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Realizing the immense clinical potential of mRNA-based drugs will require continued development of methods to safely deliver the bioactive agents with high efficiency and without triggering side effects. In this regard, lipid nanoparticles have been successfully utilized to improve mRNA delivery and protect the cargo from extracellular degradation. Encapsulation in lipid nanoparticles was an essential factor in the successful clinical application of mRNA vaccines, which conclusively demonstrated the technology's potential to yield approved medicines. In this review, we begin by describing current advances in mRNA modifications, design of novel lipids and development of lipid nanoparticle components for mRNA-based drugs. Then, we summarize key points pertaining to preclinical and clinical development of mRNA therapeutics. Finally, we cover topics related to targeted delivery systems, including endosomal escape and targeting of immune cells, tumors and organs for use with mRNA vaccines and new treatment modalities for human diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: The Colorado potato beetle, Leptinotarsa decemlineata, poses a significant threat to potato crops worldwide, causing substantial agricultural damage. To better understand how these pests develop and potentially find ways to control them, we studied a group of genes called Knickkopf (Knk) genes in the larvae of the beetle. These genes are crucial for forming and maintaining the insect's outer shell, known as the cuticle, which protects them from the environment. We identified four LdKnk-family genes in the beetle and analyzed when and where these genes are expressed during the insect's growth stages. By using RNA interference (RNAi) to silence these genes, we observed that larvae became weaker, with damaged cuticles and higher death rates. These findings indicate that LdKnk-family genes are vital for the beetle's survival and development. Targeting LdKnk-family genes could provide a new strategy for pest control, potentially weakening the beetles' defenses and making them more susceptible to environmental factors and insecticides, ultimately helping to protect potato crops. The Colorado potato beetle (Leptinotarsa decemlineata) is a major pest of potato crops. While Knickkopf (Knk) genes are essential for insect cuticle formation, their roles in pests like L. decemlineata remain unclear. This study aims to identify and characterize Knk genes in L. decemlineata and explore their functions in larval development and cuticle integrity. We used genomic and transcriptomic databases to identify LdKnk-family genes, validated through RT-PCR and RACE. Gene expression was analyzed at various developmental stages and tissues using qRT-PCR. RNA interference (RNAi) and Transmission electron microscopy (TEM) were applied to determine the functional roles of these genes. Four LdKnk-family genes were identified. Spatio-temporal expression analysis indicated significant gene expression during larval molting and pupal stages, especially in the epidermis. RNAi experiments showed that silencing LdKnk and LdKnk3-5′ led to reduced larval weight, cuticle thinning, and increased mortality, while LdKnk3-FL knockdown caused abnormal cuticle thickening and molting disruptions. LdKnk2 knockdown increased epicuticle and endocuticle thickness without visible phenotypic changes. The study highlights the essential roles of LdKnk-family genes in maintaining cuticle structure and integrity, suggesting their potential as targets for RNAi-based pest control. [ABSTRACT FROM AUTHOR]

This study investigates the propagation of dark Alfvén solitons in low-β magnetized plasma using Hall-magnetohydrodynamic (Hall-MHD) numerical simulations. The rational solution of the nonlinear Schr o ̈ dinger equation (NLSE) is presented, which is proposed as an effective tool for studying dark envelope solitons in plasma. Our results show a high degree of agreement between numerical simulations and analytical solutions derived from the NLSE via the reductive perturbation method. This agreement validates our modeling and computational approach. In addition, the simulations confirm the existence of dark Alfvén solitons in magnetized plasma. This work demonstrates the effectiveness of Hall-MHD simulations in studying complex plasma phenomena, contributing to the broader understanding of soliton propagation in plasma environments. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the relationship between the indicators for COVID-19 monitoring and the dynamic of jumps across six major financial markets including China, France, Italy, Germany, the UK, and the US. First, this paper finds that jumps occurred more frequently in the index returns during the COVID-19 pandemic. Second, the empirical findings suggest that the anxiety stemming from potential future control measures, which were prompted by updates in COVID-19 briefings, plays a significant role in explaining the jumps in index returns within financial markets. The strategies of 'zero tolerance for COVID-19', 'maximum healthcare capacity', and 'less tolerance for restriction' were carried out by China, European countries, and the US respectively. These diverse approaches to managing COVID-19 have a significant and varied impact on the market's sudden price movements. [ABSTRACT FROM AUTHOR]

Zinc-copper alloy ash contains Cu, Zn, Al, Ni, Sn, Pb and other non-ferrous metals. In this paper, t he effective treatment of zmccopper ash in different particle size ranges ss realized by screening. The effects of sulfuric acid content, temperature, time, i iquid-soiid ratio, rotation speed, oxidant and roasting conditions on the selective eaching of different meta! were investigated. The resutts show that the zinccopper ash with partid size kss than 0. 15 mm ss caHned at 750 °C for 3 hours, and then leached at 85 °C, s uHunc acid content of 1. 2 g/g ash, iiquid-to-solid ratio of 5/1, sirring speed of 400 r/min, H202 0. 075 mL/g ash for 5 h. The removal rate of zinc ss 93. 40%, and the removal rate of copper ss 0. 23%. Compared with the initia1 copper ash, the ZnO n the copper ash after roasting and leaching ss greatly reduced. The leaching residue was mixed with copper slag with a particle size of 0. 15-0. 25 mm, roasted at 750 C for 4 hours, and then washed wI 2 mol/L suHurtc acid solution for 5 hours and washed wI water under the same condiions. The steps can remove a !arge number of impurtty metal e!ements inthe copper slag. The phase composition of the copper slag after pickling is mainly Cu, and the proportion of Cu elements reach 92. 52%. [ABSTRACT FROM AUTHOR]

