Protein structures in the Protein Data Bank provide a wealth of data about the interactions that determine the native states of proteins. Using the probability theory, we derive an atomic ...distance‐dependent statistical potential from a sample of native structures that does not depend on any adjustable parameters (Discrete Optimized Protein Energy, or DOPE). DOPE is based on an improved reference state that corresponds to noninteracting atoms in a homogeneous sphere with the radius dependent on a sample native structure; it thus accounts for the finite and spherical shape of the native structures. The DOPE potential was extracted from a nonredundant set of 1472 crystallographic structures. We tested DOPE and five other scoring functions by the detection of the native state among six multiple target decoy sets, the correlation between the score and model error, and the identification of the most accurate non‐native structure in the decoy set. For all decoy sets, DOPE is the best performing function in terms of all criteria, except for a tie in one criterion for one decoy set. To facilitate its use in various applications, such as model assessment, loop modeling, and fitting into cryo‐electron microscopy mass density maps combined with comparative protein structure modeling, DOPE was incorporated into the modeling package MODELLER‐8.
Microbe‐mediated mineralization is ubiquitous in nature, involving bacteria, fungi, viruses, and algae. These mineralization processes comprise calcification, silicification, and iron mineralization. ...The mechanisms for mineral formation include extracellular and intracellular biomineralization. The mineral precipitating capability of microbes is often harnessed for green synthesis of metal nanoparticles, which are relatively less toxic compared with those synthesized through physical or chemical methods. Microbe‐mediated mineralization has important applications ranging from pollutant removal and nonreactive carriers, to other industrial and biomedical applications. Herein, the different types of microbe‐mediated biomineralization that occur in nature, their mechanisms, as well as their applications are elucidated to create a backdrop for future research.
Different types of biomineralization, including calcification, silicification, iron, carbon, nitrogen, and phosphorus mineralization, which are mediated by algae, bacteria, fungi, and viruses, are summarized. The mechanisms of extracellular and intracellular microbe‐mediated mineralization, as well as their environmental, industrial, and biotechnological applications are discussed in depth.
Adverse childhood experiences (ACEs) have been associated with poor health status later in life. The objective of the present study was to examine the relationship between ACEs and health-related ...behaviors, chronic diseases, and mental health in adults.
A cross-sectional study was performed with 1501 residents of Macheng, China. The ACE International Questionnaire (ACE-IQ) was used to assess ACEs, including psychological, physical, and sexual forms of abuse, as well as household dysfunction. The main outcome variables were lifetime drinking status, lifetime smoking status, chronic diseases, depression, and posttraumatic stress disorder. Multiple logistic regression models were used to examine the associations between overall ACE score and individual ACE component scores and risk behaviors/comorbidities in adulthood after controlling for potential confounders.
A total of 66.2% of participants reported at least one ACE, and 5.93% reported four or more ACEs. Increased ACE scores were associated with increased risks of drinking (adjusted odds ratio AOR = 1.09, 95% confidence intervals CI: 1.00-1.09), chronic disease (AOR = 1.17, 95% CI: 1.06-1.28), depression (AOR = 1.37, 95% CI: 1.27-1.48), and posttraumatic stress disorder (AOR = 1.32, 95% CI: 1.23-1.42) in adulthood. After adjusting for confounding factors, the individual ACE components had different impacts on risk behavior and health, particularly on poor mental health outcomes in adulthood.
ACEs during childhood were significantly associated with risk behaviors and poor health outcomes in adulthood, and different ACE components had different long-term effects on health outcomes in adulthood.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide because of rapid progression and high incidence of metastasis or recurrence. Accumulating evidence shows that ...CD73-expressing tumor cell is implicated in development of several types of cancer. However, the role of CD73 in HCC cell has not been systematically investigated and its underlying mechanism remains elusive.
CD73 expression in HCC cell was determined by RT-PCR, Western blot, and immunohistochemistry staining. Clinical significance of CD73 was evaluated by Cox regression analysis. Cell counting kit-8 and colony formation assays were used for proliferation evaluation. Transwell assays were used for motility evaluations. Co-immunoprecipitation, cytosolic and plasma membrane fractionation separation, and ELISA were applied for evaluating membrane localization of P110β and its catalytic activity. NOD/SCID/γc(null) (NOG) mice model was used to investigate the in vivo functions of CD73.
In the present study, we demonstrate that CD73 was crucial for epithelial-mesenchymal transition (EMT), progression and metastasis in HCC. CD73 expression is increased in HCC cells and correlated with aggressive clinicopathological characteristics. Clinically, CD73 is identified as an independent poor prognostic indicator for both time to recurrence and overall survival. CD73 knockdown dramatically inhibits HCC cells proliferation, migration, invasion, and EMT in vitro and hinders tumor growth and metastasis in vivo. Opposite results could be observed when CD73 is overexpressed. Mechanistically, adenosine produced by CD73 binds to adenosine A2A receptor (A2AR) and activates Rap1, which recruits P110β to the plasma membrane and triggers PIP3 production, thereby promoting AKT phosphorylation in HCC cells. Notably, a combination of anti-CD73 and anti-A2AR achieves synergistic depression effects on HCC growth and metastasis than single agent alone.
