Association between serum total bilirubin with Parkinson's disease among American adults (NHANES 1999 to 2018).

Background: Currently, the existing evidence on the correlation between serum total bilirubin (STB) and Parkinson's disease (PD) is insufficient. The objective of this study was to clarify the relationship between STB levels and PD within the US (United States) population. Methods: A cross-sectional analysis was conducted using data from 25,637 participants in the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted logistic regression, smooth curve fitting, subgroup analysis, and sensitivity analyses were employed to validate the research objectives. Results: Among all eligible subjects, the mean age was 57.11 ± 11.78 years. The prevalence of PD was 1.18 % overall, with 47.86 % in males. After adjusting for multiple variables, the odds ratio [OR] (95 % confidence interval [CI]) for PD associated with STB levels in T2 and T3 were 0.59 (95 % CI = 0.40-0.85, p = 0.006) and 0.67 (95 % CI = 0.45-0.99, p = 0.045), respectively, when compared to STB levels in T1. The analysis using restricted cubic splines (RCS) indicated an L-shaped relationship between STB levels and the prevalence of PD (p for nonlinearity = 0.004), with the lowest risk observed at 10.84 µmol/L. Comparable patterns of association were noted in subgroup analyses. Furthermore, consistent findings were derived from additional sensitivity analyses. Conclusions: Our study findings indicated that the level of STB is significantly negatively correlated with the prevalence of PD. Therefore, more prospective studies need to be designed to prove the causal relationship between them.

Synthesis of C-N bonds by nicotinamide-dependent oxidoreductase: an overview.

Compounds containing chiral C-N bonds play a vital role in the composition of biologically active natural products and small pharmaceutical molecules. Therefore, the development of efficient and convenient methods for synthesizing compounds containing chiral C-N bonds is a crucial area of research. Nicotinamide-dependent oxidoreductases (NDOs) emerge as promising biocatalysts for asymmetric synthesis of chiral C-N bonds due to their mild reaction conditions, exceptional stereoselectivity, high atom economy, and environmentally friendly nature. This review aims to present the structural characteristics and catalytic mechanisms of various NDOs, including imine reductases/ketimine reductases, reductive aminases, EneIRED, and amino acid dehydrogenases. Additionally, the review highlights protein engineering strategies employed to modify the stereoselectivity, substrate specificity, and cofactor preference of NDOs. Furthermore, the applications of NDOs in synthesizing essential medicinal chemicals, such as noncanonical amino acids and chiral amine compounds, are extensively examined. Finally, the review outlines future perspectives by addressing challenges and discussing the potential of utilizing NDOs to establish efficient biosynthesis platforms for C-N bond synthesis. In conclusion, NDOs provide an economical, efficient, and environmentally friendly toolbox for asymmetric synthesis of C-N bonds, thus contributing significantly to the field of pharmaceutical chemical development.

Nanoporous Polystyrene Inverse Opal Materials with Optical Interference Properties for Label-Free Biosensing.

Colloidal crystal nanomaterials have been proven to be valuable substrates for optical-based biosensing due to their ordered macroporous nanostructure and brilliant optical properties. In this work, silica colloidal crystal (SCC) thin films, as well as polystyrene-SCC composite films and inverse opal (IO) polystyrene films fabricated using SCC as templates, are investigated for their application as substrate materials in optical interferometric biosensors. The SCC films formed by the self-assembly of silica colloidal crystals have the most densely packed nano-3D structure, also known as the opal structure. IO films are fabricated by filling the opal pores of SCC with polystyrene and then removing the template, resulting in an interconnected nano-3D ordered macroporous structure, as indicated by the name inverse opal. The performance of the three materials was compared and discussed based on an ordered porous layer interferometry optical platform, focusing on refractive index response, protein adsorption response, and biomolecular interaction response. These results could potentially offer innovative material support for the advancement of label-free optical biosensors, which can be used for more biological/biochemical/biomolecular reaction monitoring studies.

