Novel xanthone antibacterials: Semi-synthesis, biological evaluation, and the action mechanisms.

α-Mangostin (α-MG) has demonstrated to display potent activities against Gram-positive bacterial. However, the contribution of phenolic hydroxyl groups of α-MG to the antibacterial activity remains obscure, severely hampering selection of structure modification to develop more potential α-MG-based anti-bacterial derivatives. Herein, twenty-one α-MG derivatives are designed, synthesized and evaluated for the antibacterial activities. The structure activity relationships (SARs) reveal that the contribution of the phenolic groups ranks as C3 > C6 > C1, and the phenolic hydroxyl group at C3 is essential to the antibacterial activity. Of note, compared to the parent compound α-MG, 10a with one acetyl at C1 exhibits the higher safety profiles due to its higher selectivity and no hemolysis, and the more potent antibacterial efficacy in an animal skin abscess model. Our evidences further present that, in comparison with α-MG, 10a has a stronger ability in depolarizing membrane potentials and leads to more leakage of bacterial proteins, consistent with the results observed by transmission electron microscopy (TEM). Transcriptomics analysis demonstrates those observations possibly relate to disturbed synthesis of proteins participating in the biological process of membrane permeability and integrity. Collectively, our findings provide a valuable insight for developing α-MG-based antibacterial agents with little hemolysis and new action mechanism via structural modifications at C1.

A Peptide Encoded by a Long Non-Coding RNA DLX6-AS1 Facilitates Cell Proliferation, Migration, and Invasion by Activating the wnt/ß-Catenin Signaling Pathway in Non-Small-Cell Lung Cancer Cell.

Recently, accumulating study shows that some long non-coding RNAs (lncRNAs) have potential protein/peptide-coding capacities. In this study, the coding potential of lncRNA distal-less homeobox 6 antisense 1 (DLX6-AS1) was examined and the roles and downstream pathways of a DLX6-AS1-encoded peptide in non-small-cell lung cancer (NSCLC) cell development were investigated. The peptide-coding potential of lncRNA DLX6-AS1 was extrapolated based on prior ribosome footprint and ribosome sequencing data, IPX0002962000 mass spectrometry dataset, and Getorf bioinformatics analysis. The peptide-coding abilities of several DLX6-AS1 open reading frame (ORF) fragments, as well as protein levels were detected by Western blot assay. Cell proliferative, migratory, and invasive abilities were tested by CCK-8 or Transwell assays, respectively. Potential key biological processes and pathways related to DLX6-AS1 expression were identified by single-gene gene set enrichment analysis (GSEA) based on RNA-seq data of 510 lung adenocarcinoma samples in the TCGA GDC database. The results showed that an ORF of lncRNA DLX6-AS1 could encode a short peptide. The exogenous overexpression of this ORF-encoded peptide promoted NSCLC cell proliferation, migration, and invasion. GSEA analysis suggested that DLX6-AS1 might play crucial roles in cancer progression and wnt signaling pathway. Further analysis revealed that the exogenous overexpression of a DLX6-AS1-encoded peptide could exert its functions by activating the wnt/ß-catenin pathway in NSCLC cells. In conclusion, the exogenous overexpression of a DLX6-AS1-encoded peptide could facilitate NSCLC cell growth by activating wnt/ß-catenin pathway.

Risk factors for ventilator-associated pneumonia due to multi-drug resistant organisms after cardiac surgery in adults.

