Search

Abstract From both economic and environmental perspectives, ethylene glycol, the principal constituent in the degradation of PET, emerges as an optimal feedstock for microbial cell factories. Traditional methods for constructing Escherichia coli chassis cells capable of utilizing ethylene glycol as a non-sugar feedstock typically involve overexpressing the genes fucO and aldA. However, these approaches have not succeeded in enabling the exclusive use of ethylene glycol as the sole source of carbon and energy for growth. Through ultraviolet radiation-induced mutagenesis and subsequent laboratory adaptive evolution, an EG02 strain emerged from E. coli MG1655 capable of utilizing ethylene glycol as its sole carbon and energy source, demonstrating an uptake rate of 8.1 ± 1.3 mmol/gDW h. Comparative transcriptome analysis guided reverse metabolic engineering, successfully enabling four wild-type E. coli strains to metabolize ethylene glycol exclusively. This was achieved through overexpression of the gcl, hyi, glxR, and glxK genes. Notably, the engineered E. coli chassis cells efficiently metabolized the 87 mM ethylene glycol found in PET enzymatic degradation products following 72 h of fermentation. This work presents a practical solution for recycling ethylene glycol from PET waste degradation products, demonstrating that simply adding M9 salts can effectively convert them into viable raw materials for E. coli cell factories. Our findings also emphasize the significant roles of genes associated with the glycolate and glyoxylate degradation I pathway in the metabolic utilization of ethylene glycol, an aspect frequently overlooked in previous research.

Abstract Background Testicular metastasis from malignant solid tumors is extremely rare. It is usually found by chance during autopsy or pathological examination of testicular specimens. Therefore, we consider it necessary to report our patient’s case of testicular metastasis from colon cancer. Case presentation We report a 61-year-old Han Chinese male patient who presented to our clinic with progressive painless swelling of the right testicle for 2 years. Positron emission tomography–computed tomography scans showed increased 18F-fluorodeoxyglucose metabolism in the right testicle, possibly owing to distant metastasis. His previous medical history suggested that he had undergone laparoscopic-assisted right hemicolectomy for ascending colon cancer 4 years ago. Considering the ascending colon cancer metastasis to the right testicle, we performed a right radical testicular resection through an inguinal approach. Postoperative histological examination showed intestinal metastatic adenocarcinoma. Conclusion Colon cancer metastasis to the testes is uncommon. The clinical and imaging manifestations of this tumor are nonspecific, so the diagnosis relies on postoperative pathology. If testicular metastasis is found, treatment principles for advanced colon cancer should be followed.

Abstract Adipose tissue-derived stem cells (ADSCs) have been shown to improve erectile function in animal models of erectile dysfunction. However, few studies have been carried out using a reliable in vivo imaging method to trace transplanted cells in real time, which is necessary for systematic investigation of cell therapy. The study aims to explore the feasibility of non-invasively monitoring intracavernous injection of ADSCs in rat and miniature pig corpus cavernosum using in vivo magnetic resonance (MR) imaging. Thirty-six male Sprague Dawley rats (10 weeks old) and six healthy, sexually mature male miniature pigs (20 kg weight) were obtained. ADSCs were isolated from paratesticular fat of donor rats and cultured. Then ADSCs were labeled with superparamagnetic iron oxide nanoparticles (SPIONs), a type of MR imaging contrast agent, before transplantation into rats and pigs. After intracavernous injection, all rats and pigs underwent and were analyzed by MR imaging at the day of ADSC transplantation and follow-up at 1, 2 and 4 weeks after transplantation. In addition, penile histological examination was performed on all rats and pigs before (n = 6) and at 1 day (n = 6), 1 week (n = 6), 2 weeks (n = 6) or 4 weeks (n = 12) after ADSC transplantation. SPION-labeled ADSCs demonstrated a strong decreased signal intensity compared with distilled water, unlabeled ADSCs or agarose gel. SPION-labeled ADSCs showed a hypointense signal at all concentrations, and the greatest hypointense signal was observed at the concentration of 1 × 106. MR images of the corpus cavernosum showed a hypointense signal located at the injection site. T2*-weighted signal intensity increased over the course of 1 week after ADSCs transplantation, and demonstrated a similar MR signal with that before ADSCs transplantation. After SPION-labeled ADSC injection, T2*-weighted MR imaging clearly demonstrated a marked hypointense signal in pig corpus cavernosum. The T2*-weighted signal faded over time, similar to the MR imaging results in rats. Obvious acute inflammatory exudation was induced by intracavernous injection, and the T2*-weighted signal intensity of these exudation was higher than that of the injection site. The presence of iron was detected by Prussian blue staining, which demonstrated ADSC retention in rat corpus cavernosum. Lack of cellular infiltrations were demonstrated by H&E staining before and 4 weeks after transplantation, which indicated no negative immune response by rats. Prussian blue staining was positive for iron oxide nanoparticles at 2 weeks after transplantation. SPION-labeled ADSCs showed a clear hypointense signal on T2-weight MRI in vitro and in vivo. The MR signal intensity in the corpus cavernosum of the rats and miniature pigs faded and disappeared over time after ADSC transplantation. These findings suggested that MR imaging could trace transplanted ADSCs in the short term in the corpus cavernosum of animals.