Josephson Diode Effect in Parallel-Coupled Double-Quantum Dots Connected to Unalike Majorana Nanowires.

We study theoretically the Josephson diode effect (JDE) when realized in a system composed of parallel-coupled double-quantum dots (DQDs) sandwiched between two semiconductor nanowires deposited on an s-wave superconductor surface. Due to the combined effects of proximity-induced superconductivity, strong Rashba spin-orbit interaction, and the Zeeman splitting inside the nanowires, a pair of Majorana bound states (MBSs) may possibly emerge at opposite ends of each nanowire. Different phase factors arising from the superconductor substrate can be generated in the coupling amplitudes between the DQDs and MBSs prepared at the left and right nanowires, and this will result in the Josephson current. We find that the critical Josephson currents in positive and negative directions are different from each other in amplitude within an oscillation period with respect to the magnetic flux penetrating through the system, a phenomenon known as the JDE. It arises from the quantum interference effect in this double-path device, and it can hardly occur in the system of one QD coupled to MBSs. Our results also show that the diode efficiency can reach up to 50%, but this depends on the overlap amplitude between the MBSs, as well as the energy levels of the DQDs adjustable by gate voltages. The present model is realizable within current nanofabrication technologies and may find practical use in the interdisciplinary field of Majorana and Josephson physics.

Macrophage membrane-based biomimetic nanocarrier system for enhanced immune activation and combination therapy in liver cancer.

Previous studies have demonstrated that the combination of photodynamic therapy, photothermal therapy and chemotherapy is highly effective in treating hepatocellular carcinoma (HCC). However, the clinical application of this approach has been hindered by the lack of efficient and low-toxicity drug delivery platforms. To address this issue, we developed a novel biomimetic nanocarrier platform named ZID@RM, which utilizes ZIF8 functional nanoparticles encapsulated with macrophage membrane and loaded with indocyanine green and doxorubicin. The bionic nanocarrier platform has good biocompatibility, reducing the risk of rapid clearance by macrophages and improving the targeting ability for HCC cells. Under the dual regulation of acidity and infrared light, ZID@RM stimulated the generation of abundant reactive oxygen species within HCC cells, induced tumor cell pyroptosis and promoted the release of damage-associated molecular patterns to induce immune responses. In the future, this technology platform has the potential to provide personalized and improved healthcare by using patients' own macrophage membranes to create an efficient drug delivery system for tumor therapy.Graphical abstract Scheme 1 Schematic representation of the synthesis of a biomimetic nanomedicine delivery platform (ZID@RM) and its application in tumor imaging-guided combination therapy.

Development of a Methodology Based on Optical Interferometry for Measuring Fibrinolytic Activity.

Fibrinolytic activity assay is particularly important for the detection, diagnosis, and treatment of cardiovascular disease and the development of fibrinolytic drugs. A novel efficacious strategy for real-time and label-free dynamic detection of fibrinolytic activity based on ordered porous layer interferometry (OPLI) was developed. Fibrin or a mixture of fibrin and plasminogen (Plg) was loaded into the highly ordered silica colloidal crystal (SCC) film scaffold to construct a fibrinolytic response interference layer to measure fibrinolytic activity with different mechanisms of action. Fibrinolytic enzyme-triggered fibrinolysis led to the migration of interference fringes in the interferogram, which could be represented by optical thickness changes (ΔOT) tracked in real time by the OPLI system. The morphology and optical property of the fibrinolytic response interference layer were characterized, and the Plg content in the fibrinolytic response interference layer and experimental parameters of the system were optimized. The method showed adequate sensitivity for the fibrinolytic activity of lumbrokinase and streptokinase, with wide linear ranges of 12-6000 and 10-2000 U/mL, respectively. Compared with the traditional fibrin plate method, it has a lower detection limit and higher linearity. The whole kinetic process of fibrinolysis by these two fibrinolytic drug models was recorded in real time, and the Michaelis constant and apparent kinetic parameters were calculated. Importantly, some other blood proteins were less interfering with this system, and it showed reliability in fibrin activity detection in real whole blood samples. This study established a better and more targeted research method of in vitro fibrinolysis and provided dynamic monitoring data for the analysis of fibrinolytic activity of whole blood.