CD73 promotes progression and metastasis through activating PI3K/AKT signaling, indicating a novel prognostic biomarker for HCC. Our data demonstrate the importance of CD73 in HCC in addition to its immunosuppressive functions and revealed that co-targeting CD73 and A2AR strategy may be a promising novel therapeutic strategy for future HCC management.
Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine ...the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease.
The field of modular self-reconfigurable robotic systems addresses the design, fabrication, motion planning, and control of autonomous kinematic machines with variable morphology. Modular ...self-reconfigurable systems have the promise of making significant technological advances to the field of robotics in general. Their promise of high versatility, high value, and high robustness may lead to a radical change in automation. Currently, a number of researchers have been addressing many of the challenges. While some progress has been made, it is clear that many challenges still exist. By illustrating several of the outstanding issues as grand challenges that have been collaboratively written by a large number of researchers in this field, this article has shown several of the key directions for the future of this growing field
A novel full state‐constrained integrated guidance and control (IGC) schema for aerial interceptors under input saturation with tunnel‐prescribed performance is proposed. To achieve an appointed‐time ...engagement with less overshoot phenomenon, the tunnel‐prescribed performance control (TPPC) technique is applied to generate virtual guidance laws, where the tracking of desired line of sight (LOS) angles possesses predefined‐time convergent property. For the sake of the flight safety of interceptors in a practical flight environment, the physical limitations on the flight angles and the angular rates of attitude systems are taken into consideration. The integral barrier Lyapunov function (iBLF) technique is adopted to ensure all the attitude states within a user‐defined domain. The nominal virtual commands are generated adaptively by the backstepping method combined with some novel dynamic surfaces. To further eliminate the possible input saturation, a novel one‐order auxiliary system is constructed to compensate for the discrepancy of the virtual input commands. All the signals in the closed‐loop system are strictly proven to be bounded by Lyapunov theory. The simulation results show the effectiveness of the proposed IGC schema by comparison with other IGC laws.
A recoverable catalyst that simultaneously stabilizes emulsions would be highly advantageous in streamlining processes such as biomass refining, in which the immiscibility and thermal instability of ...crude products greatly complicates purification procedures. Here, we report a family of solid catalysts that can stabilize water-oil emulsions and catalyze reactions at the liquid/liquid interface. By depositing palladium onto carbon nanotube-inorganic oxide hybrid nanoparticles, we demonstrate biphasic hydrodeoxygenation and condensation catalysis in three substrate classes of interest in biomass refining. Microscopic characterization of the emulsions supports localization of the hybrid particles at the interface.
With the extensive applications of biomagnetic signals derived from active biological tissue in both clinical diagnoses and human-computer-interaction, there is an increasing need for approachable ...weak biomagnetic sensing technology. The inherent merits of giant magnetoresistance (GMR) and its high integration with multiple technologies makes it possible to detect weak biomagnetic signals with micron-sized, non-cooled and low-cost sensors, considering that the magnetic field intensity attenuates rapidly with distance. This paper focuses on the state-of-art in integrated GMR technology for approachable biomagnetic sensing from the perspective of discipline fusion between them. The progress in integrated GMR to overcome the challenges in weak biomagnetic signal detection towards high resolution portable applications is addressed. The various strategies for 1/
noise reduction and sensitivity enhancement in integrated GMR technology for sub-pT biomagnetic signal recording are discussed. In this paper, we review the developments of integrated GMR technology for in vivo/vitro biomagnetic source imaging and demonstrate how integrated GMR can be utilized for biomagnetic field detection. Since the field sensitivity of integrated GMR technology is being pushed to fT/Hz
with the focused efforts, it is believed that the potential of integrated GMR technology will make it preferred choice in weak biomagnetic signal detection in the future.
Modern agricultural practices rely on synthetic fungicides to control plant disease, but the application of these fungicides has raised concerns regarding human and environmental health for many ...years. As a substitute, environmentally friendly fungicides have been increasingly introduced as alternatives to synthetic fungicides. However, the impact of these environmentally friendly fungicides on plant microbiomes has received limited attention. In this study, we used amplicon sequencing to compare the bacterial and fungal microbiomes in the leaves of powdery mildew-infected cucumber after the application of two environmentally friendly fungicides (neutralized phosphorous acid (NPA) and sulfur) and one synthetic fungicide (tebuconazole). The phyllosphere α-diversity of both the bacterial and fungal microbiomes showed no significant differences among the three fungicides. For phyllosphere β-diversity, the bacterial composition exhibited no significant differences among the three fungicides, but fungal composition was altered by the synthetic fungicide tebuconazole. While all three fungicides significantly reduced disease severity and the incidence of powdery mildew, NPA and sulfur had minimal impacts on the phyllosphere fungal microbiome relative to the untreated control. Tebuconazole altered the phyllosphere fungal microbiome by reducing the abundance of fungal OTUs such as Dothideomycetes and Sordariomycetes, which included potentially beneficial endophytic fungi. These results indicated that treatments with the environmentally friendly fungicides NPA and sulfur have fewer impacts on the phyllosphere fungal microbiome while maintaining the same control efficacy as the synthetic fungicide tebuconazole.