Metal-Ligand Bonds Based Reprogrammable and Re-processable Supramolecular Liquid Crystal Elastomer Network.

Dynamic covalent bonds endow liquid crystal elastomers (LCEs) with network rearrangeability, facilitating the fixation of mesogen alignment induced by external forces and enabling reversible actuation. In comparison, the bond exchange of supramolecular interactions is typically too significant to stably maintain the programmed alignment, particularly under intensified external stimuli. Nevertheless, the remaking and recycling of supramolecular interaction-based polymer networks are more accessible than those based on dynamic covalent bonds, as the latter are difficult to completely dissociate. Thus, preparing an LCE that possesses both supramolecular-like exchangeability and covalent bond-level stability remains a significant challenge. In this work, we addressed this issue by employing metal-ligand bonds as the crosslinking points of LCE networks. As such, mesogen alignment can be repeatedly encoded through metal-ligand bond exchange and stably maintained after programming, since the bond exchange rate is sufficiently slow when the programming and actuation temperatures are below the bond dissociation temperature. More importantly, the metal-ligand bonds can be completely dissociated at high temperatures, allowing the LCE network to be dissolved in a solvent and reshaped into desired geometries via solution casting. Building on these properties, our LCEs can be fabricated into versatile actuators, such as reversible folding origami, artificial muscles, and soft robotics.

Midterm Results of a Surgeon-Modified Device to Preserve the Flow of the Internal Iliac Artery During Endovascular Repair of Aneurysm: Single-Center Experiences.

BACKGROUND: During endovascular aneurysm repair (EVAR), commercial iliac branch devices (IBDs) have become an inescapable alternative for preserving antegrade internal iliac artery (IIA) blood flow. Due to the different morphological features of aneurysms, commercial IBDs may not be suitable for all patients. Reported experience with the implantation of the new surgeon-modified IBD (sm IBD) is limited. This investigation describes the indications, efficacy, and safety of the sm IBD. METHODS: Data from consecutive elective implantations of IBDs in patients between March 2011 and May 2021 in a single center were incorporated. The sm IBDs were indicated in patients with common iliac artery aneurysms (CIAAs) and with a challenging anatomy and in those patients with or without abdominal aortic aneurysm (AAA). RESULTS: Fifteen patients (15 male, mean age 67.6 ± 7.9 years) were included. Fifteen sm IBDs were implanted in 1 procedure (100%). Fourteen (93.3%) patients had simultaneous endovascular aneurysm repair (EVAR) and 1 (6.7%) patient previously had a bilateral CIAAs repair by EVAR. The mean common iliac artery (CIA) diameter was 36.6 ± 12.5 mm. Technical success was obtained in all patients (100%). The median operation time was 189.7 ± 78.6 min, with a median fluoroscopy time of 45.3 ± 15.9 min. Axillary artery access was used in 11 (73.3%) procedures. The mean total hospital stay was 5.6 ± 2.8 days, and the postoperative follow-up was 35.4 months (range 2-120). The estimated IIA bridge stent patency at 1 year after operation was 100% and 85.7% ± 13.2% 5 years postoperatively. One (6.7%) IIA branch was occluded, and this patient remained asymptomatic. One patient (6.7%) needed reintervention, and another (6.7%) patient had type II leakage, which is currently under close surveillance. CONCLUSIONS: Using an IBD to maintain the pelvic blood flow is an effective and feasible intravascular technique, especially for patients with an abnormal iliac artery anatomy. This novel technique has similar midterm procedural success rate compared to the use of commercial IBDs. Therefore, these devices are more suitable for patients with certain anatomic challenges and can be used as an alternative treatment.

Correlation anisotropy driven Kosterlitz-Thouless-type quantum phase transition in a Kondo simulator.

The precise manipulation of the quantum states of individual atoms/molecules adsorbed on metal surfaces is one of the most exciting frontiers in nanophysics, enabling us to realize novel single molecular logic devices and quantum information processing. Herein, by modeling an iron phthalocyanine molecule adsorbed on the Au(111) surface with a two-impurity Anderson model, we demonstrate that the quantum states of such a system could be adjusted by the uniaxial magnetic anisotropy Dz. For negative Dz, the ground state is dominated by a parallel configuration of the z component of local spins, whereas it turns to be an antiparallel one when Dz becomes positive. Interestingly, we found that these two phases are separated by a Kosterlitz-Thouless-type quantum phase transition, which is confirmed by the critical behaviors of the transmission coefficient and the local magnetic moment. Both phases are associated with spin correlation anisotropy, thus move against the Kondo effect. When the external magnetic field is applied, it first plays a role in compensating for the effect of Dz, and then it contributes significantly to the Zeeman effect for positive Dz, accompanied by the reappearance and the splitting of the Kondo peak, respectively. For fixed negative Dz, only the Zeeman behavior is revealed. Our results provide deep insights into the manipulation of the quantum phase within a single molecular junction.

