OsHRZ1 negatively regulates rice resistant to Magnaporthe oryzae infection by targeting OsVOZ2.

Rice blast disease caused by Magnaporthe oryzae significantly reduces yield production. Blast resistance is closely associated with iron (Fe) status, but the mechanistic basis linking iron status to immune function in rice remains largely unknown. Here, iron-binding haemerythrin RING ubiquitin ligases OsHRZ1 was confirmed to play key roles in iron-mediated rice blast resistance. The expression of OsHRZ1 was suppressed by M. oryzae inoculation and high iron treatment. Both mutants of OsHRZ1 enhanced rice resistance to M. oryzae. OsPR1a was up-regulated in OsHRZ1 mutants. Yeast two-hybrid, bimolecular fluorescence complementation, and Co-IP assay results indicated that OsHRZ1 interacts with Vascular Plant One Zinc Finger 2 (OsVOZ2) in the nucleus. Additionally, the vitro ubiquitination assay indicated that OsHRZ1 can ubiquitinate OsVOZ2 and mediate the degradation of OsVOZ2. The mutants of OsVOZ2 showed reduced resistance to M. oryzae and down-regulated the expression of OsPR1a. Yeast one-hybrid, EMSA, and dual-luciferase reporter assay results indicated that OsVOZ2 directly binds to the promoter of OsPR1a, activating its expression. In summary, OsHRZ1 plays an important role in rice disease resistance by mediated degradation of OsVOZ2 thus shaping PR gene expression dynamics in rice cells. This highlights an important link between iron signaling and rice pathogen defenses.

Variational quantum algorithm for node embedding.

Quantum machine learning has made remarkable progress in many important tasks. However, the gate complexity of the initial state preparation is seldom considered in lots of quantum machine learning algorithms, making them non-end-to-end. Herein, we propose a quantum algorithm for the node embedding problem that maps a node graph's topological structure to embedding vectors. The resulting quantum embedding state can be used as an input for other quantum machine learning algorithms. With O ( log ( N ) ) qubits to store the information of N nodes, our algorithm will not lose quantum advantage for the subsequent quantum information processing. Moreover, owing to the use of a parameterized quantum circuit with O ( poly ( log ( N ) ) ) depth, the resulting state can serve as an efficient quantum database. In addition, we explored the measurement complexity of the quantum node embedding algorithm, which is the main issue in training parameters, and extended the algorithm to capture high-order neighborhood information between nodes. Finally, we experimentally demonstrated our algorithm on an nuclear magnetic resonance quantum processor to solve a graph model.

Optimizing ABA-based chemically induced proximity for enhanced intracellular transcriptional activation and modification response to ABA.

Abscisic acid (ABA)-based chemically induced proximity (CIP) is primarily mediated by the interaction of the ABA receptor pyrabactin resistance 1-like 1 (PYL1) and the 2C-type protein phosphatase ABI1, which confers ABA-induced proximity to their fusion proteins, and offers precise temporal control of a wide array of biological processes. However, broad application of ABA-based CIP has been limited by ABA response intensity. In this study, we demonstrated that ABA-induced interaction between another ABA receptor pyrabactin resistance 1 (PYR1) and ABI1 exhibited higher ABA response intensity than that between PYL1 and ABI1 in HEK293T cells. We engineered PYR1-ABI1 and PYL1-ABI1 into ABA-induced transcriptional activation tools in mammalian cells by integration with CRISPR/dCas9 and found that the tool based on PYR1-ABI1 demonstrated better ABA response intensity than that based on PYL1-ABI1 for both exogenous and endogenous genes in mammalian cells. We further achieved ABA-induced RNA m6A modification installation and erasure by combining ABA-induced PYR1-ABI1 interaction with CRISPR/dCas13, successfully inhibiting tumor cell proliferation. We subsequently improved the interaction of PYR1-ABI1 through phage-assisted continuous evolution (PACE), successfully generating a PYR1 mutant (PYR1m) whose interaction with ABI1 exhibited a higher ABA response intensity than that of the wild-type. In addition, we tested the transcriptional activation tool based on PYRm-ABI1 and found that it also showed a higher ABA response intensity than that of the wild type. These results demonstrate that we have developed a novel ABA-based CIP and further improved upon it using PACE, providing a new approach for the modification of other CIP systems.