BACKGROUND: Ventilator-associated pneumonia (VAP) is one of the most common intensive care unit (ICU)-acquired infections, which can cause multiple adverse events. Due to bacterial mutation and overuse of antimicrobial drugs, multidrug-resistant organisms (MDRO) has become one of the major causes of postoperative VAP infections in cardiac patients. Therefore, this study aims to explore the risk factors for VAP with MDRO following cardiac surgery in adults. METHODS: The clinical data of adult VAP patients following cardiac surgery in the hospital from Jan 2017 to May 2021 were analyzed retrospectively, and the patients were divided into the MDRO VAP group and the non-MDRO VAP group. Univariable and multivariable logistic regression analyses were performed on risk factors in patients with MDRO VAP. The species and drug sensitivity of pathogens isolated from the VAP patients were also analyzed. RESULTS: A total of 61 VAP cases were involved in this study, with 34 cases in the MDRO VAP group (55.7%) and 27 cases in the non-MDRO VAP group (44.3%). Multivariable logistic regression analysis showed that independent risk factors for MDRO VAP included preoperative creatinine clearance rate (CCR) ≥ 86.6ml, intraoperative cardiopulmonary bypass (CPB) time ≥ 151 min, postoperative acute kidney injury (AKI) and nasal feeding. Gram-negative bacilli were the main pathogens in VAP patients (n = 54, 90.0%), with the highest rate of Acinetobacter baumannii (n = 24, 40.0%). Additionally, patients with MDRO VAP had a significantly longer postoperative intensive care unit (ICU) duration and higher hospitalization costs than non-MDRO VAP patients, but there was no notable difference in the 28-day mortality rate between the two groups. CONCLUSION: Based on implementing measures to prevent VAP, clinicians should pay more attention to patients with kidney disease, longer intraoperative CPB time, and postoperative nasal feeding to avoid MDRO infections.

Design and synthesis of epigallocatechin (EGC) analogs selective to inhibit α-amylase over α-glucosidases via the incorporation of caffeine acid and its derivatives.

Natural products are a promising and underappreciated reservoir for the preferred chemical scaffolds in the search of antidiabetic drugs. In this study twenty-one EGC-based derivatives selective to inhibit human pancreatic α-amylase (HPA), the enzyme at the top of the starch digestion pyramid, have been designed and synthesized in terms of the lead myricetin-caffeic acid conjugate 1 reported ever. We focus on methylation of caffeic acid, length of a liker, a double bond contained in the linker on the inhibition activity and selectivity of EGC-based conjugates. As a result, methylation of caffeic acid and the length of a linker affect significantly the activity and selectivity of EGC-based conjugates, but the effect of a double in caffeic acid is limited. Conjugate 2a-1 having a six-carbon-atom linker fused to EGC and caffeic acid demonstrates the most ponent inhibitory activity to HPA and its selectivity towards HPA over α-glucosidase by far superior to that construct 1. Molecular docking studies reveal that conjugate 2a-1 accommodates well to the active site of HPA with four hydrogen bonds in the form of the preorganization of two moieties EGC and caffeic acid via π-stacking interaction. Collectively, conjugating caffeic acid and EGC with an appropriate linker possibly provides a new strategy for finding the specific HPA inhibitors in the discovery of anti-diabetes mellitus drugs.

Current Non-Contact Road Surface Condition Detection Schemes and Technical Challenges.

Given the continuous improvement in the capabilities of road vehicles to detect obstacles, the road friction coefficient is closely related to vehicular braking control, thus the detection of road surface conditions (RSC), and the level is crucial for driving safety. Non-contact technology for RSC sensing is becoming the main technological and research hotspot for RSC detection because of its fast, non-destructive, efficient, and portable characteristics and attributes. This study started with mapping the relationship between friction coefficients and RSC based on the requirement for autonomous driving. We then compared and analysed the main methods and research application status of non-contact detection schemes. In particular, the use of infrared spectroscopy is expected to be the most approachable technology path to practicality in the field of autonomous driving RSC detection owing to its high accuracy and environmental adaptability properties. We systematically analysed the technical challenges in the practical application of infrared spectroscopy road surface detection, studied the causes, and discussed feasible solutions. Finally, the application prospects and development trends of RSC detection in the fields of automatic driving and exploration robotics are presented and discussed.

α-naphthoflavone-derived cytochrome P450 (CYP)1B1 degraders specific for sensitizing CYP1B1-mediated drug resistance to prostate cancer DU145: Structure activity relationship.