Network pharmacology and molecular docking reveal potential mechanisms of ginseng in the treatment of diabetes mellitus-induced erectile dysfunction and asthenospermia.

Diabetes mellitus (DM) is a chronic metabolic disease that predisposes to chronic damage and dysfunction of various organs, including leading to erectile dysfunction (ED) and asthenospermia. Literature suggests that ginseng plays an important role in the treatment and management of DM. Ginseng may have a therapeutic effect on the complications of DM-induced ED and asthenospermia. The study aimed to explore the mechanisms of ginseng in the treatment of DM-induced ED and asthenospermia following the Traditional Chinese Medicine (TCM) theory of "treating different diseases with the same treatment." This study used network pharmacology and molecular docking to examine the potential targets and pharmacological mechanism of Ginseng for the treatment of DM-induced ED and asthenospermia. The chemical ingredients and targets of ginseng were acquired using the Traditional Chinese Medicine Systems Pharmacology database and analysis platform. The targets of DM, ED, and asthenospermia were extracted with the GeneCards and Online Mendelian Inheritance in Man databases. A protein-protein interaction network analysis was constructed. The Metascape platform was applied for analyzing the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways. AutoDock Vina was used to perform molecular docking. Network pharmacology revealed that the main active components of the target of action were kaempferol, beta-sitosterol, ginsenoside rh2, stigmasterol, and fumarine. Core targets of the protein-protein interaction network included TNF, IL-1ß, AKT1, PTGS2, BCL2, and JUN. Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that they were mainly involved in AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, Lipid and atherosclerosis. The interactions of core active components and targets were analyzed by molecular docking. Ginseng may play a comprehensive therapeutic role in the treatment of DM-induced ED and asthenospermia through "multicomponent, multi-target, and multi-pathway" biological mechanisms such as inflammation and oxidative stress.

[Metabolic engineering of Klebsiella pneumoniae for 1, 3-propanediol production].

1, 3-propanediol is an important monomer for the production of polytrimethylene terephthalate (PTT). Currently, it is mainly produced by microbial fermentation, which, however, has low production efficiency. To address this problem, this study employed atmospheric room temperature plasma (ARTP) mutagenesis technology and high-throughput screening to obtain a strain with high tolerance to osmotic pressure, which achieved a 1, 3-propanediol titer of 87 g/L. Furthermore, the gene expression elements suitable for Klebsiella pneumoniae were screened, and metabolic engineering was employed to block redundant metabolic pathways (deletion of ldhA, budA, and aldA) and enhance the synthesis pathway (overexpression of dhaB and yqhD). The titer of 1, 3-propanediol produced by the engineered strain increased to 107 g/L. Finally, in a 5 L fermenter, the optimal strain KP-FMME-6 achieved a 1, 3-propanediol titer of 118 g/L, with a glycerol conversion rate of 42% and productivity of 2.46 g/(h·L), after optimization of the fermentation parameters. This study provides a reference for the industrial production of 1, 3-propanediol.

[Preface for special issue on Microbial Chemical Factories].

Microbial chemical factories utilize engineering design principles to re-build natural production pathways, enabling the precise, quantitative, and efficient synthesis of chemicals. This is achieved through the optimization of synthetic pathways, the reconstruction of biochemical networks, the development of novel components, and the integration of pathways with cellular and environmental contexts. As a transformative approach to chemical production, microbial chemical factories play a critical role in establishing renewable raw material pathways for industrial economic development and advancing sustainable growth. This innovative model has become a strategic priority for technological advancement and industrial competitiveness in developed nations. This industry has expanded into diverse sectors, including pharmaceuticals, food production, chemicals, and energy. To showcase the most recent scientific advancements in the field of microbial chemical production and to promote the evolution of the bio-manufacturing industry, we organized a special issue entitled "Microbial Chemical Factories". This edition features the latest research conducted by domestic scientists, focusing on areas such as the synthesis of material monomers, pharmaceutical intermediates, functional food ingredients, organic acid biosynthesis, and the development and utilization of non-food feedstock. It provides reference and guidance for the further development of microbial chemical factories.