Phosphodiesterase type 5 inhibitor tadalafil reduces prostatic fibrosis via MiR-3126-3p/FGF9 axis in benign prostatic hyperplasia.

Myofibroblast buildup and prostatic fibrosis play a crucial role in the development of benign prostatic hyperplasia (BPH). Treatments specifically targeting myofibroblasts could be a promising approach for treating BPH. Tadalafil, a phosphodiesterase type 5 (PDE5) inhibitor, holds the potential to intervene in this biological process. This study employs prostatic stromal fibroblasts to induce myofibroblast differentiation through TGFß1 stimulation. As a result, tadalafil significantly inhibited prostatic stromal fibroblast proliferation and fibrosis process, compared to the control group. Furthermore, our transcriptome sequencing results revealed that tadalafil inhibited FGF9 secretion and simultaneously improved miR-3126-3p expression via TGFß1 suppression. Overall, TGFß1 can trigger pro-fibrotic signaling through miR-3126-3p in the prostatic stroma, and the use of tadalafil can inhibit this process.

Causal associations of physical activity and leisure sedentary behaviors with age at onset of Huntington's disease: A mendelian randomization study.

BACKGROUND: Huntington's disease (HD) is a neurodegenerative disorder for which effective therapies are currently lacking. Studies suggest that increasing physical activity (PA) and reducing leisure sedentary behavior (LSB) mitigate the progression of HD, but their causal relationship with the age at onset (AAO) of HD remains uncertain. To investigate this, we conducted the Two-sample Mendelian Randomization (MR). METHODS: Exposure were retrieved from the UK BioBank's (UKB) Genome-Wide Association Study (GWAS). PA included accelerometer-based average PA, vigorous PA, self-reported moderate-to-vigorous PA (MVPA), and light do-it-yourself activity. LSB included television (TV) time, computer time, and driving time. Outcome came from the GWAS of the GEM-HD Consortium. We applied several MR methods such as inverse variance weighted (IVW), MR-Egger regression, weighted median (WM) for sensitivity analysis. RESULTS: Increases in light PA (ß = 8.53 years, 95 % CI = 10.64 to 44.09, P = 0.001) and accelerometer-based vigorous PA (ß = 5.18, 95 % CI = 0.92 to 9.43, P = 0.017) delayed AAO of HD, while longer TV time was associated with earlier AAO of HD (ß = -2.88 years, 95 % CI = -4.99 to -0.77, P = 0.007). However, other PA and LSB phenotypes did not significantly affect AAO of HD. CONCLUSION: The study revealed a unidirectional causality between PA, LSB and the AAO of HD. Increasing PA and reducing TV time delay HD onset. Therefore, we recommend increasing physical activity and reducing sedentary behavior to delay the occurrence of motor symptoms for premanifest HD individuals.

Cross-shore parallel tidal channel systems formed by alongshore currents.

Parallel tidal channel systems, characterized by commonly cross-shore orientation and regular spacing, represent a distinct class of tidal channel networks in coastal environments worldwide. Intriguingly, these cross-shore oriented channel systems can develop in environments dominated by alongshore tidal currents, for which the mechanisms remain elusive. Here, we combine remote sensing imagery analysis and morphodynamic simulations to demonstrate that the deflection of alongshore tidal currents at transitions in bed elevation determines the characteristic orientation of the parallel tidal channels. Numerical results reveal that sharp changes in bed elevation lead to nearly 90-degree intersection angles, while smoother transitions in bed profiles result in less perpendicular channel alignments. These findings shed light on the potential manipulation of tidal channel patterns in coastal wetlands, thus equipping coastal managers with a broader range of strategies for the sustainable management of these vital ecosystems in the face of climate change and sea level rise.

Review of recent advances in bone scaffold fabrication methods for tissue engineering for treating bone diseases and sport injuries.

