Tradeoff between productivity and stability across above- and below-ground communities.

An 11-year nitrogen addition experiment reveals that for both plants and soil microorganisms, the ruderal strategists had higher productivity but lower stability, while the tolerant strategists had higher stability and lower productivity, leading to the tradeoff between productivity and stability within and across above- and below-ground communities.

MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway.

The Hippo pathway is an evolutionarily conserved signaling pathway that controls organ size in animals via the regulation of cell proliferation and apoptosis. It consists of a kinase cascade, in which MST1/2 and MAP4Ks phosphorylate and activate LATS1/2, which in turn phosphorylate and inhibit YAP/TAZ activity. A variety of signals can modulate LATS1/2 kinase activity to regulate Hippo pathway. However, the full mechanistic details of kinase-mediated regulation of Hippo pathway signaling remain elusive. Here, we report that TNF activates LATS1/2 and inhibits YAP/TAZ activity through MEKK2/3. Furthermore, MEKK2/3 act in parallel to MST1/2 and MAP4Ks to regulate LATS1/2 and YAP/TAZ in response to various signals, such as serum and actin dynamics. Mechanistically, we show that MEKK2/3 interact with LATS1/2 and YAP/TAZ and phosphorylate them. In addition, Striatin-interacting phosphatase and kinase (STRIPAK) complex associates with MEKK3 via CCM2 and CCM3 to inactivate MEKK3 kinase activity. Upstream signals of Hippo pathway trigger the dissociation of MEKK3 from STRIPAK complex to release MEKK3 activity. Our work has uncovered a previous unrecognized regulation of Hippo pathway via MEKK2/3 and provides new insights into molecular mechanisms for the interplay between Hippo-YAP and NF-κB signaling and the pathogenesis of cerebral cavernous malformations.

Bacterial Bioreporter-Based Mercury and Phenanthrene Assessment in Yangtze River Delta Soils of China.

Genetically engineered bacterial whole-cell bioreporters were deployed to investigate bioavailable mercury (b-Hg) and phenanthrene (b-PHE). Characterized by high sensitivity and specificity in aqueous solutions, the bioreporter system could detect in amended soils the concentrations of b-Hg and b-PHE in the ranges of 19.6 to 111.6 and 21.5 to 110.9 µg kg, respectively. The sensitivity of the system allowed for the combined analysis of b-Hg and b-PHE from real environmental samples. Therefore, soil samples from three large refinery facilities were tested, and the results from the instrumental analysis strongly correlated with the ones obtained with the bioreporter method. Large-scale and fast screening of soil contamination across the Yangtze River Delta in Eastern China was conducted. More than 36% of the samples contained b-Hg, whereas the fractions of b-PHE were below the detection limit for all the samples. These results indicated a higher toxicity and more hazardous condition for Hg contamination than for PHE. Population densities and airborne 10-µm particulate matter (PM10) concentrations were used as parameters for comparison with the spatial distribution of the b-Hg and b-PHE fractions. The results revealed that the bioreporters could offer a rapid and cost-efficient method to test soil samples from contaminated areas and provide a screening tool for environmental risk assessment.

Cannabidiol and its application in the treatment of oral diseases: therapeutic potentials, routes of administration and prospects.

Cannabidiol (CBD), one of the most important active ingredients in cannabis, has been reported to have some pharmacological effects such as antibacterial and analgesic effects, and to have therapeutic potential in the treatment of oral diseases such as oral cancer, gingivitis and periodontal diseases. However, there is a lack of relevant systematic research and reviews. Therefore, based on the etiology and clinical symptoms of several common oral diseases, this paper focuses on the therapeutic potential of CBD in periodontal diseases, pulp diseases, oral mucosal diseases, oral cancer and temporomandibular joint diseases. The pharmacological effects of CBD and the distribution and function of its receptors in the oral cavity are also summarized. In order to provide reference for future research and further clinical application of CBD, we also summarize several possible routes of administration and corresponding characteristics. Finally, the challenges faced while applying CBD clinically and possible solutions are discussed, and we also look to the future.

Nitrogen deposition mediates more stochastic processes in structuring plant community than soil microbial community in the Eurasian steppe.