Flax powdery mildew (PM), caused by Oidium lini, is a globally distributed fungal disease of flax, and seriously impairs its yield and quality. To data, only three resistance genes and a few putative quantitative trait loci (QTL) have been reported for flax PM resistance. To dissect the resistance mechanism against PM and identify resistant genetic regions, based on four years of phenotypic datasets (2017, 2019 to 2021), a genome-wide association study (GWAS) was performed on 200 flax core accessions using 674,074 SNPs and 7 models. A total of 434 unique quantitative trait nucleotides (QTNs) associated with 331 QTL were detected. Sixty-four loci shared in at least two datasets were found to be significant in haplotype analyses, and 20 of these sites were shared by multiple models. Simultaneously, a large-effect locus (qDI 11.2) was detected repeatedly, which was present in the mapping study of flax pasmo resistance loci. Oil flax had more QTL with positive-effect or favorable alleles (PQTL) and showed higher PM resistance than fiber flax, indicating that effects of these QTL were mainly additive. Furthermore, an excellent resistant variety C120 was identified and can be used to promote planting. Based on 331 QTLs identified through GWAS and the statistical model GBLUP, a genomic selection (GS) model related to flax PM resistance was constructed, and the prediction accuracy rate was 0.96. Our results provide valuable insights into the genetic basis of resistance and contribute to the advancement of breeding programs.

Abstract The purpose of this study was to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of SN1011, a novel Bruton tyrosine kinase (BTK) inhibitor, and food effects in healthy subjects. In this phase I trial, subjects received single ascending doses (SADs) of SN1011 (100 to 800 mg), multiple ascending doses (MADs) of SN1011 (200 to 600 mg), or placebo q.d. Additionally, 12 subjects randomly received a single dose of SN1011 600 mg under fasting states and then fed states, vice versa. Safety was assessed per Common Terminology Criteria for Adverse Events version 5.0. Pharmacokinetic parameters were calculated by noncompartmental analysis and BTK receptor occupancy in peripheral blood monocytes was determined. Seventy‐one healthy subjects were dosed in five SAD cohorts, three MAD cohorts, and one food effect cohort, with 57 receiving SN1011 and 14 receiving placebo. No serious adverse events (AEs) were reported. There was no correlation between AE occurrences and SN1011 exposure. The three most frequent AEs with SN1011 were increased blood triglycerides, decreased neutrophil count, and decreased leucocyte count. SN1011 exhibited a dose‐proportional increase in maximum plasma concentration and area under the time concentration curve following single and multiple dose administrations, with an accumulation ratio of 1.5 to 2.2 after multiple dose administrations. No difference in SN1011 exposure was observed between fed states. BTK receptor occupancy remained above 83% over 24 h after single administration and remained above 80% for the MAD groups for 10 days of continuous q.d. administration. SN1011 was well‐tolerated and safe after single or multiple exposures to healthy subjects, supporting further clinical development of SN1011 for treatment of autoimmune diseases.

Abstract Background The long non-coding RNAs (lncRNAs) are critical regulators of diverse biological processes. Nevertheless, a global view of its expression and function in the mouse retina, a crucial model for neurogenesis study, still needs to be made available. Results Herein, by integrating the established gene models and the result from ab initio prediction using short- and long-read sequencing, we characterized 4,523 lncRNA genes (MRLGs) in developing mouse retinas (from the embryonic day of 12.5 to the neonatal day of P28), which was so far the most comprehensive collection of retinal lncRNAs. Next, derived from transcriptomics analyses of different tissues and developing retinas, we found that the MRLGs were highly spatiotemporal specific in expression and played essential roles in regulating the genesis and function of mouse retinas. In addition, we investigated the expression of MRLGs in some mouse mutants and revealed that 97 intergenic MRLGs might be involved in regulating differentiation and development of retinal neurons through Math5, Isl1, Brn3b, NRL, Onecut1, or Onecut2 mediated pathways. Conclusions In summary, this work significantly enhanced our knowledge of lncRNA genes in mouse retina development and provided valuable clues for future exploration of their biological roles.