Metabolic compartmentalization in yeast mitochondria: Burden and solution for squalene overproduction.

Harnessing mitochondria is considered as a promising method for biosynthesis of terpenes due to the adequate supply of acetyl-CoA and redox equivalents in mitochondria. However, mitochondrial engineering often causes serious metabolic burden indicated by poor cell growth. Here, we systematically analyzed the metabolic burden caused by the compartmentalization of the MVA pathway in yeast mitochondria for squalene synthesis. The phosphorylated intermediates of the MVA pathway, especially mevalonate-5-P and mevalonate-5-PP, conferred serious toxicity within mitochondria, which significantly compromised its possible advantages for squalene synthesis and was difficult to be significantly improved by routine pathway optimization. These phosphorylated intermediates were converted into ATP analogues, which strongly inhibited ATP-related cell function, such as mitochondrial oxidative respiration. Fortunately, the introduction of a partial MVA pathway from acetyl-CoA to mevalonate in mitochondria as well as the augmentation of the synthesis of mevalonate in cytosol could significantly promote the growth of yeasts. Accordingly, a combinatorial strategy of cytoplasmic and mitochondrial engineering was proposed to alleviate the metabolic burden caused by the compartmentalized MVA pathway in mitochondria and improve cell growth. The strategy also displayed the superimposed effect of cytoplasmic engineering and mitochondrial engineering on squalene production. Through a two-stage fermentation process, the squalene titer reached 21.1 g/L with a specific squalene titer of 437.1 mg/g dcw, which was the highest at present. This provides new insight into the production of squalene and other terpenes in yeasts based on the advantages of mitochondrial engineering.

[Tadalafil combined with behavioral therapy and psychological counseling for erectile dysfunction].

OBJECTIVE: To investigate the clinical effect of tadalafil combined with behavioral therapy and psychological counseling in the treatment of erectile dysfunction (ED). METHODS: We collected the clinical data on 338 cases of ED treated in our andrology clinic with tadalafil combined with behavioral therapy and psychological counseling (the trial group, n = 159) or with tadalafil alone (the control group, n = 179) from January to December 2019. Using chief complaints scores as the main observation indexes, we evaluated the subjective feelings and objective symptoms of the patients during their sexual life. RESULTS: After treatment, the patients in the trial group, compared with the controls, showed significantly lower chief complaints scores (1.96 ± 1.38 vs 2.73 ± 1.80, P < 0.01) and higher satisfaction with the therapeutic effect (67.9% vs 47.5%, P < 0.01). No statistically significant difference was observed in the IIEF-5 scores between the two groups before and after treatment. CONCLUSIONS: Tadalafil combined with behavior therapy and psychological counseling is superior to oral tadalafil alone in the treatment of ED, which affords greater satisfaction with the therapeutic effect, higher quality of sexual life, and better relationship between the partners.

B, N-co-doped graphene-supported Ir and Pt clusters for methane activation and C─C coupling: A density functional theory study.

Methane conversion by using transition metal catalysts plays in an important role in various usages of the industrial process. The mechanism of methane conversion on B, N-co-doped graphene supported Ir and Pt clusters, BNG-Ir4 and BNG-Pt4, have been investigated using density functional theory calculations. Methane was found to adsorb on BNG-Ir4 and BNG-Pt4 clusters via strong agostic interactions. The first step of methane dehydrogenation on BNG-Ir4 has a lower energy barrier, indicating a facile methane dissociation on BNG-Ir4. In addition, it shows that hydrogen molecule can form on the BNG-Ir4 and hydrogen can desorb from the surface. Besides, the C-C coupling reaction of CH3 to form ethane is a more thermodynamically favorable process than CH3 dehydrogenation on BNG-Ir4. Further, ethane is easier to desorb from the surface due to its low desorption energy. Therefore, the BNG-Ir4 cluster is a potential catalyst for activating methane to form ethane and to produce hydrogen. © 2019 Wiley Periodicals, Inc.