We previously discovered extrahepatic cytochrome P450 1B1 (CYP1B1) degraders able to overcome drug resistance toward docetaxel using a PROTACs technology, however, the underexplored structure activity relationships and poor water solubility posed a major hurdle in the development of CYP1B1 degraders. Herein, continuous efforts are made to develop more promising α-naphthoflavone (ANF)-derived chimeras for degrading CYP1B1. Guided by the strongest ANF-derived CYP1B1 degrader 3a we ever reported, 17 ANF analogues are designed and synthesized to evaluate the CYP1B1 degradation and resultant resistance reversal. In degrading CYP1B1 and sensitizing drug resistance, 4d with a 1, 5-cis triazole coupling mode at (C3') of B ring of ANF exhibited the similar potency as 3a carrying a 1, 4-trans triazole fragment at (C4') of B ring, but more obvious selectivity of 4d toward CYP1B1 over CYP1A2 is observed. When an oxygen was inserted into the linker of 4d, 4f demonstrated better water solubility, a more potent ability in degrading CYP1B1 and reversing drug resistance, and a promising selectivity. Collectively, a substitution position, an alkyne-azide cyclization and a liker type significantly affect the ability of ANF-thalidomide conjugates in eliminating drug resistance of CYP1B1-expressing DU145 (DU145/CY) cells to docetaxel via targeted CYP1B1 degradation.

Vulcaniibacterium gelatinicum sp. nov., a moderately thermophilic bacterium isolated from a hot spring.

The present study aimed to determine the taxonomic positions of strains designated R-5-52-3T, R-5-33-5-1-2, R-5-48-2 and R-5-51-4 isolated from hot spring water samples. Cells of these strains were Gram-stain-negative, non-motile and rod-shaped. The strains shared highest 16S rRNA gene sequence similarity with Vulcaniibacterium thermophilum KCTC 32020T (95.1%). Growth occurred at 28-55 °C, at pH 6-8 and with up to 3 % (w/v) NaCl. DNA fingerprinting, biochemical, phylogenetic and 16S rRNA gene sequence analyses suggested that R-5-52-3T, R-5-33-5-1-2, R-5-48-2 and R-5-51-4 were different strains but belonged to the same species. Hence, R-5-52-3T was chosen for further analysis and R-5-33-5-1-2, R-5-48-2 and R-5-51-4 were considered as additional strains of this species. R-5-52-3T possessed Q-8 as the only quinone and iso-C15:0, iso-C11:0, C16 : 0 and iso-C17 : 0 as major fatty acids. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified polar lipids and two unidentified phospholipids. The genomic G+C content was 71.6 mol%. Heat shock proteins (e.g. Hsp20, GroEL, DnaK and Clp ATPases) were noted in the R-5-52-3T genome, which could suggest its protection in the hot spring environment. Pan-genome analysis showed the number of singleton gene clusters among Vulcaniibacterium members varied. Average nucleotide identity (ANI) values between R-5-52-3T, Vulcaniibacterium tengchongense YIM 77520T and V. thermophilum KCTC 32020T were 80.1-85.8 %, which were below the cut-off level (95-96 %) recommended as the ANI criterion for interspecies identity. Thus, based on the above results, strain R-5-52-3T represents a novel species of the genus Vulcaniibacterium, for which the name Vulcaniibacterium gelatinicum sp. nov. is proposed. The type strain is R-5-52-3T (=KCTC 72061T=CGMCC 1.16678T).

Pseudomonas Saliphila sp. nov., a Bacterium Isolated from Oil-Well Production Water in Qinghai Oilfield of China.

Strain 16W4-4-3 T was isolated from the oil-well production water in Qinghai Oilfield, China. Cells were Gram-stain-negative, rod-shaped, catalase- and oxidase-positive, facultatively anaerobic and motile by single polar flagellum. The 16S rRNA gene sequences of strain 16W4-4-3 T showed the highest similarities with Pseudomonas profundi M5T (98.8%), P. pelagia CL-AP6T (98.0%), P. salina XCD-X85T (97.7%), and P. sabulinigri J64T (97.5%). The phylogenetic trees based on multilocus sequence analyses with concatenating 16S rRNA, gyrB, rpoD and rpoB genes suggested that this strain should be affiliated to the genus Pseudomonas but remotely related from other species. In addition, whole genome analyses revealed that the digital DNA-DNA hybridization values and average nucleotide identities of strain 16W4-4-3 T against its close relatives were all below 28.8% and 86.5%, respectively. Furthermore, the isolate had totally different whole cell protein profile as compared to those of other species. Major fatty acids were summed feature 8 (C18:1ω7c and/or C18:1ω6c), C16:0, summed feature 3 (C16:1ω7c and/or C16:1ω6c) and C17:0cyclo. Major isoprenoid quinone was ubiquinone (Q-9), and major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, and phosphatidylethanolamine. The DNA G + C content was 58.5 mol%. Therefore, phenotypic, phylogenetic, genomic, chemotaxonomic, and proteomic traits showed that the isolate represented a novel species of the genus Pseudomonas, the name Pseudomonas saliphila sp. nov. is proposed. Type strain is 16W4-4-3 T (= CGMCC 1.13350 T = KCTC 72619 T).

