2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a ...diarylpentanoid-producing polyketide synthase (PECPS) identified from Aquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS in Nicotiana benthamiana, and knockdown of PECPS expression in A. sinensis calli, we demonstrate that the C
-C
-C
scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å
), PECPS employs a one-pot formation mechanism including a "diketide-CoA intermediate-released" step for the formation of the C
-C
-C
scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.
High‐performance thermal insulating aerogels are attractive candidates for thermal protection in extreme environments. However, inorganic aerogels’ brittleness and poor machinability limit their ...applications, while organic aerogels suffer from severe strength degradation and structural collapse at high temperatures. Herein, for the first time, a thermo‐responsive self‐ceramifiable aerogel is demonstrated with exceptional strengthening and thermal insulation at high temperatures. This aerogel exhibits excellent toughness and processability like polymers under normal conditions but spontaneously transforms into high‐strength semi‐crystalline hard ceramics upon exposure to high temperatures. After prolonged thermal attack at 800 °C, the strength of the aerogels does not decrease but significantly increases several‐fold (from 0.739 to 2.726 MPa). The self‐ceramization behavior and mechanism of the aerogel are illustrated in detail. The unique self‐ceramifiable capacity enables aerogels to provide fire resistance, high‐strength support, and excellent thermal insulation at ultrahigh temperatures. Even with continuous burning at 1300 °C for 60 min, the 15 mm thick aerogel shows low backside temperature below 300 °C, crack‐free overall structure, and invariant porous morphology. This self‐ceramifiable aerogel opens up a new avenue for developing thermal‐protection materials with toughness, machinability, high strength, and thermal insulation in extreme environments.
A new thermo‐responsive self‐ceramifiable aerogel is for the first time reported with exceptional strengthening and thermal insulation at high temperatures. Under normal conditions, the aerogel exhibits excellent toughness and machinability. Upon exposure to high temperatures, the aerogel spontaneously and rapidly transforms into robust semi‐crystalline hard ceramics, thus leading to fire resistance, high strength, and thermal insulation in extreme environments.
Background and Aims
Hepatic ischemia‐reperfusion (I/R) injury, which mainly involves inflammatory responses and apoptosis, is a common cause of organ dysfunction in liver transplantation (LT). As a ...critical mediator of inflammation and apoptosis in various cell types, the role of tripartite motif‐containing (TRIM) 27 in hepatic I/R injury remains worthy of study.
Approach and Results
This study systemically evaluated the putative role of TRIM27/transforming growth factor β–activated kinase 1 (TAK1)/JNK (c‐Jun N‐terminal kinase)/p38 signaling in hepatic I/R injury. TRIM27 expression was significantly down‐regulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Subsequently, using global Trim27 knockout mice (Trim27‐KO mice) and hepatocyte‐specific Trim27 transgenic mice (Trim27‐HTG mice), TRIM27 functions to ameliorate liver damage, reduce the inflammatory response, and prevent cell apoptosis. In parallel in vitro studies, activating TRIM27 also prevented H/R‐induced hepatocyte inflammation and apoptosis. Mechanistically, TRIM27 constitutively interacted with the critical components, TAK1 and TAK1 binding protein 2/3 (TAB2/3), and promoted the degradation of TAB2/3, leading to inactivation of TAK1 and the subsequent suppression of downstream JNK/p38 signaling.
Conclusions
TRIM27 is a key regulator of hepatic I/R injury by mediating the degradation of TAB2/3 and suppression of downstream TAK1‐JNK/p38 signaling. TRIM27 may be a promising approach to protect the liver against I/R‐mediated hepatocellular damage in transplant recipients.
Background and Aims
Hepatic ischemia‐reperfusion (I/R) injury remains a major challenge affecting the morbidity and mortality of liver transplantation. Effective strategies to improve liver function ...after hepatic I/R injury are limited. Six‐transmembrane epithelial antigen of the prostate 3 (Steap3), a key regulator of iron uptake, was reported to be involved in immunity and apoptotic processes in various cell types. However, the role of Steap3 in hepatic I/R‐induced liver damage remains largely unclear.