RNA-Seq analysis uncovers non-coding small RNA system of Mycobacterium neoaurum in the metabolism of sterols to accumulate steroid intermediates.

BACKGROUND: Understanding the metabolic mechanism of sterols to produce valuable steroid intermediates in mycobacterium by a noncoding small RNA (sRNA) view is still limited. In the work, RNA-seq was implemented to investigate the noncoding transcriptome of Mycobacterium neoaurum (Mn) in the transformation process of sterols to valuable steroid intermediates, including 9α-hydroxy-4-androstene-3,17-dione (9OHAD), 1,4-androstadiene-3,17-dione (ADD), and 22-hydroxy-23, 24-bisnorchola-1,4-dien-3-one (1,4-BNA). RESULTS: A total of 263 sRNA candidates were predicted from the intergenic regions in Mn. Differential expression of sRNA candidates was explored in the wide type Mn with vs without sterol addition, and the steroid intermediate producing Mn strains vs wide type Mn with sterol addition, respectively. Generally, sRNA candidates were differentially expressed in various strains, but there were still some shared candidates with outstandingly upregulated or downregulated expression in these steroid producing strains. Accordingly, four regulatory networks were constructed to reveal the direct and/or indirect interactions between sRNA candidates and their target genes in four groups, including wide type Mn with vs without sterol addition, 9OHAD, ADD, and BNA producing strains vs wide type Mn with sterol addition, respectively. Based on these constructed networks, several highly focused sRNA candidates were discovered to be prevalent in the networks, which showed comprehensive regulatory roles in various cellular processes, including lipid transport and metabolism, amino acid transport and metabolism, signal transduction, cell envelope biosynthesis and ATP synthesis. To explore the functional role of sRNA candidates in Mn cells, we manipulated the overexpression of candidates 131 and 138 in strain Mn-9OHAD, which led to enhanced production of 9OHAD from 1.5- to 2.3-fold during 6 d' fermentation and a slight effect on growth rate. CONCLUSIONS: This study revealed the complex and important regulatory roles of noncoding small RNAs in the metabolism of sterols to produce steroid intermediates in Mn, further analysis of which will promote the better understanding about the molecular metabolism of these sRNA candidates and open a broad range of opportunities in the field.

Single nucleotide polymorphism analysis for the production of valuable steroid intermediates in Mycobacterium neoaurum.

OBJECTIVES: To investigate single nucleotide polymorphism (SNP) in the transformation process of phytosterol to valuable steroid intermediates in three steroid-producing Mycobacterium neoaurum strains using deep sequencing and bioinformation analysis. RESULTS: The assembled contig sequences from RNA sequencing of strains producing 9α-hydroxy-4-androstene-3,17-dione (9OHAD), 1,4-androstadiene-3,17-dione (ADD), and 22-hydroxy-23, 24-bisnorchola-1,4-dien-3-one (1,4-BNA) were analyzed for the presence of putative SNPs for steroid catabolism. 413, 375, and 491 SNPs were detected in the coding domain sequences and non-coding domain sequences of RNA sequencing reads of M. neoaurum strains producing 9OHAD, ADD, and BNA, respectively. Special attention was focused on SNPs associated with genes showing differential expression at proteome level, including the genes for sterol catabolism, glycerol catabolic process, signal transduction systems, transport system and energy metabolism. CONCLUSIONS: The work facilitates the understanding of underlying genetic changes that may be responsible for steroid accumulation in M. neoaurum and is useful for its targeted genetic engineering.

Effects of two pesticides, TZP and JGM, on reproduction of three planthopper species, Nilaparvata lugens Stål, Sogatella furcifera Horvath, and Laodelphax striatella Fallén.

Three planthopper species, the brown planthopper (BPH), Nilaparvata lugens Stål, the white-backed planthopper (WBPH), Sogatella furcifera Horvath, and the small brown planthopper (SBPH), Laodelphax striatella Fallén, often co-occur in rice grown regions of China. The present investigation examined effects of two pesticides, triazophos (TZP) and jinggangmycin (JGM) (a fungicide), on reproduction of BPH, WBPH, and SBPH. The results showed that TZP stimulated the fecundity of the three planthopper species. Interestingly, JGM stimulated the fecundity of BPH but suppressed the fecundity of WBPH. In addition, TZP and JGM had a significant effect on the preoviposition period (PVD), the oviposition period (OPD), and the longevity of adult females (LAF) of BPH and WBPH. Based on these findings, to avoid resurgence occurrence of planthoppers, we suggest that the application of TZP should be banned in rice fields, that JGM should be used to control rice sheath blight at the early growth stages of rice (with WBPH occurrence and without BPH occurrence).