[Metabolic engineering of Escherichia coli for the production of cadaverine].

Cadaverine is a fundamental C5 building block in the production of polyamides. Due to the limited regeneration efficiency of intracellular pyridoxal 5'-phosphate (PLP), the current fermentation-based production of cadaverine exhibits low efficiency. In this study, we developed an Escherichia coli strain L01 by introducing lysine decarboxylase (lysine decarboxylase, LDC, a key enzyme in the synthesis of cadaverine) into a lysine-producing strain E. coli LY-4, achieving a cadaverine tier of 1.07 g/L in shake flask fermentation. Subsequently, a dual metabolic pathway enhancement strategy was proposed to synergistically strengthen both endogenous and exogenous PLP synthesis modules, thereby improving intracellular PLP synthesis. The optimized strain L11 achieved a cadaverine titer of 9.23 g/L in shake flask fermentation. Finally, the fermentation process for cadaverine production by strain L11 was optimized in a 5 L fermenter. After 48 h of fed-batch fermentation, the engineered strain L11 achieved the cadaverine titer, yield, and productivity of 54.43 g/L, 0.22 g/g, and 1.13 g/(L·h), respectively. This study provides a theoretical and technical foundation for establishing microbial cell factories for bioamine production.

[Metabolic engineering of the substrate utilization pathway in Escherichia coli increases L-lysine production].

L-lysine is an essential amino acid with broad applications in the animal feed, human food, and pharmaceutical industries. The fermentation production of L-lysine by Escherichia coli has limitations such as poor substrate utilization efficiency and low saccharide conversion rates. We deleted the global regulatory factor gene mlc and introduced heterologous genes, including the maltose phosphotransferase genes (malAP) from Bacillus subtilis, to enhance the use efficiency of disaccharides and trisaccharides. The engineered strain E. coli XC3 demonstrated improved L-lysine production, yield, and productivity, which reached 160.00 g/L, 63.78%, and 4.44 g/(L‧h), respectively. Furthermore, we overexpressed the glutamate dehydrogenase gene (gdhA) and assimilated nitrate reductase genes (BsnasBC) from B. subtilis, along with nitrite reductase genes (EcnirBD) from E. coli, in strain E. coli XC3. This allowed the construction of E. coli XC4 with a nitrate assimilation pathway. The L-lysine production, yield, and productivity of E. coli XC4 were elevated to 188.00 g/L, 69.44%, and 5.22 g/(L‧h), respectively. After optimization of the residual sugar concentration and carbon to nitrogen ratio, the L-lysine production, yield, and productivity were increased to 204.00 g/L, 72.32%, and 5.67 g/(L‧h), respectively, in a 5 L fermenter. These values represented the increases of 40.69%, 20.03%, and 40.69%, respectively, compared with those of the starting strain XC1. By engineering the substrate utilization pathway, we successfully constructed a high-yield L-lysine producing strain, laying a solid foundation for the industrial production of L-lysine.

[A dual-enzyme cascade for production of indigo from L-tryptophan].