Anthropogenic environmental changes may affect community assembly through mediating both deterministic (e.g., competitive exclusion and environmental filtering) and stochastic processes (e.g., birth/death and dispersal/colonization). It is traditionally thought that environmental changes have a larger mediation effect on stochastic processes in structuring soil microbial community than aboveground plant community; however, this hypothesis remains largely untested. Here we report an unexpected pattern that nitrogen (N) deposition has a larger mediation effect on stochastic processes in structuring plant community than soil microbial community (those <2 mm in diameter, including archaea, bacteria, fungi, and protists) in the Eurasian steppe. We performed a ten-year nitrogen deposition experiment in a semiarid grassland ecosystem in Inner Mongolia, manipulating nine rates (0-50 g N m-2 per year) at two frequencies (nitrogen added twice or 12 times per year) under two grassland management strategies (fencing or mowing). We separated the compositional variation of plant and soil microbial communities caused by each treatment into the deterministic and stochastic components with a recently-developed method. As nitrogen addition rate increased, the relative importance of stochastic component of plant community first increased and then decreased, while that of soil microbial community first decreased and then increased. On the whole, the relative importance of stochastic component was significantly larger in plant community (0.552±0.035; mean±standard error) than in microbial community (0.427±0.035). Consistently, the proportion of compositional variation explained by the deterministic soil and community indices was smaller for plant community (0.172-0.186) than microbial community (0.240-0.767). Meanwhile, as nitrogen addition rate increased, the linkage between plant and microbial community composition first became weaker and then became stronger. The larger stochasticity in plant community relative to microbial community assembly suggested that more stochastic strategies (e.g., seeds addition) should be adopted to maintain above- than below-ground biodiversity under the pressure of nitrogen deposition.

A nomogram for predicting survival in Patients with oral tongue keratinized squamous cell carcinoma: A SEER-based study.

OBJECTIVE: Oral tongue keratinized squamous cell carcinoma (OTKSCC), a relatively rare form of tongue cancer (TC) in clinical practice, accompanied by features of cell keratosis, is an uncommon histological subtype. However, its specific clinicopathological features and prognosis have not been adequately described. In this study, we aimed to create a nomogram using R language software to predict overall survival (OS) of patients with OTKSCC to assess the prognosis of OTKSCC patients. METHODS: We extracted clinical and related prognostic data of OTKSCC patients from 1975 to 2019 from the Surveillance, Epidemiology, and End Results database. Independent prognostic factors were selected using univariate and multivariate Cox analyses, and a nomogram was constructed using R software. The C-index, area under the curve (AUC) of receiver operating characteristic curves, calibration curves, and decision curve analysis (DCA) were used to assess the clinical utility of the nomogram. Finally, OS was assessed using the Kaplan-Meier method. RESULTS: A total of 2450 OTKSCC patients were included in the study. Univariate and multivariate Cox regression analyses were used to identify age, T stage, N stage, surgery, and radiation therapy as independent risk factors (p<0.05). In the training cohort, the calibration index of the nomogram was 0.725, while the AUC values for nomogram, age, T stage, N stage, surgery and radiation therapy were 0.878, 0.639, 0.781, 0.661, 0.724 and 0.354, respectively. At the same time, in the verification queue, the calibration index of the nomogram was 0.726, while the AUC values for nomogram, age, T stage, N stage, surgery and radiation therapy were 0.859,0.612,0.826,0.675,0.758 and 0.303, respectively. Ideal uniformity of the models from the training and validation cohorts was demonstrated in the calibration and DCA curves. Univariate survival analysis showed that age, T stage, N stage, surgery, and radiotherapy were statistically significant for prognosis (p<0.05). CONCLUSION: Age, T stage, N stage, surgery, and radiation therapy are independently associated with the OS, and the established nomogram is an effective visualization tool for predicting the OS of OTKSCC patients.

Construction and application of dynamic online nomogram for prognosis prediction of patients with advanced (Stage III/IV) tongue squamous cell carcinoma.

OBJECTIVES: The prognosis of patients with advanced tongue squamous cell carcinoma (ATSCC) is poor, and their overall survival (OS) is relatively short. Currently, the TNM stage system is often used clinically to assess the prognosis of patients, but the evaluation index of the TNM stage system is relatively single and does not specifically demonstrate relevant prognostic data. Therefore, the purpose of this study was to construct a dynamic online nomogram for predicting the prognosis of patients with ATSCC and to provide some reference for personalized clinical treatment of patients. METHODS: Clinical and prognostic information on patients with pathologically confirmed ATSCC from 2000 to 2018 was extracted from the SEER database and randomly divided into a training cohort and a validation cohort in a 7:3 ratio. Multifactorial and univariate Cox regression analyses were used to identify prognostic risk factors. Dynamic online nomogram were constructed using R software. Area under the curve (AUC), C-index, calibration curve, and decision curve analysis (DCA) with time-dependent ROC curves were used to assess the clinical utility of the nomogram. Kaplan-Meier survival curves were used to compare the prognosis of different patient categories. RESULTS: A total of 3828 patients with ATSCC were screened in the SEER database.Age,race, primary site, AJCC T,N and M stage, lymph nodes surgery, radiotherapy, chemotherapy and marital status were independent influences on OS(P < 0.05). In the training cohort, the C-index of the OS-related line plot was 0.733 and the AUC for predicting 3-year OS was 0.867. In the validation cohort, the C-index was 0.738 and the AUC for 3-year OS was 0.899. Calibration plots and DCA curves showed good predictive performance of the model in both the training and validation cohorts. Kaplan-Meier survival curves showed that chemotherapy, lymph nodes surgery,married,primary site(tongue base) and radiotherapy had better OS than the non-chemotherapy, non-surgery, single, primary site(tongue anterior), and non-radiotherapy groups, respectively (all P < 0.05). CONCLUSION: The established dynamic online nomogram has good predictive performance, which helps to personalize and combine the actual clinical patients to comprehensively predict the prognosis of ATSCC patients and may have better clinical application than the TNM stage system.

