Rational construction of a high-quality and high-efficiency biosynthetic system and fermentation optimization for A82846B based on combinatorial strategies in Amycolatopsis orientalis.

BACKGROUND: Oritavancin is a new generation of semi-synthetic glycopeptide antibiotics against Gram-positive bacteria, which served as the first and only antibiotic with a single-dose therapeutic regimen to treat ABSSSI. A naturally occurring glycopeptide A82846B is the direct precursor of oritavancin. However, its application has been hampered by low yields and homologous impurities. This study established a multi-step combinatorial strategy to rationally construct a high-quality and high-efficiency biosynthesis system for A82846B and systematically optimize its fermentation process to break through the bottleneck of microbial fermentation production. RESULTS: Firstly, based on the genome sequencing and analysis, we deleted putative competitive pathways and constructed a better A82846B-producing strain with a cleaner metabolic background, increasing A82846B production from 92 to 174 mg/L. Subsequently, the PhiC31 integrase system was introduced based on the CRISPR-Cas12a system. Then, the fermentation level of A82846B was improved to 226 mg/L by over-expressing the pathway-specific regulator StrR via the constructed PhiC31 system. Furthermore, overexpressing glycosyl-synthesis gene evaE enhanced the production to 332 mg/L due to the great conversion of the intermediate to target product. Finally, the scale-up production of A82846B reached 725 mg/L in a 15 L fermenter under fermentation optimization, which is the highest reported yield of A82846B without the generation of homologous impurities. CONCLUSION: Under approaches including blocking competitive pathways, inserting site-specific recombination system, overexpressing regulator, overexpressing glycosyl-synthesis gene and optimizing fermentation process, a multi-step combinatorial strategy for the high-level production of A82846B was developed, constructing a high-producing strain AO-6. The combinatorial strategies employed here can be widely applied to improve the fermentation level of other microbial secondary metabolites, providing a reference for constructing an efficient microbial cell factory for high-value natural products.

Endoglucanase H from Aspergillus westerdijkiae Plays an Important Role in the Virulence on Pear Fruits.

Aspergillus westerdijkiae can infect many agricultural products including cereals, grapes, and pear. Pathogenic fungi secrete diverse effectors as invasive weapons for successful invasion the host plant. During the pathogen-host interaction, 4486 differentially expressed genes were observed in A. westerdijkiae with 2773 up-regulated and 1713 down-regulated, whereas 8456 differentially expressed genes were detected in pear fruits with 4777 up-regulated and 3679 down-regulated. A total of 309 effector candidate genes were identified from the up-regulated genes in A. westerdijkiae. Endoglucanase H (AwEGH) was significantly induced during the pathogen-host interaction. Deletion of AwEGH resulted in altered fungal growth and morphology and reduced conidia production and germination compared to the wild-type. Further experiments demonstrated that AwEGH plays a role in cell wall integrity. Importantly, disruption of AwEGH significantly reduced the fungal virulence on pear fruits, and this defect can be partly explained by the impaired ability of A. westerdijkiae to penetrate host plants.

Chitosan inhibits Penicillium expansum possibly by binding to DNA and triggering apoptosis.

Chitosan is a natural polysaccharide that is abundant, biocompatible and exhibits effective antifungal activity against various pathogenic fungi. However, the potential intracellular targets of chitosan in pathogenic fungi and the way of activity of chitosan are far from well known. The present work demonstrated that chitosan could inhibit Penicillium expansum, the principal causal agent of postharvest blue mold decay on apple fruits, by binding to DNA and triggering apoptosis. UV-visible spectroscopy, fluorescence spectroscopy and electrophoretic mobility assay proved the interaction between chitosan and DNA, while atomic force microscope (AFM) observation revealed the binding morphology of chitosan to DNA. Chitosan could inhibit in vitro DNA replication, and cell cycle analysis employing flow cytometry demonstrated that cell cycle was retarded by chitosan treatment. Furthermore, the reactive oxygen species (ROS) assay and membrane potential analysis showed that apoptosis was induced in P. expansum cells after exposure to chitosan. In conclusion, our results confirmed that chitosan interacts with DNA and induces apoptosis. These findings are expected to provide a feasible theoretical basis and practical direction for the promoting and implementing of chitosan in plant protection and further illuminate the possible antifungal mechanisms of chitosan against fungal pathogens.