This study presents a pioneering investigation into the complex Holocene paleo-morphologies of the Yilan Plain, located at the southwestern edge of the Okinawa Trough. We employed a novel approach that synergized resistivity measurements with machine learning techniques to unlock valuable insights into the geological history, sedimentary patterns, and seismic activity of this dynamic region. Our methodology involved the creation of an Apparent Geological Model (AGM) through the interpolation of inverted resistivity data and the application of supervised machine learning algorithms. Classification criteria, derived from the relationship between resistivity values and sediment types found in nearby boreholes, were developed using the random forest machine-learning method. The resultant 3D resistivity model was transformed into a clay-sand-gravel model, offering a comprehensive depiction of sediment distribution within the Yilan Plain. Notably, our findings revealed distinct sedimentary patterns. Gravel-dominated regions, characterized by resistivity values above 140 Ohm-m, were identified alongside areas dominated by sand and clay sediments. The Carbon-14 dating ages in the sand sediments exhibited remarkable consistency, shedding light on the depositional history of the region. Furthermore, our research unveiled a previously unknown phenomenon of rapid subsidence in the Yilan Plain. Through meticulous analysis and correction for sea-level changes, we estimated an average subsidence rate of approximately 8.5 mm/year. This subsidence was punctuated by abrupt events around 6000–7000 years BP and 2000–3000 years BP, associated with a sudden increase. These events suggested a potential link to prehistoric seismic activity, with variable subsidence rates between episodes hinting at recurrent active seismic periods every 4000–5000 years. In conclusion, our multidisciplinary approach has provided unprecedented insights into the Holocene paleo-morphologies of the Yilan Plain. By combining resistivity measurements, machine learning, and geological analysis, we have enriched our understanding of the region's geological history, sedimentary dynamics, and seismic behavior. These findings not only contribute to the knowledge of Yilan's past but also offer vital data for future environmental and geological studies in similarly dynamic regions. Key Points: The study investigates Holocene paleo-morphologies in Taiwan's Yilan Plain, providing insights into its geological history. By combining resistivity measurements with machine learning, the research unveils valuable data on sedimentary patterns and seismic activity in the region. The methodology includes creating an Apparent Geological Model (AGM) using machine learning algorithms and resistivity data interpolation. The study establishes classification criteria and models sediment distribution, identifying distinct patterns in clay, sand, and gravel. The research reveals rapid subsidence and suggests links to prehistoric seismic events with a 4000-5000 recurrence period. [ABSTRACT FROM AUTHOR]

Cohabitation has become more common in communities that have experienced demographic transitions, including in Taiwan, and hence it has become a research interest. However, our understanding of cohabitation in Taiwan has been limited to indirect estimations and cross-sectional analysis due to the lack of appropriate data. These analyses can provide a quick overview of the prevalence of cohabitation at specific periods, but they cannot portray the risk of cohabitation over the life course. Using recent panel data from the Taiwan Youth Project, we estimate cohabitation risk among young adults in their mid-20s to early-30s. We also examine the determinants of cohabitation. Results show that being a woman, not employed, living in emerging regions, not having varying residential locations, ever having sex (especially at an earlier age), and being more open to premarital intimacy were associated with higher odds of cohabitation. [ABSTRACT FROM AUTHOR]

Sialyltransferase-catalyzed membrane protein and lipid glycosylation plays a vital role as one of the most abundant post-translational modifications and diversification reactions in eukaryotes. However, aberrant sialylation has been associated with cancer malignancy and metastasis. Sialyltransferases thus represent emerging targets for the development of small molecule cancer drugs. Herein, we report the inhibitory effects of a recently discovered lithocholic acid derivative FCW393 on sialyltransferase catalytic activity, integrin sialyation, cancer-associated signal transduction, MDA-MB-231 and B16F10 cell migration and invasion, and in in vivo studies, on tumor growth, metastasis, and angiogenesis. FCW393 showed effective and selective inhibition of the sialyltransferases ST6GAL1 (IC50 = 7.8 μM) and ST3GAL3 (IC50 = 9.45 μM) relative to ST3GAL1 (IC50 > 400 μM) and ST8SIA4 (IC50 > 100 μM). FCW393 reduced integrin sialylation in breast cancer and melanoma cells dose-dependently and downregulated proteins associated with the integrin-regulated FAK/paxillin and GEF/Rho/ROCK pathways, and with the VEGF-regulated Akt/NFκB/HIF-1α pathway. FCW393 inhibited cell migration (IC50 = 2.6 μM) and invasion in in vitro experiments, and in in vivo studies of tumor-bearing mice, FCW393 reduced tumor size, angiogenesis, and metastatic potential. Based on its demonstrated selectivity, cell permeability, relatively low cytotoxicity (IC50 = 55 μM), and high efficacy, FCW393 shows promising potential as a small molecule experimental tool compound and a lead for further development of a novel cancer therapeutic. [ABSTRACT FROM AUTHOR]

Knowledge about biological rhythms of diseases may not only help in understanding the pathophysiology of diseases but can also help health service policy makers and emergency department directors to allocate resources efficiently. Aneurysmal subarachnoid haemorrhage (SAH) has high rates of morbidity and mortality. The incidence of SAH has been attributed to patient-related factors such as characteristics of aneurysms, smoking, and hypertension. There are studies showing that the incidence of aneurysmal SAH appears to behave in periodic fashions over long time periods. However, there are inconsistencies in the literature regarding the impact of chronobiological factors such as circadian, seasonal, and lunar cycle factors on the occurrence of SAH. In this study, we focused on the analysis of a temporal pattern of SAH (infradian rhythms) with a novel approach using circular statistical methods. We aimed to see whether there is a circular pattern for the occurrence of SAH at all and if so, whether it can be related to known temporal patterns based on available literature. Our study did not support the notion that aneurysmal subarachnoid haemorrhages occur on any specific day in a cycle with specific lengths up to 365 days including specific weekdays, full moon, equinoxes, and solstices. Hence, we found no relationship between SAH incidence and timing. Study in larger populations using similar circular statistical methods is suggested. [ABSTRACT FROM AUTHOR]

Lightning strikes can cause equipment damage and power outages, so the distribution system's reliability in withstanding lightning strikes is crucial. This research paper presents a model that aims to optimise the configuration of a lightning protection system (LPS) in the power distribution system and minimise the System Average Interruption Frequency Index (SAIFI), a measure of reliability, and the associated cost investment. The proposed lightning electromagnetic transient model considers LPS factors such as feeder shielding, grounding design, and soil types, which affect critical current, flashover rates, SAIFI, and cost. A metaheuristic algorithm, PSOGSA, is used to obtain the optimal solution. The paper's main contribution is exploring grounding schemes and soil resistivity's impact on SAIFI. Using 4 grounding rods arranged in a straight line under the soil with 10 Ωm resistivity reduces grounding resistance and decreases SAIFI from 3.783 int./yr (no LPS) to 0.146 int./yr. Unshielded LPS has no significant effect on critical current for soil resistivity. Four test cases with different cost investments are considered, and numerical simulations are conducted. Shielded LPSs are more sensitive to grounding topologies and soil resistivities, wherein higher investment, with 10 Ωm soil resistivity, SAIFI decreases the most by 73.34%. In contrast, SAIFIs for 1 kΩm and 10 kΩm soil resistivities show minor decreases compared to SAIFIs with no LPS. The study emphasises the importance of considering soil resistivity and investment cost when selecting the optimal LPS configuration for distribution systems, as well as the significance of LPS selection in reducing interruptions to customers. [ABSTRACT FROM AUTHOR]