Approach and Results
In the present study, we found that Steap3 expression was significantly up‐regulated in liver tissue from mice subjected to hepatic I/R surgery and primary hepatocytes challenged with hypoxia/reoxygenation insult. Subsequently, global Steap3 knockout (Steap3‐KO) mice, hepatocyte‐specific Steap3 transgenic (Steap3‐HTG) mice, and their corresponding controls were subjected to partial hepatic warm I/R injury. Hepatic histology, the inflammatory response, and apoptosis were monitored to assess liver damage. The molecular mechanisms of Steap3 function were explored in vivo and in vitro. The results demonstrated that, compared with control mice, Steap3‐KO mice exhibited alleviated liver damage after hepatic I/R injury, as shown by smaller necrotic areas, lower serum transaminase levels, decreased apoptosis rates, and reduced inflammatory cell infiltration, whereas Steap3‐HTG mice had the opposite phenotype. Further molecular experiments showed that Steap3 deficiency could inhibit transforming growth factor‐β–activated kinase 1 (TAK1) activation and downstream c‐Jun N‐terminal kinase (JNK) and p38 signaling during hepatic I/R injury.
Conclusions
Steap3 is a mediator of hepatic I/R injury that functions by regulating inflammatory responses as well as apoptosis through TAK1‐dependent activation of the JNK/p38 pathways. Targeting hepatocytes, Steap3 may be a promising approach to protect the liver against I/R injury.
Whether species demography and diversification are driven primarily by extrinsic environmental changes such as climatic oscillations in the Quaternary or by intrinsic biological interactions like ...coevolution between antagonists is a matter of active debate. In fact, their relative importance can be assessed by tracking past population fluctuations over considerable time periods.
We applied the pairwise sequentially Markovian coalescent approach on the genomes of 11 temperate Juglans species to estimate trajectories of changes in effective population size (N
e) and used a Bayesian-coalescent based approach that simultaneously considers multiple genomes (G-PhoCS) to estimate divergence times between lineages.
N
e curves of all study species converged 1.0 million yr ago, probably reflecting the time when the walnut genus last shared a common ancestor. This estimate was confirmed by the G-PhoCS estimates of divergence times. But all species did not react similarly to the dramatic climatic oscillations following early Pleistocene cooling, so the timing and amplitude of changes in N
e differed among species and even among conspecific lineages.
The population histories of temperate walnut species were not driven by extrinsic environmental changes alone, and a key role was probably played by species-specific factors such as coevolutionary interactions with specialized pathogens.
Pancreatic cancer (PC) is a serious malignancy with high mortality and poor prognosis due to nonspecific incipient symptoms and early metastasis. Also, increasing evidence indicates that a panel of ...genes is newly identified in the pathogenesis of PC. As is a regulatory subunit, elevated cyclin B1 (CCNB1) expression has been detected in different cancers including PC. This study is designed to investigate the effects of CCNB1 silencing on cell cycle, senescence, and apoptosis through the p53 signaling pathway in PC. PC tissues and normal pancreatic tissues were collected. Cells were transfected and assigned into different groups. The expressions of CCNB1, p53, MDM2, Bax, caspase‐9, caspase‐3, and p21 in tissues and cells were detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. β‐Galactosidase staining, MTT assay, and flow cytometry were conducted to test cell senescence, proliferation, cell cycle, and apoptosis. PC tissues showed higher expressions of CCNB1 and MDM2 and lower expressions of Bax, caspase‐9, caspase‐3, and p21. Cells transfected with shCCNB1 had lower expressions of CCNB1 and MDM2, whereas higher expressions of Bax, caspase‐9, caspase‐3, p53, and p21. The shCCNB1 group had decreased proliferation and S‐phase cell proportion and increased apoptosis, senescence, and G0/G1‐phase cell proportion. The PFT‐α group showed higher expressions of MDM2 and lower expressions of Bax, caspase‐9, caspase‐3, p53, and p21. The PFT‐α group had increased proliferation and S‐phase cell proportion and declined apoptosis, senescence, and G0/G1‐phase cell proportion. CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in PC.
CCNB1 silencing inhibits cell proliferation and promotes cell senescence via activation of the p53 signaling pathway in pancreatic cancer.