Comparisons of topical and spray applications of two pesticides, triazophos and jinggangmycin, on the protein content in the ovaries and fat bodies of the brown planthopper Nilaparvata lugens Stål (Hemiptera:Delphacidae).

The pesticide-induced stimulation of reproduction in pests is one of the most important mechanisms of pest resurgence. There have been numerous reports on the insecticide-induced stimulation of reproduction. However, the relationship between pesticide application method and pest resurgence (stimulation of reproduction) has received little attention. Here, we studied the effect of two treatment methods, triazophos (TZP) and jinggangmycin (JGM), on the protein content in the ovaries and fat bodies of the brown planthopper (BPH) Nilaparvata lugens Stål. The results showed that pesticide treatment methods significantly affected the protein content in the ovaries and fat bodies of BPH. In addition, grand means (means of main effect) of the protein content at 2 and 3 days after emergence (2 and 3 DAE) for foliar sprays was significantly higher than that observed after topical treatments, which increased by 23.9% (from 1.42 to 1.76) and 8.82% (from 4.42 to 4.81), respectively. No significant differences on the protein content in the ovaries and fat bodies for the JGM topical treatment were observed compared with controls. However, the protein content for JGM foliar sprays was significantly higher than that for the controls. The protein contents in both topical and spray treatments of TZP were significantly higher than those of the controls. Ovarian protein is mainly yolk protein. There is a positive correlation between ovarian protein content and the number of eggs laid. These findings show that foliar spray of the pesticides promotes the resurgence of BPH. Therefore, the foliar spray of some pesticides, such as JGM, should be avoided for the control of pests, which is the sideeffects of the fungicide on non-target insect pests' occurrence.

Reprogramming Photoresponsive Liquid Crystalline Elastomer via Force-Directed Evaporation.

Incorporating photothermal agents into thermoresponsive liquid crystalline elastomers (LCEs) offers remote and spatio-temporal control in actuation. Typically, both the light responsiveness and actuation behaviors are fixed since the agent doping and mesogen alignment are conducted before network formation. Here, we report an approach that enables programming photoresponsive LCEs after synthesis via force-directed evaporation. Different photothermal agents can be doped or removed by swelling the fully cross-linked LCEs in a specific solution, achieving the introduction and erasing of the photoresponsiveness. Moreover, the network swelling deletes the registered alignment, which allows for redefining the molecular order via re-evaporating the solvent with force imposed. This "one stone, two birds" strategy paves the way to simultaneously program/reprogram the actuation mode and responsiveness of LCEs, even in a spatio-selective manner to achieve complex actuations. Our approach is expandable to three-dimensional (3D) printed LCEs to access geometrically sophisticated shape-changing.

Exploring the Risk Factors for Deep Vein Thrombosis after Percutaneous Nephrolithotomy.

BACKGROUND: Deep vein thrombosis (DVT), a frequent complication following percutaneous nephrolithotomy (PCNL), may lead to severe conditions like pulmonary embolism. Current knowledge on postoperative DVT risk factors is, however, limited. The aim of our study was to investigate the risk of DVT after PCNL. METHODS: A retrospective study was conducted on patients who underwent PCNL from March 2020 to March 2023 at our institution. Patient demographics and clinical data, including, DVT-specific information, preoperative labs, and surgical details, was evaluated. RESULTS: One hundred patients were included. Thirty-two (20 males, 12 females, mean age 52.5 ± 7.4 years) developed lower limb DVT post-surgery, while the remaining 68 (48 males, 20 females, mean age 51.1 ± 5.5 years) had no DVT symptoms. Analysis revealed significant correlations between hyperlipidemia, operating time, postoperative bed rest duration, D-dimer level on the first day after surgery, Caprini risk assessment model (RAM) score, and DVT risk. D-dimer on the first day after percutaneous nephrolithotomy, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL. Sex, age, hypertension status, diabetes status and smoking and drinking habits were not significantly associated with DVT risk. CONCLUSIONS: D-dimer on the first day after PCNL, postoperative bed rest time and Caprini RAM scores were independent risk factors for DVT after PCNL.