Indigo, as a water-soluble non-azo colorant, is widely used in textile, food, pharmaceutical and other industrial fields. Currently, indigo is primarily synthesized by chemical methods, which causes environmental pollution, potential safety hazards, and other issues. Therefore, there is an urgent need to find a safer and greener synthetic method. In this study, a dual-enzyme cascade pathway was constructed with the tryptophan synthase (tryptophanase, EcTnaA) from Escherichia coli and flavin-dependent monooxygenase (flavin-dependent monooxygenase, MaFMO) from Methylophaga aminisulfidivorans to synthesize indigo with L-tryptophan as substrate. A recombinant strain EM-IND01 was obtained. The beneficial mutant MaFMOD197E was obtained by protein engineering of the rate-limiting enzyme MaFMO. MaFMOD197E showed the specific activity and kcat/Km value 2.36 times and 1.34 times higher than that of the wild type, respectively. Furthermore, MaFMOD197E was introduced into the strain EM-IND01 to construct the strain EM-IND02. After the fermentation conditions were optimized, the strain achieved the indigo titer of (1 288.59±7.50) mg/L, the yield of 0.86 mg/mg L-tryptophan, and the productivity of 26.85 mg/(L·h) in a 5 L fermenter. Protein engineering was used to obtain mutants with increased MaFMO activity in this study, which laid a foundation for industrial production of indigo.

Construction of scalable multi-channel DNA nanoplatform for the combined detection of ctDNA biomarkers of ovarian cancer.

Single-level biomarker detection has the limitation of insufficient accuracy in cancer diagnosis. Therefore, the strategy of developing highly sensitive, multi-channel biosensors for high-throughput ctDNA determination is critical to improve the accuracy of early diagnosis of clinical tumors. Herein, in order to achieve efficient detection of up to ten targets for early diagnosis of ovarian cancer, a DNA-nanoswitch-based multi-channel (DNA-NSMC) biosensor was built based on the multi-module catalytic hairpin assembly-mediated signal amplification (CHA) and toehold-mediated DNA strand displacement (TDSD) reaction. Only two different fluorescence signals were used as outputs, combined with modular segmentation strategy of DNA-nanoswitch-based reaction platform; the multi-channel detection of up to ten targets was successfully achieved for the first time. The experimental results suggest that the proposed biosensor is a promising tool for simultaneously detecting multiple biomarkers for the early diagnosis of ovarian cancer, offering new strategies for the early screening, diagnosis, and treatment not only for ovarian cancer but also for other cancers.

Real-time monitoring of peptic and tryptic digestions of immunoglobulin G and the impact of dietary hydrocolloids on digestion.

Immunoglobulin G (IgG) exhibits potent antiviral, antibacterial, and immunological activities. The digestion process and bioavailability of IgG are often a concern. Dietary hydrocolloids are crucial for regulating healthy digestion and the bioavailability of protein as functional components. Understanding the effects of dietary hydrocolloids on the digestive kinetics of IgG is requisite. Herein, the pepsin and trypsin digestion of IgG was investigated using ordered porous layer interferometry (OPLI). The real-time variation in the interference spectral shift reflected by OPLI can be converted into changes in the optical thickness (OT) to obtain a degradation kinetics curve. The impact of dietary hydrocolloids, including alginic acid sodium salt (ALG), polydextrose (PD), and konjac glucomannan (KG), on IgG degradation was evaluated using OPLI. The results demonstrated that ALG significantly inhibited the degradation of IgG by pepsin under acidic conditions, whereas the addition of PD increased the Michaelis-Menten constant for IgG degradation by trypsin. Notably, this dependence is not based on the hydrocolloid viscosity, but relies more on the electrical properties. The study enhances our understanding of how hydrocolloids affect IgG digestion and could provide valuable insights into preserving IgG activity and facilitating the development of oral drugs or health products related to IgG.

Ultrahigh humidity-resistance ppb-level formaldehyde sensing at room temperature induced by fluorinated dipole based "umbrella" and "bridge".

