A bacterial-like Pictet-Spenglerase drives the evolution of fungi to produce ß-carboline glycosides together with separate genes.

Diverse ß-carboline (ßC) alkaloids are produced by microbes, plants, and animals with myriad bioactivities and drug potentials. However, the biosynthetic mechanism of ßCs remains largely elusive, especially regarding the hydroxyl and glucosyl modifications of ßCs. Here, we report the presence of the bacterial-like Pictet-Spenglerase gene Fcs1 in the entomopathogenic Beauveria fungi that can catalyze the biosynthesis of the ßC skeleton. The overexpression of Fcs1 in Beauveria bassiana led to the identification of six ßC methyl glycosides, termed bassicarbosides (BCSs) A-F. We verified that the cytochrome P450 (CYP) genes adjacent to Fcs1 cannot oxidize ßCs. Alternatively, the separated CYP684B2 family gene Fcs2 was identified to catalyze ßC hydroxylation together with its cofactor gene Fcs3. The functional homologue of Fcs2 is only present in the Fcs1-containing fungi and highly similar to the Fcs1-connected yet nonfunctional CYP. Both evolved quicker than those from fungi without Fcs1 homologues. Finally, the paired methyl/glucosyl transferase genes were verified to mediate the production of BCSs from hydroxy-ßCs. All these functionally verified genes are located on different chromosomes of Beauveria, which is in contrast to the typical content-clustered feature of fungal biosynthetic gene clusters (BGCs). We also found that the production of BCSs selectively contributed to fungal infection of different insect species. Our findings shed light on the biosynthetic mechanism of ßC glycosides, including the identification of a ßC hydroxylase. The results of this study also propose an evolving process of fungal BGC formation following the horizontal transfer of a bacterial gene to fungi.

Synthesis of surficial-modified green biochar catalyst generated by biogas residue biochar and potential application for catalytic ozonation degradation of ciprofloxacin.

This study synthesized novel, green, and easily recoverable surface-modified economical catalysts via hydrothermal treatment (HT) successfully, utilizing biogas residue biochar (BRB), a food waste product from anaerobic fermentation, pyrolyzed at 500 °C for 50 min. Using autoclaves, a total of six solutions were prepared, each having 1 g fine-grinded BRB, surficial modified by adding glycerol (GL) (10 or 20 mL) and SDI water (70 or 60 mL), and heated in an oven at 240 °C, 180 °C, and 120 °C for 24 h. Afterward, the catalysts showed the potential for degradation of widely used emerging pollutants like ciprofloxacin. Taking advantage of catalytic surface modification, the catalytic ozonation degradation was more effective than that of a single ozonation. However, under similar conditions, catalyst amount 0.20 g, ozone dose 15 mg L-1, and ciprofloxacin 80 mg L-1, the performance of the 10 mL GL-180 °C catalyst was excellent. It showed a 92.45%-94.41% optimum removal rate in the 8-10 min interval. After five continuous cycles, the 10 mL GL-180 °C catalyst exhibited excellent stability and reusability. XPS, FT-IR, BET, XRD, and SEM before and after the reaction confirmed the successful synthesis and degradation mechanism. A possible degradation pathway was unrevealed based on a liquid chromatography-mass spectrometer (LC-MS) and scavenger test, proving the significant roles of superoxide radicals (O2•-), hydroxyl radicals (•OH), and singlet oxygen (1O2). Further, Electron paramagnetic resonance (EPR) analysis confirmed the presence of active oxygen species. Subsequently, 10 mL GL-180 °C showed promising degradation for the actual water environment, such as groundwater (73.55%) and river water (64.74%). This work provides a valuable economic strategy to convert biogas residue biochar into a low-cost catalyst for organic pollutant decomposition.

A Novel Bacillus amyloliquefaciens Specifically Improving the Solubility and Antioxidant Activities of Edible Bird's Nest.