Cell electrospinning and its application in wound healing: principles, techniques and prospects.

Currently, clinical strategies for the treatment of wounds are limited, especially in terms of achieving rapid wound healing. In recent years, based on the technique of electrospinning (ES), cell electrospinning (C-ES) has been developed to better repair related tissues or organs (such as skin, fat and muscle) by encapsulating living cells in a microfiber or nanofiber environment and constructing 3D living fiber scaffolds. Therefore, C-ES has promising prospects for promoting wound healing. In this article, C-ES technology and its advantages, the differences between C-ES and traditional ES, the parameters suitable for maintaining cytoactivity, and material selection and design issues are summarized. In addition, we review the application of C-ES in the fields of biomaterials and cells. Finally, the limitations and improved methods of C-ES are discussed. In conclusion, the potential advantages, limitations and prospects of C-ES application in wound healing are presented.

A high-performance porous flexible composite film sensor for tension monitoring.

Flexible, lightweight sensors with a wide strain-sensing range are showing increasing significance in structural health monitoring compared with conventional hard sensors, which typically have a small strain range, are heavyweight, and have a large volume. In this work, salt particle precipitation and mechanical coating methods are used to fabricate porous graphene nanoplatelet (GNP)/polydimethylsiloxane (PDMS) flexible sensors for tension monitoring in structural health applications. The signal transformation through the Back Propagation (BP) algorithm is integrated to provide monitoring data that are comparable with other sensors. The results reveal that the flexible sensors with a low content of GNPs (0.1-0.25 wt%) possess better flexibility, allowing tensile strains over 200% to be measured. In addition, due to the enhanced deformation capacity of the pore structures, they can achieve high sensitivity (1-1000) under 65% strain, and a fast response time (70 ms) under 10% strain at 60 mm min-1. They also show high performance in the fatigue test (20 000 cycles) under 5% strain, and can effectively respond to bending and torsion. In addition, the sensors show an obvious response to temperature. Overall, the prepared flexible composite sensors in this work have the advantages of a wide strain-sensing range, a full-coverage conductive network, and being lightweight, and show potential for structural health monitoring in the near future.

Deficiency of PPP6C protects TNF-induced necroptosis through activation of TAK1.

Necroptotic cell death is mediated by a super-molecular complex called necrosome which consists of receptor-interacting protein kinase 1 and 3 (RIPK1, RIPK3) and mixed-lineage kinase domain-like protein (MLKL). The role of these kinases has been extensively investigated in the regulation of necroptosis. However, whether the protein phosphatase is involved in necroptosis is still largely unknown. Here, we identified protein phosphatase 6 catalytic subunit (PPP6C) promotes TNF-induced necroptosis by genome-wide CRISPR/Cas9 library screening. We found that PPP6C deficiency protects cells from TNF-induced necroptosis in a phosphatase-activity-dependent manner. Mechanistically, PPP6C acts as a TGF-ß activated kinase 1 (TAK1) phosphatase to inactivate its kinase activity. Deletion of PPP6C leads to hyperactivation of TAK1 and reduced RIPK1 kinase activity upon TNF stimulation. We further showed that heterozygous deletion of Ppp6c in mouse gastrointestinal tract alleviates necroptosis-related tissue injury and inflammation. Thus, our study identifies PPP6C as an important regulator of necroptosis and highlights a central role of phosphatase in the regulation of necroptosis-related diseases.

Mechanosensitive Channel PIEZO1 Senses Shear Force to Induce KLF2/4 Expression via CaMKII/MEKK3/ERK5 Axis in Endothelial Cells.

Shear stress exerted by the blood stream modulates endothelial functions through altering gene expression. KLF2 and KLF4, the mechanosensitive transcription factors, are promoted by laminar flow to maintain endothelial homeostasis. However, how the expression of KLF2/4 is regulated by shear stress is poorly understood. Here, we showed that the activation of PIEZO1 upregulates the expression of KLF2/4 in endothelial cells. Mice with endothelial-specific deletion of Piezo1 exhibit reduced KLF2/4 expression in thoracic aorta and pulmonary vascular endothelial cells. Mechanistically, shear stress activates PIEZO1, which results in a calcium influx and subsequently activation of CaMKII. CaMKII interacts with and activates MEKK3 to promote MEKK3/MEK5/ERK5 signaling and ultimately induce the transcription of KLF2/4. Our data provide the molecular insight into how endothelial cells sense and convert mechanical stimuli into a biological response to promote KLF2/4 expression for the maintenance of endothelial function and homeostasis.