Cutting-edge plant natural product pathway elucidation.

Plant natural products (PNPs) play important roles in plant physiology and have been applied across diverse fields of human society. Understanding their biosynthetic pathways informs plant evolution and meanwhile enables sustainable production through metabolic engineering. However, the discovery of PNP biosynthetic pathways remains challenging due to the diversity of enzymes involved and limitations in traditional gene mining approaches. In this review, we will summarize state-of-the-art strategies and recent examples for predicting and characterizing PNP biosynthetic pathways, respectively, with multiomics-guided tools and heterologous host systems and share our perspectives on the systematic pipelines integrating these various bioinformatic and biochemical approaches.

Exploring the experiences of peer support participation for HIV peer volunteers: A meta-synthesis of qualitative research.

BACKGROUND: Gaining insights and feedback from HIV peer volunteers about their peer support practice is crucial for optimizing and enhancing the effectiveness and sustainability of peer support for people with HIV. There is a dearth of systematic reviews that explore the experiences of HIV peer volunteers about their peer support experience. This study aims to consolidate qualitative research on the experiences of peer support participation for HIV peer volunteers, to provide inspiration and reference for HIV peer support practice. METHODS: A meta-aggregation approach was employed to synthesize qualitative studies. Electronic databases were searched for peer-reviewed and gray literature published in English and Chinese between 1996 and September 2022. Two independent reviewers assessed the methodological quality and extracted data from the included studies. The meta-aggregation approach developed by the Joanna Briggs Institute (JBI) was utilized to synthesize the findings. RESULTS: A total of 2610 studies were initially identified through the database search, and twenty-two eligible studies were included in the meta-synthesis. Among the included studies, five presented synthesized findings on the following topics: firstly, taking people with HIV as HIV peer volunteers shows specific motivations and advantages when engaging in peer support practice. Secondly, HIV peer volunteers reinforce the connections between people with HIV and medical institutions, ensuring continuity of care and compensating for the limited availability of medical resources. Thirdly, HIV peer volunteers are capable of providing people with HIV with a higher level of support. Additionally, participating in peer support practice can also yield personal benefits for HIV peer volunteers. Finally, HIV peer support programs face both opportunities and challenges. CONCLUSION: It is necessary to take more flexible and effective approaches to address resource allocation and social support for people with HIV. Peer support presents a mutually beneficial option that holds significant implications for public health systems, clinical healthcare providers, people with HIV, and HIV peer volunteers. It is imperative to develop effective models for HIV peer support practice. Collaborative efforts between relevant departments and personnel, alongside HIV peer volunteers, should be undertaken to formulate support strategies. Additionally, efforts should be made to identify and guide people with HIV into the healthcare system, facilitating comprehensive treatment and care continuity. These measures aim to further reduce HIV transmission, improve the quality of life for people with HIV, and advance the "normalization" of HIV.

Skin-Friendly Flexible Ultraviolet Detectors Based on Reversibly Deformable Worm-Like Polymer Nanoparticles.

Flexible ultraviolet (UV) light detection technology has important applications in wearable devices, smart sensors, and other fields and attracts much attention in recent years. However, for most semiconductor-based UV detectors, the elastic modulus between rigid semiconductors and flexible substrates is mismatched, which makes it difficult to fabricate UV detectors that meet the needs of wearable devices. Herein, a fully flexible, large-scale, skin-friendly UV photodetector component centered on photo-responsive worm-like polymer nanoparticles (NPs) is developed, and the resulting device can quantitatively detect UV illumination. Skin-friendly poly(vinyl alcohol) (PVA), amphiphilic azobenzene-containing polymer NPs (AzNPs), and water-soluble ionic liquids (IL) are formed into (AzNPs-IL)/PVA fabrics by electrospinning. There are interactions such as hydrogen bonding among PVA, AzNPs, and IL, which make the material system stable. The UV detector made of the fabric realizes UV sensing through the illuminance-mechanical stress-electrical signal conversion mechanism. It is capable of achieving a response time of 9 s, a detection range of 10-150 mW cm-2 , and stability for 1000 cycle tests upon 365 nm UV irradiation. Moreover, it has good skin affinity, and the water contact angle of the fabric is only 23.57°, which holds great promise for wearable smart devices.