Ultrathin Boundary-Less SnO2 Films with Surface-Activated Two-Dimensional Nanograins Enable Fast and Sensitive Hydrogen Gas Sensing.

Fast and reliable semiconductor hydrogen sensors are crucially important for the large-scale utilization of hydrogen energy. One major challenge that hinders their practical application is the elevated temperature required, arising from undesirable surface passivation and grain-boundary-dominated electron transportation in the conventional nanocrystalline sensing layers. To address this long-standing issue, in the present work, we report a class of highly reactive and boundary-less ultrathin SnO2 films, which are fabricated by the topochemical transformation of 2D SnO transferred from liquid Sn-Bi droplets. The ultrathin SnO2 films are purposely made to consist of well-crystallized quasi-2D nanograins with in-plane grain sizes going beyond 30 nm, whereby the hydroxyl adsorption and grain boundary side-effects are effectively suppressed, giving rise to an activated (101)-dominating dangling-bond surface and a surface-controlled electrical transportation with an exceptional electron mobility of 209 cm2 V-1 s-1. Our work provides a new cost-effective strategy to disruptively improve the gas reception and transduction of SnO2. The proposed chemiresistive sensors exhibit fast, sensitive, and selective hydrogen sensing performance at a much-reduced working temperature of 60 °C. The remarkable sensing performance as well as the simple and scalable fabrication process of the ultrathin SnO2 films render the thus-developed sensors attractive for long awaited practical applications in hydrogen-related industries.

Effects of Brown Fishmeal on Growth Performance, Digestibility, and Lipid Metabolism of the Chinese Soft-Shelled Turtle (Pelodiscus sinensis).

The aim of this study was to evaluate the effect of brown fishmeal in replacement of white fishmeal in the diet of Chinese soft-shelled turtles and to find the optimal amount of brown fishmeal to add. Five experimental groups were set up and fed to animals, and they were composed by different proportions of white and brown fishmeal: G1 (30% white and 25% brown fishmeal), G2 (25% white and 30% brown fishmeal), G3 (20% white and 35% brown fishmeal), G4 (15% white and 40% brown fishmeal), G5 (10% white and 45% brown fishmeal). G1 is regarded as the control group. Turtles were randomly divided into five experimental groups with four replicates each. The experiment lasted 72 days. The results showed that the WGR, SGR, FCR, and HSI of the G3 group were not significantly different from those of the control group (P > 0.05). In addition, brown fishmeal can increase the crude protein content in the muscles of them. Among the serum biochemical indices, there was no significant difference between the G3 group and the G1 group, except for the level of TG (P > 0.05). Meanwhile, the activities of AST, ALT, and CAT in the liver of the G3 group did not differ significantly from those of the G1 group (P > 0.05). However, the activities of ACP, AKP, and T-AOC were significantly decreased in the G3 group (P < 0.05). In addition, the alteration of fishmeal did not affect the digestive enzyme activities in the stomach, liver, and intestine, and there is no significant difference (P > 0.05). Importantly, with increasing brown fishmeal addition, the expression of Fas, Pparγ, Scd, and Stat3 showed a significant increase, while the expression of Bmp4 decreased significantly (P < 0.05). In this study, the addition of 20% white fishmeal and 35% brown fishmeal to the diet of Chinese soft-shelled turtles did not adversely affect growth performance. Therefore, 20% white fishmeal and 35% brown fishmeal are the most practical feed formulations for Chinese soft-shelled turtles in this study.

PI3K/AKT mediated De novo fatty acid synthesis regulates RIG-1/MDA-5-dependent type I IFN responses in BVDV-infected CD8+T cells.