BackgroundOpen repair and replacement of the diseased aorta is still the standard treatment for type A aortic dissection (TAAD) in most patients. In endovascular treatment alone, ensuring adequate blood supply to the brain while covering the dissection with a stent is difficult.Case presentationThis study includes a 71-year-old male patient with type A aortic dissection presented at a recent follow-up examination after having undergone thoracic endovascular aortic repair (TEVAR) plus left subclavian artery chimney stent reconstruction for descending aortic dissection 5 years ago. Preoperative computed tomographic angiography, computed tomographic perfusion, and transcranial Doppler showed an intact cerebral arterial ring and good collateral circulation. We successfully performed an endovascular repair of the thoracic aorta with venoarterial extracorporeal membrane oxygenation (V-A ECMO) to protect the craniocerebral blood supply, greatly increase the safety of the operation, and ensure a good prognosis.ConclusionTEVAR under V-A ECMO protection is beneficial for patients with TAAD because of its minimal trauma, rapid recovery, few complications, and low mortality.

Abstract Background Combined therapy based on the effects of cascade reactions of nanoplatforms to combat specific solid tumor microenvironments is considered a cancer treatment strategy with transformative clinical value. Unfortunately, an insufficient O2 supply and the lack of a visual indication hinder further applications of most nanoplatforms for solid tumor therapy. Results A visualizable nanoplatform of liposome nanoparticles loaded with GOD, H(Gd), and PFP and grafted with the peptide tLyP-1, named tLyP-1H(Gd)-GOD@PFP, was constructed. The double-domain peptide tLyP-1 was used to specifically target and penetrate the tumor cells; then, US imaging, starvation therapy and sonodynamic therapy (SDT) were then achieved by the ultrasound (US)-activated cavitation effect under the guidance of MR/PA imaging. GOD not only deprived the glucose for starvation therapy but also produced H2O2, which in coordination with 1O2 produced by H(Gd), enable the effects of SDT to achieve a synergistic therapeutic effect. Moreover, the synergistic therapy was enhanced by O2 from PFP and low-intensity focused ultrasound (LIFU)-accelerated redox effects of the GOD. The present study demonstrated that the nanoplatform could generate a 3.3-fold increase in ROS, produce a 1.5-fold increase in the maximum rate of redox reactions and a 2.3-fold increase in the O2 supply in vitro, and achieve significant tumor inhibition in vivo. Conclusion We present a visualizable nanoplatform with tumor-penetrating ability that can be unlocked by US to overcome the current treatment problems by improving the controllability of the O2 supply, which ultimately synergistically enhanced cascade therapy.

Extreme heavy precipitation in the Yellow River basin mainly occurred between June and August in summer. It is of great significance for improving climate prediction and preventing and reducing disaster events to study the characteristics of synoptic conditions of extreme heavy precipitation in summer in this basin. Using the daily precipitation data in summer at the 247 ground-based meteorological stations in the Yellow River basin from 1961 to 2017, we first analyze the distribution characteristics of regional extreme heavy precipitation events in this basin. Second,according to the dominant circulation systems at 500 hPa,the typical circulation patterns affecting regional extreme heavy precipitation in summer in this basin are classified into the blocking type,the low-trough type,and the typhoon-peripheral type. The characteristics of extreme heavy precipitation,water vapor transport and evolution,and circulation under the blocking type and low-trough type of synoptic conditions before the events are analyzed. The results show that (1) the thresholds of extreme heavy precipitation in summer in the Yellow River basin gradually increase from the east to the west and from the north to the south during past 57 years. The frequency of extreme heavy precipitation in the upstream area is higher than that in other areas. (2) The distribution characteristics of zonal wind anomalies at 200 hPa are similar for the blocking-type and low-trough type synoptic conditions,whose anomalies show a "- + -" pattern in the range of 20°-55°N from the north to the south. Their circulation patterns at 500 hPa vary greatly,with the low-trough type dominated by the zonal circulation and the blocking type dominated by the meridional circulation in the mid- and high- latitudes of Eurasia. The former has many small troughs and ridges in the range of 30°-65°N,while the latter is controlled by positive geopotential height anomalies in the low latitudes. (3) The water vapor of blocking-type synoptic condition mainly comes from the Indian Ocean and the Pacific Ocean,while that of the low-trough type mainly comes from the Pacific Ocean and the South China Sea. (4) The blocking high that causes extreme heavy precipitation mainly develops locally,and the signal of its development can be captured 1-2 weeks before its occurrence. The trough that causes extreme heavy precipitation mainly moves,and its initial signal and strong signal appear about 7 d and 2-3 d before the occurrence of extreme heavy precipitation,respectively.