Inducing abundant magnetic phases and enhancing magnetic stability by edge modifications and physical regulations for NiI2 nanoribbons.

Recently, a magnetic semiconducting NiI2 monolayer was successfully fabricated. To obtain richer magneto-electronic properties and find new physics for NiI2, we studied the zigzag-type NiI2 nanoribbon (ZNiI2NR) with edges modified by different concentrations of H and/or O atoms. Results show that these ribbons hold a higher energy stability, thermal stability, and magnetic stability, and the Curie temperature can be increased to 143 from 15 K for the bare-edged ribbons. They feature a half-semiconductor, bipolar magnetic semiconductor, or half-metal, depending on the edge-terminated atomic species and concentrations, and are closely related to the ribbon edge states, impurity bands or hybridized bands. By applying strain or an electric field, ribbons can achieve a reversible multi-magnetic phase transition among a bipolar magnetic semiconductor, half-semiconductor, half-metal, and magnetic metal. This is because strain changes the Ni-I bond length, resulting in a variation of bond configurations (weight of ionic and covalent bonds) and the number of unpaired electrons. The compressive strain can increase the Curie temperature because it makes the edged Ni-I-Ni bond angle closer to 90°, leading to the FM d-p-d superexchange interaction being increased. The electric field varies the magnetic phase because it alters the electrostatic potential of the ribbon edges, and the Curie temperature is enhanced under the electric field because the ribbon is changed to a metallic state (half-metal or magnetic metal), in which the magnetic Ni atoms satisfy the Stoner criterion and hold a large magnetic exchange coefficient and electron state density at the Fermi surface.

Single-layer PtSe2 adsorbed with non-metallic atoms: geometrical, mechanical, electronic and optical properties and strain effects.

Recently, single-layer PtSe2, possessing high carrier mobility and optical response, has been successfully fabricated. To further expand its application scope and find new physics, in this work, we functionalized it via the adsorption of non-metallic atoms X (X = H, B, C, N, O, and F) to form hybrid systems X-PtSe2, and their geometrical, mechanical, electronic, and optical properties as well as strain tuning effects were studied deeply. Calculations show that the energy stability of X-PtSe2 systems is significantly enhanced, and they also hold higher thermal and mechanical stability. Particularly, X-PtSe2 systems present excellent in-plane tenacity and out-of plane stiffness against deformations, which make them more applicable for designing nanodevices. Intrinsic PtSe2 is a semiconductor, while the X-PtSe2 system can be a band-gap narrowed semiconductor or metal, thus expanding the application scope for PtSe2, and the odd-even effect of electronic phase variation related to the atomic number is found. Besides, the wavelength range of optical adsorption is increased in X-PtSe2 systems, implying that its optical response region is wide, providing more options for developing optoelectronic devices. Moreover, it is shown that strain can flexibly tune the electronic property of X-PtSe2 systems, especially enhancing the optical absorption ability substantially, beneficial for their applications in solar devices.

Efficient removal of per- and polyfluoroalkyl substances from biochar composites: Cyclic adsorption and spent regenerant degradation.

In order to solve the problem of efficient desorption of per- and polyfluoroalkyl substances (PFAS) and regeneration of adsorbents, a novel biochar composite was prepared based on the quaternary ammonium groups and hydrophobicity of sulfobetaine polymer, which can be used for the efficient removal of various PFASs and has great regeneration ability. Through adsorption, regeneration and degradation experiment, the comprehensive effect of the novel biochar composite on the whole process of removal of PFAS was systematically investigated. The results showed that the maximum adsorption capacity of PFOS, PFOA, PFBS, and PFBA reached 634 mg/g, 536 mg/g, 301 mg/g and 264 mg/g, respectively. The adsorption process involved hydrophobicity, electrostatic, pore diffusion and complexation. The NaI + NaOH solution was used at 50 °C to achieve efficient regeneration of the adsorbent, which can be recycled more than 4 times. When the vacuum-ultraviolet (VUV)/sulfite reduction system was used for deep degradation of the regenerated solution, the effect of hydrated electrons on PFAS was enhanced due to the inclusion of NaI and NaOH in the regeneration reagent, resulting in an increase in the degradation efficiency (89.1%-99.9%) and defluorination efficiency (63.3%-84.1%). Based on the performance of BC-P(SB-co-AM) and the treatment efficiency of PFAS, the design idea of the whole process treatment technology of PFAS proposed in this work is expected to hold great promise in environmental applications. This work provides a novel idea and system for the efficient adsorption removal and desorption of PFAS, and subsequent deep degradation.