Cardiovascular benefits and safety of sotagliflozin in type 2 diabetes mellitus patients with heart failure or cardiovascular risk factors: a bayesian network meta-analysis.

Background: As an antidiabetic agent, sotagliflozin was recently approved for heart failure (HF). However, its cardiovascular benefits in type 2 diabetic mellitus (T2DM) patients with HF or cardiovascular (CV) risk factors have not been systematically evaluated. The aim of this study is to evaluate the cardiovascular benefits and safety of sotagliflozin in T2DM patients with HF or CV risk factors using Bayesian network meta-analysis. Methods: Data were retrieved from PubMed, Embase, Web of Science, ClinicalTrials.gov, and Cochrane Library from their inception to 16 August 2023. Randomized controlled trials (RCTs) comparing sotagliflozin with a placebo, dapagliflozin, and empagliflozin in adult T2DM patients with HF or CV risks for at least 12 weeks were included in the study. Data analysis was conducted using R 4.2.3 and Stata 17.0. Cardiovascular efficacy outcomes included HF events (hospitalization or urgent visits for HF), MACE (deaths from CV causes, hospitalizations for HF, nonfatal myocardial infarctions, and strokes), cardiovascular death, the decrease in SBP, and weight loss. Safety outcomes are urinary tract infection, diarrhea, and diabetic ketoacidosis. Results: Eleven studies with 30,952 patients were included. Compared to dapagliflozin and empagliflozin, 200 mg of sotagliflozin showed the best effect in reducing HF events [OR (95% CI), 0.79 (0.66, 0.94) and 0.90 (0.63, 1.27)]. Compared to dapagliflozin, 200 mg of sotagliflozin [OR (95% CI), 0.76 (0.66, 0.87)] was superior in preventing MACE. Compared to empagliflozin, 200 mg of sotagliflozin [OR (95% CI), 1.46 (1.04, 2.05)] was inferior in preventing CV death. Sotagliflozin showed a poorer SBP decreasing effect than empagliflozin and dapagliflozin [MD (95% CI), 1.30 (0.03, 2.56) and 2.25 (0.35, 4.14), respectively]. There was no significant difference between sotagliflozin and other interventions in weight loss. Sotagliflozin exhibited no increased risk for diabetic ketoacidosis or urinary tract infection among all interventions, however, it showed a mild risk for diarrhea than placebo [OR (95% CI), 1.47 (1.28, 1.69)]. Conclusion: Sotagliflozin displayed moderate CV benefits and acceptable safety. Sotagliflozin can be one of the recommended options for T2DM patients with HF or CV risk factors, which will be important for evidence-based use of sotagliflozin as well as decision-making of T2DM medication.

Daptomycin production enhancement by ARTP mutagenesis and fermentation optimization in Streptomyces roseosporus.

AIMS: We evaluated whether the randomness of mutation breeding can be regulated through a double-reporter system. We hope that by establishing a new precursor feeding strategy, the production capacity of industrial microorganisms after pilot scale-up can be further improved. METHODS AND RESULTS: In this study, the industrial strain Streptomyces roseosporus L2796 was used as the starter strain for daptomycin production, and a double-reporter system with the kanamycin resistance gene Neo and the chromogenic gene gusA was constructed to screen for high-yield strain L2201 through atmospheric and room temperature plasma (ARTP). Furthermore, the composition of the culture medium and the parameters of precursor replenishment were optimized, resulting in a significant enhancement of the daptomycin yield of the mutant strain L2201(752.67 mg/l). CONCLUSIONS: This study successfully screened a high-yield strain of daptomycin through a double-reporter system combined with ARTP mutation. The expression level of two reporter genes can evaluate the strength of dptEp promoter, which can stimulate the expression level of dptE in the biosynthesis of daptomycin, thus producing more daptomycin. The developed multi-stage feeding rate strategy provides a novel way to increase daptomycin in industrial fermentation.