Bovine viral diarrhea virus (BVDV) has caused massive economic losses in the cattle business worldwide. Fatty acid synthase (FASN), a key enzyme of the fatty acid synthesis (FAS) pathway, has been shown to support virus replication. To investigate the role of fatty acids (FAs) in BVDV infection, we infected CD8+T lymphocytes obtained from healthy cattle with BVDV in vitro. During early cytopathic (CP) and noncytopathic (NCP) BVDV infection in CD8+ T cells, there is an increase in de novo lipid biosynthesis, resulting in elevated levels of free fatty acids (FFAs) and triglycerides (TG). BVDV infection promotes de novo lipid biosynthesis in a dose-dependent manner. Treatment with the FASN inhibitor C75 significantly reduces the phosphorylation of PI3K and AKT in BVDV-infected CD8+ T cells, while inhibition of PI3K with LY294002 decreases FASN expression. Both CP and NCP BVDV strains promote de novo fatty acid synthesis by activating the PI3K/AKT pathway. Further investigation shows that pharmacological inhibitors targeting FASN and PI3K concurrently reduce FFAs, TG levels, and ATP production, effectively inhibiting BVDV replication. Conversely, the in vitro supplementation of oleic acid (OA) to replace fatty acids successfully restored BVDV replication, underscoring the impact of abnormal de novo fatty acid metabolism on BVDV replication. Intriguingly, during BVDV infection of CD8+T cells, the use of FASN inhibitors prompted the production of IFN-α and IFN-ß, as well as the expression of interferon-stimulated genes (ISGs). Moreover, FASN inhibitors induce TBK-1 phosphorylation through the activation of RIG-1 and MDA-5, subsequently activating IRF-3 and ultimately enhancing the IFN-1 response. In conclusion, our study demonstrates that BVDV infection activates the PI3K/AKT pathway to boost de novo fatty acid synthesis, and inhibition of FASN suppresses BVDV replication by activating the RIG-1/MDA-5-dependent IFN response.

Network Topology Optimization for Alignment Programming of a Dynamic Liquid Crystalline Organo-Gel.

Liquid crystalline elastomers (LCEs) exhibit muscle-like actuation upon an external stimulus. To control this, various alignment programming strategies have been developed over the past decades. Among them, force-directed solvent evaporation, namely, that the alignment depends on the applied external force during solvent evaporation, is appreciated for its universality in material design and versatility in attainable actuations. Here, we investigate the influence of network topology on the alignment programming of a liquid crystalline (LC) organo-gel via varying feeding ratios of the monomers. As a result, distinct self-supporting actuations can be repeatedly introduced into a topology-optimized LC organo-gel. Beyond this, the bond exchange reaction of the embedded ester groups can be activated upon heating, which enables alignment manipulation based on dynamic network reconfiguration after drying. The availability of inviting two distinct programming strategies into one LCE network allows us to regulate the LCE alignment at both the gel and dried states, offering ample room to diversify actuation manners. Our design principle shall be adopted by other dynamic LCE systems owing to its maneuverability.

Transcriptomic and weighted gene co-expression network analysis of tropic and temperate maize inbred lines recovering from heat stress.

Heat stress (HS) causes imbalance of cellular homeostasis, growth impairment and extensively yield loss in crop production. In the present study, the tropic maize inbred CIMBL55 showed more thermotolerance than the maize temperate inbred B73, with less leaf damage rate and ROS accumulation. Transcriptome profiling of CIMBL55 and B73 upon (exposing at 45 â„ƒ for 0, 1, and 6 h) and post (recovering at 28 â„ƒ for 1 and 6 h) HS were further assessed and a total of 20204 DEGs were identified. Functional annotation revealed that HS activated unfolded protein response in endoplasmic reticulum in both two inbreds. Moreover, in CIMBL55, far more primary and secondary metabolism pathways were transcriptional altered. Afterwards, weighted gene co-expression analysis grouped all expressed genes into eighteen co-expressed modules. Four HS responsive and four CIMBL55 recovery-related modules were subsequently identified. Highly connected genes (hub genes) in these modules were characterized as transcription factors, heat shock proteins, Ca2+ signaling related genes and various enzymes. Moreover, one hub gene, ZmHsftf13 was verified to positively regulate thermotolerance by heterologous expressing in Arabidopsis and its Mu insertion mutant. The present research provides promising genes related to HS response in maize and is of great significance for breeding.

Imbalance of helper T cell subtypes and adipokine secretion in perivascular adipose tissue as a trigger of atherosclerosis in chronic Porphyromonas gingivalis W83 infection.

