High Performance Rotating Triboelectric Nanogenerator with Coaxial Rolling Charge Pump Strategy.

With the development of society and the advancement of technology, the emergence of the Internet of Things (IoT) has changed people's lifestyles and raised the demand for energy to a new level. However, there are some drawbacks in terms of energy supply for IoT sensors, such as limited battery capacity and limitations in replacement and maintenance. Therefore, it has become urgent to develop a sustainable green energy source (wind energy) using the surrounding environment. Meanwhile, triboelectric nanogenerators (TENGs) with advantages such as flexible structure, low manufacturing cost, and environmental friendliness provide enormous potential for constructing self-powered sensing systems. In this work, we present a novel coaxial rolling charge pump TENG (CR-TENG) based on wind energy to enhance the output performance and durability. The rolling friction charge pump TENG directly injects positive and negative charges into the main TENG, which is more wear-resistant compared to sliding friction, and greatly increases the charge density and output power. In addition, the charge pumping part and the main TENG adopt the coaxial design, reducing the complexity of the structural design. On comparing the output performance of the CR-TENG under the initial state, rectifier bridge supplemental charge strategy, and charge pump supplemental charge strategy, results shown that the output voltage performance of the CR-TENG can be improved by 5800% under the charge pump supplemental charge strategy. Moreover, the output performance of the CR-TENG remains stable after 72,000 cycles. The output power of the CR-TENG can reach 1.21 mW with a load resistance of 3 × 107 Ω. And the CR-TENG can charge a 0.1 µF capacitor to 5 V in just 1.6 s. This work provides new insights for the rotary durable high output charge pump compensating a triboelectric nanogenerator and demonstrates the important potential of harvesting environmental energy to supply intelligent IoT nodes.

Optimized Design of an Ultrasonic-Based High-Efficiency Wireless Passive Monitoring System for Sealed Metal Compartments.

The condition monitoring (CM) of sealed metal compartments (SMCs) is an urgently required restructure. Ultrasound penetrates SMCs to power and communicate with built-in sensors, enabling the CM of SMCs. However, current ultrasonic wireless power transfer and data communication (UWPTADC) systems are large and complex, and limited by the efficiency of energy transfer and data reliability. In this paper, an optimized design of a high-efficiency wireless passive monitoring system using UWPTADC techniques is proposed for SMC. The circuit model of the system is developed and analyzed to achieve an optimal design for efficient wireless power transfer and effective data communication coupling. A test system was constructed using a steel wall of 11 mm thickness as a validation object. At the ultrasonic carrier frequency of 1.045 MHz, the system has an energy transfer efficiency of 60%, and a communication rate of 50 kbps. In addition, the system realizes temperature and humidity monitoring inside a 13 mm thick cylindrical SMC, simulating the process of ultrasonic CM of an actual engine compartment. The system provides a wiring-free and battery-free solution for CM in SMCs, advancing CM in aerospace, marine and other fields.

Brain metastatic outgrowth and osimertinib resistance are potentiated by RhoA in EGFR-mutant lung cancer.

The brain is a major sanctuary site for metastatic cancer cells that evade systemic therapies. Through pre-clinical pharmacological, biological, and molecular studies, we characterize the functional link between drug resistance and central nervous system (CNS) relapse in Epidermal Growth Factor Receptor- (EGFR-) mutant non-small cell lung cancer, which can progress in the brain when treated with the CNS-penetrant EGFR inhibitor osimertinib. Despite widespread osimertinib distribution in vivo, the brain microvascular tumor microenvironment (TME) is associated with the persistence of malignant cell sub-populations, which are poised to proliferate in the brain as osimertinib-resistant lesions over time. Cellular and molecular features of this poised state are regulated through a Ras homolog family member A (RhoA) and Serum Responsive Factor (SRF) gene expression program. RhoA potentiates the outgrowth of disseminated tumor cells on osimertinib treatment, preferentially in response to extracellular laminin and in the brain. Thus, we identify pre-existing and adaptive features of metastatic and drug-resistant cancer cells, which are enhanced by RhoA/SRF signaling and the brain TME during the evolution of osimertinib-resistant disease.

A Multifunctional Cytochrome P450 and a Meroterpenoid Cyclase in the Biosynthesis of Fungal Meroterpenoid Atlantinone B.