Multifunctional hemostatic polysaccharide-based sponge enhanced by tunicate cellulose: A promising approach for photothermal antibacterial activity and accelerated wound healing.

Fast and effective hemostasis and protection against wound infection play a crucial role in trauma care. In this study, a sponge scaffold with a self-expanding interpenetrating macropore structure was designed via two-step cross-linking method for hemostasis and photothermal antimicrobial activity. Oxidized Konjac glucomannan (OKGM) and chitosan (CS) were crosslinked once to form a dynamic covalent bonding network, and a basic three-dimensional fiber porous network framework was constructed by uniformly dispersing Tunicate nanocellulose (TCNCs). Secondary crosslinking introduced Polydopamine (PDA NPs) into the sponge, while dynamic hydrogen bonds were interleaved to stabilize the frame. PDA NPs enhanced the sponge's antibacterial and antioxidant properties due to its good photothermal conversion efficiency and oxygen radical scavenging ability. Compared to cotton gauze and gelatin sponges, the composite sponges showed superior blood cell adhesion and platelet activation. In tests on rat liver trauma models, composite sponges showed shorter hemostasis time (12 ± 2.17 s) and less blood loss (0.1 ± 0.052 g). Sponges can protect wound tissue through their adhesion properties. In the full-thickness wound model infected with S. aureus, the composite sponge accelerated wound healing. Overall, this composite sponge has great potential for clinical use as a wound dressing.

Plastic bottles for chilled carbonated beverages as a source of microplastics and nanoplastics.

Carbonated beverages are characterized by low temperatures, multiple microbubbles, high pressure, and an acidic environment, creating ideal conditions for releasing contaminants from plastic bottles. However, the release patterns of microplastics (MPs) and nanoplastics (NPs) are poorly understood. We investigated the effects of plastic type, CO2 filling volume, temperature, sugar content, and additive on the leakage of MPs/NPs and heavy metals. Our results showed that polypropylene bottles released greater MPs (234±9.66 particles/L) and NPs (9.21±0.73 × 107 particles/L) than polyethylene and polyethylene terephthalate bottles. However, subjecting the plastic bottles to 3 repeated inflation treatments resulted in 91.65-93.18% removal of MPs/NPs. The release of MPs/NPs increased with increasing CO2 filling volume, driven by the synergistic effect of CO2 bubbles and pressure. After 4 freeze-thaw cycles, the release of MPs and NPs significantly increased, reaching 450±38.65 MPs and 2.91±0.10 × 108 NPs per liter, respectively. The presence of sugar leads to an elevation in MPs release compared to sucrose-free carbonated water, while the addition of additives to carbonated water exhibits negligible effects on MPs release. Interestingly, actual carbonated beverages demonstrated higher MPs concentrations (260.52±27.18-281.38±61.33 particles/L) than those observed in our well-controlled experimental setup. Our study highlights the non-negligible risk of MPs/NPs in carbonated beverages at low temperatures and suggests strategies to mitigate human ingestion of MPs/NPs, such as selecting appropriate plastic materials, high-pressure carbonated water pretreatment, and minimizing freeze-thaw cycles. Our findings provide insights for further study of the release patterns of the contaminants in natural environments with bubbles, pressure, low temperature, and freeze-thaw conditions.

De novo biosynthesis of berberine and halogenated benzylisoquinoline alkaloids in Saccharomyces cerevisiae.

