate this risk is the separator membrane, a porous polymer film that prevents physical contact between the electrodes. Traditional polyolefin-based separators display significant thermal shrinkage (TS) above 100 °C, which increases the risk of battery failure; hence, suppressing the TS up to 180 °C is critical to enhancing the cell's safety. In this article, we deposited thin-film coatings (less than 10 nm) of aluminum oxide by atomic layer deposition (ALD) on three different types of separator membranes. The deposition conditions and the plasma pretreatment were optimized to decrease the number of ALD cycles necessary to suppress TS without hindering the battery performance for all of the studied separators. A dependency on the separator composition and porosity was found. After 100 ALD cycles, the thermal shrinkage of a 15 µm thick polyethylene membrane with 50% porosity was measured to be below 1% at 180 °C, with ionic conductivity >1 mS/cm. Full battery cycling with NMC532 cathodes demonstrates no hindrance to the battery's rate capability or the capacity retention rate compared to that of bare membranes during the first 100 cycles. These results display the potential of separators functionalized by ALD to enhance battery safety and improve battery performance without increasing the separator thickness and hence preserving excellent volumetric energy.

CDK4/6 inhibitor resistance: A bibliometric analysis.

Background: Cyclin-dependent kinases (CDKs) 4/6 inhibitors are a type of cell cycle regulation that prevents cell proliferation by blocking retinoblastoma protein (Rb) phosphorylation in the G1 to S phase transition. CDK 4/6 inhibitors are currently used mainly in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2) negative breast cancer in combination with endocrine therapy. However, primary or acquired resistance to drugs severely affect drug efficacy. Our study aims at summarizing and visualizing the current research direction and development trend of CDK4/6 inhibitor resistance to provide clinicians and research power with a summary of the past and ideas for the future. Methods: The Web of Science Core Collection and PubMed was searched for all included articles on CDK4/6 inhibitor resistance for bibliometric statistics and graph plotting. The metrological software and graphing tools used were R language version 4.2.0, Bibliometrix 4.0.0, Vosviewer 1.6.18, GraphPad Prism 9, and Microsoft Excel 2019. Results: A total of 1278 English-language articles related to CDK4/6 inhibitor resistance were included in the Web of Science core dataset from 1996-2022, with an annual growth rate of14.56%. In PubMed, a total of 1123 articles were counted in the statistics, with an annual growth rate of 17.41% Cancer Research is the most included journal (102/1278, 7.98%) with an impact factor of 13.312 and is the Q1 of the Oncology category of the Journal Citation Reports. Professor Malorni Luca from Italy is probably the most contributing author in the current field (Publications 21/1278, 1.64%), while Prof. Turner Nicholas C from the USA is perhaps the most authoritative new author in the field of CDK4/6 inhibitor resistance (Total Citations2584, M-index 1.429). The main research efforts in this field are currently focused on Palbociclib and Abemaciclib. Studies on drug resistance mechanisms or post-drug resistance therapies focus on MEK inhibitors and related pathways, PI3K-AKT-MTOR pathways or inhibitors, EGFR-related pathways, EGFR inhibitors, TKI inhibitors, MAPK pathways and inhibitors, and so on. Conclusion: This study provides researchers with a reliable basis and guidance for finding authoritative references, understanding research trends, and mining research neglect directions.

Changes in rhizospheric microbiome structure and soil metabolic function in response to continuous cucumber cultivation.

With the increasing reliance on intensive arable agriculture, analysis of the problems associated with continuous cropping has become a global research focus. Here, high-throughput sequencing and nontargeted metabolomics were used to evaluate the responses of soil microbial community structure and soil metabolic function to continuous cucumber cultivation (from 1 to 18 years of continuous cultivation) in greenhouses. Continuous cucumber cropping resulted in increased soil nutrient concentrations, but decreased concentrations of available nutrients. The abundance of several bacterial genera associated with nutrient cycling, such as Bacillus and Sphingomonas, was reduced by continuous cucumber cultivation. The abundance of several beneficial fungal genera, including pathogen antagonists (e.g. Chaetomium, Mortierella, Aspergillus, and Penicillium), were found to gradually decrease in response to the increased duration of continuous cropping. 3-amino-2-naphthoic acid and L-valine increased initially and then decreased as the cropping continued, which were related to fatty acid metabolism and amino acid biosynthesis. We also confirmed a close association between microbial community structure and soil metabolites. This study linked the changes in microbial community structure and metabolites in the rhizosphere soil and provided new insights into soil-microbial interactions in continuous cucumber culture systems.

Endothelial Nogo-B Suppresses Cancer Cell Proliferation via a Paracrine TGF-ß/Smad Signaling.

Nogo-B has been reported to play a critical role in angiogenesis and the repair of damaged blood vessels; however, its role in the tumor microenvironment remains unclear. Here, we observed the differential expression of Nogo-B in endothelial cells from hepatocellular carcinoma (HCC) and glioma samples. Downregulation of Nogo-B expression correlated with the malignant phenotype of cancer and a poor prognosis for patients. In subsequent studies, endothelial Nogo-B inhibition robustly promoted the growth of HCC or glioma xenografts in nude mice. Intriguingly, endothelial Nogo-B silencing dramatically suppressed endothelial cell expansion and tumor angiogenesis, but potently enhanced the proliferation of neighboring HCC and glioma cells. Based on the results of the ELISA assay, Nogo-B silencing reduced TGF-ß production in endothelial cells, which attenuated the phosphorylation and nuclear translocation of Smad in neighboring cancer cells. The endothelial Nogo-B silencing-mediated increase in cancer cell proliferation was abolished by either a TGF-ß neutralizing antibody or TGF-ß receptor inhibitor, indicating the essential role for TGF-ß in endothelial Nogo-B-mediated suppression of cancer growth. These findings not only broaden our understanding of the crosstalk between cancer cells and endothelial cells but also provide a novel prognostic biomarker and a therapeutic target for cancer treatments.