[Weidiao-3 Mixture Improves the Clinical Efficacy of Immunotherapy for Advanced Gastric Cancer by Regulating Intestinal Flora].

Objective To investigate the effects of Weidiao-3(WD-3)Mixture on the clinical efficacy of immunotherapy for advanced gastric cancer and the intestinal flora.Methods Fifty-one patients with advanced gastric cancer treated in Wuxi Traditional Chinese Medicine Hospital from January 2020 to December 2021 were randomized into a WD-3 group(immunotherapy + WD-3 Mixture,one dose per day)(n=25)and a gastric cancer(GC) group(only immunotherapy)(n=26)according to the admission time.Ten healthy volunteers were included as the healthy control group.The Karnofsky score and the Quality of Life Questionnare-Core score were evaluated before and after treatment,and the clinical efficacy was compared after treatment.After treatment,the stool samples were collected for 16SrRNA gene high-throughput sequencing and targeted metabolomics.The α and ß diversity and structure of the intestinal flora and the content of short-chain fatty acids were compared between groups.Results The quality of life in both groups improved after treatment and was better in the WD-3 group than in the GC group(P=0.035).The dry mouth(P=0.038)and altered taste(P=0.008)were mitigated in the WD-3 group after treatment,and the reflux(P=0.001)and dry mouth(P=0.022)were mitigated in the GC group after treatment.After treatment,the WD-3 group outperformed the GC group in terms of dysphagia(P=0.047)and dry mouth(P=0.045).The WD-3 group was superior to the GC group in terms of objective remission rate and disease control rate,with prolonged median progression-free survival and median overall survival(P=0.039,P=0.043).The α and ß diversity indexes of the intestinal flora showed no significant differences between WD-3 and GC groups(all P>0.05).At the phylum level,WD-3 and GC groups had lower relative abundance of Firmicutes(P=0.038,P=0.042)and higher relative abundance of Proteobacteria(P=0.016,P=0.015)than the healthy control group.The relative abundance of Actinomycetes in the GC group was lower than that in the healthy control group(P=0.035)and the WD-3 group(P=0.046).At the genus level,the GC group had lower relative abundance of Bifidobacteria and Coprococcus than the healthy control group and the WD-3 group(all P<0.001).LEfSe revealed the differences in the relative abundance of 6 intestinal bacterial taxa between the WD-3 group and the GC group.At the genus level,Saccharopolyspora had higher relative abundance in the WD-3 group than in the healthy control group and only existed in the WD-3 group.The content of isobutyric acid and isovaleric acid in the WD-3 group was higher than that in the healthy control group(P=0.037,P=0.004).Conclusion WD-3 Mixture may increase the relative abundance of Bifidobacteria and Coprococcus and the content of isobutyric acid and isovaleric acid to alter the intestinal microecology,thereby improving the efficacy of immunotherapy for gastric cancer.

SuperUDF: Self-supervised UDF Estimation for Surface Reconstruction.

Learning-based surface reconstruction based on unsigned distance functions (UDF) has many advantages such as handling open surfaces. We propose SuperUDF, a self-supervised UDF learning which exploits a learned geometry prior for efficient training and a novel regularization for robustness to sparse sampling. The core idea of SuperUDF draws inspiration from the classical surface approximation operator of locally optimal projection (LOP). The key insight is that if the UDF is estimated correctly, the 3D points should be locally projected onto the underlying surface following the gradient of the UDF. Based on that, a number of inductive biases on UDF geometry and a pre-learned geometry prior are devised to learn UDF estimation efficiently. A novel regularization loss is proposed to make SuperUDF robust to sparse sampling. Furthermore, we also contribute a learning-based mesh extraction from the estimated UDFs. Extensive evaluations demonstrate that SuperUDF outperforms the state of the arts on several public datasets in terms of both quality and efficiency. Code will be released after accteptance.

Comprehension of rectosigmoid junction cancer molecular features by comparison to the rectum or sigmoid colon cancer.