Berberine is an extensively used pharmaceutical benzylisoquinoline alkaloid (BIA) derived from plants. Microbial manufacturing has emerged as a promising approach to source valuable BIAs. Here, we demonstrated the complete biosynthesis of berberine in Saccharomyces cerevisiae by engineering 19 genes including 12 heterologous genes from plants and bacteria. Overexpressing bottleneck enzymes, fermentation scale-up, and heating treatment after fermentation increased berberine titer by 643-fold to 1.08 mg L-1. This pathway also showed high efficiency to incorporate halogenated tyrosine for the synthesis of unnatural BIA derivatives that have higher therapeutical potentials. We firstly demonstrate the in vivo biosynthesis of 11-fluoro-tetrahydrocolumbamine via nine enzymatic reactions. The efficiency and promiscuity of our pathway also allow for the simultaneous incorporation of two fluorine-substituted tyrosine derivatives to 8, 3'-di-fluoro-coclaurine. This work highlights the potential of yeast as a versatile microbial biosynthetic platform to strengthen current pharmaceutical supply chain and to advance drug development.

Diverse effects of gaze direction on heading perception in humans.

Gaze change can misalign spatial reference frames encoding visual and vestibular signals in cortex, which may affect the heading discrimination. Here, by systematically manipulating the eye-in-head and head-on-body positions to change the gaze direction of subjects, the performance of heading discrimination was tested with visual, vestibular, and combined stimuli in a reaction-time task in which the reaction time is under the control of subjects. We found the gaze change induced substantial biases in perceived heading, increased the threshold of discrimination and reaction time of subjects in all stimulus conditions. For the visual stimulus, the gaze effects were induced by changing the eye-in-world position, and the perceived heading was biased in the opposite direction of gaze. In contrast, the vestibular gaze effects were induced by changing the eye-in-head position, and the perceived heading was biased in the same direction of gaze. Although the bias was reduced when the visual and vestibular stimuli were combined, integration of the 2 signals substantially deviated from predictions of an extended diffusion model that accumulates evidence optimally over time and across sensory modalities. These findings reveal diverse gaze effects on the heading discrimination and emphasize that the transformation of spatial reference frames may underlie the effects.

Temporal and spatial differentiation characteristics of ecosystem service values based on the ecogeographical division of China: a case study in the Yellow River Basin, China.

The identification of spatiotemporal changes in ecosystem service values (ESVs) and their drivers is the basis for ecosystem service administration and decision-making. This research focuses on the Yellow River Basin (YRB). With a multitemporal land use and land cover (LULC) dataset (1995-2018), the equivalence coefficient method with spatiotemporal dynamic correction and exploratory spatial data analysis methods were used to evaluate ESV changes due to LULC changes and their spatial characteristics. The contributions of the ESV driving factors and their mutual effects were also investigated via geographic detectors. The results revealed that (1) the land use structure of the YRB, mainly grassland and cultivated land, was stable from 1995 to 2018. However, the transition between land use types was dramatic, including urban expansion accompanied by losses of farmland, grassland, and unused land; increased forestland; and significant increases in water bodies and wetland areas. (2) During the study period, the overall ESV of the YRB increased, and hydrological regulation and climate regulation services dominated the change in the ESVs in the study area. The ESV exhibited obvious ecogeographical pattern differentiation and evident positive spatial autocorrelation. High values were concentrated in the southern part of the study area, including the southeastern part of the Qinghai-Tibet Plateau region and the central part of the East Asian monsoon region. Low values were concentrated in the northwestern arid zone, dominated by desert and grassland ecosystems. (3) Because of the fragility of the regional ecological background, the spatial differentiation of the ESVs in the YRB is dependent on natural factors; however, anthropogenic factors such as the degree of land use and the human activity intensity also lead to ESV differentiation. The synergistic effects of human activities, landscape pattern changes, and natural factors result in the spatial differentiation of the ESVs in the research region. Therefore, human activities affecting the ecological environment should be controlled, nature-based solutions should be advocated, patch diversity should be increased, landscape fragmentation should be reduced, LULC ecosystem service functions should be improved, and the relationship among economic, social, and ecological landscape resources should be coordinated.