Despite advancements in medical care, the management of bone injuries remains one of the most significant challenges in the fields of medicine and sports medicine globally. Bone tissue damage is often associated with aging, reduced quality of life, and various conditions such as trauma, cancer, and infection. While bone tissue possesses the natural capacity for self-repair and regeneration, severe damage may render conventional treatments ineffective, and bone grafting may be limited due to secondary surgical procedures and potential disease transmission. In such cases, bone tissue engineering has emerged as a viable approach, utilizing cells, scaffolds, and growth factors to repair damaged bone tissue. This research shows a comprehensive review of the current literature on the most important and effective methods and materials for improving the treatment of these injuries. Commonly employed cell types include osteogenic cells, embryonic stem cells, and mesenchymal cells, while scaffolds play a crucial role in bone tissue regeneration. To create an effective bone scaffold, a thorough understanding of bone structure, material selection, and examination of scaffold fabrication techniques from inception to the present day is necessary. By gaining insights into these three key components, the ability to design and construct appropriate bone scaffolds can be achieved. Bone tissue engineering scaffolds are evaluated based on factors such as strength, porosity, cell adhesion, biocompatibility, and biodegradability. This article examines the diverse categories of bone scaffolds, the materials and techniques used in their fabrication, as well as the associated merits and drawbacks of these approaches. Furthermore, the review explores the utilization of various scaffold types in bone tissue engineering applications.

Causal associations of immune cells with benign prostatic hyperplasia: insights from a Mendelian randomization study.

BACKGROUND: Previous research has focused on the association between immune cells and the development of benign prostatic hyperplasia (BPH). Nevertheless, the causal relationships in this context remain uncertain. METHODS: This study employed a comprehensive and systematic two-sample Mendelian randomization (MR) analysis to determine the causal relationships between immunophenotypes and BPH. We examined the causal associations between 731 immunophenotypes and the risk of BPH by utilizing publicly available genetic data. Integrated sensitivity analyses were performed to validate the robustness, assess heterogeneity, and examine horizontal pleiotropy in the results. RESULTS: We discovered that 38 immunophenotypes have a causal effect on BPH. Subsequently, four of these immunophenotypes underwent verification using weighted median, weighted mode, and inverse variance weighted (IVW) algorithms, which included CD19 on CD24+ CD27+, CD19 on naive-mature B cell, HLA DR on CD14- CD16+ and HLA DR+ T cell%lymphocyte. Furthermore, BPH exhibited a significant association with three immunophenotypes: CD19 on IgD+ CD38dim (ß = -0.152, 95% CI = 0.746-0.989, P = 0.034), CD19 on IgD+ (ß = -0.167, 95% CI = 0.737-0.973, P = 0.019), and CD19 on naive-mature B cell (ß = -0.166, 95% CI = 0.737-0.972, P = 0.018). CONCLUSIONS: Our study provides valuable insights for future clinical investigations by establishing a significant association between immune cells and BPH.

Frequency of Vigorous physical activity and sleep difficulty in adolescents: A multiply-country cross-sectional study.

BACKGROUND: Sleep is an essential health behavior, and sleep difficulties are strongly associated with adolescent health, potentially leading to more severe sleep disorders. The beneficial effects of physical activity (PA) in alleviating sleep difficulties have been well-documented. Numerous investigations reveal influence in moderate to high-intensity physical activity (PA) positively influences sleep quality. Despite these findings, a gap in the literature exists, particularly regarding the association between frequency of vigorous-intensity physical activity (VPA) and sleep difficulties. AIM: This study aims to bridge the knowledge gap by exploring the link between sleep difficulty and frequency of VPA among adolescents. Insights are derived from analyzing data accumulated from the Health Behavior in School-aged Children (HBSC) project. METHODS: The analysis in this study utilized cross-sectional data from the HBSC (2017/2018). The study sample comprised a total of 171,233 respondents aged 11, 13, and 15 years, with males representing 51.1% of sample. Measurement instruments included a self-administered questionnaire, providing direct insight into sleep difficulty and frequency of VPA levels. Statistical analysis on the associaiton between frequency of VPA and sleep difficulties was conducted using Generalized Linear Models. RESULTS: 50.0% of adolescents reported no sleep difficulties, while 12.3% experienced sleep issues daily. Additionally, 17.1% of adolescents engaged in frequency of VPA on a daily basis, while 6.4% never participated in such activities. daily VPA was associated with fewer sleep difficulties (OR = 1.07 [1.00, 1.15]), 4-6 times a week (OR = 1.08 [1.01, 1.15]), and 2-3 times a week (OR = 1.08 [1.02, 1.16]). However, no significant association was found between sleep difficulties and frequency of VPA in girls. Furthermore, a negative association was observed between sleep difficulties and all frequencies of VPA (p < 0.05) in 11-year-old adolescents. For 13-year-olds, daily VPA was significantly associated with fewer sleep difficulties (OR = 1.10 [1.02, 1.19]), 4-6 times a week (OR = 1.15 [1.07, 1.24]), 2-3 times a week (OR = 1.19 [1.10, 1.27]), and once a week (OR = 1.13 [1.05, 1.22]). However, no significant association was found between sleep difficulties and frequency of VPA in 15-year-old adolescents. CONCLUSION: More participations in VPA would be an effective approach to reduce sleep difficulties in adolescents. Insights gleaned from this research illustrate a discernible link between sleep difficulty and frequency of VPA, particularly notable in male and 13-year-old participants. It is also imperative to underscore the variability in the connection between sleep difficulty and frequency of VPA, distinctly influenced by factors such as gender and age. Consequently, tailoring sleep intervention methodologies to align with the specific needs dictated by these variables emerges as a pivotal recommendation.