The development of antibiotics was a turning point in the history of medicine; however, their misuse and overuse have contributed to the current global epidemic of antibiotic resistance. According to epidemiological studies, early antibiotic exposure increases the risk of immunological and metabolic disorders. This study investigated the effects of exposure to different doses of sulfamethazine (SMZ) on offspring mice and compared the effects of exposure to SMZ on offspring mice in prenatal and early postnatal periods and continuous periods. Furthermore, the effects of SMZ exposure on the gut microbiota of offspring mice were analyzed using metagenome. According to the results, continuous exposure to high-dose SMZ caused weight gain in mice. IL-6, IL-17A, and IL-10 levels in the female offspring significantly increased after high-dose SMZ exposure. In addition, there was a significant gender difference in the impact of SMZ exposure on the gut microbiota of offspring: Continuous high-dose SMZ exposure significantly decreased the relative abundance of Ligilactobacillus murinus, Limosilactobacillus reuteri, Lactobacillus johnsonii, and Bifidobacterium pseudolongum (p < 0.05) in female offspring mice; however, these significant changes were not observed in male offspring mice.

Abstract Background High bifurcation of the deep femoral artery (DFA) is rare in clinical practice, and patients with this variation are less likely to receive venoarterial extracorporeal membrane oxygenation (V-A ECMO) treatment. Therefore, the method by which V-A ECMO is introduced in patients with vascular variation is very important. Case presentation A 52-year-old male patient had ST elevation myocardial infarction due to coronary heart disease. Angiography showed tripartite coronary artery lesions, and coronary artery stenting supported by V-A ECMO was needed. Vascular evaluation before ECMO catheterization revealed high bifurcation of the bilateral DFA located at the inguinal ligament. After discussion, the perfusion cannula was placed in the left superficial femoral artery (SFA) towards the heart, and the distal perfusion catheter (DPC) was placed in the left SFA towards the distal end. Nevertheless, after the patient's heart recovered, necrosis of the toe of the left lower limb still occurred. Conclusion Common femoral artery assessment must be performed before V-A ECMO for patients with high bifurcation of the DFA. Incision catheterization and DPC placement are recommended. After decannulation, arterial repair under direct visualisation is recommended, and rigorous distal vascular assessment and management are needed.

Abstract Catalytic valorization of raw glycerol derived from biodiesel into high-value chemicals has attracted great attention. Here, we report chemoenzymatic cascade reactions that convert glycerol to lactic acid and glycolic acid. In the enzymatic step, a coenzyme recycling system was developed to convert glycerol into 1,3-dihydroxyacetone (DHA) with a yield of 92.3% in potassium phosphate buffer (300 mM, pH 7.1) containing 100 mM glycerol, 2 mM NAD+, 242 U/mL glycerol dehydrogenase-GldA and NADH oxidase-SpNoxK184R at 30 °C. Subsequently, NaOH or NaClO2 catalyzes the formation of lactic acid and glycolic acid from DHA. The high yield of lactic acid (72.3%) and glycolic acid (78.2%) verify the benefit of the chemoenzymatic approaches. Graphical Abstract

Abstract Background Cough is a common complication after pulmonary surgery. Previous studies lacked a standard measure to assess postoperative cough-related quality of life and recovery. The purpose of this study is to compare postoperative cough regarding changes in health-related quality of life (HRQOL) and recovery trajectory between video-assisted thoracic surgery (VATS) lobectomy and sublobectomy (segmentectomy or wedge resection) for early-stage non-small cell lung cancer (NSCLC) patients via the Leicester Cough Questionnaire in Mandarin Chinese (LCQ-MC). Methods Overall, 156 patients with NSCLC underwent either VATS lobectomy or VATS sublobectomy; LCQ-MC was used to report the impact of postoperative cough on HRQOL for 6 months after surgery. The total scores of LCQ-MC range from 3 to 21, with a higher score indicating better health. Recovery from postoperative cough was defined as LCQ-MC scores returning to preoperative levels. The sensitivity of LCQ-MC to changes in postoperative cough recovery over time was evaluated via its ability to distinguish between surgery types. Results The VATS sublobectomy group reported significantly higher mean LCQ-MC scores at 1 month after surgery, but no significant difference postoperatively at 3 and 6 months after surgery, and returned to preoperative physical (69 vs. 99 days), psychological (67 vs. 99 days), social (50 vs. 98 days) and total (69 vs. 99 days) scores faster than the VATS lobectomy group (all p