Background: The interdisciplinary realm of medical humanities explores narratives and experiences that can enhance medical education for physicians through perspective-taking and reflective practice. However, there is a gap in comprehension regarding its appropriateness at the postgraduate level, especially when utilising art therapists as faculty. This study aims to assess the acceptability of an innovative art therapy-focused educational initiative among junior doctors during a palliative care rotation, with the goal of cultivating empathy and promoting well-being. Methods: A qualitative research project was conducted at the Division of Supportive and Palliative Care (DSPC) in the National Cancer Centre Singapore (NCCS). The study involved the recruitment of junior doctors who had successfully completed a three-month palliative care rotation program, spanning from January 2020 to April 2021. In a single small-group session lasting 1.5 h, with 3 to 4 participants each time, the individuals participated in activities such as collage making, group reflection, and sharing of artistic creations. These sessions were facilitated by an accredited art therapist and a clinical psychologist, focusing on themes related to empathy and wellbeing. To assess the acceptability of the program, two individual interviews were conducted three months apart with each participant. An independent research assistant utilised a semi-structured question guide that considered affective attitude, burden, perceived effectiveness, coherence, and self-efficacy. Thematic analysis of the transcribed data was then employed to scrutinise the participants' experiences. Results: A total of 20 individual interviews were completed with 11 participants. The three themes identified were lack of pre-existing knowledge of the humanities, promotors, and barriers to program acceptability. Conclusions: The participants have mixed perceptions of the program's acceptability. While all completed the program in its entirety, the acceptability of the program is impeded by wider systemic factors such as service and manpower needs. It is vital to address these structural limitations as failing to do so risks skewing current ambivalence towards outright rejection of future endeavours to integrate humanities programs into medical education. [ABSTRACT FROM AUTHOR]

Introduction: Limited studies have evaluated the association between Clostridium difficile infection (CDI) and the duration of proton pump inhibitor (PPI) or histamine H2-receptor blocker (H2RA) use and provided a cutoff duration for PPI or H2RA use to mitigate a substantially increased risk of CDI. We aimed to evaluate these associations in hospitalized patients using a nationwide insurance claims database. Methods: We conducted a nested case–control study to identify cases with a first ever record of CDI in a study cohort undergoing PPI or H2RA therapy from the National Health Insurance Database from 2012 to 2018. Each case was matched with one control by age, sex, and calendar year. We used conditional logistic regression to estimate the sensitivity, specificity, and area under the receiver operating characteristic curve (AUC ROC). Youden's J statistic was used to identify the optimal cutoff duration in days for PPI or H2RA use. Results: In the main analysis, the AUC ROC was 0.64 (95% CI 0.63–0.66) and optimal cutoff duration was 15 days for PPI users. The AUC ROC was 0.63 (95% CI 0.62–0.64) and optimal cutoff duration was 16 days for H2RA users. In the sensitivity analyses, the results were similar to those of the main analysis, and the optimal cutoff duration was in the range of 14–15 days. Conclusions: The optimal cutoff duration for PPI and H2RA use was about 2 weeks. It is necessary to be cautious regarding the risk of CDI in patients taking PPIs or H2RAs for longer than 2 weeks. [ABSTRACT FROM AUTHOR]

To distinguish the Rayleigh-Taylor (RT) instability between a dusty plasma fluid and a general fluid, the present study focuses on the RT instability in interfaces where there is a discontinuity in the mass density of the dust particle fluid, by considering two cases. One is neglecting the impact of the electric field, and the other is considering the effects of the electric field. It is found that neglecting the impact of the electric field may lead to RT instability. In this case, the growth rate increases as the perturbed wavelength decreases and as the ratio of number density in the upper region to that in the lower region increases. It also depends on the width of both regions. However, when accounting for the effect of the electric field, RT instability is restrained at the interface. To sum up, the electric field has the obvious effect to suppress the Rayleigh-Taylor instability in dusty plasma, which could have practical implications. [ABSTRACT FROM AUTHOR]

Imagine having a knowledge graph that can extract medical health knowledge related to patient diagnosis solutions and treatments from thousands of research papers, distilled using machine learning techniques in healthcare applications. Medical doctors can quickly determine treatments and medications for urgent patients, while researchers can discover innovative treatments for existing and unknown diseases. This would be incredible! Our approach serves as an all-in-one solution, enabling users to employ a unified design methodology for creating their own knowledge graphs. Our rigorous validation process involves multiple stages of refinement, ensuring that the resulting answers are of the utmost professionalism and solidity, surpassing the capabilities of other solutions. However, building a high-quality knowledge graph from scratch, with complete triplets consisting of subject entities, relations, and object entities, is a complex and important task that requires a systematic approach. To address this, we have developed a comprehensive design flow for knowledge graph development and a high-quality entities database. We also developed knowledge distillation schemes that allow you to input a keyword (entity) and display all related entities and relations. Our proprietary methodology, multiple levels refinement (MLR), is a novel approach to constructing knowledge graphs and refining entities level-by-level. This ensures the generation of high-quality triplets and a readable knowledge graph through keyword searching. We have generated multiple knowledge graphs and developed a scheme to find the corresponding inputs and outputs of entity linking. Entities with multiple inputs and outputs are referred to as joints, and we have created a joint-version knowledge graph based on this. Additionally, we developed an interactive knowledge graph, providing a user-friendly environment for medical professionals to explore entities related to existing or unknown treatments/diseases. Finally, we have advanced knowledge distillation techniques. [ABSTRACT FROM AUTHOR]