Background: Colorectal cancer (CRC) is a heterogeneous cancer. Its treatment depends on its anatomical site and molecular features. Carcinomas of the rectosigmoid junction are frequent; however, specific data on these tumors are sparse, as they are frequently assigned to either the colon or rectum. This study sought to identify the molecular features of rectosigmoid junction cancer to determine whether there should be any difference between the therapeutic management of rectosigmoid junction cancer and that of sigmoid colon or rectum cancer. Methods: The data of 96 CRC patients with carcinomas in the sigmoid colon, rectosigmoid junction, and rectum were retrospectively summarized. The next-generation sequencing (NGS) data of the patients were analyzed to study the molecular characteristics of the carcinomas in different locations of the bowel. Results: In total, there was no difference in the clinicopathologic characteristics of the three groups. TP53, APC, and KRAS genes were the top 3 alteration genes in sigmoid colon, rectosigmoid junction, and rectum cancer. The rates of the KRAS, NRAS, and PIK3CA increased as the location moved distally, while the rates of APC and BRAF decreased. Almost no significant molecular differences were found among the three groups. The prevalence of the FLT3, fms-related tyrosine kinase 1 (FLT1), and phosphoenolpyruvate carboxykinase 1 (PCK1) mutation was lower in the rectosigmoid junction group than the sigmoid colon and rectum groups (P>0.05). The proportion of the transforming growth factor beta pathway was higher in the rectosigmoid junction and rectum groups than the sigmoid colon group (39.3% vs. 34.3% vs. 18.2%, respectively, P=0.121, P=0.067, P=0.682); a higher proportion of MYC pathway was also observed in the rectosigmoid junction than that in rectum and sigmoid colon (28.6% vs. 15.2% vs. 17.1%, P=0.278, P=0.202, P=0.171). Regardless of the clustering method employed, the patients were divided into two clusters, and the composition of clusters revealed no significant differences in terms of the different locations. Conclusions: Rectosigmoid junction cancer has a distinctive molecular profile compared to the molecular profiles of the adjacent bowel segment cancers.

Identification and Characterization of a New Regulator, TagR, for Environmental Stress Resistance Based on the DNA Methylome of Streptomyces roseosporus.

DNA methylation is a defense that microorganisms use against extreme environmental stress, and improving resistance against environmental stress is essential for industrial actinomycetes. However, research on strain optimization utilizing DNA methylation for breakthroughs is rare. Based on DNA methylome analysis and KEGG pathway assignment in Streptomyces roseosporus, we discovered an environmental stress resistance regulator, TagR. A series of in vivo and in vitro experiments identified TagR as a negative regulator, and it is the first reported regulator of the wall teichoic acid (WTA) ABC transport system. Further study showed that TagR had a positive self-regulatory loop and m4C methylation in the promoter improved its expression. The ΔtagR mutant exhibited better hyperosmotic resistance and higher decanoic acid tolerance than the wild type, which led to a 100% increase in the yield of daptomycin. Moreover, enhancing the expression of the WTA transporter resulted in better osmotic stress resistance in Streptomyces lividans TK24, indicating the potential for wide application of the TagR-WTA transporter regulatory pathway. This research confirmed the feasibility and effectiveness of mining regulators of environmental stress resistance based on the DNA methylome, characterized the mechanism of TagR, and improved the resistance and daptomycin yield of strains. Furthermore, this research provides a new perspective on the optimization of industrial actinomycetes. IMPORTANCE This study established a novel strategy for screening regulators of environmental stress resistance based on the DNA methylome and discovered a new regulator, TagR. The TagR-WTA transporter regulatory pathway improved the resistance and antibiotic yield of strains and has the potential for wide application. Our research provides a new perspective on the optimization and reconstruction of industrial actinomycetes.

OncoVee™-MiniPDX-guided anticancer treatment for HER2-negative intermediate-advanced gastric cancer patients: a single-arm, open-label phase I clinical study.