Virulence and antifungal susceptibility of microsatellite genotypes of Candida albicans from superficial and deep locations.

A set of 185 strains of Candida albicans from patients with vulvovaginal candidiasis (VVC) and from non-VVC clinical sources in southwest China was analysed. Strains were subjected to genotyping using CAI microsatellite typing and amplification of an intron-containing region of the 25S rRNA gene. Microsatellite genotypes of strains from non-VVC sources showed high polymorphism, whereas those of VVC were dominated by few, closely similar genotypes. However, among non-VVC strains, two genotypes were particularly prevalent in patients with lung cancer. 25S rDNA genotype A was dominant in VVC sources (86.7%), whereas genotypes A, B, and C were rather evenly distributed among non-VVC sources; known genotypes D and E were not found. In an experimental mouse model, isolates from lung cancer and AIDS patients proved to have higher virulence than VVC strains. Among 156 mice infected with C. albicans, 19 developed non-invasive urothelial carcinoma. No correlation could be established between parameters of virulence, source of infection, and incidence of carcinoma. C. albicans strains from VVC were less susceptible to itraconazole than the strains from non-VVC sources, whereas there was small difference in antifungal susceptibility between different 25S rDNA genotypes of C. albicans tested against amphotericin B, itraconazole, fluconazole, and flucytosine.

Comparative pathogenicity of opportunistic black yeasts in Aureobasidium.

Aureobasidium pullulans and A. melanogenum are black-yeast-like surface colonisers and are commonly encountered as contaminants in the hospital. The species are able to produce melanin which play a role in protection against environmental stress and irradiation. Aureobasidium melanogenum shows higher frequency in opportunistic infections compared to A. pullulans. Comparative pathogenicity of opportunistic black yeasts between Aureobasidium pullulans and A. melanogenum to explain the observed differences in frequency in infection. Degrees of melanisation and thermotolerance were measured, and virulence of strains from different sources was examined in Galleria mellonela and murine infection models. Aureobasidium melanogenum responds with increased melanisation to temperature stress and generally survives at 37°C, A. pullulans on average scored less on these parameters. In the murine model, differences between species were not significant, but the melanised A. melanogenum group showed the highest virulence. This result was not reproducible in Galleria mellonella larvae at 25°C. The A. melanogenum black group showed higher pathogenicity in murine model, indicating that the combination of melanisation and thermotolerance rather than species affiliation is instrumental. Galleria larvae did not survive very well at 37°C, and hence, this model is judged insufficient to detect the small virulence differences observed in Aureobasidium.

TAT-HSA-α-MSH fusion protein with extended half-life inhibits tumor necrosis factor-α in brain inflammation of mice.

Neuroinflammation constitutes a principal process involved in the progression of various central nervous system (CNS) disorders, including Parkinson's disease, Alzheimer's disease, ischemic stroke, and traumatic brain injury. The safety and efficacy of potential neuroprotective therapeutic agents is controversial and limited. Alpha-melanocyte-stimulating hormone (α-MSH) as a tridecapeptide derived from pro-opiomelanocortin displays potent anti-inflammatory and protective effects with a wide therapeutic window in brain damage. However, it is difficult to deliver effective concentrations of α-MSH into brain tissue via nondirect application. Besides, the half-life of the tridecapeptide is only a few minutes. In the present study, we generated a novel TAT-HSA-α-MSH by genetically fusing α-MSH with N-terminus 11-amino acid protein transduction domain of the human immunodeficiency virus Tat protein (TAT) and human serum albumin (HSA), which showed favorable pharmacokinetic properties and can effectively cross the blood brain barrier (BBB). The findings showed that TAT-HSA-α-MSH significantly inhibits NF-κB activation in human glioma cells A172 and tumor necrosis factor-α (TNF-α) production in experimental brain inflammation. These results indicate that TAT-HSA-α-MSH may be a potential therapeutic agent for treating neuroinflammation which plays a fundamental role in CNS disorders.