The biosynthetic gene cluster of atlantinone B (10) was discovered in Penicillium chrysogenum MT-40. A multifunctional cytochrome P450 (AtlD) encoded by the cluster is responsible for the formation of the unique lactone-bridged ring and the 16ß-hydroxyl of atlantinone B, and a new terpene cyclase (AtlC) can unprecedentedly accept the demethylated substrate epoxyfarnesyl-DMOA (4a) to generate three bicyclic meroterpenoids (5a-5c). This study paves the way for combinatorial synthesis of structurally diverse meroterpenoids for drug discovery.

Identification of a diarylpentanoid-producing polyketide synthase revealing an unusual biosynthetic pathway of 2-(2-phenylethyl)chromones in agarwood.

2-(2-Phenylethyl)chromones (PECs) are the principal constituents contributing to the distinctive fragrance of agarwood. How PECs are biosynthesized is currently unknown. In this work, we describe a diarylpentanoid-producing polyketide synthase (PECPS) identified from Aquilaria sinensis. Through biotransformation experiments using fluorine-labeled substrate, transient expression of PECPS in Nicotiana benthamiana, and knockdown of PECPS expression in A. sinensis calli, we demonstrate that the C6-C5-C6 scaffold of diarylpentanoid is the common precursor of PECs, and PECPS plays a crucial role in PECs biosynthesis. Crystal structure (1.98 Å) analyses and site-directed mutagenesis reveal that, due to its small active site cavity (247 Å3), PECPS employs a one-pot formation mechanism including a "diketide-CoA intermediate-released" step for the formation of the C6-C5-C6 scaffold. The identification of PECPS, the pivotal enzyme of PECs biosynthesis, provides insight into not only the feasibility of overproduction of pharmaceutically important PECs using metabolic engineering approaches, but also further exploration of how agarwood is formed.

Two new diterpenoids from Penicillium chrysogenum MT-12, an endophytic fungus isolated from Huperzia serrata.

Two new diterpenoids, penicichrysogene A (1) and penicichrysogene B (2), were isolated from the solid substrate fermentation cultures of Penicillium chrysogenum MT-12, an endophytic fungus isolated from the medicinal plant of Huperzia serrata. Their structures were elucidated on the basis of extensive spectroscopic and spectrometric data (1D and 2D NMR, UV, IR, and HRESIMS). The absolute configurations of 1 and 2 were assigned on the basis of experimental and calculated electronic circular dichroism spectra. Compound 1 exhibited inhibitory activity on ATP release of thrombin-activated platelets with IC50 = 42.7 ± 3.5 µM.

Divergent improvement of two cultivated allotetraploid cotton species.

Interspecific genomic variation can provide a genetic basis for local adaptation and domestication. A series of studies have presented its role of interspecific haplotypes and introgressions in adaptive traits, but few studies have addressed their role in improving agronomic character. Two allotetraploid Gossypium species, Gossypium barbadense (Gb) and G. hirsutum (Gh) originating from the Americas, are cultivated independently. Here, through sequencing and the comparison of one GWAS panel in 229 Gb accessions and two GWAS panels in 491 Gh accessions, we found that most associated loci or functional haplotypes for agronomic traits were highly divergent, representing the strong divergent improvement between Gb and Gh. Using a comprehensive interspecific haplotype map, we revealed that six interspecific introgressions from Gh to Gb were significantly associated with the phenotypic performance of Gb, which could explain 5%-40% of phenotypic variation in yield and fibre qualities. In addition, three introgressions overlapped with six associated loci in Gb, indicating that these introgression regions were under further selection and stabilized during improvement. A single interspecific introgression often possessed yield-increasing potential but decreased fibre qualities, or the opposite, making it difficult to simultaneously improve yield and fibre qualities. Our study not only has proved the importance of interspecific functional haplotypes or introgressions in the divergent improvement of Gb and Gh, but also supports their potential value in further human-mediated hybridization or precision breeding.

Subgenome Bias and Temporal Postponement of Gene Expression Contributes to the Distinctions of Fiber Quality in Gossypium Species.