Periodontal disease, a prevalent oral disease, is an independent risk factor for atherosclerosis. Porphyromonas gingivalis (P.g), a keystone pathogen of periodontal disease, contributes to the pathogenesis of atherosclerosis. However, the exact mechanism remains unclear. An increasing number of studies have proposed the atherogenic influence of perivascular adipose tissue (PVAT) in pathological conditions including hyperlipidemia and diabetes. Nevertheless, the role of PVAT in atherosclerosis promoted by P.g infection has not been explored. In our study, we investigated the association between P.g colonization in PVAT and progression of atherosclerosis through experiments on clinical samples. We further investigated P.g invasion of PVAT, PVAT inflammation, aortic endothelial inflammation, aortic lipid deposition, and systemic inflammation in C57BL/6 J mice with or without P.g infection at 20, 24, and 28 weeks of age. PVAT inflammation, characterized by imbalance in Th1/Treg and dysregulated adipokine levels, was associated with P.g invasion, preceding endothelial inflammation that occurred independently of its direct invasion. The phenotype of systemic inflammation coincided with that of PVAT inflammation, but systemic inflammation occurred after endothelial inflammation. Therefore PVAT inflammation in early atherosclerosis could be a primary trigger of aortic endothelial inflammation and lipid deposition in chronic P.g infection, through the dysregulated paracrine secretion of T helper-1-related adipokines.

Boosting the epoxidation of squalene to produce triterpenoids in Saccharomyces cerevisiae.

BACKGROUND: Polycyclic triterpenoids (PTs) are common in plants, and have attracted considerable interest due to their remarkable biological activities. Currently, engineering the ergosterol synthesis pathway in Saccharomyces cerevisiae is a safe and cost-competitive way to produce triterpenoids. However, the strict regulation of ERG1 involved in the epoxidation of squalene limits the triterpenoid production. RESULTS: In this study, we found that the decrease in ERG7 protein level could dramatically boost the epoxidation of squalene by improving the protein stability of ERG1. We next explored the potential factors that affected the degradation process of ERG1 and confirmed that ERG7 was involved in the degradation process of ERG1. Subsequently, expression of four different triterpene cyclases utilizing either 2,3-oxidosqualene or 2,3:22,23-dioxidosqualene as the substrate in ERG7-degraded strains showed that the degradation of ERG7 to prompt the epoxidation of squalene could significantly increase triterpenoid production. To better display the potential of the strategy, we increased the supply of 2,3-oxidosqualene, optimized flux distribution between ergosterol synthesis pathway and ß-amyrin synthesis pathway, and modified the GAL-regulation system to separate the growth stage from the production stage. The best-performing strain ultimately produced 4216.6 ± 68.4 mg/L of ß-amyrin in a two-stage fed-fermentation (a 47-fold improvement over the initial strain). CONCLUSIONS: This study showed that deregulation of the native restriction in ergosterol pathway was an effective strategy to increase triterpenoid production in yeast, which provided a new insight into triterpenoids biosynthesis.

A contrast-enhanced CT-based radiomic nomogram for the differential diagnosis of intravenous leiomyomatosis and uterine leiomyoma.

Objective: Uterine intravenous leiomyomatosis (IVL) is a rare and unique leiomyoma that is difficult to surgery due to its ability to extend into intra- and extra-uterine vasculature. And it is difficult to differentiate from uterine leiomyoma (LM) by conventional CT scanning, which results in a large number of missed diagnoses. This study aimed to evaluate the utility of a contrast-enhanced CT-based radiomic nomogram for preoperative differentiation of IVL and LM. Methods: 124 patients (37 IVL and 87 LM) were retrospectively enrolled in the study. Radiomic features were extracted from contrast-enhanced CT before surgery. Clinical, radiomic, and combined models were developed using LightGBM (Light Gradient Boosting Machine) algorithm to differentiate IVL and LM. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC) and decision curve analysis (DCA). Results: Clinical factors, such as symptoms, menopausal status, age, and selected imaging features, were found to have significant correlations with the differential diagnosis of IVL and LM. A total of 108 radiomic features were extracted from contrast-enhanced CT images and selected for analysis. 29 radiomics features were selected to establish the Rad-score. A clinical model was developed to discriminate IVL and LM (AUC=0.826). Radiomic models were used to effectively differentiate IVL and LM (AUC=0.980). This radiological nomogram combined the Rad-score with independent clinical factors showed better differentiation efficiency than the clinical model (AUC=0.985, p=0.046). Conclusion: This study provides evidence for the utility of a radiomic nomogram integrating clinical and radiomic signatures for differentiating IVL and LM with improved diagnostic accuracy. The nomogram may be useful in clinical decision-making and provide recommendations for clinical treatment.