Genome-wide identification and comprehensive analysis heat shock transcription factor (Hsf) members in asparagus (Asparagus officinalis) at the seeding stage under abiotic stresses.

Heat shock transcription factors (Hsf) are pivotal as essential transcription factors. They function as direct transcriptional activators of genes regulated by thermal stress and are closely associated with various abiotic stresses. Asparagus (Asparagus officinalis) is a vegetable of considerable economic and nutritional significance, abundant in essential vitamins, minerals, and dietary fiber. Nevertheless, asparagus is sensitive to environmental stresses, and specific abiotic stresses harm its yield and quality. In this context, Hsf members have been discerned through the reference genome, and a comprehensive analysis encompassing physical and chemical attributes, evolutionary aspects, motifs, gene structure, cis-acting elements, collinearity, and expression patterns under abiotic stresses has been conducted. The findings identified 18 members, categorized into five distinct subgroups. Members within each subgroup exhibited analogous motifs, gene structures, and cis-acting elements. Collinearity analysis unveiled a noteworthy pattern, revealing that Hsf members within asparagus shared one, two, and three pairs with counterparts in Arabidopsis, Oryza sativa, and Glycine max, respectively.Furthermore, members displayed tissue-specific expression during the seedling stage, with roots emerging as viable target tissue. Notably, the expression levels of certain members underwent modification under the influence of abiotic stresses. This study establishes a foundational framework for understanding Hsf members and offers valuable insights into the potential application of molecular breeding in the context of asparagus cultivation.

LPS induces SGPP2 to participate metabolic reprogramming in endothelial cells.

Sepsis often causes organ dysfunction and is manifested in increased endothelial cell permeability in blood vessels. Early-stage inflammation is accompanied by metabolic changes, but it is unclear how the metabolic alterations in the endothelial cells following lipopolysaccharide (LPS) stimulation affect endothelial cell function. In this study, the effects of 1 µg/ml of LPS on the metabolism of human umbilical vein endothelial cells (HUVECs) were investigated, and the metabolic changes after LPS stimulation were explained from the perspective of mRNA expression, chromatin openness and metabolic flux. We found changes in the central metabolism of endothelial cells after LPS stimulation, such as enhanced glycolysis function, decreased mitochondrial membrane potential, and increased production of reactive oxygen species (ROS). Sphingolipid metabolic pathways change at the transcriptome level, and sphingosine-1-phosphatase 2 (SGPP2) was upregulated in LPS-stimulated endothelial cells and zebrafish models. Overexpression of SGPP2 improved cell barrier function, enhanced mitochondrial respiration capacity, but also produced oxidative respiration chain uncoupling. In addition, SGPP2 overexpression inhibited the degradation of HIF-1α protein. The molecular and biochemical processes identified in this study are not only beneficial for understanding the metabolic-related mechanisms of LPS-induced endothelial injury, but also for the discovery of general therapeutic targets for inflammation and inflammation-related diseases.