As two cultivated widely allotetraploid cotton species, although Gossypium hirsutum and Gossypium barbadense evolved from the same ancestor, they differ in fiber quality; the molecular mechanism of that difference should be deeply studied. Here, we performed RNA-seq of fiber samples from four G. hirsutum and three G. barbadense cultivars to compare their gene expression patterns on multiple dimensions. We found that 15.90-37.96% of differentially expressed genes showed biased expression toward the A or D subgenome. In particular, interspecific biased expression was exhibited by a total of 330 and 486 gene pairs at 10 days post-anthesis (DPA) and 20 DPA, respectively. Moreover, 6791 genes demonstrated temporal differences in expression, including 346 genes predominantly expressed at 10 DPA in G. hirsutum (TM-1) but postponed to 20 DPA in G. barbadense (Hai7124), and 367 genes predominantly expressed at 20 DPA in TM-1 but postponed to 25 DPA in Hai7124. These postponed genes mainly participated in carbohydrate metabolism, lipid metabolism, plant hormone signal transduction, and starch and sucrose metabolism. In addition, most of the co-expression network and hub genes involved in fiber development showed asymmetric expression between TM-1 and Hai7124, like three hub genes detected at 10 DPA in TM-1 but not until 25 DPA in Hai7124. Our study provides new insights into interspecific expression bias and postponed expression of genes associated with fiber quality, which are mainly tied to asymmetric hub gene network. This work will facilitate further research aimed at understanding the mechanisms underlying cotton fiber improvement.

Deciphering the Biosynthetic Mechanism of Pelletierine in Lycopodium Alkaloid Biosynthesis.

Pelletierine, a proposed building block of Lycopodium alkaloids (LAs), was demonstrated to be synthesized via the non-enzymatic Mannich-like condensation of Δ1-piperideine and 3-oxoglutaric acid produced by two new type III PKSs (HsPKS4 and PcPKS1) characterized from Huperzia serrata and Phlegmariurus cryptomerianus, respectively. The findings provide new insights for further understanding the biosynthesis of LAs such as huperzine A.

Tuned near infrared fluorescent hyaluronic acid conjugates for delivery to pancreatic cancer for intraoperative imaging.

The prognosis of pancreatic cancer remains poor. Intraoperative fluorescence imaging of tumors could improve staging and surgical resection, thereby improving prognosis. However, imaging pancreatic cancer with macromolecular delivery systems, is often hampered by nonspecific organ accumulation. Methods: We describe the rational development of hyaluronic acid (HA) conjugates that vary in molecular weight and are conjugated to near infrared fluorescent (NIRF) dyes that have differences in hydrophilicity, serum protein binding affinity, and clearance mechanism. We systematically investigated the roles of each of these properties on tumor accumulation, relative biodistribution, and the impact of intraoperative imaging of orthotopic, syngeneic pancreatic cancer. Results: Each HA-NIRF conjugate displayed intrapancreatic tumor enhancement. Regardless of HA molecular weight, Cy7.5 conjugation directed biodistribution to the liver, spleen, and bowels. Conjugation of IRDye800 to 5 and 20 kDa HA resulted in low liver and spleen signal while enhancing the tumor up to 14-fold compared to healthy pancreas, while 100 kDa HA conjugated to IRDye800 resulting in liver and spleen accumulation. Conclusion: These studies demonstrate that by tuning HA molecular weight and the physicochemical properties of the conjugated moiety, in this case a NIRF probe, peritoneal biodistribution can be substantially altered to achieve optimized delivery to tumors intraoperative abdominal imaging.

Enzymatic synthesis of 2-hydroxy-4H-quinolizin-4-one scaffolds by integrating coenzyme a ligases and a type III PKS from Huperzia serrata.

2-Hydroxy-4H-quinolizin-4-one scaffolds were enzymatically synthesized by integrating three enzymes including phenylacetate-CoA ligase (PcPCL) from an endophytic fungus Penicillium chrysogenum MT-12, malonyl-CoA synthase (AtMatB) from Arabidopsis thaliana, and a type III polyketide synthase (HsPKS3) from Chinese club moss Huperzia serrata. The findings paved the way to produce these kinds of structurally interesting alkaloids by engineered microorganisms.

[Isolation and identification of endophytic fungi from Huperzia serrata and their metabolites' inhibitory activities against acetylcholinesterase and anti-inflammatory activities].

A total of 27 endophytic fungal strains were isolated from Huperzia serrata,which were richly distributed in the stems and leaves while less distributed in roots. The 27 strains were identified by Internal Transcribed Spacer( ITS) r DNA molecular method and one of the strains belongs to Basidiomycota phylum,and other 26 stains belong to 26 species,9 general,6 families,5 orders,3 classes of Ascomycota Phylum. The dominant strains were Colletotrichum genus,belonging to Glomerellaceae family,Glomerellales order,Sordariomycetes class,Ascomycota Phylum,with the percentage of 48. 15%. The inhibitory activities of the crude extracts of 27 endophytic fungal strains against acetylcholinesterase( ACh E) and nitric oxide( NO) production were evaluated by Ellman's method and Griess method,respectively. Crude extracts of four fungi exhibited inhibitory activities against ACh E with an IC50 value of 42. 5-62. 4 mg·L~(-1),and some fungi's crude extracts were found to inhibit nitric oxide( NO) production in lipopolysaccharide( LPS)-activated RAW264. 7 macrophage cells with an IC50 value of 2. 2-51. 3 mg·L~(-1),which indicated that these fungi had potential anti-inflammatory activities.The chemical composition of the Et OAc extract of endophytic fungus HS21 was also analyzed by LCMS-IT-TOF. Seventeen compounds including six polyketides,four diphenyl ether derivatives and seven meroterpenoids were putatively identified.