Genomics-based neoantigen discovery can be enhanced by proteomic evidence, but there remains a lack of consensus on the performance of different quality control methods for variant peptide ...identification in proteogenomics. We propose to use the difference between accurately predicted and observed retention times for each peptide as a metric to evaluate different quality control methods. To this end, we develop AutoRT, a deep learning algorithm with high accuracy in retention time prediction. Analysis of three cancer data sets with a total of 287 tumor samples using different quality control strategies results in substantially different numbers of identified variant peptides and putative neoantigens. Our systematic evaluation, using the proposed retention time metric, provides insights and practical guidance on the selection of quality control strategies. We implement the recommended strategy in a computational workflow named NeoFlow to support proteogenomics-based neoantigen prioritization, enabling more sensitive discovery of putative neoantigens.
This paper presents a fast rolling soft robot (RSR) driven by dielectric elastomer. Through novel structure design based on multisegment dielectric elastomer minimum energy structure, the robot ...appears to be a fully flexible circular configuration with excellent ability of active deformation for its body controlled by applied voltages. An equivalent pseudo-rigid-body model is developed to provide an effective analysis for the deformation and rolling mechanism. The detailed fabrication process is described, and then a robot prototype is fabricated. The resulting RSR weighs 0.88 g with a diameter of 49.66 mm, which exhibits uniquely advantageous properties including low mass, mechanical flexibility and resilience, silent operation, and fast response. Controlled by three sequential open-loop control signals generated by a developed multiplex high-voltage control system, the robot prototype can realize continuous and steady rolling locomotion on flat ground. The response time of active deformation and restoration of the robot is less than 50 ms, the speed-mass ratio is about 41.22 mm/(s·g) and the maximum speed-diameter ratio reaches approximately 0.95 s -1 . Compared with the previous similar rolling soft robots, our robot demonstrates higher rolling speed and larger speed-mass ratio, which can find potential future use in scouting and exploration missions.
•A magnetically coupled two-degree-of-freedom harvester for rotation is proposed.•The electromechanical coupling model is developed and validated experimentally.•The harvester can generate high ...voltage at low rotating speeds.•The harvester can harvest vibration energy in multiple frequency bands.
Energy can be harvested from rotational motion for powering wireless autonomous electronic devices. The paper presents a magnetically coupled two-degree-of-freedom vibration energy harvester for rotary motion applications. The design consists of two inverted piezoelectric cantilever beams whose free ends point to the rotating shaft. The centrifugal force of the inverted cantilever beam is beneficial to producing large amplitude in a low speed range. The electromechanical coupling dynamical model is developed by the energy method from Hamilton’s principle and validated experimentally. The experimental results indicate that the presented harvester is suitable for low speed rotation and can harvest vibration energy in multiple frequency bands. The first and second resonant behaviors of voltage can be obtained at 420 r/min and 550 r/min, and the average output powers are 564μW and 535.3μW, respectively.
To systematically review the epidemiologic relationship between periodontitis and type 2 diabetes mellitus (T2DM).
Four electronic databases were searched up until December 2018. The manual search ...included the reference lists of the included studies and relevant journals. Observational studies evaluating the relationship between T2DM and periodontitis were included. Meta-analyses were conducted using STATA.
A total of 53 observational studies were included. The Adjusted T2DM prevalence was significantly higher in periodontitis patients (OR = 4.04, p = 0.000), and vice versa (OR = 1.58, p = 0.000). T2DM patients had significantly worse periodontal status, as reflected in a 0.61 mm deeper periodontal pocket, a 0.89 mm higher attachment loss and approximately 2 more lost teeth (all p = 0.000), than those without T2DM. The results of the cohort studies found that T2DM could elevate the risk of developing periodontitis by 34% (p = 0.002). The glycemic control of T2DM patients might result in different periodontitis outcomes. Severe periodontitis increased the incidence of T2DM by 53% (p = 0.000), and this result was stable. In contrast, the impact of mild periodontitis on T2DM incidence (RR = 1.28, p = 0.007) was less robust.
There is an evident bidirectional relationship between T2DM and periodontitis. Further well-designed cohort studies are needed to confirm this finding. Our results suggest that both dentists and physicians need to be aware of the strong connection between periodontitis and T2DM. Controlling these two diseases might help prevent each other's incidence.
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