Depression is gradually becoming a primary mental disease threatening human health. Therefore, there is an urgent need to clarify the pathogenesis of depression and identify new effective natural antidepressants. This study aimed to investigate the antidepressant effects of baicalin and explore its potential mechanism in a mouse model of depression induced by chronic unpredictable mild stress (CUMS). Following a 6-week exposure to CUMS, mice were treated with baicalin (10 mg/kg) or fluoxetine (10 mg/kg) for 4 weeks by oral gavage. A sucrose preference test and a forced swimming test were performed to evaluate depression-like behaviors, and the levels of adenosine triphosphate (ATP) in the prefrontal cortex were measured. Moreover, gene expression and enzyme activities related to ATP production, and mitochondrial function, were monitored. The results indicated that baicalin and fluoxetine could alleviate CUMS-induced depression-like behaviors of mice. In addition, baicalin significantly elevated the ATP content and the expression of genes hexokinase 1 (Hk1), pyruvate dehydrogenase E1 alpha 1 (Pdha-1), isocitrate dehydrogenase (Idh), peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha (Pgc-1α), and sirtuin-1 (Sirt1) in the prefrontal cortex. Furthermore, baicalin increased the activity of the respiratory chain complexes I and V as well as the mitochondrial membrane potential. In conclusion, baicalin may exert its antidepressant effect partly by upregulating the expression of some genes coding for enzymes involved in the glycolysis and the tricarboxylic acid cycle, and improving the mitochondrial function to enhance the ATP level in the brain.

Abstract Background Starch is one of the most important renewable polysaccharides in nature for production of bio-ethanol. The starch saccharification step facilitates the depolymerization of starch to yield glucose for biofuels production. The filamentous fungus Aspergillus niger (A. niger) is the most used microbial cell factory for production of the commercial glucoamylase. However, the role of each component in glucoamylases cocktail of A. niger O1 for starch saccharification remains unclear except glucoamylase. Results In this study, we identified the key enzymes contributing to the starch saccharification process are glucoamylase, α-amylase and acid α-amylase out of 29 glycoside hydrolases from the 6-day fermentation products of A. niger O1. Through the synergistic study of the multienzymes for the starch saccharification in vitro, we found that increasing the amount of α-amylase by 5-10 times enhanced the efficiency of starch saccharification by 14.2-23.2%. Overexpression of acid α-amylase in strain O1 in vivo increased the total glucoamylase activity of O1 cultures by 15.0%. Conclusions Our study clarifies the synergistic effects among the components of glucoamylases cocktail, and provides an effective approach to optimize the profile of saccharifying enzymes of strain O1 for improving the total glucoamylase activity.

Seed size is a key determinant of crop yields. Understanding the regulatory mechanisms of seed size is beneficial for improving flax seed yield. In this study, the development of large flax seeds lagged behind that of small seeds, and 1,751 protein-coding genes were differentially expressed in early seeds, torpedo-stage embryos, and endosperms of CIli2719 and Z11637 using RNA sequencing. Homologous alignment revealed that 129 differentially expressed genes (DEGs) in flax were homologous with 71 known seed size–related genes in Arabidopsis thaliana and rice (Oryza sativa L.). These DEGs controlled seed size through multiple processes and factors, among which phytohormone pathways and transcription factors were the most important. Moreover, 54 DEGs were found to be associated with seed size and weight in a DEG-based association study. Nucleotide diversity (π) analysis of seed size–related candidate DEGs by homologous alignment and association analysis showed that the π values decreased significantly during flax acclimation from oil to fiber flax, suggesting that some seed size–related candidate genes were selected in this acclimation process. These results provide important resources and genetic foundation for further research on seed size regulation and seed improvement in flax.

Abstract V–VI antimony chalcogenide semiconductors have shown exciting potentials for thin film photovoltaic applications. However, their solar cell efficiencies are strongly hampered by anomalously large voltage loss (>0.6 V), whose origin remains controversial so far. Herein, by combining ultrafast pump–probe spectroscopy and density functional theory (DFT) calculation, the coupled electronic and structural dynamics leading to excited state self‐trapping in antimony chalcogenides with atomic level characterizations is reported. The electronic dynamics in Sb2Se3 indicates a ≈20 ps barrierless intrinsic self‐trapping, with electron localization and accompanied lattice distortion given by DFT calculations. Furthermore, impulsive vibrational coherences unveil key SbSe vibrational modes and their real‐time interplay that drive initial excited state relaxation and energy dissipation toward stabilized small polaron through electron–phonon and subsequent phonon–phonon coupling. This study's findings provide conclusive evidence of carrier self‐trapping arising from intrinsic lattice anharmonicity and polaronic effect in antimony chalcogenides and a new understanding on the coupled electronic and structural dynamics for redefining excited state properties in soft semiconductor materials.