Edible bird's nest (EBN), a most highly priced and valuable foodstuff, contains high percentage of proteins and carbohydrates. However, proteins adhering to these carbohydrates make the EBN hard and tough, which need to be boiled as the bird's nest soup to make the Chinese cuisine. To overcome the hard and tough texture of EBN and improve the digestion degrees, the present study screened and identified a probiotic strain Bacillus amyloliquefaciens YZW02 from 5-year stored EBN sample completely solubilizing EBN for the first time. The 24-h B. amyloliquefaciens fermented EBN contained 20.30-21.48 mg/mL of the soluble protein contents with a recovery rate of 98-100%, DPPH radical scavenging rate of 84.76% and ABTS radical scavenging capacity of 41.05%. The mixed fermentation of B. amyloliquefaciens YZW02 and Bacillus natto BN1 were further applied to improve the low-MW peptide percentages and antioxidant activities. The mixed-fermentation of B. natto BN1 with 4-h cultured B. amyloliquefaciens YZW02 had the lowest percentage (82.23%) of >12-kDa proteins/peptides and highest percentages of 3-12 kDa, 1-3 kDa and 0.1-1 kDa peptides of 8.6% ± 0.08, 7.57% ± 0.09, 1.77% ± 0.05 and 0.73% ± 0.05, with the highest DPPH, ABTS and •OH scavenging capacity of 90.23%, 46.45% and 49.12%, respectively. These findings would provide an efficient strategy for improving the solubility and antioxidant activities of EBNs.

Fully printed non-contact touch sensors based on GCN/PDMS composites: enabling over-the-bottom detection, 3D recognition, and wireless transmission.

The rapid advancement in intelligent bionics has elevated electronic skin to a pivotal component in bionic robots, enabling swift responses to diverse external stimuli. Combining wearable touch sensors with IoT technology lays the groundwork for achieving the versatile functionality of electronic skin. However, most current touch sensors rely on capacitive layer deformations induced by pressure, leading to changes in capacitance values. Unfortunately, sensors of this kind often face limitations in practical applications due to their uniform sensing capabilities. This study presents a novel approach by incorporating graphitic carbon nitride (GCN) into polydimethylsiloxane (PDMS) at a low concentration. Surprisingly, this blend of materials with higher dielectric constants yields composite films with lower dielectric constants, contrary to expectations. Unlike traditional capacitive sensors, our non-contact touch sensors exploit electric field interference between the object and the sensor's edge, with enhanced effects from the low dielectric constant GCN/PDMS film. Consequently, we have fabricated touch sensor grids using an array configuration of dispensing printing techniques, facilitating fast response and ultra-low-limit contact detection with finger-to-device distances ranging from 5 to 100 mm. These sensors exhibit excellent resolution in recognizing 3D object shapes and accurately detecting positional motion. Moreover, they enable real-time monitoring of array data with signal transmission over a 4G network. In summary, our proposed approach for fabricating low dielectric constant thin films, as employed in non-contact touch sensors, opens new avenues for advancing electronic skin technology.

We've created 3D recognition sensing arrays using a printed method, enabling remote data transmission. We've identified an intriguing interfacial effect in GCN/PDMS doping, opening new possibilities in smart skin technology.

Framework-Topology-Controlled Singlet Fission in Metal-Organic Frameworks.

Singlet fission (SF) has been explored as a viable route to improve photovoltaic performance by producing more excitons. Efficient SF is achieved through a high degree of interchromophoric coupling that facilitates electron superexchange to generate triplet pairs. However, strongly coupled chromophores often form excimers that can serve as an SF intermediate or a low-energy trap site. The succeeding decoherence process, however, requires an optimum electronic coupling to facilitate the isolation of triplet production from the initially prepared correlated triplet pair. Conformational flexibility and dielectric modulation can provide a means to tune the SF mechanism and efficiency by modulating the interchromophoric electronic interaction. Such a strategy cannot be easily adopted in densely stacked traditional organic solids. Here, we show that the assembly of the SF-active chromophores around well-defined pores of solution-stable metal-organic frameworks (MOFs) can be a great platform for a modular SF process. A series of three new MOFs, built out from 9,10-bis(ethynylenephenyl)anthracene-derived struts, show a topology-defined packing density and conformational flexibility of the anthracene core to dictate the SF mechanism. Various steady-state and transient spectroscopic data suggest that the initially prepared singlet population can prefer either an excimer-mediated SF or a direct SF (both through a virtual charge-transfer (CT) state). These solution-stable frameworks offer the tunability of the dielectric environment to facilitate the SF process by stabilizing the CT state. Given that MOFs are a great platform for various photophysical and photochemical developments, generating a large population of long-lived triplets can expand their utilities in various photon energy conversion schemes.