Expression and bioactivity of recombinant human serum albumin and dTMP fusion proteins in CHO cells.

The 14-amino acid (IEGPTLRQWLAARA) thrombopoietin mimetic peptide (TMP) shares no sequence homology with native thrombopoietin (TPO). When dimerized, it displays a high-binding affinity for the TPO receptor and has equipotent bioactivity with recombinant human TPO (rhTPO) in stimulating proliferation and maturation of megakaryocytes in vitro. However, TMP is limited for clinical usage because of its short half-life in vivo. In this study, fusion proteins that composed of tandem dimer of TMP (dTMP) genetically fused at the C- or N-terminus of human serum albumin (HSA) were separately expressed in Chinese hamster ovary (CHO) cells. In vitro bioactivity assays showed that purified fusion proteins promoted the proliferation of megakaryocytes in a dose-dependent manner and activated signal transducer and activator of transcription (STAT) pathway in TPO receptor-dependent manner. Following subcutaneous administration, both HSA-dTMP and dTMP-HSA significantly elevated peripheral platelet counts in normal mice in a dose-dependent manner. In addition, fusion with HSA successfully prolonged dTMP half-life in mice. However, when HSA was fused at the C-terminus of dTMP, the bioactivity of dTMP-HSA was about half of that of HSA-dTMP. In conclusion, these results suggested that HSA/dTMP fusion proteins might be potential drugs for thrombocytopenia and, when HSA was fused at the N-terminus of dTMP, the fusion protein had a higher activity.

Functional expression of human serum albumin-tandem thrombopoietin mimetic peptide fusion protein as a novel thrombopoietin analog in Pichia pastoris.

OBJECTIVES: To develop a novel thrombopoietin (TPO) analog by fusing the tandem TPO mimetic peptide (TMP-TMP) to human serum albumin (HSA) and performing functional expression of recombinant fusion protein HSA-TMP-TMP. RESULTS: After optimizing the fusion orientation in shake-flask culture, HSA-TMP-TMP was expressed at 0.4 g/l in Pichia pastoris grown in a 20 l bioreactor, during which pH was controlled at 5 by addition of NH4OH and citric acid. The fusion protein significantly activated signal transducer and activator of transcription-mediated transcription in TPO receptor-dependent manner, which was demonstrated by a luciferase reporter assay. Following subcutaneous administration, HSA-TMP-TMP effectively stimulated the platelet production in healthy mice in a dose-dependent manner. CONCLUSION: Successful expression of HSA-TMP-TMP fusion protein in P. pastoris was achieved and the recombinant HSA-TMP-TMP is a promising TPO analog.

Retina Fundus Photograph-Based Artificial Intelligence Algorithms in Medicine: A Systematic Review.

We conducted a systematic review of research in artificial intelligence (AI) for retinal fundus photographic images. We highlighted the use of various AI algorithms, including deep learning (DL) models, for application in ophthalmic and non-ophthalmic (i.e., systemic) disorders. We found that the use of AI algorithms for the interpretation of retinal images, compared to clinical data and physician experts, represents an innovative solution with demonstrated superior accuracy in identifying many ophthalmic (e.g., diabetic retinopathy (DR), age-related macular degeneration (AMD), optic nerve disorders), and non-ophthalmic disorders (e.g., dementia, cardiovascular disease). There has been a significant amount of clinical and imaging data for this research, leading to the potential incorporation of AI and DL for automated analysis. AI has the potential to transform healthcare by improving accuracy, speed, and workflow, lowering cost, increasing access, reducing mistakes, and transforming healthcare worker education and training.

A comparative study on the effects of human serum albumin and α-melanocyte-stimulating hormone fusion proteins on the anti-neuroinflammatory in the central nervous system of adult mice.