Identification and validation of cancer-associated fibroblast-related subtypes and the prognosis model of biochemical recurrence in prostate cancer based on single-cell and bulk RNA sequencing.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are an essential component of the tumor immune microenvironment that are involved in extracellular matrix (ECM) remodeling. We aim to investigate the characteristics of CAFs in prostate cancer and develop a biochemical recurrence (BCR)-related CAF signature for predicting the prognosis of PCa patients. METHODS: The bulk RNA-seq and relevant clinical information were obtained from the TCGA and GEO databases, respectively. The infiltration scores of CAFs in prostate cancer patients were calculated using the MCP counter and EPIC algorithms. The single-cell RNA sequencing (scRNA-seq) was downloaded from the GEO database. Subsequently, univariate Cox regression analysis was employed to identify prognostic genes associated with CAFs. We identified two subtypes (C1 and C2) of prostate cancer that were associated with CAFs via non-negative matrix factorization (NMF) clustering. In addition, the BCR-related CAF signatures were constructed using Lasso regression analysis. Finally, a nomogram model was established based on the risk score and clinical characteristics of the patients. RESULTS: Initially, we found that patients with high CAF infiltration scores had shorter biochemical recurrence-free survival (BCRFS) times. Subsequently, CAFs in four pairs of tumors and paracancerous tissues were identified. We discovered 253 significantly differentially expressed genes, of which 13 had prognostic significance. Using NMF clustering, we divided PCa patients into C1 and C2 subgroups, with the C1 subgroup having a worse prognosis and substantially enriched cell cycle, homologous recombination, and mismatch repair pathways. Furthermore, a BCR-related CAFs signature was established. Multivariate COX regression analysis confirmed that the BCR-related CAFs signature was an independent prognostic factor for BCR in PCa. In addition, the nomogram was based on the clinical characteristics and risk scores of the patient and demonstrated high accuracy and reliability for predicting BCR. Lastly, our findings indicate that the risk score may be a useful tool for predicting PCa patients' sensitivity to immunotherapy and drug treatment. CONCLUSION: NMF clustering based on CAF-related genes revealed distinct TME immune characteristics between groups. The BCR-related CAF signature accurately predicted prognosis and immunotherapy response in prostate cancer patients, offering a promising new approach to cancer treatment.

Evaluation of traditional Chinese medicine fitness' effect on improving the health of adults' intestinal flora: An optical tool based on ultrasensitive bioluminescent imaging and applications.

The design of the probes is based on bioluminescence imaging, which has been widely adopted in studies of many important biological processes. Traditional Chinese Medicine (TCM) fitness could improve the state of health of adults' intestinal flora. The research aims at analyzing the impact of TCM fitness on the intestinal probiotics (Bifidobacterium, Lactobacillus) and opportunistic pathogen (Enterococcus, Enterobacteriaceae) by the noninvasive imaging. In accordance with the searching results, the researchers have found that TCM fitness has a significant impact on improving Bifidobacterium (SDM = 1.55; P = 0.02) and Lactobacillus (SDM = 1.26; P <0.01), while the impact could not be seen on Enterococcus (SDM = 0.29;P = 0.68) and Enterobacteriaceae (SDM = 0.05;P = 0.94). And there is no significant difference between the two interventions of Tai Chi and Fitness Qigong. The results of the present review show that TCM fitness could significantly better the probiotics of intestinal flora while the influence on opportunistic pathogen needs to be further investigated with the precise and reasonable proof of scientific studies.The findings suggest that TCM fitness can be used as an effective intervention, and there is no significant difference between the two interventions on the improvement of the intestinal flora. The using of optical tool based on ultrasensitive bioluminescent imaging may lead to better precision medicine treatments in the future.

Implications of Coastal Conditions and Sea-Level Rise on Mangrove Vulnerability: A Bio-Morphodynamic Modeling Study.

Mangrove forests are valuable coastal ecosystems that have been shown to persist on muddy intertidal flats through bio-morphodynamic feedbacks. However, the role of coastal conditions on mangrove behavior remains uncertain. This study conducts numerical experiments to systematically explore the effects of tidal range, small wind waves, sediment supply and coastal slope on mangrove development under sea-level rise (SLR). Our results show that mangroves in micro-tidal conditions are more vulnerable because of the gentler coastal equilibrium slope and the limited ability to capture sediment, which leads to substantial mangrove landward displacement even under slow SLR. Macro-tidal conditions with large sediment supply promote accretion along the profile and platform formation, reducing mangrove vulnerability for slow and medium SLR, but still cause rapid mangrove retreat under fast SLR. Small wind waves promote sediment accretion, and exert an extra bed shear stress that confines the mangrove forest to higher elevations with more favorable inundation regimes, offsetting SLR impacts. These processes also have important implications for the development of new landward habitats under SLR. In particular, our experiments show that landward habitat can be created even with limited sediment supply and thus without complete infilling of the available accommodation space. Nevertheless, new accommodation space may be filled over time with sediment originating from erosion of the lower coastal profile. Consistent with field data, model simulations indicate that sediment accretion within the forest can accelerate under SLR, but the timing and magnitude of accretion depend non-linearly on coastal conditions and distance from the mangrove seaward edge.