Measurement of electrons from albedo neutron decay and neutron density in near-Earth space.

The Galaxy is filled with cosmic-ray particles, mostly protons with kinetic energies greater than hundreds of megaelectronvolts. Around Earth, trapped energetic protons, electrons and other particles circulate at altitudes from about 500 to 40,000 kilometres in the Van Allen radiation belts. Soon after these radiation belts were discovered six decades ago, it was recognized that the main source of inner-belt protons (with kinetic energies of tens to hundreds of megaelectronvolts) is cosmic-ray albedo neutron decay (CRAND). In this process, cosmic rays that reach the upper atmosphere interact with neutral atoms to produce albedo neutrons, which, being prone to ß-decay, are a possible source of geomagnetically trapped protons and electrons. These protons would retain most of the kinetic energy of the neutrons, while the electrons would have lower energies, mostly less than one megaelectronvolt. The viability of CRAND as an electron source has, however, been uncertain, because measurements have shown that the electron intensity in the inner Van Allen belt can vary greatly, while the neutron-decay rate should be almost constant. Here we report measurements of relativistic electrons near the inner edge of the inner radiation belt. We demonstrate that the main source of these electrons is indeed CRAND, and that this process also contributes to electrons in the inner belt elsewhere. Furthermore, measurement of the intensity of electrons generated by CRAND provides an experimental determination of the neutron density in near-Earth space-2 × 10-9 per cubic centimetre-confirming theoretical estimates.

Differences in the prevalence and risk factors of osteoporosis in chinese urban and rural regions: a cross-sectional study.

BACKGROUND: Bone mineral density (BMD) and prevalence of osteoporosis may differ between urban and rural populations. This study aimed to investigate the differences in BMD characteristics between urban and rural populations in Jiangsu, China. METHODS: A total of 2,711 participants aged 20 years and older were included in the cross-sectional study. Multistage and stratified cluster random sampling was used as the sampling strategy. BMD was measured by the method of dual-energy x-ray absorptiometry (DXA). Data were collected through questionnaires/interview. BMD values at the lumbar spine (L1-L4), femoral neck, total hip, and greater trochanter were collected. Descriptive statistics were used to demonstrate the characteristics of urban and rural participants. Multivariate logistic regression analysis was utilized to analyze the factors that may be associated with osteoporosis in urban and rural populations. RESULTS: Of these participants, 1,540 (50.49%) were females and 1,363 (42.14%) were from urban. The prevalence of osteoporosis in urban and rural populations was 5.52% and 10.33%, respectively. In terms of gender, the prevalence of osteoporosis was 2.68% in males and 13.82% in females. For menopausal status, the prevalence of osteoporosis was 30.34% in postmenopausal females and 4.78% in premenopausal females. In urban populations, older age [adjusted odds ratio (AOR) = 2.36, 95%CI, 2.35-2.36), hypertension (AOR = 1.37, 95%CI, 1.36-1.37), unmarried (AOR = 4.04, 95%CI, 3.99-4.09), smoking everyday (AOR = 2.26, 95%CI, 2.23-2.28), family history of osteoporosis (AOR = 1.66, 95%CI, 1.65-1.67), dyslipidemia (AOR = 1.05, 95%CI, 1.04-1.05), and higher ß-crosslaps (ß-CTX) level (AOR = 1.02, 95%CI, 1.02-1.02) were associated with an increased risk of osteoporosis, while males (AOR = 0.04, 95%CI, 0.04-0.04), higher education level (AOR = 0.95, 95%CI, 0.95-0.95), and aquatic product intake (AOR = 0.99, 95%CI, 0.99-0.99) were related to decreased risk of osteoporosis. Similar results were also observed in rural populations, and (all P < 0.05). CONCLUSION: The prevalence of osteoporosis in rural populations was higher than that in urban populations, and the factors associated with the risk of osteoporosis were similar in urban and rural populations.