Lignan Glycosides from Urena lobata.

Four new lignan glycosides; urenalignosides A-D (1-4), along with 12 known ones (5-16) were isolated from Urena lobata. Their structures were determined on the basis of extensive spectroscopic and spectrometric data (1D and 2D NMR; IR; CD; and HRESIMS). Compounds 2-4; 6; 7; 10; and 11 showed inhibition of nitric oxide production in lipopolysaccharide-induced RAW 264.7 macrophage cells with IC50 values in the range of 25.5-98.4 µM (positive control; quercetin; IC50 = 7.2 ± 0.2 µM).

Polyketides from Alternaria alternata MT-47, an endophytic fungus isolated from Huperzia serrata.

Four new polyketides, alternatains A-D (1-4), along with 17 known compounds (5-21) were obtained from the solid substrate fermentation cultures of Alternaria alternata MT-47, an endophytic fungus isolated from the medicinal plant of Huperzia serrata. Their structures were elucidated by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) method. Compounds 4, 6, 15, and 21 exhibited inhibitory activities on ATP release of thrombin-activated platelets with IC50 values in the range of 18.2-68.8 µM.

Lycopodium alkaloids from Huperzia serrata.

Five new Lycopodium alkaloids, huperzine Y1 (1), huperzine Y2 (2), huperzine Y3 (3), (+)-huperzine Z (4a) and (-)-huperzine Z (4b) as well as ten known alkaloids (5-14) were isolated from Huperzia serrata. The structures of the new compounds were established using extensive spectroscopic (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Compounds 4a and 4b were a pair of enantiomers successfully separated by chiral HPLC resolution. Compounds 2 and 3 indicated inhibitory activities against acetylcholinesterase with IC50 value of 57.1 ±â€¯1.6 and 32.7 ±â€¯1.0 µΜ, respectively. However, no compound showed inhibitory effect on butyrocholinesterase at the concentration of 100 µΜ.

Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica.

Six new pyrrole 2-carbaldehyde derived alkaloids, dahurines A-F (1-6), along with five known ones (7-11) and butyl 2-pyrrolidone-5-carboxylate (12) were isolated from the roots of Angelica dahurica. Their structures were determined by extensive spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism (ECD) methods. Although compounds 7 and 8 have been chemically synthesized, they were obtained from natural materials for the first time. Compounds 2, 3, 4, 10, and 11 exhibited acetylcholinesterase inhibitory activity with IC50 values in the range of 47.5-52.5 µM. Pyrrole 2-carbaldehyde derived alkaloids from the roots of Angelica dahurica.

Radix Salviae miltiorrhizae improves bone microstructure and strength through Wnt/ß-catenin and osteoprotegerin/receptor activator for nuclear factor-κB ligand/cathepsin K signaling in ovariectomized rats.

Although radix Salviae miltiorrhizae (RSM) is reported to exhibit the antiosteoporotic effect in preclinical study, the underlying mechanism is unclear. To this end, ovariectomized (OVX) rats were employed with administration of RSM (5 g/kg) for 14 weeks. The disturbed serum levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), tartrate-resistant acid phosphatase, and receptor activator of nuclear factor-κB ligand (RANKL) in OVX rats were improved by RSM treatment. Furthermore, supplement of RSM to OVX rats resulted in an increase in femoral bone mineral density and bone strength as well as an improvement in bone microstructures. Moreover, the decreased expression of phosphor (p)-LRP6, insulin-like growth factor-1(IGF-1), ALP, and OPG, as well as increased expression of RANKL and cathepsin K in the tibias and femurs of OVX rats were shifted by RSM treatment. Additionally, RSM reversed the decreased ratio of p-glycogen synthase kinase 3ß (GSK3ß) to GSK3ß and increased ratio of p-ß-catenin to ß-catenin in OVX rats. Altogether, it is suggestive that RSM improves bone quantity and quality by favoring Wnt/ß-catenin and OPG/RANKL/cathepsin K signaling pathways in OVX rats thereby suggesting the potential of this herb to be a novel source of antiosteoporosis drugs.