Background: Citrus is one of the most valuable fruits worldwide and an economic pillar industry in southern China. Nevertheless, it frequently suffers from undesirable environmental stresses during the growth cycle, which severely restricts the growth, development and yield of citrus. In plants, the growth-regulating factor (GRF) family of transcription factors (TF) is extensively distributed and plays an vital part in plant growth and development, hormone response, as well as stress adaptation. However, the systematic identification and functional analysis of GRF TFs in citrus have not been reported. Results: Here, a genome-wide identification of GRF TFs was performed in Citrus sinensis, 9 members of CsGRFs were systematically identified and discovered to be scattered throughout 5 chromosomes. Subsequently, physical and chemical properties, phylogenetic relationships, structural characteristics, gene duplication events, collinearity and cis-elements of promoter were elaborately analyzed. In particular, the expression patterns of the CsGRF genes in response to multiple phytohormone and abiotic stress treatments were investigated. Predicated on this result, CsGRF04, which exhibited the most differential expression pattern under multiple phytohormone and abiotic stress treatments was screened out. Virus-induced gene silencing (VIGS) technology was utilized to obtain gene silenced plants for CsGRF04 successfully. After the three stress treatments of high salinity, low temperature and drought, the CsGRF04-VIGS lines showed significantly reduced resistance to high salinity and low temperature stresses, but extremely increased resistance to drought stress. Conclusions: Taken together, our findings systematically analyzed the genomic characterization of GRF family in Citrus sinensis, and excavated a CsGRF04 with potential functions under multiple abiotic stresses. Our study lay a foundation for further study on the function of CsGRFs in abiotic stress and hormone signaling response. [ABSTRACT FROM AUTHOR]

A modulational instability of nonlinearly interacting electron whistlers and magnetosonic perturbations is studied in the present paper. For typical parameters, there is no modulational instability. However, modulational instability appears in special cases. For example, when the whistler wavenumber is small enough, there is modulational instability. Its growth rate decreases as the angle between the external magnetic field and the perturbed wave's direction increases, while it increases as the whistler wavenumber increases. It is also found that there is no modulational instability when the whistler wavenumber is larger than a critical value ($k_0 > 0.05$), in which the perturbed wave frequency increases as the angle between the external magnetic field and the perturbed wave's direction increases when the angle between the external magnetic field and the perturbed wave's direction is large enough. Whereas, the perturbed wave frequency first increases as the whistler wavenumber increases, reaches a peak value and then decreases as whistler wavenumber increases. [ABSTRACT FROM AUTHOR]

Porous organic cages (POCs) are meanwhile an established class of porous materials. Most of them are soluble to a certain extend and thus processable in or from solution. However, a few of larger salicylimine cages were reported to be insoluble in any organic solvents and thus characterized as amorphous materials. These cages were now synthesized as single‐crystalline materials to get insight into packing motifs and preferred intermolecular interactions. Furthermore, the pairs of crystalline and amorphous materials for each cage allowed to compare their gas‐sorption properties in both morphological states. [ABSTRACT FROM AUTHOR]

Highly efficient genetic transformation technology is beneficial for plant gene functional research and molecular improvement breeding. However, the most commonly used Agrobacterium tumefaciens-mediated genetic transformation technology is time-consuming and recalcitrant for some woody plants such as citrus, hampering the high-throughput functional analysis of citrus genes. Thus, we dedicated to develop a rapid, simple, and highly efficient hairy root transformation system induced by Agrobacterium rhizogenes to analyze citrus gene function. In this report, a rapid, universal, and highly efficient hairy root transformation system in citrus seeds was described. Only 15 days were required for the entire workflow and the system was applicable for various citrus genotypes, with a maximum transformation frequency of 96.1%. After optimization, the transformation frequency of Citrus sinensis, which shows the lowest transformation frequency of 52.3% among four citrus genotypes initially, was increased to 71.4% successfully. To test the applicability of the hairy roots transformation system for gene functional analysis of citrus genes, we evaluated the subcellular localization, gene overexpression and gene editing in transformed hairy roots. Compared with the traditional transient transformation system performed in tobacco leaves, the transgenic citrus hairy roots displayed a more clear and specific subcellular fluorescence localization. Transcript levels of genes were significantly increased in overexpressing transgenic citrus hairy roots as compared with wild-type (WT). Additionally, hairy root transformation system in citrus seeds was successful in obtaining transformants with knocked out targets, indicating that the Agrobacterium rhizogenes-mediated transformation enables the CRISPR/Cas9-mediated gene editing. In summary, we established a highly efficient genetic transformation technology with non-tissue-culture in citrus that can be used for functional analysis such as protein subcellular localization, gene overexpression and gene editing. Since the material used for genetic transformation are roots protruding out of citrus seeds, the process of planting seedlings prior to transformation of conventional tissue culture or non-tissue-culture was eliminated, and the experimental time was greatly reduced. We anticipate that this genetic transformation technology will be a valuable tool for routine research of citrus genes in the future. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) is a central nervous system disease with a high disability. Immune activation of microglia cells can be induced, and the activated microglia cells are mainly divided into two different subtypes, namely, proinflammatory phenotype (M1) and anti-inflammatory phenotype (M2). Regulating the transformation of microglial subtypes is the key to alleviating inflammation. However, because of the blood–spinal cord barrier (BSCB), most drugs cannot reach the target site and give a full effect. Therefore, the purpose of this study was to design a nanoscale glutathione-functionalized bone marrow mesenchymal stem cell-derived exosome (Exos-GSH) as a delivery carrier for metformin. Using Exos-GSH's ability to cross BSCB, metformin can be efficiently delivered to the injured spinal cord tissue and taken up by neurons and microglia cells at the injured site. Exos-GSH loading metformin (Exos-Met-GSH) had a particle size of about 154 ± 17 nm, and the encapsulation rate was 87.49 ± 3.36%. In vitro and in vivo experiments showed that Exos-Met-GSH could exert good anti-inflammatory effects by inducing the polarization of microglia from the M1 phenotype to the M2 phenotype. In addition, Exos-Met-GSH can also protect mitochondria by relieving the oxidative stress of neurons, thus inhibiting neuronal apoptosis. Finally, Exos-Met-GSH can protect nerve cells through anti-inflammatory, antioxidant stress, and inhibition of apoptosis, thus promoting the recovery of motor function in SCI mice, which is a potential drug for SCI treatment. [ABSTRACT FROM AUTHOR]