Formaldehyde (HCHO) is a major indoor pollutant that is extremely harmful to human health even at ppb-level. Meanwhile, ppb-level HCHO is also a potential disease marker in the exhalation of patients with respiratory diseases. Higher humidity resistance and lower practical limit of detection (pLOD) both have to be pursued for practical HCHO sensors. In this work, by assembling indium oxide (In2O3) and fluorinated dipole modified reduced graphene oxide (rGO), we prepared a high-performance room temperature HCHO sensor (In2O3 @ATQ-rGO). Excellent sensing properties toward HCHO under visible illumination have been achieved, including ultra-low pLOD of 3 ppb and high humidity-resistance. By control experiments and density functional theory calculation, it is indicated that the introduced fluorinated dipoles act as not only an "umbrella" to improve the humidity resistance of the composite, but also a "bridge" to accelerate the electron transport, improving the sensitivity of the material. The significant practicality and reliability of the obtained sensors were verified by in-situ simulation experiments using a 3 m3 test chamber with a humidity control system and by detection of the simulated lung disease patient's exhalation. This work provides an effective strategy of simultaneously achieving high humidity-resistance and low pLOD of room temperature formaldehyde sensing materials.

Whole-genome sequencing of multidrug-resistant Klebsiella pneumoniae with capsular serotype K2 isolates from mink in China.

BACKGROUND: Klebsiella pneumoniae is a zoonotic opportunistic pathogen, and also one of the common pathogenic bacteria causing mink pneumonia. The aim of this study was to get a better understanding of the whole-genome of multi-drug resistant Klebsiella pneumoniae with K2 serotype in China. This study for the first time to analyze Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, resistance and virulence genes of Klebsiella pneumoniae in mink. RESULTS: The isolate was Klebsiella pneumoniae with serotype K2 and ST6189 by PCR method. The string test was positive and showed high mucus phenotype. There was one plasmid with IncFIB replicons in the genome. The virulence factors including capsule, lipopolysaccharide, adhesin, iron uptake system, urease, secretory system, regulatory gene (rcsA, rcsB), determinants of pili adhesion, enolase and magnesium ion absorption related genes. The strain was multi-drug resistant. A total of 26  resistance genes, including beta-lactam, aminoglycosides, tetracycline, fluoroquinolones, sulfonamides, amide alcohols, macrolides, rifampicin, fosfomycin, vancomycin, diaminopyrimidines and polymyxin. Multidrug-resistant efflux protein AcrA, AcrB, TolC, were predicted in the strain. CONCLUSION: It was the first to identify that serotype K2 K. pneumonia with ST6189 isolated from mink in China. The finding indicated that hypervirulent and multi-drug resistant K. pneumoniae was exist in Chinese mink. The whole-genome of K. pneumoniae isolates have importance in mink farming practice.

Protein nanoparticles induce the activation of voltage-dependent non-selective ion channels to modulate biological osmotic pressure in cytotoxic cerebral edema.

Introduction: Cytotoxic cerebral edema is a serious complication associated with cerebral ischemic stroke and is widely treated using the hypertonic dehydrant. Here, we propose, for the first time, the decrease of intracellular osmosis as a treatment strategy for alleviating cytotoxic cerebral edema. Methods: We established a fluorescence resonance energy transfer-based intermediate filament tension probe for the study and in situ evaluation of osmotic gradients, which were examined in real-time in living cells from primary cultures as well as cell lines. The MCAO rat model was used to confirm our therapy of cerebral edema. Results: Depolymerization of microfilaments/microtubules and the production of NLRP3 inflammasome resulted in an abundance of protein nanoparticles (PNs) in the glutamate-induced swelling of astrocytes. PNs induced changes in membrane potential and intracellular second messengers, thereby contributing to hyper-osmosis and the resultant astrocyte swelling via the activation of voltage-dependent nonselective ion channels. Therefore, multiple inhibitors of PNs, sodium and chloride ion channels were screened as compound combinations, based on a decrease in cell osmosis and astrocyte swelling, which was followed by further confirmation of the effectiveness of the compound combination against alleviated cerebral edema after ischemia. Discussion: The present study proposes new pathological mechanisms underlying "electrophysiology-biochemical signal-osmotic tension," which are responsible for cascade regulation in cerebral edema. It also explores various compound combinations as a potential treatment strategy for cerebral edema, which act by multi-targeting intracellular PNs and voltage-dependent nonselective ion flux to reduce astrocyte osmosis.