Increased river flow enhances the resilience of spatially patterned mudflats to erosion.

Estuarine mudflats are profoundly affected by increased coastal erosion and reduced sediment delivery from major rivers. Although managers are having difficulties to control the cause of increased coastal erosion, they can help to manage the resilience of mudflat ecosystems to erosion through river flow regulation. In this study, we associated the resilience of a mudflat ecosystem to erosion with various magnitudes of river flow using a mechanism-based eco-morphodynamic model. Ecosystem resilience was reported in terms of i) what range of erosion rate the system can withstand before function collapse (persistence), ii) at which point function can be recovered (recovery), and iii) the uncertainty of system response to disturbances (response uncertainty). Specifically, the function of intertidal mudflat was characterized by landscape heterogeneity, primary productivity, and sediment stabilization. In a case study of the Yellow River Estuary (YRE) of China, it is found that increased erosion induced a collapse of the functioning state. Once collapsed, the erosion rate at which mudflat could recovered was lower than the erosion rate at which mudflat collapsed. Increased river flow enhanced the resilience of the mudflat ecosystem to erosion by increasing sediment deposition rate, which was an important attribute in the interaction process driving ecosystem resilience. Furthermore, given the same river flow allocation, the system with dynamic grazer population was more resilient than the system with a constant grazer number, highlighting the importance of controlling mudflat aquaculture to optimize the performance of river flow regulation. Our modeling results are dependent on the environment with several assumptions, however, as a preliminary, we believe our work represents a fundamental shift to modeling ecosystem resilience based on the mechanism of bio-physical interactions rather than relying on just quantifying the vital rates of particular species to compare river flow scenarios.

Transcutaneous Auricular Vagus Nerve Stimulation Modulates the Prefrontal Cortex in Chronic Insomnia Patients: fMRI Study in the First Session.

Objectives: Transcutaneous auricular vagus nerve stimulation (taVNS) has been reported to be effective for chronic insomnia (CI). However, the appropriate population for taVNS to treat insomnia is unclear. Methods: Total twenty-four patients with CI and eighteen health controls (HC) were recruited. Rest-state functional magnetic resonance imaging (Rs-fMRI) was performed before and after 30 min' taVNS at baseline. The activated and deactivated brain regions were revealed by different voxel-based analyses, then the seed-voxel functional connectivity analysis was calculated. In the CI group, 30 min of taVNS were applied twice daily for 4 weeks. Pittsburgh Sleep Quality Index (PSQI) and Flinders Fatigue Scale (FFS) were also assessed before and after 4 weeks of treatment in the CI group. The HC group did not receive any treatment. The correlations were estimated between the clinical scales' score and the brain changes. Results: The scores of PSQI (p < 0.01) and FFS (p < 0.05) decreased after 4 weeks in the CI group. Compared to the HC group, the first taVNS session up-regulated left dorsolateral prefrontal cortex (dlPFC) and decreased the functional connectivity (FCs) between dlPFC and bilateral medial prefrontal cortex in the CI group. The CI groups' baseline voxel wised fMRI value in the dlPFC were negatively correlated to the PSQI and the FFS score after 4 weeks treatment. Conclusions: It manifests that taVNS has a modulatory effect on the prefrontal cortex in patients with CI. The initial state of dlPFC may predict the efficacy for taVNS on CI.

Transcriptional regulation of intermolecular Ca2+ signaling in hibernating ground squirrel cardiomyocytes: The myocardin-junctophilin axis.