AmMYB24 Regulates Floral Terpenoid Biosynthesis Induced by Blue Light in Snapdragon Flowers.

Floral terpenoid volatiles are impacted by light quality. In snapdragon, blue light can significantly enhance the emissions of ocimene and myrcene and the expression of ocimene synthase (AmOCS) and myrcene synthase (AmMYS). However, the mechanisms underlying the response to blue light are largely unknown. In this study, two transcription factors (TFs), AmMYB24 and AmMYB63 were screened which showed high expression level under blue light. AmMYB24 exhibited synchronous expression with AmOCS. Moreover, AmOCS transcript expression was up-regulated in response to AmMYB24 overexpression. This activation is direct and occurs through binding of AmMYB24 to MYBCORECYCATB1 sites in the AmOCS promoter. In addition, AmMYB24 interacts with the blue light signal key receptor AmCRY1 and the transcriptional activation activity of AmMYB24 was decreased in AmCRY1 silencing flowers. Taken together, our results revealed the regulatory pathway of biosynthesis of ocimene induced by blue light mediated by AmMYB24 and AmCRY1. When snapdragon flowers were exposed to blue light, AmCRY1 was first activated, the light signal is transduced to AmMYB24 through interaction with AmCRY1, and finally AmMYB24 activates AmOCS by binding to its MYBCOREATCYCB1 motif, resulting in abundant ocimene emission.

MULTI-SCULPT: Multiplex Integration via Selective, CRISPR-Mediated, Ultralong Pathway Transformation in Yeast for Plant Natural Product Synthesis.

Yeast has been a versatile model host for complex and valuable natural product biosynthesis via the reconstruction of heterologous biosynthetic pathways. Recent advances in natural product pathway elucidation have uncovered many large and complicated plant pathways that contain 10-30 genes for the biosynthesis of structurally complex, valuable natural products. However, the ability to reconstruct ultralong pathways efficiently in yeast does not match the increasing demand for valuable plant natural product biomanufacturing. Here, we developed a one-pot, multigene pathway integration method in yeast, named MULTI-SCULPT for multiplex integration via selective, CRISPR-mediated, ultralong pathway transformation. Leveraging multilocus genomic disruption via CRISPR/Cas9, newly developed native and synthetic genetic parts, and fine-tuned gene integration and characterization methods, we managed to integrate 21 DNA inserts that contain a 12-gene plant isoflavone biosynthetic pathway into yeast with a 90-100% success rate in 12 days. This method enables fast and efficient ultralong biosynthetic pathway integration and can allow for the fast iterative integration of even longer pathways in the future. Ultimately, this method will accelerate combinatorial optimization of elucidated plant natural product pathways and accelerate putative pathway characterization heterologously.

Engineering Saccharomyces cerevisiae to produce plant benzylisoquinoline alkaloids.

Benzylisoquinoline alkaloids (BIAs) are a diverse family of plant natural products with extensive pharmacological properties, but the yield of BIAs from plant is limited. The understanding of BIA biosynthetic mechanism in plant and the development of synthetic biology enable the possibility to produce BIAs through microbial fermentation, as an alternative to agriculture-based supply chains. In this review, we discussed the engineering strategies to synthesize BIAs in Saccharomyces cerevisiae (yeast) and improve BIA production level, including heterologous pathway reconstruction, enzyme engineering, expression regulation, host engineering and fermentation engineering. We also highlight recent metabolic engineering advances in the production of BIAs in yeast.

Reversible thermal regulation for bifunctional dynamic control of gene expression in Escherichia coli.