Structural Design of Nanowire Wearable Stretchable Thermoelectric Generator.

Wearable thermoelectric generators as renewable energy conversion technologies have witnessed rapid development in the past decade. Herein, we design a nanowire (NW) film wavy structure which possesses an excellent temperature gradient ratio for stretchable thermoelectric generators. Taking advantage of the photothermal effect of Te NWs as the hot side and p-n NWs heterofilms (n-type Ag2Te and p-type Cu1.75Te NWs) as thermoelectric materials, a considerable output voltage can be achieved under light irradiation. Besides the electricity output, the wearable device can also make our skin warm and comfortable in cold weather. Meanwhile, we combine thermoelectric generators with passive radiative cooling technology to reduce insolation of the human body and improve the performance of the device under intense solar irradiation in hot weather. Interestingly, it can also offer continuous green energy to realize various signal perceptions, suggesting a robust strategy for electricity output and self-powered wearable electronics.

Decoupling Redox Hopping and Catalysis in Metal-Organic Frameworks -based Electrocatalytic CO2 Reduction.

Traditional MOF e-CRR, constructed from catalytic linkers, manifest a kinetic bottleneck during their multi-electron activation. Decoupling catalysis and charge transport can address such issues. Here, we build two MOF/e-CRR systems, CoPc@NU-1000 and TPP(Co)@NU-1000, by installing cobalt metalated phthalocyanine and tetraphenylporphyrin electrocatalysts within the redox active NU-1000 MOF. For CoPc@NU-1000, the e-CRR responsive CoI/0 potential is close to that of NU-1000 reduction compared to the TPP(Co)@NU-1000. Efficient charge delivery, defined by a higher diffusion (Dhop =4.1×10-12  cm2 s-1 ) and low charge-transport resistance ( R C T M O F ${{R}_{{\rm C}{\rm T}}^{{\rm M}{\rm O}{\rm F}}}$ =59.5 Ω) in CoPC@NU-1000 led FECO =80 %. In contrast, TPP(Co)@NU-1000 fared a poor FECO =24 % (Dhop =1.4×10-12  cm2 s-1 and R C T M O F ${{R}_{{\rm C}{\rm T}}^{{\rm M}{\rm O}{\rm F}}}$ =91.4 Ω). For such a decoupling strategy, careful choice of the host framework is critical in pairing up with the underlying electrochemical properties of the catalysts to facilitate the charge delivery for its activation.

Anomalously Large Antiphase Signals from Hyperpolarized Orthohydrogen Using a MOF-Based SABRE Catalyst.

Hyperpolarized orthohydrogen (o-H2 ) is a frequent product of parahydrogen-based hyperpolarization approaches like signal amplification by reversible exchange (SABRE), where the hyperpolarized o-H2 signal is usually absorptive. We describe a novel manifestation of this effect wherein large antiphase o-H2 signals are observed, with 1 H enhancements up to ≈500-fold (effective polarization PH ≈1.6 %). This anomalous effect is attained only when using an intact heterogeneous catalyst constructed using a metal-organic framework (MOF) and is qualitatively independent of substrate nature. This seemingly paradoxical observation is analogous to the "partial negative line" (PNL) effect recently explained in the context of Parahydrogen Induced Polarization (PHIP) by Ivanov and co-workers. The two-spin order of the o-H2 resonance is manifested by a two-fold higher Rabi frequency, and the lifetime of the antiphase HP o-H2 resonance is extended by several-fold.

DNA hypomethylation activation Wnt/TCF7L2/TDRD1 pathway promotes spermatogonial stem cell formation.