BACKGROUND: Chemotherapy is the main treatment strategy for patients with advanced HER2-negative gastric cancer (GC); yet, many patients do not respond well to treatment. This study evaluated the sensitivity of a mini patient-derived xenograft (MiniPDX) animal model in patients with HER2-negative intermediate-advanced GC. METHODS: In this single-arm, open-label clinical study, we consecutively recruited patients with HER2-negative advanced or recurrent GC from September 2018 to July 2021. Tumor tissues were subjected to MiniPDX drug sensitivity tests for screening individualized anti-tumor drugs; appropriate drug types or combinations were selected based on drug screening results. The primary endpoints were progression-free survival (PFS) and safety, and the secondary endpoints were overall survival (OS) and objective response rate (ORR). RESULTS: A total of 17 patients were screened, and 14 eligible patients were included.The median follow-up time was 9 (2-34) months. The median PFS time was 14.1 (2-34) months, the median OS time was 16.9 (2-34) months, ORR was 42.9% (6/14), and DCR was 92.9% (13/14). The most common treatment-related adverse events (TRAE) were fatigue (14 (100%)), anorexia (13 (93%)) and insomnia (12 (86%)), and the most common grade 3 or worse TRAE was fatigue (6 (43%)), and anorexia (6 (43%)). The occurrence rate of myelosuppression, nausea and vomiting, abnormal liver enzymes, and other grade 3-4 chemotherapy adverse reactions were relatively low, and no grade 5 treatment-related adverse events occurred. CONCLUSION: Screening HER2-negative medium-advanced GC/GJC chemotherapy regimens and targeted drugs based on MiniPDX animal models showed good tumor activity and safety.

Degradation mechanism of AtrA mediated by ClpXP and its application in daptomycin production in Streptomyces roseosporus.

The efficiency of drug biosynthesis depends on different transcriptional regulatory pathways in Streptomyces, and the protein degradation system adds another layer of complexity to the regulatory processes. AtrA, a transcriptional regulator in the A-factor regulatory cascade, stimulates the production of daptomycin by binding to the dptE promoter in Streptomyces roseosporus. Using pull-down assays, bacterial two-hybrid system and knockout verification, we demonstrated that AtrA is a substrate for ClpP protease. Furthermore, we showed that ClpX is necessary for AtrA recognition and subsequent degradation. Bioinformatics analysis, truncating mutation, and overexpression proved that the AAA motifs of AtrA were essential for initial recognition in the degradation process. Finally, overexpression of mutated atrA (AAA-QQQ) in S. roseosporus increased the yield of daptomycin by 225% in shake flask and by 164% in the 15 L bioreactor. Thus, improving the stability of key regulators is an effective method to promote the ability of antibiotic synthesis.

Experimental study on reducing the viscosity of sewage containing PAM catalyzed by low temperature plasma synergistic AC/Mn + TiO2.

With the wide application of polymer flooding technology in oil fields, wastewater containing PAM (polyacrylamide) is produced. Its high viscosity makes it difficult to degrade. In this paper, the low-temperature plasma produced by DBD (Dielectric Barrier Discharge) was studied to reduce the viscosity of wastewater containing PAM under the synergistic action of AC (Activated carbon)/Mn + TiO2 catalyst. The effects of different amount of AC/Mn + TiO2 catalyst, discharge voltage and initial concentration of solution on viscosity reduction were studied. The change of functional groups in wastewater containing PAM was detected by FTIR (Fourier transform infrared absorption spectrometer), and the mechanism of catalytic viscosity reduction was analysed. The AC/Mn + TiO2 catalysts were analysed by XPS (X-ray photoelectron spectroscopy), XRD (X-Ray Diffraction) and ESEM (Field emission electron microscopy). With the increase of discharge voltage, the effect of catalytic viscosity reduction is enhanced. After 10 min of discharge, the effect of catalytic viscosity reduction is significantly enhanced. The catalytic viscosity reduction is best when discharge voltage is 18 KV and discharge time is 30 min. The viscosity reduction of polyacrylamide solution by low-temperature plasma AC/Mn + TiO2 is significant. When the amount of AC/Mn + TiO2 catalyst added is 544 mg, the viscosity of polymer containing solution can be reduced from 1758 mPa·s to 11.9 mPa·s, and the shear rate can be changed from 0 1/sec to 30 1/sec after the discharge for 30 min. The functional groups in solution did not change significantly and the element composition of AC/Mn + TiO2 catalyst did not change before and after catalytic discharge.