Genetically programmed circuits allowing bifunctional dynamic regulation of enzyme expression have far-reaching significances for various bio-manufactural purposes. However, building a bio-switch with a post log-phase response and reversibility during scale-up bioprocesses is still a challenge in metabolic engineering due to the lack of robustness. Here, we report a robust thermosensitive bio-switch that enables stringent bidirectional control of gene expression over time and levels in living cells. Based on the bio-switch, we obtain tree ring-like colonies with spatially distributed patterns and transformer cells shifting among spherical-, rod- and fiber-shapes of the engineered Escherichia coli. Moreover, fed-batch fermentations of recombinant E. coli are conducted to obtain ordered assembly of tailor-made biopolymers polyhydroxyalkanoates including diblock- and random-copolymer, composed of 3-hydroxybutyrate and 4-hydroxybutyrate with controllable monomer molar fraction. This study demonstrates the possibility of well-organized, chemosynthesis-like block polymerization on a molecular scale by reprogrammed microbes, exemplifying the versatility of thermo-response control for various practical uses.

Utilization of a Mobile Multifunctional Workstation for Coronavirus Nasopharyngeal/Oropharyngeal Specimen Collection.

Objectives: This study aimed to explore the utilization of a mobile multifunctional workstation for COVID-19 sample collection. Methods: Twenty-four nurses and 150 individuals who took nucleic acid tests using mobile multifunctional workstations in Beijing Youan Hospital, Capital Medical University, from September to November 2020, were enrolled in the study as the observation group. As the control group, we included 36 nurses and 150 individuals who did not use the workstations from June to September 2020. We compared the two groups on (1) comfort of working environment, self-perceived security, the convenience of information system, operational process flexibility, pharyngeal acquisition visibility, and effectiveness of communication among nurses; and (2) self-perceived safety, waiting time, and overall satisfaction among individuals who took nucleic acid tests. Results: The satisfaction score of nurses in the observation group of nurses were significantly higher than those of the control group (OR = 17.297 95% CI:4.294, 69.673), as well as the convenience of the information system (OR = 6.250 95% CI: 1.775, 22.008), and communication effectiveness (OR = 5.588 95% CI: 1.590, 19.646). Among individuals who took nucleic acid tests, the overall satisfaction (P < 0.05) and self-perceived security (P < 0.05) had statistical differences between the observation group and the control group. Conclusions: The mobile multifunctional workstation for specimen collection could improve the comfort of the working environment, the convenience of information systems, and the effectiveness of communication among nurses.It can improve satisfaction and self-perceived security among people who took nucleic acid tests.

Stimulus response-based fine-tuning of polyhydroxyalkanoate pathway in Halomonas.

Optimization of intracellular biosynthesis process involving regulation of multiple gene expressions is dependent on the efficient and accurate expression of each expression unit independently. However, challenges of analyzing intermediate products seriously hinder the application of high throughput assays. This study aimed to develop an engineering approach for unsterile production of poly(3-hydroxybutyrate-co-4-hydroxybutyrate) or (P3HB4HB) by recombinant Halomonas bluephagenesis (H. bluephagenesis) constructed via coupling the design of GFP-mediated transcriptional mapping and high-resolution control of gene expressions (HRCGE), which consists of two inducible systems with high- and low-dynamic ranges employed to search the exquisite transcription level of each expression module in the presence of γ-butyrolactone, the intermediate for 4-hydroxybutyrate (4HB) synthesis. It has been successful to generate a recombinant H. bluephagenesis, namely TD68-194, able to produce over 36 g/L P3HB4HB consisting of 16 mol% 4HB during a 7-L lab-scale fed-batch growth process, of which cell dry weight and PHA content reached up to 48.22 g/L and 74.67%, respectively, in 36 h cultivation. HRCGE has been found useful for metabolic pathway construction.

Many-body ionization in a frozen Rydberg gas.

In a dense gas of 300 microK 85Rb atoms of n approximately 50 ionization occurs on a 100 ns time scale, far too fast to be explained by the motion of the atoms or photoionization by 300 K blackbody radiation. Rapid ionization is accompanied by spectral broadening, with the spectrum becoming continuous at n=88 at a density of 5x10(10)cm(-3). The atomic transitions broaden both smoothly and by the emergence of new features, which we attribute to multiple atom absorptions. We attribute the rapid ionization to a sequence of near resonant dipole-dipole transitions through virtual states in this intrinsically many-body system, culminating in the ionization of some of the atoms.