BackgroundAs more health care organizations transition to using electronic health record (EHR) systems, it is important for these organizations to maximize the secondary use of their data to support service improvement and clinical research. These organizations will find it challenging to have systems capable of harnessing the unstructured data fields in the record (clinical notes, letters, etc) and more practically have such systems interact with all of the hospital data systems (legacy and current). ObjectiveWe describe the deployment of the EHR interfacing information extraction and retrieval platform CogStack at University College London Hospitals (UCLH). MethodsAt UCLH, we have deployed the CogStack platform, an information retrieval platform with natural language processing capabilities. The platform addresses the problem of data ingestion and harmonization from multiple data sources using the Apache NiFi module for managing complex data flows. The platform also facilitates the extraction of structured data from free-text records through use of the MedCAT natural language processing library. Finally, data science tools are made available to support data scientists and the development of downstream applications dependent upon data ingested and analyzed by CogStack. ResultsThe platform has been deployed at the hospital, and in particular, it has facilitated a number of research and service evaluation projects. To date, we have processed over 30 million records, and the insights produced from CogStack have informed a number of clinical research use cases at the hospital. ConclusionsThe CogStack platform can be configured to handle the data ingestion and harmonization challenges faced by a hospital. More importantly, the platform enables the hospital to unlock important clinical information from the unstructured portion of the record using natural language processing technology.

BackgroundResearch gaps exist in addressing the psychological harm related to the cervical cancer screening. Anxiety is the most common distress driven by the screening procedures, which may be affected by past screening experience (PSE) but with uncertainty. This study aimed to evaluate the pre-procedural anxiety in cervical cancer screening and to identify the influence attributed to PSE.MethodsA cross-sectional survey targeted women seeking for cervical cancer screening services was conducted from June 5th to December 31st, 2020 in Shenzhen. The 20-item state anxiety scale of the State-Trait Anxiety Inventory (STAI-S) was applied to measure pre-procedural anxiety, in which a score of 40 or higher was regarded with anxiety symptom. Logistic regression models were established to explore potential associated factors of pre-procedural anxiety both for women with and without PSE.ResultsOverall, 3,651 women were enrolled, in which 36.1% had never been screened and the remaining 63.9% had been screened at least once before. Women without PSE demonstrated more prevalent pre-procedural anxiety (74.5% vs. 67.8%, P

Under a multiscenario environment with frequent bursts of data in the edge cloud, the resource allocation in the edge cloud will affect the stability of its nodes. To address this problem, a balanced virtual resource allocation model based on conflict conditions is proposed. Based on a thorough study of the similarity between task attributes and resources used by the host, the concept of a task backlog is implemented to achieve a preliminary balanced allocation of tasks; thus, a conflict condition based on the remaining resources of the physical and virtual machines is proposed. Further, a matrix of phased conflict coefficients is built to establish a balanced virtual machine allocation model. The results of experiments comparing the performance of the proposed model with that of other existing models indicate that the proposed model can reduce the virtual machine scheduling time by up to 8.33%, save up to 6.25% of host energy consumption, and improve the algorithm efficiency by 20.47% compared with the other algorithms. To avoid the local optimal problem caused by dynamic virtual machine migration, an improved ant colony algorithm is combined with the above model, and concepts of a pheromone volatility factor and suppression factor are implemented to optimize the pheromone measurement function and ensure that the virtual machine migration path is globally optimal. Overall, the model reduces the conflict rate of resources on the physical machine and can maintain stable operation under CPU usage fluctuation, thus realizing a balanced allocation of node resources.

In traditional Chinese medicine, the role of the liver in depression is highly valued, and liver-relieving drugs, such as Sinisan, are often used to treat depression; however, the mechanism whereby these drugs work remains unclear. The present study aimed to reveal possible antidepressant mechanisms of Sinisan (SNS) by analyzing hepatic proteomics in chronic unpredictable mild stress (CUMS) mice. Using the CUMS mouse model of depression, the antidepressant effects of SNS were assessed by the sucrose preference test (SPT) and forced swimming test (FST). Hepatic differentially expressed proteins (DEPs) after SNS treatment were investigated by tandem mass tag (TMT) based quantitative proteomics analysis. Then, a bioinformatics analysis of DEPs was conducted through hierarchical clustering, Venn analysis, Gene Ontology (GO) annotation enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. DEP genes were further validated by quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blotting. Behavioral results demonstrated that SNS significantly increased sucrose intake in SPT and shortened the immobility time in FST in model mice. Eighty-two DEPs were identified, including 37 upregulated and 45 downregulated proteins, between model and SNS groups. Enrichment analysis of GO annotations indicated that SNS primarily maintained cellular iron ion homeostasis by iron ion transportation and regulated expression of some extracellular structural proteins for oxidation-reduction processes. KEGG and Venn analysis showed that mineral absorption, steroid hormone biosynthesis and metabolism might be the principal pathways through which SNS acts on depression. Furthermore, several proteins involved in the biosynthesis and metabolism of steroid hormone pathways were significantly up/downregulated by SNS, including CYP2B19, CYP7B1 (validated by qRT-PCR) and HSD3b5 (validated by qRT-PCR and western blotting). Our results indicate that SNS plays important roles in antidepressant actions by restoring DEPs, resulting in the biosynthesis and metabolism of steroid hormones. The current results provide novel perspectives for revealing potential protein targets of SNS in depression.