How pom cheerleading improves the executive function of preschool children: the mediating role of speed and agility.

Physical exercises can improve individuals' physical health and cognition, but the internal influence path is unclear. This study aims to examine the influence of pom cheerleading training on physical fitness and executive function of preschool children and explore the relationship between sports training, physical fitness, and executive function. We selected seventy-one preschool children and divided them into the experimental group (n = 36) and the control group (n = 35). The experimental group kept a 12-week pom cheerleading training, and the exercises of the control group remained normal. Children's physical fitness and executive function were tested, in one week before and after the experiment, respectively. Results of repeated measurements analysis of variance and structural equation model test showed: (1) after 12-week pom cheerleading training, in terms of physical fitness, the experimental group has a significant improvement over the control group on agility and speed; in terms of executive function, the inhibitory control and working memory of the experimental group were significantly enhanced over the control group. (2) Speed quality plays a partial mediating role between pom cheerleading training and inhibitory control; agility plays a major mediating role between pom cheerleading training and working memory. It is concluded that physical exercise can directly improve preschool children's executive function, and indirectly enhance executive function mediated by physical fitness. Furthermore, structured and systematic physical education should be adopted for preschool children to cultivate their interest in sports and enhance their cognition.

ACP-check: An anticancer peptide prediction model based on bidirectional long short-term memory and multi-features fusion strategy.

The anticancer peptide is an emerging anticancer drug that has become an effective alternative to chemotherapy and targeted therapy due to fewer side effects and resistance. The traditional biological experimental method for identifying anticancer peptides is a time-consuming and complicated process that hinders large-scale, rapid, and effective identification. In this paper, we propose a model based on a bidirectional long short-term memory network and multi-features fusion, called ACP-check, which employs a bidirectional long short-term memory network to extract time-dependent information features from peptide sequences, and combines them with amino acid sequence features including binary profile feature, dipeptide composition, the composition of k-spaced amino acid group pairs, amino acid composition, and sequence-order-coupling number. To verify the performance of the model, six benchmark datasets are selected, including ACPred-Fuse, ACPred-FL, ACP240, ACP740, main and alternate datasets of AntiCP2.0. In terms of Matthews correlation coefficients, ACP-check obtains 0.37, 0.82, 0.80, 0.75, 0.56, and 0.86 on six datasets respectively, which is an improvement by 2%-86% than existing state-of-the-art anticancer peptides prediction methods. Furthermore, ACP-check achieves prediction accuracy with 0.91, 0.91, 0.90, 0.87, 0.78, and 0.93 respectively, which increases range from 1%-49%. Overall, the comparison experiment shows that ACP-check can accurately identify anticancer peptides by sequence-level information. The code and data are available at http://www.cczubio.top/ACP-check/.

Improving the Yield and Quality of Daptomycin in Streptomyces roseosporus by Multilevel Metabolic Engineering.

Daptomycin is a cyclic lipopeptide antibiotic with a significant antibacterial action against antibiotic-resistant Gram-positive bacteria. Despite numerous attempts to enhance daptomycin yield throughout the years, the production remains unsatisfactory. This study reports the application of multilevel metabolic engineering strategies in Streptomyces roseosporus to reconstruct high-quality daptomycin overproducing strain L2797-VHb, including precursor engineering (i.e., refactoring kynurenine pathway), regulatory pathway reconstruction (i.e., knocking out negative regulatory genes arpA and phaR), byproduct engineering (i.e., removing pigment), multicopy biosynthetic gene cluster (BGC), and fermentation process engineering (i.e., enhancing O2 supply). The daptomycin titer of L2797-VHb arrived at 113 mg/l with 565% higher comparing the starting strain L2790 (17 mg/l) in shake flasks and was further increased to 786 mg/l in 15 L fermenter. This multilevel metabolic engineering method not only effectively increases daptomycin production, but can also be applied to enhance antibiotic production in other industrial strains.

A novel strategy of gene screen based on multi-omics in Streptomyces roseosporus.