Background: Epidural anesthesia (EA) is the regional anesthesia technique preferred over spinal anesthesia for pregnant women requiring cesarean section and post-operative pain control. EA failure requires additional sedation or conversion to general anesthesia (GA). This may be hazardous during sedation or GA conversion because of potentially difficult airways. Therefore, this retrospective study aimed to determine the risk factors for epidural failure during cesarean section anesthesia. Methods: We retrospectively analyzed parturients who underwent cesarean section under EA and catheterization at the Chang Gung Memorial Hospital in Taiwan between January 1 and December 31, 2018. Patient data were collected from the medical records. EA failure was defined as the administration of any intravenous anesthetic at any time during a cesarean section, converting it into GA. Results: A total of 534 parturients who underwent cesarean section were recruited for this study. Of them, 94 (17.6%) experienced EA failure during cesarean section. Compared to the patients with successful EA, those with EA failure were younger (33.0 years vs. 34.7 years), had received EA previously (60.6% vs. 37%), were parous (72.3% vs. 55%), and had a shorter waiting time (14.9 min vs. 16.5 min) (p < 0.05). Younger age (OR 0.91, 95% CI 0.86–0.95), history of epidural analgesia (OR 2.61, 95% CI 1.38–4.94), and shorter waiting time (OR 0.91, 95% CI 0.87–0.97) were estimated to be significantly associated with a higher risk of epidural anesthesia failure. Conclusion: The retrospective study found that parturients of younger age, previous epidural catheterization history, and inadequate waiting time may have a higher risk of EA failure. Previous epidural catheterization increased the risk of EA failure by 2.6-fold compared to patient with no history of catheterization. [ABSTRACT FROM AUTHOR]

Introduction: Spinal cord injury (SCI) is a central nervous system injury that is primarily traumatic and manifests as motor, sensory, and autonomic dysfunction below the level of damage. Our previous studies confirmed the ability of zinc to protect mitochondria, protect neurons and promote spinal cord recovery. However, the role of zinc in Parthanatos is unknown. Aim: We investigated the effects of zinc in Parthanatos from oxidative stress and mitophagy. We elucidated the role of SIRT3 in providing new ideas for treating spinal cord injury. The Results: Zinc protected SCI mice by regulating Parthanatos. On the one hand, zinc eliminated ROS directly through SIRT3 deacetylation targeting SOD2 to alleviate Parthanatos. On the other hand, zinc eliminated ROS indirectly through SIRT3‐mediated promotion of mitophagy to alleviate Parthanatos. Conclusion: Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3‐mediated anti‐oxidative stress and mitophagy. [ABSTRACT FROM AUTHOR]

The imbalance of immune response plays a crucial role in the development of diseases, including glioblastoma. It is essential to comprehend how the innate immune system detects tumors and pathogens. Endosomal and cytoplasmic sensors can identify diverse cancer cell antigens, triggering the production of type I interferon and pro-inflammatory cytokines. This, in turn, stimulates interferon stimulating genes, enhancing the presentation of cancer antigens, and promoting T cell recognition and destruction of cancer cells. While RNA and DNA sensing of tumors and pathogens typically involve different receptors and adapters, their interaction can activate adaptive immune response mechanisms. This review highlights the similarity in RNA and DNA sensing mechanisms in the innate immunity of both tumors and pathogens. The aim is to enhance the antitumor innate immune response, identify regions of the tumor that are not responsive to treatment, and explore new targets to improve the response to conventional tumor therapy and immunotherapy. [ABSTRACT FROM AUTHOR]

We conducted a study on the confinement properties of non-neutral proton plasma in an asymmetric magnetic mirror using the three-dimensional (3D) particle-in-cell simulation method. Our findings indicate a close relationship between the ability of the magnetic mirror to confine protons and the incidence orientation of the proton beam. This relationship can only be accurately assessed through 3D simulation, as opposed to two-dimensional simulation. In addition, we observed that a higher velocity parallel to the magnetic field direction results in a shorter confinement time. The electric field at and near the central point of the mirror exhibits quasi-periodic vibrations, attributed to the electrostatic oscillation of the proton and the cyclotron motion. Furthermore, we discovered a drift motion of the confined proton plasma in the direction of the magnetic field gradient. These findings hold implications for the design of magnetic mirrors capable of effectively confining charged particle beams. [ABSTRACT FROM AUTHOR]

The numerical investigation of shock waves in a chain of dust particles is conducted using the molecular dynamics simulation method. Assuming that the first pulse in the shock front is a solitary wave, we derive an analytical approximate expression to demonstrate how the shock velocity depends on the piston velocity and the system parameters, such as the charge of the dust particles, the initial lattice constant, and the screening parameter. It is found that the shock wave velocity increases as the piston velocity and coupling parameter increase, while it decreases as the screening parameter increases. The analytical results are in good agreement with the molecular dynamics simulation results. [ABSTRACT FROM AUTHOR]

Among the elderly, hypertension remains one of the prevalent health conditions, which requires monitoring and intervention strategies. Nevertheless, regular reporting of blood pressure (BP) from these individuals still poses multiple challenges. However, most people own cell phone and are engaged in phone conversations daily. Here, we propose an adjustable cuffless smartphone attachment (ACSA+) equipped with a PPG sensor for the estimation of BP during phone conversations. ACSA+ can be easily attached to the back of any modern cell phone. ACSA+ will help to continuously collect BP data and store it as a trend line. [ABSTRACT FROM AUTHOR]

The increasing integration between biological and digital interfaces has led to heightened interest in utilizing biological materials to store digital data, with the most promising one involving the storage of data within defined sequences of DNA that are created by de novo DNA synthesis. However, there is a lack of methods that can obviate the need for de novo DNA synthesis, which tends to be costly and inefficient. Here, in this work, we detail a method of capturing 2-dimensional light patterns into DNA, by utilizing optogenetic circuits to record light exposure into DNA, encoding spatial locations with barcoding, and retrieving stored images via high-throughput next-generation sequencing. We demonstrate the encoding of multiple images into DNA, totaling 1152 bits, selective image retrieval, as well as robustness to drying, heat and UV. We also demonstrate successful multiplexing using multiple wavelengths of light, capturing 2 different images simultaneously using red and blue light. This work thus establishes a 'living digital camera', paving the way towards integrating biological systems with digital devices. DNA data storage has gained recent interest due to the high information density of DNA. Here, the authors have developed a method to directly capture information in the form of light and encode it into DNA via bacteria, analogous to a digital camera. [ABSTRACT FROM AUTHOR]