Detailed analysis of the regulatory mechanism of spermatogonia stem cell (SSCs) genesis can provide a novel strategy for the application of SSCs in the fields of transgenic animal production and regenerative medicine. Previous studies in this study showed that WNT signaling can positively regulate the formation of SSCs, but the exact regulatory mechanism is not clear. Here, we predicted the target gene of the Wnt/TCF7L2 pathway, namely TDRD1, by bioinformatics analysis. Functional studies revealed that overexpression of TDRD1 during RA-induced SSCs formation in vitro significantly upregulated the expression of reproductive marker genes (Integrinß1 and Integrinα6), and further flow cytometric analysis also confirmed that the formation efficiency of SSCs was significantly increased after overexpression of TDRD1; while interference with TDRD1 showed the exact opposite result. The in vivo experiments were consistent with the results of the in vitro experiments. Interestingly, although Wnt/TCF7L2 can promote the formation of SSCs, its function must be dependent on the expression of TDRD1, which was also repeatedly demonstrated as a target gene of the Wnt/TCF7L2 signaling pathway. Mechanistically, we found a large number of CpG sites in the TDRD1 promoter, and BSP analysis also confirmed that DNA methylation modifications in the TDRD1 promoter were significantly higher in embryonic stem cells than in SSCs, and further dual-luciferase reporter system assays revealed that low DNA methylation modification levels could enhance TDRD1 promoter activity; although previous studies demonstrated that TCF7L2 could enrich in the TDRD1 promoter region, the binding of the two was dependent on low DNA methylation modification. Taken together, we confirmed that low DNA methylation mediates Wnt/TCF7L2 regulation of TDRD1 to promote the formation of SSCs, providing a basis for SSCs in improving animal productivity.

Superradiance and Directional Exciton Migration in Metal-Organic Frameworks.

Crystalline metal-organic frameworks (MOFs) are promising synthetic analogues of photosynthetic light-harvesting complexes (LHCs). The precise assembly of linkers (organic chromophores) around the topology-defined pores offers the evolution of unique photophysical behaviors that are reminiscence of LHCs. These include MOF excited states with photoabsorbed energy that is spatially dispersed over multiple linkers defining the molecular excitons. The multilinker molecular excitons display superradiance─a hallmark of coupled oscillators seen in LHCs─with radiative rate constant (krad) exceeding that of a single linker. Our theoretical model and experimental results on three zirconium MOFs, namely, PCN-222(Zn), NU-1000, and SIU-100, with similar topology but varying linkers suggest that the size of such molecular excitons depends on the electronic symmetry of the linker. This multilinker exciton model effectively predicts the energy transfer rate constant; corresponding single-step exciton hopping time, ranging from a few picoseconds in SIU-100 and NU-1000 to a few hundreds of picoseconds in PCN-222(Zn), matches well with the experimental data. The model also predicts the anisotropy of exciton displacement with preferential migration along the crystallographic c-axis. Overall, these findings establish various missing links defining the exciton size and dynamics in MOF-assembled linkers. The understandings will provide design principles, especially, positioning the catalysts or electrode relative to the linker orientation for low-density solar energy conversion systems.

A Generalized Robot Navigation Analysis Platform (RoNAP) with Visual Results Using Multiple Navigation Algorithms.

The robotic navigation task is to find a collision-free path among a mass of stationary or migratory obstacles. Various well-established algorithms have been applied to solve navigation tasks. It is necessary to test the performance of designed navigation algorithms in practice. However, it seems an extremely unwise choice to implement them in a real environment directly unless their performance is guaranteed to be acceptable. Otherwise, it takes time to test navigation algorithms because of a long training process, and imperfect performance may cause damage if the robot collides with obstacles. Hence, it is of key significance to develop a mobile robot analysis platform to simulate the real environment which has the ability to replicate the exact application scenario and be operated in a simple manner. This paper introduces a brand new analysis platform named robot navigation analysis platform (RoNAP), which is an open-source platform developed using the Python environment. A user-friendly interface supports its realization for the evaluation of various navigation algorithms. A variety of existing algorithms were able to achieve desired test results on this platform, indicating its feasibility and efficiency for navigation algorithm analysis.