Hyaluronic acid formulation of near infrared fluorophores optimizes surgical imaging in a prostate tumor xenograft.

The presence of positive surgical margins confers an increased risk of biochemical relapse and need for salvage therapy in men undergoing radical prostatectomy. Image-guided surgery using near-infrared (NIR) fluorescent contrast agents is a potential method to detect remaining cancerous tissue. The objective of this study was to evaluate three hyaluronic acid (HA) nanoparticle (NP) formulations loaded with NIR fluorophore for their ability to contrast-enhance prostate cancer. HA was modified by conjugation with the hydrophobic ligand, aminopropyl-1-pyrenebutanamide to drive nanoparticle self-assembly. Indocyanine green (ICG) was physicochemically entrapped in the HA-NP, termed NanoICG. Alternatively, Cy7.5 was directly conjugated to amphiphilic HA, termed NanoCy7.5. NanoCy7.5 was synthesized with two HA molecular weights to determine the HA size contribution to delivery to PC3 prostate tumor xenografts. Contrast-enhancement of the tumors and relative biodistribution were assessed by a series of fluorescence imaging, image-guided surgery with spectroscopy, and microscopic techniques. Intravenously administered NanoICG improved tumor signal-to-noise ratio (SNR) at 24 h over ICG by 2.9-fold. NanoCy7.5 with 10 kDa and 100 kDa HA improved tumor SNR by 6.6- and 3.1-fold over Cy7.5 alone, respectively. The PC3 xenograft was clearly identified with the image-guided system providing increased contrast enhancement compared to surrounding tissue for NanoICG and NanoCy7.5 with 10 kDa HA. NIR fluorescence microscopy showed that Cy7.5 in NPs with 10 kDa HA were distributed throughout the tumor, while NanoCy7.5 with 100 kDa HA or NanoICG delivered dye mainly to the edge of the tumor. CD31 staining suggested that PC3 tumors are poorly vascularized. These studies demonstrate the efficacy of a panel of HA-derived NPs in identifying prostate tumors in vivo, and suggest that by tuning the structural properties of these NPs, optimized delivery can be achieved to poorly vascularized tumors. STATEMENT OF SIGNIFICANCE: We have demonstrated the potential of a panel of near-infrared fluorescent (NIRF) nanoparticles (NPs) for image-guided surgery in a prostate cancer xenograft model. Image-guided surgery and imaging of organs ex vivo showed greater tumor signal and contrast when mice were administered NIRF dyes that were covalently conjugated to (NanoCy7.510k-PBA) or physicochemically entrapped in (NanoICGPBA) hyaluronic acid (HA) NPs, compared to free dyes. These results show the potential to use these NPs as tools to detect the margins of tumors and to differentiate healthy and tumor tissue intraoperatively. Moreover, this project provides insight into selecting optimal formulation strategies for poorly vascularized tumors.

Megastigmane glycosides from Urena lobata.

Five new megastigmane glycosides, urenalobasides A-E (1-5), together with 11 known ones (6-16) were isolated from Urena lobata. Their structures were determined by extensive spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS) and calculated electronic circular dichroism method. Compounds 1 and 2 are two unusual megastigmanes structurally containing a 6/5 fused ring system. Compound 3 exhibits inhibition of nitric oxide production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage cells with IC50 value of 53.7 ±â€¯1.0 µM (positive control, dexamethasone, IC50 = 16.6 ±â€¯0.8 µM).

Indocyanine green loaded hyaluronan-derived nanoparticles for fluorescence-enhanced surgical imaging of pancreatic cancer.

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. In this study, hyaluronic acid derived nanoparticles with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG was not cytotoxic to healthy pancreatic epithelial cells and did not induce chemotaxis or phagocytosis, it accumulated significantly within the pancreas in an orthotopic pancreatic ductal adenocarcinoma model, and demonstrated contrast-enhancement for pancreatic lesions relative to non-diseased portions of the pancreas. Fluorescence microscopy showed higher fluorescence intensity in pancreatic lesions and splenic metastases due to NanoICG compared to ICG alone. The in vivo safety profile of NanoICG, including, biochemical, hematological, and pathological analysis of NanoICG-treated healthy mice, indicates negligible toxicity. These results suggest that NanoICG is a promising contrast agent for intraoperative detection of pancreatic tumors.