First Genomic Evidence of California Hare Coltivirus from Natural Populations of Ixodes persulcatus Ticks in Northeast China.

Background: California hare coltivirus (CHCV) was isolated in California in 1976 from a hare. Despite its long history, it remained unclear whether CHCV was exclusively distributed in California with limited host ranges. Main body: By next-generation sequencing (NGS), we obtained a complete sequence of CHCV from Ixodes persulcatus collected in 2019 in northeast China. An expanded epidemiological investigation was subsequently performed on ticks belonging to four species (Ix. persulcatus, Haemaphysalis concinna, Devmacentor silvarum, Haemaphysalis longicornis) collected in northeastern China by applying CHCV-specific RT-PCR and sequencing. CHCV RNA-positive results were found in 1.56% of the tick samples. Positive ticks were obtained in three of four sampled locations, with the highest rate observed in Inner Mongolia (2.69%), followed by Heilongjiang (1.94%) and Jilin provinces (0.55%). All positive results were derived from Ix. persulcatus ticks (2.33%), while no positive detection was found in the other tick species, even at the same location. Sequence analysis revealed that the current CHCV showed a high genetic identity (>80% amino acid identity) with the previously reported CHCV in all segments except segment seven (64.59% amino acid identity). Phylogenetic analysis based on RNA-dependent RNA polymerase (RdRp) amino acid sequences demonstrated that both the current and previously reported CHCV strains were grouped phylogenetically into the genus Coltivirus. Both CHCV strains formed a distinct clade, clustering with three human pathogenic coltiviruses (Colorado tick fever virus, Salmon River virus, and Eyach virus), and were distant from the other coltiviruses. Conclusions: We report the identification and characterization of CHCV for the first time in Ix. persulcatus ticks, expanding the currently known geographic scope, host, and genetic heterogeneity in CHCV.

Unlocking the function promiscuity of old yellow enzyme to catalyze asymmetric Morita-Baylis-Hillman reaction.

Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly for catalyzing challenging reactions in non-native contexts. In this study, we explore the promiscuous potential of old yellow enzymes (OYEs) to facilitate the Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH reaction and reduction reaction. Using mass spectrometry and spectroscopic techniques, we confirm promiscuity of GkOYE in both MBH and reduction reactions. By blocking H- and H+ transfer pathways, we engineer GkOYE.8, which loses its reduction ability but enhances its MBH activity. The structural basis of MBH reaction catalyzed by GkOYE.8 is obtained through mutation studies and kinetic simulations. Furthermore, enantiocomplementary mutants GkOYE.11 and GkOYE.13 are obtained by directed evolution, exhibiting the ability to accept various aromatic aldehydes and alkenes as substrates. This study demonstrates the potential of leveraging substrate similarities to unlock enzyme functionalities, enabling the catalysis of new-to-nature reactions.

Quantum Transport through a Quantum Dot Coupled to Majorana Nanowire and Two Ferromagnets with Noncollinear Magnetizations.

We study the electron tunneling (ET) and local Andreev reflection (AR) processes in a quantum dot (QD) coupled to the left and right ferromagnetic leads with noncollinear ferromagnetisms. In particular, we consider that the QD is also side-coupled to a nanowire hosting Majorana bound states (MBSs) at its ends. Our results show that when one mode of the MBSs is coupled simultaneously to both spin-up and spin-down electrons on the QD, the height of the central peak is different from that if the MBS is coupled to only one spin component electrons. The ET and AR conductances, which are mediated by the dot-MBS hybridization, strongly depend on the angle between the left and right magnetic moments in the leads. Interaction between the QD and the MBSs will result in sign change of the angle-dependent tunnel magnetoresistance. This is very different from the case when the QD is coupled to regular fermonic mode, and can be used for detecting the existence of MBSs, a current challenge in condensed matter physics under extensive investigations.