The seahorse is one of the most unique teleost fishes in its morphology. The body is surrounded by bony plates and spines, and the male fish possess a brooding organ, called the brood pouch, on their tail. The surfaces of the brood pouch and the spines are surrounded by characteristic so-called flame cone cells. Based on our histological observations, flame cone cells are present in the seahorse Hippocampus abdominalis, but not in the barbed pipefish Urocampus nanus or the seaweed pipefish Syngnathus schlegeli, both of which belong to the same family as the seahorse. In the flame cone cells, we observed expression of an "orphan gene" lacking homologs in other lineages. This gene, which we named the proline-glycine rich (pgrich) gene, codes for an amino acid sequence composed of repetitive units. In situ hybridization and immunohistochemical analyses detected pgrich-positive signals from the flame cone cells. Based on a survey of the genome sequences of 15 teleost species, the pgrich gene is only found from some species of Syngnathiformes (namely, the genera Syngnathus and Hippocampus). The amino acid sequence of the seahorse PGrich is somewhat similar to the sequence deduced from the antisense strand of elastin. Furthermore, there are many transposable elements around the pgrich gene. These results suggest that the pgrich gene may have originated from the elastin gene with the involvement of transposable elements and obtained its novel function in the flame cone cells during the evolution of the seahorse. [ABSTRACT FROM AUTHOR]

Simple Summary: This population-based study, spanning 20 years, revealed trends regarding the incidence and mortality due to malignant neoplasm of the brain (MNB) in association with mobile phone usage in Taiwan. The findings indicate a trend of increase in the number of mobile phone users over the study period, accompanied by a slight rise in the incidence and death rates of MNB. The compound annual growth rates further support these observations, highlighting consistent growth in mobile phone users and a corresponding increase in MNB incidences and deaths. While this study suggests a weak association between mobile phone users and MNB incidence and mortality, it is important to acknowledge that conclusive results cannot be drawn at this stage. Further investigation is required to obtain more definitive findings. Continued research in this area will contribute to better understanding of the potential risks and aid in the development of safer mobile phone usage practices in the future. (1) Objective: This population-based study was performed to examine the trends of incidence and deaths due to malignant neoplasm of the brain (MNB) in association with mobile phone usage for a period of 20 years (January 2000–December 2019) in Taiwan. (2) Methods: Pearson correlation, regression analysis, and joinpoint regression analysis were used to examine the trends of incidence of MNB and deaths due to MNB in association with mobile phone usage. (3) Results: The findings indicate a trend of increase in the number of mobile phone users over the study period, accompanied by a slight rise in the incidence and death rates of MNB. The compound annual growth rates further support these observations, highlighting consistent growth in mobile phone users and a corresponding increase in MNB incidences and deaths. (4) Conclusions: The results suggest a weaker association between the growing number of mobile phone users and the rising rates of MNB, and no significant correlation was observed between MNB incidences and deaths and mobile phone usage. Ultimately, it is important to acknowledge that conclusive results cannot be drawn at this stage and further investigation is required by considering various other confounding factors and potential risks to obtain more definitive findings and a clearer picture. [ABSTRACT FROM AUTHOR]

This paper aims at investigating how leadership style can enhance workplace climate in the setting of virtual teams. Drawing from the theories of authentic leadership (AL) and social penetration (SPT), this study aims at investigating the role of IT usage of telework communicating tools in building and shaping the relationship between a subordinate (follower) and his or her supervisor at workplace. Variables of trust, identifications with leaders, intentions of knowledge sharing (self-disclosure, knowledge sharing and online voice behavior) are introduced in this research framework. Valid samples of 351 subjects of full-time workers reveal that the social penetration theory applies not only to face-to-face interactions but also to online interactions amongst members of virtual teams. It is projectsed that supervisors' transparency contributes to subordinates' self-disclosure and consequently leads to better working cohesion and relationship quality. Further, our study demonstrated that the disclosure of work-related knowledge and opinions related to workplace improvements in the computer-mediated communication (CMC) manner that are common at workplaces could positively influence the building of a constructive relationship between authentic leaders and their subordinates. This paper confirmed that the cohesion engaged amongst members of virtual teams and the relationship at work can be enhanced based on reciprocal information disclosure behavior. Especially in the season of epidemic prevention season, enterprises should quickly adopt the changing business environment and encourage staff to work from home. The self-disclosure behavior including online voicing should be promoted. Discussion and implications for theory and practices are given. [ABSTRACT FROM AUTHOR]

This paper reports notable observations regarding the ion charge states of thermally stable cytochrome c, generated using an alternating current (AC) electrospray ionization (ESI) device. An AC ESI sprayer entrains low‐mobility ions to accumulate at the meniscus cone tip prior to the ejection of detached aerosols to produce analyte ions. Therefore, as the solvent acidity varies, protein ions entrained in the AC cone tip are found to change conformation less significantly compared with those in the direct current (DC) cone. We acquired the AC ESI mass spectra of cytochrome c at pH range from 2 to 4. Unlike the DC ESI mass spectra showing clear conformation changes due to denaturing, the AC spectra indicated that only partial denaturing occurs even at extremely acidic pH 2. More native cytochrome c in lower charge states therefore remained. Moreover, with a solvent mixture of aqueous buffer and acetonitrile (70:30), partially denatured cytochrome c was still preserved at pH 2 by using AC ESI. Completely denatured proteins are observed at pH 2 by using DC ESI. [ABSTRACT FROM AUTHOR]

Acupuncture treatment in local areas is commonly used to treat pain or soreness; however, acupuncture around the neck or shoulder may be a risk factor for pneumothorax. Herein, we report two cases of iatrogenic pneumothorax after acupuncture. These points indicate that physicians should be aware of these risk factors through history-taking before acupuncture. Chronic pulmonary diseases, such as chronic bronchitis, emphysema, tuberculosis, lung cancer, pneumonia, and thoracic surgery, may be associated with a higher risk of iatrogenic pneumothorax after acupuncture. Even if the incidence of pneumothorax should be low under caution and fully evaluated, it is still recommended to arrange further imaging examinations to rule out the possibility of iatrogenic pneumothorax. [ABSTRACT FROM AUTHOR]