The mechanisms involved in brain damage during chronic glucocorticoid exposure are poorly understood. Since mineralocorticoid receptor (MR) activation has been proven to be important in the pathophysiology of vascular damage and MRs are highly expressed in many brain regions, we hypothesized that the cerebral injury observed in subjects with Cushing syndrome is in part associated with the overactivation of MR. The aim of this study was to determine whether the cerebral injury observed in chronic hyperglucocorticoidemia animal models is related to excessive MR activation. Male SD rats were divided into five groups: vehicle, hydrocortisone (HC, 5 mg/kg/day, i.g.), HC + spironolactone (SL, 20 mg/kg/d in chow), dexamethasone (DXM, 0.25 mg/kg/day, i.g.), and DXM + SL (20 mg/kg/d in chow). Compared to the vehicle-treated group, HC-treated rats had higher blood pressure and higher levels of cerebral vascular fibrosis, cortical/hippocampal atrophy, reactive oxygen species (ROS) production and proinflammatory gene expression. However, in HC-treated animals, treatment with SL markedly alleviated ROS production, cerebral and cerebrovascular morphological changes and inflammation but failed to reduce blood pressure. In contrast, DXM induced no cerebral morphological changes except fibrosis in cerebral vessels, an effect that was not ameliorated by SL treatment. These findings demonstrate that the excessive MR activation observed following chronic hyperglucocorticoidemia exposure contributes to cerebrovascular fibrosis and remodeling and promotes neural apoptosis in the cerebral cortex/hippocampus.

A number of studies have confirmed the relationship between constipation and gut microbiota. Additionally, many human and animal experiments have identified probiotics as effectors for the relief of constipation symptoms. In this study, probiotic compounds, including Lactobacillus acidophilus LA11-Onlly, Lacticaseibacillus rhamnosus LR22, Limosilactobacillus reuteri LE16, Lactiplantibacillus plantarum LP-Onlly, and Bifidobacterium animalis subsp. lactis BI516, were administered to mice with loperamide-induced constipation, and the impacts of these strains on constipation-related indicators and gut microbiota were evaluated. The effects of probiotic compounds on constipation relief were associated with various aspects, including gastrointestinal transit rate, number and weight of stools, serum and intestinal gastrointestinal regulatory hormones, and serum cytokines. Some of the probiotic compounds, including Limosilactobacillus reuteri, Lactiplantibacillus plantarum, and Lacticaseibacillus rhamnosus, were found to colonize the intestinal tract. Furthermore, higher dosages promoted the colonization of specific strains. This study yields a new perspective for the clinical use of probiotics to improve constipation symptoms by combining strains with different mechanisms for the alleviation of constipation.

Abstract Background Insulin resistance has been independently related to heart failure. However, the specific mechanisms of high FFA levels in the pathophysiology of heart failure in insulin-resistant states are remain largely unclear. This study investigated whether elevated circulating free fatty acids (FFA) levels result in impaired cardiac structure and function in vivo via insulin-related signaling pathways in myocardium. Methods Male Wistar rats were randomly divided into the intralipid group (20% intralipid plus heparin infusion) and the control group (glycerol infusion). Blood samples were collected before and after 6-, 12-, and 24-h infusions. Cardiac structure and function were measured using echocardiography. Maximum velocity of myocardial contraction (+dP/dt max) and diastole (−dP/dt max) were measured using a physiological polygraph in vivo. Heart tissues were collected for western blotting. Results Compared with the control group, plasma FFA, plasma glucose, and serum insulin levels increased significantly in the intralipid group. With increasing infusion time, cardiac function in the intralipid group decreased gradually compared with the control group. After a 24-h infusion, early (E’, cm/s) diastolic peak velocities and (−dP/dt max) decreased significantly. Protein expression of phosphatidylinositol 3-kinase (PI3K), the serine/threonine kinase Akt, and phosphorylated Akt in myocardium increased after a 6-h infusion and decreased significantly after a 24-h infusion in the intralipid group. Protein expression of glucose transporter type 4 (GLUT4), Adenosine 5′-monophosphate -activated protein kinase (AMPK), phosphorylated AMPK(p-AMPK), and endothelial nitric oxide synthase (eNOS) in myocardium gradually decreased in the intralipid group. Conclusions Elevated FFA levels may impair cardiac function and cardiac dysfunction might result from myocardial insulin resistance with significant changes to PI3K-Akt-GLUT4 and AMPK-eNOS signaling pathways with increasing FFA levels.