Photoinduced Charge Transfer with a Small Driving Force Facilitated by Exciplex-like Complex Formation in Metal-Organic Frameworks.

Photoinduced charge transfer (PCT) is a key step in the light-harvesting (LH) process producing the redox equivalents for energy conversion. However, like traditional macromolecular donor-acceptor assemblies, most MOF-derived LH systems are designed with a large ΔG0 to drive PCT. To emulate the functionality of the reaction center of the natural LH complex that drives PCT within a pair of identical chromophores producing charge carriers with maximum potentials, we prepared two electronically diverse carboxy-terminated zinc porphyrins, BFBP(Zn)-COOH and TFP(Zn)-COOH, and installed them into the hexagonal pores of NU-1000 via solvent-assisted ligand incorporation (SALI), resulting in BFBP(Zn)@NU-1000 and TFP(Zn)@NU-1000 compositions. Varying the number of trifluoromethyl groups at the porphyrin core, we tuned the ground-state redox potentials of the porphyrins within ca. 0.1 V relative to that of NU-1000, defining a small ΔG0 for PCT. For BFBP(Zn)@NU-1000, the relative ground- and excited-state redox potentials of the components facilitate an energy transfer (EnT) from NU-1000* to BFBP(Zn), forming BFBP(Zn)S1* which entails a long-lived charge-separated complex formed through an exciplex-like [BFBP(Zn)S1*-TBAPy] intermediate. Various time-resolved spectroscopic data suggest that EnT from NU-1000* may not involve a fast Förster-like resonance energy transfer (FRET) but rather through a slow [NU-1000*-BFBP(Zn)] intermediate formation. In contrast, TFP(Zn)@NU-1000 displays an efficient EnT from NU-1000* to [TFP(Zn)-TBAPy], a complex that formed at the ground state through electronic interaction, and thereon showed the excited-state feature of [TFP(Zn)-TBAPy]*. The results will help to develop synthetic LHC systems that can produce long-lived photogenerated charge carriers with high potentials, i.e., high open-circuit voltage in photoelectrochemical setups.

Comparative transcriptome analysis of genes involved in the drought stress response of two peanut (Arachis hypogaea L.) varieties.

BACKGROUND: The peanut is one of the most important oil crops worldwide. Qualities and yields of peanut can be dramatically diminished by abiotic stresses particularly by drought. Therefore, it would be beneficial to gain a comprehensive understanding on peanut drought-responsive transcriptional regulatory activities, and hopefully to extract critical drought-tolerance-related molecular mechanism from it. RESULTS: In this study, two peanut Arachis hypogaea L. varieties, NH5 (tolerant) and FH18 (sensitive), which show significantly differential drought tolerance, were screened from 23 main commercial peanut cultivars and used for physiological characterization and transcriptomic analysis. NH5 leaves showed higher water and GSH contents, faster stomatal closure, and lower relative conductivity (REC) than FH18. Under the time-course of drought-treatments 0 h (CK), 4 h (DT1), 8 h (DT2) and 24 h (DT3), the number of down-regulated differential expressed genes (DEGs) increased with the progression of treatments indicating repressive impacts on transcriptomes by drought in both peanut varieties. CONCLUSIONS: Nevertheless, NH5 maintained more stable transcriptomic dynamics than FH18. Furthermore, annotations of identified DEGs implicate signal transduction, the elimination of reactive oxygen species, and the maintenance of cell osmotic potential which are key drought-tolerance-related pathways. Finally, evidences from the examination of ABA and SA components suggested that the fast stomatal closure in NH5 was likely mediated through SA rather than ABA signaling. In all, these results have provided us a comprehensive overview of peanut drought-responsive transcriptomic changes, which could serve as solid foundation for further identification of the molecular drought-tolerance mechanism in peanut and other oil crops.