Daptomycin is a new lipopeptide antibiotic for treatment of severe infection caused by multi-drug-resistant bacteria, but its production cost remains high currently. Thus, it is very important to improve the fermentation ability of the daptomycin producer Streptomyces roseosporus. Here, we found that the deletion of proteasome in S. roseosporus would result in the loss of ability to produce daptomycin. Therefore, transcriptome and 4D label-free proteome analyses of the proteasome mutant (Δprc) and wild type were carried out, showing 457 differential genes. Further, five genes were screened by integrated crotonylation omics analysis. Among them, two genes (orf04750/orf05959) could significantly promote the daptomycin synthesis by overexpression, and the fermentation yield in shake flask increased by 54% and 76.7%, respectively. By enhancing the crotonylation modification via lysine site mutation (K-Q), the daptomycin production in shake flask was finally increased by 98.8% and 206.3%, respectively. This result proved that the crotonylation modification of appropriate proteins could effectively modulate daptomycin biosynthesis. In summary, we established a novel strategy of gene screen for antibiotic biosynthesis process, which is more convenient than the previous screening method based on pathway-specific regulators. KEY POINTS: • Δprc strain has lost the ability of daptomycin production • Five genes were screened by multi-omics analysis • Two genes (orf04750/orf05959) could promote the daptomycin synthesis by overexpression.

Multiphoton upconversion and non-resonant optical nonlinearity in perovskite quantum dot doped glasses.

By incorporating the CsPbBr3 quantum dots (QDs) into a glass host, we report for the first time, to our knowledge, the measurement of non-resonant optical nonlinearity and multiphoton upconversion (UC) processes for this QD-in-glass composite. We observe up to four-photon stable UC photoluminescence under excitation by infrared femtosecond pulses, low optical limiting thresholds, and high nonlinear optical absorption coefficients close to those of colloid processed metal halide perovskite (MHP) QDs. Combined with high robustness against air and moisture, the monolithic inorganic glass with incorporated MHP QDs could be a better platform for exploiting strong light-matter interaction for MHPs.

Nanoscale Engineering of Optical nonlinearity Based on a Metal Nitride/Oxide Heterostructure.

The abilities to modulate linear and nonlinear optical response of materials in the nanoscale are of central importance in the design and fabrication of photonic devices for applications like optical modulators. Here, based on a simple transition metal oxide/nitride (TiO2/TiN) system, we show that it is possible to tune the optical properties by controlling the nanoscale architecture. Through controlled oxidation of the plasmonic TiN nanoparticle surfaces, we observe a continuous change of linear and nonlinear optical (NLO) properties with the increase of the thickness of the oxide layer in the TiN/TiO2 heterogeneous architecture. The NLO response is manifested by the strong saturable absorption with a structurally tunable negative NLO absorption coefficient. The variation in the NLO absorption coefficient by up to 7-fold can be connected to the relative change in the volume fraction of the metallic core and the dielectric shell. We demonstrate further that the optimized TiN-TiO2 heterostructures can be used to drive an optical switch for pulse laser generation in the 1.5 µm wavelength region. Our results delineate a topochemical process for optimization of the NLO properties of common plasmonic materials for photonic applications based on simple materials chemistry.

General Model Based on Artificial Neural Networks for Estimating the Viscosities of Oxygenated Fuels.

Oxygenated fuel is a promising alternative fuel for engines because of the advantage of low emission. In this work, a general model based on back-propagation neural networks was developed for estimating the viscosities of different kinds of oxygenated fuels including esters, alcohols, and ethers, whose input variables are pressure, temperature, critical pressure, critical temperature, molar mass, and acentric factor. The viscosity data of 31 oxygenated fuels (1574 points) at temperatures ranging from 243.15 to 413.15 K and at pressures ranging from 0.1 to 200 MPa were collected to train and test the back-propagation neural network model. The comparison result shows that the predictions of the proposed back-propagation neural network model agree well with the experimental viscosity data of all studied oxygenated fuels using the general parameters (weight and bias). The average absolute relative deviations for training data, validation data, and testing data are 1.19%, 1.27%, and 1.30%, respectively.