Abstract Objectives Protein engineering has been employed to successfully improve organic solvent resistance of enzymes. Exploration of nature’s full potential (how many beneficial positions/beneficial substitutions of the target enzyme) to improve organic solvent resistance of enzymes by a systematic study was performed. Results We report the results of screening the previously generated BSLA (Bacillus subtilis lipase A)-SSM (site saturation mutagenesis) library (covering the full natural diversity of BSLA with one amino acid exchange) in presence of three cosolvents. The potential of single amino acid substitution that nature offers to improve the cosolvent resistance of BSLA was determined by analyzing the number of beneficial positions/substitutions, accessibility and chemical compositions. Conclusion Lessons learned from analysis of BSLA-SSM library are: (1) 41–59% of BSLA positions with in total 4–10% of all possible substitutions improve the cosolvent resistance against TFE, DOx, and DMSO; (2) charged substitutions are preferred to improve DOx and TFE resistance whereas polar ones are preferred for DMSO; (3) charged substitutions on the surface predominantly improved resistance while polar ones were preferred in buried “regions”. (4) Interestingly, 58–93% of beneficial substitutions led to chemically different amino acids.

Background Dysregulated long non-coding RNAs (lncRNAs) may serve as potential biomarkers of cancers including breast cancer (BRCA). This study aimed to identify lncRNAs with strong prognostic value for BRCA. Methods LncRNA expression profiles of 929 tissue samples were downloaded from TANRIC database. We performed differential expression analysis between paired BRCA and adjacent normal tissues. Survival analysis was used to identify lncRNAs with prognostic value. Univariate and multivariate Cox regression analyses were performed to confirm the independent prognostic value of potential lncRNAs. Dysregulated signaling pathways associated with lncRNA expression were evaluated using gene set enrichment analysis. Results We found that a total of 398 lncRNAs were significantly differentially expressed between BRCA and adjacent normal tissues (adjusted P value = 1). Additionally, 381 potential lncRNAs were correlated Overall Survival (OS) (P value < 0.05). A total of 48 lncRNAs remained when differentially expressed lncRNAs overlapped with lncRNAs that had prognostic value. Among the 48 lncRNAs, one lncRNA (LINC01614) had stronger prognostic value and was highly expressed in BRCA tissues. LINC01614 expression was validated as an independent prognostic factor using univariate and multivariate analyses. Higher LINC01614 expression was observed in several molecular subgroups including estrogen receptors+, progesterone receptors+ and human epidermal growth factor receptor 2 (HER2)+ subgroup, respectively. Also, BRCA carrying one of four gene mutations had higher expression of LINC01614 including AOAH, CIT, HER2 and ODZ1. Higher expression of LINC01614 was positively correlated with several gene sets including TGF-β1 response, CDH1 signals and cell adhesion pathways. Conclusions A novel lncRNA LINC01614 was identified as a potential biomarker for prognosis prediction of BRCA. This study emphasized the importance of LINC01614 and further research should be focused on it.

High speed and heavy loads have become more prevalent in the traction power supply system recently. To ensure system operating stability, better power quality, and sufficient power capacity, improvements are needed over the conventional traction system. Inspired by the concept of a microgrid (MG), an AC co-phase traction MG system was proposed. Substations were connected to the traction grid as distributed generators operate in islanded mode. Droop control was adopted as the primary control to stabilize the system’s operating frequency and voltage. Considering the operating features of the substation and locomotive load, a de-centralized secondary control strategy was proposed for AC co-phase traction MG system operation with enhanced resiliency. The proposed control strategy could increase system stability and prevent circulation currents between substations. Moreover, the proposed de-centralized coordination between substations does not rely on communication, which promotes the system’s “plug-and-play” functionality. Stability analysis was undertaken and the proposed controller was proved to be exponentially stable. The dynamic response of the proposed controller was validated using comprehensive case studies in MATLAB/Simulink.