The immunomodulatory effects of α-melanocyte stimulating hormone (α-MSH) in the central nervous system (CNS) have been investigated for forty years. The clinical applications of α-MSH are limited due to its short half-life. Our previous study has indicated that the short half-life of α-MSH can be extended by fusion with carrier human serum albumin (HSA) and this fusion protein has also retained the anti-inflammatory effect on the CNS. This improvement is still far from the clinical requirements. Thus, we expected to enhance the half-life and activity of the fusion protein by optimizing the linker peptide to get closer to clinical requirements. In a previous study, we screened out two candidates in vitro experiments with a flexible linker peptide (fusion protein with flexible linker peptide, FPFL) and a rigid linker peptide (fusion protein with rigid linker peptide, FPRL), respectively. However, it was not sure whether the anti-inflammatory effects in vitro could be reproduced in vivo. Our results show that FPRL is the best candidate with a longer half-life compared to the traditional flexible linker peptides. Meanwhile, the ability of FPRL to penetrate the blood-brain barrier (BBB) was enhanced, and the inhibition of TNF-α and IL-6 was improved. We also found that the toxicity of FPRL was decreased. All of the results suggested that trying to choose the rigid linker peptide in some fusion proteins may be a potential choice for improving the unsatisfactory characteristics.

Rigid linker peptides improve the stability and anti-inflammation effect of human serum albumin and α-melanocyte-stimulating hormone fusion proteins.

The anti-inflammatory effect of α-melanocyte-stimulating hormone (α-MSH) in the central nervous system (CNS) has been reported for 40 years. However, the short half-life of α-MSH limits its clinical applications. The previous study has shown that a fusion protein comprising protein transduction domain (PTD), human serum albumin (HSA), and α-MSH extends the half-life of α-MSH, but its anti-inflammatory effect is not satisfactory. In this study, optimization of the structures of fusion proteins was attempted by changing the linker peptide between HSA and α-MSH. The optimization resulted in the improvement of various important characteristics, especially the stability and anti-inflammatory bioactivity, which are important features in protein medicines. Compared to the original linker peptide L0, the 5-amino-acid rigid linker peptide L6 (PAPAP) is the best option for further investigation due to its higher expression (increased by 6.27%), improved purification recovery (increased by 60.8%), excellent thermal stability (Tm = 83.5°C) and better inhibition in NF-κB expression (increased by 81.5%). From this study, the significance of the design of linker peptides in the study of structure-activity relationship of fusion proteins was proved.

Geological Characteristics of Low-Yield and Low-Efficiency CBM Wells and Practical Measures for Production Increase in the Qinshui Basin.

Many low-production and low-efficiency wells in the Zhengzhuang, Fanzhuang, Lu'an, and Yangquan blocks of the Qinshui Basin seriously hinder the development of coalbed methane in China. Through in-depth research on the geological conditions and development technology of coalbed methane, it was found that the main reasons for the existence of a large number of low-production and low-efficiency wells are the fragmentation of coal structure, poor adaptability of vertical well types, sizable well spacing, and mismatched stimulation measures. On this basis, it is proposed to adopt an L-shaped horizontal well and staged Fracking technology in the block with a complete coal structure but low permeability. For stress-concentration areas, the first fracturing of a vertical well has a single crack and a small coverage area; After a period of drainage and production, the use of repeated fracturing technology can increase the complexity of fractures and increase gas production; For the fractured area of coal structure, the use of roof fracturing technology effectively solves the problem of coal fragmentation. In natural fracture development areas, new fractures are formed using fracture turning technology to achieve the effect of increasing production. The above technologies have achieved good results in the Qinshui Basin engineering experiment. Therefore, in-depth research on the geological conditions of coalbed methane and matching related development technologies are the main ways to solve low-efficiency and low-production wells in coalbed methane development blocks.

Potential Fungi Isolated From Anti-biodegradable Chinese Medicine Residue to Degrade Lignocellulose.