This paper aims to investigate the antecedents of how crowdfunded projects succeed over crowdsourcing platforms (CFPs) on the Internet. As CFPs make quite a large number of open innovations feasible, little is known about knowledge sharing and cross-project learning (CPL) in association with the success of crowdfunded projects. No study has considered the success of CFP projects in terms of gaining crowd capital with respect to generating ideas, achieving innovation or meeting the budget plan. However, the notion of project learning occurring on CFPs is essential. Therefore, this paper first adopted theories of project management and social exchange in one study. A developing region in the Asia-Pacific area is selected for examination as a case study. By doing so, it fills the gap in terms of the scarce research on this type of market, which is full of potential and possibilities. An empirical study was conducted on 43 project teams that had successfully won crowdsourcing projects. The results reveal that CPL in relation to project learning and esteem support in relation to social support are both positively associated with the success of crowd-funded projects. The discussion, implications and contributions of the study are presented at the end of the paper. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: In this report we investigated two‐dimensionally triptycene end‐capped QPPs in terms of their solution and solid‐state behavior. For this purpose, a triphenylene based ortho‐diamine decorated with two triptycenyl units as well as a phenylene diamine with two non‐annulated triptycene units have been synthesized. Sequences of condensation reactions with a pyrene‐based tetraketone and ortho‐diamines yielded a series of QPPs and UV/Vis investigations of the corresponding compounds led to the conclusion, that the QPPs form dimers in solution, which was further supported by MALDI‐TIMS‐TOF‐MS. Single‐crystal X‐ray analysis of the triply and quadruply triptycene end‐capped QPPs furthermore showed short π‐π‐distances of 3.3—3.4 Å and a perfect shape match during the dimerization of the triply triptycenyl end‐capped QPP making it possible synthon for crystal engineering. [ABSTRACT FROM AUTHOR]

We study the interplay of two ion-acoustic solitary waves (IASWs) with in a 2D hot ion plasma by using the method of the extended Poincaré-Lighthill-Kuo (PLK) perturbation, and obtain two Korteweg-de Vries (KdV) equations describing two solitary waves travling with the different directions. We demonstrate that the phase shifts and trajectories in the head-on collision of two solitary waves with different impingement angles. The results suggest that the plasma parameters can affect deeply the phase shifts in the collision of the solitary waves. [ABSTRACT FROM AUTHOR]

Objectives: A vast amount of literature has been conducted for investigating the association of different lunar phases with human health; and it has mixed reviews for association and non-association of diseases with lunar phases. This study investigates the existence of any impact of moon phases on humans by exploring the difference in the rate of outpatient visits and type of diseases that prevail in either non-moon or moon phases. Methods: We retrieved dates of non-moon and moon phases for eight years (1st January 2001-31st December 2008) from the timeanddate.com website for Taiwan. The study cohort consisted of 1 million people from Taiwan's National Health Insurance Research Database (NHIRD) followed over eight years (1st January 2001-31st December 2008). We used the two-tailed, paired-t-test to compare the significance of difference among outpatient visits for 1229 moon phase days and 1074 non-moon phase days by using International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes from NHIRD records. Results: We found 58 diseases that showed statistical differences in number of outpatient visits in the non-moon and moon phases. Conclusions: The results of our study identified diseases that have significant variations during different lunar phases (non-moon and moon phases) for outpatient visits in the hospital. In order to fully understand the reality of the pervasive myth of lunar effects on human health, behaviors and diseases, more in-depth research investigations are required for providing comprehensive evidence covering all the factors, such as biological, psychological and environmental aspects. [ABSTRACT FROM AUTHOR]

Electric vehicles (EVs) are proportionally increasing day-by-day with the inclusion of upgraded technology toward considered zero carbon emission efforts. To mitigate greenhouse gas emissions from the transportation sector, grid-to-vehicle (G2V) and vehicle-to-grid (V2G) technologies are getting significant attention nowadays. EVs equipped with modern technology can help to stabilize the power grids through load-balancing topology during peak hours. The improvement in EVs can support the surroundings in numerous ways, such as power grid voltage and frequency regulations, harmonics distortions, accessible solar energy implemented to the grids, and peak load stabilizations. This literature review analyzes G2V and V2G impacts in more depth, namely opportunities, improvements in strategies, operation, control, issues, and new technology adoptions. This paper emphasizes the possibilities of bringing advancements in EV technology, smooth operations between grids and EVs, fast bidirectional charging and discharging scopes, control of grids and EVs structures, issues, benefits, pitfalls, challenges, and recommendations. [ABSTRACT FROM AUTHOR]

Background: Salicylic Acid (SA) is a pivotal phytohormone in plant innate immunity enhancement of triggered by various pathogens, such as Candidatus Liberibacter asiaticus (CLas), the causal agent of Huanglongbing (HLB). WRKY is a plant specific transcription factor (TF) family, which plays crucial roles in plant response to biotic stresses. So far, the evolutionary history, functions, and expression patterns under SA treatment and CLas infection of WRKY family are poorly understood in Citrus, despite the release of the genome of several Citrus species. A comprehensive genomic and expressional analysis is worth to conduct for this family. Results: Here, a genome-wide identification of WRKY TFs was performed in two Citrus species: Citrus sinensis (HLB-sensitive) and Poncirus trifoliata (HLB-tolerant). In total, 52 CsWRKYs and 51 PtrWRKYs were identified, whose physical and chemical properties, chromosome locations, phylogenetic relationships and structural characteristics were comparatively analyzed. Especially, expression patterns of these WRKY genes before and after SA treatment and CLas infection were compared. Based on this result, seven pairs of orthologous WRKY genes showing opposite expression patterns in two Citrus species were screened out. Moreover, two pairs of orthologous WRKY genes with significant differences in the number or type of stress-responsive cis-elements in the promoter regions were discovered. Subcellular localization and transcriptional activation activity assays revealed that these two pairs of orthologous genes are classic WRKY TFs localize in the nucleus and could function as transcriptional activators. Conclusion: In this study, we systematically analyzed the genomic characterization of WRKY family in two Citrus species, together with the analyses of expression patterns under SA signaling and CLas infection. Our study laid a foundation for further study on the function of WRKY TFs in HLB response and SA signaling of Citrus. [ABSTRACT FROM AUTHOR]