The contraction of heart cells is controlled by the intermolecular signaling between L-type Ca2+ channels (LCCs) and ryanodine receptors (RyRs), and the nanodistance between them depends on the interaction between junctophilin-2 (JPH2) in the sarcoplasmic reticulum (SR) and caveolin-3 (CAV3) in the transversal tubule (TT). In heart failure, decreased expression of JPH2 compromises LCC-RyR communication leading to deficient blood-pumping power. In the present study, we found that JPH2 and CAV3 transcription was concurrently regulated by serum response factor (SRF) and myocardin. In cardiomyocytes from torpid ground squirrels, compared with those from euthermic counterparts, myocardin expression was up-regulated, which boosted both JPH2 and CAV3 expression. Transmission electron microscopic imaging showed that the physical coupling between TTs and SRs was tightened during hibernation and after myocardin overexpression. Confocal Ca2+ imaging under the whole-cell patch clamp condition revealed that these changes enhanced the efficiency of LCC-RyR intermolecular signaling and fully compensated the adaptive down-regulation of LCCs, maintaining the power of heart contraction while avoiding the risk of calcium overload during hibernation. Our finding not only revealed an essential molecular mechanism underlying the survival of hibernating mammals, but also demonstrated a "reverse model of heart failure" at the molecular level, suggesting a strategy for treating heart diseases.

Using phage-assisted continuous evolution (PACE) to evolve human PD1.

PD1/PDL1 pathway plays a critical role in cancer immune responses. The immune checkpoint inhibitors of PD1/PDL1 have been well explored and developed for immunotherapies of solid tumors. Recently, various monoclonal antibodies targeting the PD1/PDL1 pathway have emerged and achieved remarkable success in clinical trials. However, challenges with these monoclonal antibodies have appeared during cancer therapies, including predictors of response, patient selection, and innate resistance. Thus, a competitive antagonist of native PD1/PDL1, with smaller size and lower side-effect, is required for future cancer therapies. In this study, we utilized a protein evolution system of phage-assisted continuous evolution (PACE) to evolve PD1 continuously. Our results indicated that the newly evolved PD1 bound to PDL1 with higher affinity. The interactome analysis further suggested that these evolved PD1s exhibited higher specificity with PDL1. Therefore, these evolved PD1s may be applied as a new tool for tumor immunotherapy.

Variation trends and principal component analysis of nitrogen oxide emissions from motor vehicles in Wuhan City from 2012 to 2017.

In addition to fine particulate matter and oxysulfides, nitrogen oxides (NOx) emitted by motor vehicles are among the most important pollutants affecting air quality and public health in those urban areas where centralized heating and chemical industry absent. We utilized correlation analysis (pearson correlation coefficient and spearman correlation coefficient) and principal component analysis (PCA) to identify the variation trends and main causes of NOx emissions from motor vehicles in Wuhan City. We considered the total number of motor vehicles (TN), ratios of motor vehicles of different emission standards (RE), rations of labeled motor vehicles (RL), and rations of motor vehicles' fuel types (RF). The results show that: 1) with an increase in the total amount of motor vehicles, the NOx emissions of motor vehicles have been decreasing since 2015; 2) three sub-categories (the ratio of the State III emission standard, the ration of yellow label diesel vehicles, and the ration of diesel vehicles) were recognized as key indexes of PE, PL and PF, respectively, in the PCA; 3) a new parameter, the ESindex is proposed as an index to represent the variation trend of the NOx emissions of motor vehicles in Wuhan City.

Increased serum levels of miR-214 in patients with PCa with bone metastasis may serve as a potential biomarker by targeting PTEN.

MicroRNAs (miRNAs/miRs) are identified to serve key functions in the progression of various tumors. miR-214 is aberrantly expressed in various types of cancer. In the present study, the function of miR-214 and its feasibility as a potential non-invasive biomarker for patients with prostate cancer (PCa) in a hyperplasia group and a control group were investigated. First, RNA was isolated from the serum of 75 patients with PCa with bone metastasis, 65 patients with PCa with no bone metastasis and 70 healthy controls. The level of miR-214 expression was significantly upregulated in the serum of the bone metastasis group compared with the healthy control and non-bone metastasis groups. Expression levels of alkaline phosphatase (ALP), bone sialoprotein (BSP), collagen type I pyridine crosslinking peptide (ICTP) were also evaluated. The results indicated that serum levels of BSP, ALP and ICTP were increased in the bone metastasis group compared with that in the non-bone metastasis group, hyperplasia group and the control group (P<0.05). The expression level of miR-214 is positively associated with poorly differentiated tumors in patients with PCa with a Gleason score >7 (P<0.05). Western blot analysis demonstrated that phosphatase and tensin homolog (PTEN) was a target gene of miR-214. Additionally, silencing of PTEN significantly increased the invasive ability of PC3 cells even when miR-214 expression was inhibited. In summary, serum miR-214 expression may serve as a potential novel non-invasive biomarker for PCa screening through targeting PTEN.