Traditional Chinese medicine is one of the ancient medicines which is popular in Asian countries, among which the residue produced by the use of anti-biodegradables is endless, and causes significant adverse impacts on the environment. However, the high acidity of anti-biodegradable residues and some special biological activities make it difficult for microorganisms to survive, resulting in a very low degradation rate of lignocellulose in naturally stacked residues, which directly impedes the degradation of residues. We aimed to identify the fungal strains that efficiently biodegrade anti-biodegradable residue and see the possibility to improve the biodegradation of it and other agricultural wastes by co-cultivating these fungi. We isolated 302 fungal strains from anti-biodegradable residue to test hydrolysis ability. Finally, we found Coniochaeta sp., Fomitopsis sp., Nemania sp., Talaromyces sp., Phaeophlebiopsis sp. which inhabit the anti-biodegradable residues are capable of producing higher concentrations of extracellular enzymes. Synergistic fungal combinations (viz., Fomitopsis sp. + Phaeophlebiopsis sp.; Talaromyces sp. + Coniochaeta sp. + Fomitopsis sp.; Talaromyces sp. + Fomitopsis sp. + Piloderma sp. and Talaromyces sp. + Nemania sp. + Piloderma sp.) have better overall degradation effect on lignocellulose. Therefore, these fungi and their combinations have strong potential to be further developed for bioremediation and biological enzyme industrial production.

Protective effect of Terminalia chebula Retz. extract against Aß aggregation and Aß-induced toxicity in Caenorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia chebula Retz. (T.chebula) is an important medicinal plant in Tibetan medicine and Ayurveda. T.chebula is known as the "King of Tibetan Medicine", due to its widespread clinical pharmacological activity such as anti-inflammatory, antioxidative, antidiabetic as well as anticancer in lots of in vivo and in vitro models. In this study, we use transgenic and/or RNAi Caenorhabditis elegans (C.elegans) model to simulation the AD pathological features induced by Aß, to detect the effect of TWE on improving Aß-induced toxicity and the corresponding molecular mechanism. AIM OF STUDY: The study aimed to tested the activities and its possible mechanism of T.chebula to against Aß1-42 induced toxicity and Aß1-42 aggregation. MATERIALS AND METHODS: Using transgenic C.elegans strain CL2006 and CL4176 as models respond to paralytic induced by Aß toxicity. The transcription factors DAF-16 and SKN-1 were analyzed used a fluorescence microscope in transgenic strains (DAF-16:GFP, SKN-1:GFP). The function of DAF-16 and SKN-1 was further investigated using loss-of-function strains by feeding RNA interference (RNAi) bacteria. To evaluate the aggregation level of Aß in the transgenic C.elegans, Thioflavin S (ThS) staining and WB visualized the levels of Aß monomers and oligomers. RESULTS: TWE treatment can significantly improve the paralysis of transgenic C.elegans caused by Aß aggregation (up to 14%). The Aß aggregates in transgenic C.elegans are significantly inhibited under TWE exposure (up to 70%). TWE increases the nuclear localization of the key transcription factor DAF-16 and HSF-1, which in turn leads to the expression of downstream Hsp-16.2 protein and exerts its inhibitory effect on Aß aggregation. Meanwhile, paralysis improved has not observed in SKN-1 mutation and/or RNAi C.elegans. CONCLUSION: Our results indicate that TWE can protect C.elegans against the Aß1-42-induced toxicity, inhibition Aß1-42 aggregation and delaying Aß-induced paralysis. The neuroprotective effect of TWE involves the activation of DAF-16/HSF-1/Hsp-16.2 pathway.

A route pruning algorithm for an automated geographic location graph construction.

Automated construction of location graphs is instrumental but challenging, particularly in logistics optimisation problems and agent-based movement simulations. Hence, we propose an algorithm for automated construction of location graphs, in which vertices correspond to geographic locations of interest and edges to direct travelling routes between them. Our approach involves two steps. In the first step, we use a routing service to compute distances between all pairs of L locations, resulting in a complete graph. In the second step, we prune this graph by removing edges corresponding to indirect routes, identified using the triangle inequality. The computational complexity of this second step is [Formula: see text], which enables the computation of location graphs for all towns and cities on the road network of an entire continent. To illustrate the utility of our algorithm in an application, we constructed location graphs for four regions of different size and road infrastructures and compared them to manually created ground truths. Our algorithm simultaneously achieved precision and recall values around 0.9 for a wide range of the single hyperparameter, suggesting that it is a valid approach to create large location graphs for which a manual creation is infeasible.