Most ergot alkaloid drugs are semi-synthetically derived from the natural product lysergic acid, a valuable precursor for the development of novel ergot alkaloid drugs. Clavine oxidase (CloA) is a putative cytochrome P450, identified in the ergot alkaloid biosynthesis pathway, and a key enzyme that catalyzes the formation of lysergic acid from the precursor alkaloid agroclavine in a two-step oxidation reaction. We demonstrated in this study that Saccharomyces cerevisiae can be used as a viable host for the functional expression of CloA from Claviceps purpurea and its orthologs. We also showed that CloA orthologs differ in their ability to oxidize the substrate agroclavine, with some orthologs only able to perform the first oxidation reaction to produce elymoclavine. Of particular note, we identified a region between the F-G helices of the enzyme that may be involved in directing oxidation of agroclavine by substrate recognition and uptake. Using this knowledge, engineered CloAs were shown to produce lysergic acid at levels exceeding that of wildtype CloA orthologs; a CloA variant, chimeric AT5 9Hypo CloA, increased production levels of lysergic acid to 15 times higher as compared to the wildtype enzyme, demonstrating future utility for the industrial production of ergot alkaloids using biosynthetic routes. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic era that began in 2020, there has been a growing trend in the literature to tackle the problem of health stress (HS) for promoting a sense of public health. In turn, this developing area of research has a high level of relevancy linked to business and economic recovery (Čvirik, 2020). Since HS has increased sharply during the COVID-19 pandemic era, there has been a need to further investigate the balance between coping with HS and the positive continuous intention to use mobile health applications (mHealth apps) among the public. This is the first study that takes the Asia-Pacific region as its case study and empirically investigates the validity of extensions based on the theories of expectation confirmation theory (ECT) (Bhattacherjee, 2001) on user continuous behavior relating to mHealth apps during the COVID-19 pandemic. Results reveal that HS as an emotion can positively affect perceived usefulness and satisfaction in relation to the continuous intention to use mHealth apps. The differences between new and frequent users are confirmed. Discussion and implications for practices are provided in the end. [ABSTRACT FROM AUTHOR]

The Kelvin-Helmholtz (KH) waves have been frequently observed during the northward interplanetary magnetic field (IMF) but have been much less frequently observed during the southward IMF. Here, we performed a 3D MHD simulation of a KH wave to investigate the evolution of KH instability under the pure southward IMF condition. In the linear phase of KH instability, there are almost no jet flows along northward and southward. In the nonlinear growth phase, the width of the KH vortex is about ∼ 12 λ , and the duration time of the KH vortex is about ∼ 20 t A . Moreover, the obvious jet flows whose peak V z value is about ∼ 0.5 V A are distributed in both the spine region and the edge of the KH vortex. [ABSTRACT FROM AUTHOR]

The evolution of the Taiwan orogen, an active arc–continent collision zone between the North Luzon Arc (NLA) and the Eurasian continent, is recorded in arc volcanic and sedimentary rocks from the Taiyuan retro‐foredeep basin of the Coastal Range, eastern Taiwan. Arc volcanism in the northern NLA experienced a magmatic culmination at 9–7 Ma and a cessation at 5.3–4.3 Ma, based on new U‐Pb zircon ages. Young zircon U‐Pb ages (1.74, 1.58, and <1.2 Ma) and low Hf isotope signatures also indicate that three biotite‐bearing lapilli tuff layers deposited in the retro‐foredeep basin are associated with eruptions of the Lutao volcano in the southern NLA. NLA volcanism terminated progressively from ∼5.3 to <1.2 Ma in response to a southward‐propagating collision zone that followed the uplift of the orogenic wedge by <3 myr. The detrital zircon U‐Pb age spectra suggest no significant shift in provenance during the Plio‐Pleistocene period and indicate that the synorogenic sediments in the Taiyuan Basin were mainly derived from the Yuli Belt, a Miocene accretionary complex in the eastern Taiwan orogen. The accumulation rate of synorogenic deposits varies from 0.53 to 5.14 km/myr, with an abrupt increase at ∼2 Ma. This new rate is higher than the previously proposed rates and that of the pro‐foreland basin to the west, suggesting asymmetric and rapid uplift of the Taiwan orogen. Plain Language Summary: Taiwan was formed by the northwestward convergence of the North Luzon Arc (NLA) with the Eurasian continental margin. Most of the uppermost parts of the arc volcanoes and orogens have been intensely eroded; nevertheless, their detritus is well preserved in the Taiyuan Basin in the southern Coastal Range, eastern Taiwan. In this study, zircons separated from remnant arc volcanic and sedimentary sequences are dated by an in situ U‐Pb method to offer temporal constraints and provide insight into the arc‐continental collision evolution in Taiwan. The latest ages from the NLA volcanoes reveal a southward cessation of magmatism from ∼5.3 to <1.2 Ma, which is consistent with an oblique collision. Detritus from the Yuli Belt, a Miocene accretionary prism in the eastern Taiwan orogen, started to fill the Taiyuan Basin beginning at <4.3 Ma. Meanwhile, three embedded tuff layers dated at 1.74, 1.58, and <1.2 Ma indicate eruptions associated with Lutao, an offshore NLA volcanic islet, and suggest an abrupt increase in the deposition rate at ∼2 Ma, corresponding to rapid and extensive exhumation of the Taiwan orogen. Key Points: New zircon U‐Pb ages confirm the history of the volcanic arc and retro‐foredeep sediments and their linkages to the nearby Taiwan orogenThe previously proposed shift in clastic composition of the retro‐foredeep sediments is interpreted as an unroofing record of the Yuli BeltOur zircon ages confirm the abrupt increase in the deposition rate of retro‐foredeep basin infilling from 0.53 to 5.14 km/myr at ∼2 Ma [ABSTRACT FROM AUTHOR]

We present a general scheme for hierarchical controlled remote preparation of an arbitrary m-qudit state by using m four-qudit cluster states as the quantum channel. The sender first performs m-qudit positive operator-valued measurement in accordance with her knowledge of prepared state and then performs generalized X-basis measurements on her entangled particles. The upper-grade agent only needs perform unitary operation in accordance with one of the lower-grade agents’ measurement results for controlled remote preparation of an arbitrary m-qudit state. The lower-grade agent needs perform corresponding unitary operations in accordance with all the other agents’ measurement results. The protocol has the advantage of transmitting less entangled particles for hierarchical controlled remote preparation of an arbitrary m-qudit state via four-qudit cluster states. [ABSTRACT FROM AUTHOR]

We report enzymes from the berberine bridge enzyme (BBE) superfamily that catalyze the oxidative cyclization of the monoterpene moiety in cannabigerolic acid (CBGA) to form cannabielsoin (CBE). The enzymes are from a variety of organisms and are previously uncharacterized. Out of 232 homologues chosen from the enzyme superfamily, four orthologues were shown to accept CBGA as a substrate and catalyze the biosynthesis of CBE. The four enzymes discovered in this study were recombinantly expressed and purified in Pichia pastoris. These enzymes are the first report of heterologous expression of BBEs that did not originate from the Cannabis plant that catalyze the production of cannabinoids using CBGA as substrate. This study details a new avenue for discovering and producing natural and unnatural cannabinoids. [ABSTRACT FROM AUTHOR]