Improving Energy Transfer within Metal-Organic Frameworks by Aligning Linker Transition Dipoles along the Framework Axis.

Crystalline metal-organic frameworks (MOFs) can assemble chromophoric molecules into a wide range of spatial arrangements, which are controlled by the MOF topology. Like natural light-harvesting complexes (LHCs), the precise arrangement modulates interchromophoric interactions, in turn determining excitonic behavior and migration dynamics. To unveil the key factors that control efficient exciton displacements within MOFs, we first developed linkers with low electronic symmetry (as defined by large transition dipoles) and then assembled them into MOFs. These linkers possess extended conjugation along one molecular axis, engendering low optical bandgaps and improved oscillator strength for their lowest-energy transition (S0 → S1). This enhances absorption-emission spectral overlap and boosts the efficiency of Förster resonance energy transfer, which was observed experimentally by a sizable decrease in emission quantum yield (QY), accompanied by a faster population decay profile. We find that MOFs that orient these elongated linkers along their asymmetric pore channel, e.g., the hexagonal pores in an xly network, manifested >50% decrease in their emission QY with faster decay profiles relative to their corresponding solution dissolved linkers. This is due to an efficient migration of photogenerated excitons at the crystallite peripheral sites to internal sites, which was facilitated by polarized absorption-emission overlap among the parallelly aligned linkers. In contrast, symmetric MOFs, such as those with sqc-a topological net, orient elongated linkers along two perpendicular crystal axes, which hinders efficient exciton migration. The present study underscores that MOFs are promising to develop artificial LHCs, but that to achieve an efficient exciton displacement, appropriate topology-guided assembly is required to fully realize the true potential of linkers with low electronic symmetry.

Engineering chimeric diterpene synthases and isoprenoid biosynthetic pathways enables high-level production of miltiradiene in yeast.

Miltiradiene is a key intermediate in the biosynthesis of many important natural diterpene compounds with significant pharmacological activity, including triptolide, tanshinones, carnosic acid and carnosol. Sufficient accumulation of miltiradiene is vital for the production of these medicinal compounds. In this study, comprehensive engineering strategies were applied to construct a high-yielding miltiradiene producing yeast strain. First, a chassis strain that can accumulate 2.1 g L-1 geranylgeraniol was constructed. Then, diterpene synthases from various species were evaluated for their ability to produce miltiradiene, and a chimeric miltiradiene synthase, consisting of class II diterpene synthase (di-TPS) CfTPS1 from Coleus forskohlii (Plectranthus barbatus) and class I di-TPS SmKSL1 from Salvia miltiorrhiza showed the highest efficiency in the conversion of GGPP to miltiradiene in yeast. Moreover, the miltiradiene yield was further improved by protein modification, which resulted in a final yield of 550.7 mg L-1 in shake flasks and 3.5 g L-1 in a 5-L bioreactor. This work offers an efficient and green process for the production of the important intermediate miltiradiene, and lays a foundation for further pathway reconstruction and the biotechnological production of valuable natural diterpenes.

Wavelength-Dependent Energy and Charge Transfer in MOF: A Step toward Artificial Porous Light-Harvesting System.

Chromophore assemblies within well-defined porous coordination polymers, such as metal-organic frameworks (MOFs), can emulate the functionality of the antenna rings of chlorophylls in light-harvesting complexes (LHCs). The chemical, electronic, and structural diversities define MOFs as a promising platform where photogenerated excitons can be displaced to redox catalysts similar to the reaction center of the LHC. The precise positioning of the pigments and complementary redox units enables us to understand the charge/energy-transfer process within these crystalline solid compositions. In this study, we postsynthetically anchored tetraphenylporphyrinato zinc(II) (TPPZn)-derived complementary pigment within the 1D pores of 1,3,6,8-tetrakis(p-benzoicacid)pyrene (H4TBAPy)-derived NU-1000 MOF to form a high-density donor-acceptor system. The ground- and excited-state redox potentials of the donor and acceptor were chosen to facilitate an energy transfer (EnT) from the excited MOF (i.e., NU-1000*) to TPPZn and a charge transfer (CT) from excited porphyrin (i.e., TPPZn*). Thus, the processes depend on the excitation wavelength. The energy transfer process was spectroscopically probed by excitation-emission mapping: MOF emission was completely quenched at 460 nm, where the pyrene-centered emission was expected. Instead, the excited MOF efficiently transfers the energy to manifest a TPPZn-centered emission at 670 nm (kEnT ≈ 4.7 × 1011 s-1). The excited TPPZn pigment, with a neighboring TBAPy linker, forms an artificial "special-pair"-like system driving the charge-separation process (kCT = 1.2 × 1010 s-1). The findings demonstrate a synthetic MOF-based artificial LHC system where their well-defined structure will open up new possibilities as the separated charge can hop along the 1D pore channel for further mechanistic understanding and future developments.

Rapid discovery and functional characterization of diterpene synthases from basidiomycete fungi by genome mining.

Basidiomycete fungi are a rich source of bioactive diterpenoid secondary metabolites. However, compared with the large number of diterpene synthases (di-TPSs) identified in plants and ascomycete fungi, only three di-TPSs have been described from basidiomycete fungi. Large scale genome sequencing projects combined with the development of synthetic biology techniques now has enabled the rapidly discovery and characterization of di-TPSs from basidiomycete fungi. In this study, we discovered and functionally characterized four di-TPSs from 220 genome sequenced basidiomycete fungi by a combined strategy of genomic data mining, phylogenetic analysis and fast products characterization with synthetic biology techniques. Among them, SteTC1 of Stereum histurum was characterized as the first fungal cembrane diterpene synthase; PunTC of Punctularia strigosozonata and SerTC of Serpula lacrymans were characterized as ent-kauran-16α-ol synthase and DenTC3 of Dentipellis sp was characterized as a cyathane synthase. Our results provide opportunities for the discovery of new diterpenoids from basidiomycete fungi by genome mining.

Fast-track multidisciplinary treatment versus conventional treatment for colorectal cancer: a multicenter, open-label randomized controlled study.

BACKGROUND: Laparoscopic surgery, fast-track perioperative treatment and XELOX chemotherapy are effective strategies for shortening the duration of hospital stay for cancer patients. This trial aimed to clarify the safety and efficacy of the fast-track multidisciplinary treatment (FTMDT) model compared to conventional surgery combined with chemotherapy in Chinese colorectal cancer patients. METHODS: This trial was a prospective randomized controlled study with a 2 × 2 balanced factorial design and was conducted at six hospitals. Patients in group 1 (FTMDT) received fast-track perioperative treatment and XELOX adjuvant chemotherapy. Patients in group 2 (conventional treatment) received conventional perioperative treatment and mFOLFOX6 adjuvant chemotherapy. Subgroups 1a and 2a had laparoscopic surgery and subgroups 1b and 2b had open surgery. The primary endpoint was total length of hospital stay during treatment. RESULTS: A total of 374 patients were randomly assigned to the four subgroups, and 342 patients were finally analyzed, including 87 patients in subgroup 1a, 85 in subgroup 1b, 86 in subgroup 2a, and 84 in subgroup 2b. The total hospital stay of group 1 was shorter than that of group 2 [13 days, (IQR, 11-17 days) vs. 23.5 days (IQR, 15-42 days), P = 0.0001]. Compared to group 2, group 1 had lower surgical costs, fewer in-hospital complications and faster recovery (all P < 0.05). Subgroup 1a showed faster surgical recovery than that of subgroup 1b (all P < 0.05). There was no difference in 5-year overall survival between groups 1 and 2 [87.1% (95% CI, 80.7-91.5%) vs. 87.1% (95% CI, 80.8-91.4%), P = 0.7420]. CONCLUSIONS: The FTMDT model, which integrates laparoscopic surgery, fast-track treatment, and XELOX chemotherapy, was the superior model for enhancing the recovery of Chinese patients with colorectal cancer. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01080547 , registered on March 4, 2010.