Decreased brain iron deposition based on quantitative susceptibility mapping correlates with reduced neurodevelopmental status in children with autism spectrum disorder.

To investigate potential correlations between the susceptibility values of certain brain regions and the severity of disease or neurodevelopmental status in children with autism spectrum disorder (ASD), 18 ASD children and 15 healthy controls (HCs) were recruited. The neurodevelopmental status was assessed by the Gesell Developmental Schedules (GDS) and the severity of the disease was evaluated by the Autism Behavior Checklist (ABC). Eleven brain regions were selected as regions of interest and the susceptibility values were measured by quantitative susceptibility mapping. To evaluate the diagnostic capacity of susceptibility values in distinguishing ASD and HC, the receiver operating characteristic (ROC) curve was computed. Pearson and Spearman partial correlation analysis were used to depict the correlations between the susceptibility values, the ABC scores, and the GDS scores in the ASD group. ROC curves showed that the susceptibility values of the left and right frontal white matter had a larger area under the curve in the ASD group. The susceptibility value of the right globus pallidus was positively correlated with the GDS-fine motor scale score. These findings indicated that the susceptibility value of the right globus pallidus might be a viable imaging biomarker for evaluating the neurodevelopmental status of ASD children.

LiGa(IO3 )4 : An Excellent NLO Material with Unprecedented 2D [Ga(IO3 )4 ]∞ - Layer Synthesized by Aliovalent Substitution.

Nonlinear optical (NLO) crystals are indispensable for the solid-state lasers for their ability to expand wavelength spectral to the regions where the directing lasing is difficult or even impossible, yet the rational design of a high-performance NLO crystal remains a great challenge owing to the severe structural and properties' requirements. Herein, a new noncentrosymmetric (NCS) and polar gallium iodate, LiGa(IO3 )4 , with a novel 2D anionic layer, is successfully designed and synthesized by the aliovalent substitution strategy based on classic α-LiIO3 . The 2D [Ga(IO3 )4 ]∞ - layer in LiGa(IO3 )4 is built from the GaO6 octahedra and highly polarizable units IO3 . Compared with its parent compound, the partial replacement of A-site Li+ cation with main group Ga3+ cation facilitates LiGa(IO3 )4 to possess excellent NLO properties, including the large second-harmonic generation (SHG) response (14 × KH2 PO4 (KDP) @ 1064 nm), wide bandgap (4.25 eV), large birefringence (0.23 @ 1064 nm), and wide optical transparency from UV to mid-IR. These reveal that LiGa(IO3 )4 will be a promising NLO crystal.

Immune-related lncRNAs signature and radiomics signature predict the prognosis and immune microenvironment of glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults. This study aimed to construct immune-related long non-coding RNAs (lncRNAs) signature and radiomics signature to probe the prognosis and immune infiltration of GBM patients. METHODS: We downloaded GBM RNA-seq data and clinical information from The Cancer Genome Atlas (TCGA) project database, and MRI data were obtained from The Cancer Imaging Archive (TCIA). Then, we conducted a cox regression analysis to establish the immune-related lncRNAs signature and radiomics signature. Afterward, we employed a gene set enrichment analysis (GSEA) to explore the biological processes and pathways. Besides, we used CIBERSORT to estimate the abundance of tumor-infiltrating immune cells (TIICs). Furthermore, we investigated the relationship between the immune-related lncRNAs signature, radiomics signature and immune checkpoint genes. Finally, we constructed a multifactors prognostic model and compared it with the clinical prognostic model. RESULTS: We identified four immune-related lncRNAs and two radiomics features, which show the ability to stratify patients into high-risk and low-risk groups with significantly different survival rates. The risk score curves and Kaplan-Meier curves confirmed that the immune-related lncRNAs signature and radiomics signature were a novel independent prognostic factor in GBM patients. The GSEA suggested that the immune-related lncRNAs signature were involved in L1 cell adhesion molecular (L1CAM) interactions and the radiomics signature were involved signaling by Robo receptors. Besides, the two signatures was associated with the infiltration of immune cells. Furthermore, they were linked with the expression of critical immune genes and could predict immunotherapy's clinical response. Finally, the area under the curve (AUC) (0.890,0.887) and C-index (0.737,0.817) of the multifactors prognostic model were greater than those of the clinical prognostic model in both the training and validation sets, indicated significantly improved discrimination. CONCLUSIONS: We identified the immune-related lncRNAs signature and tradiomics signature that can predict the outcomes, immune cell infiltration, and immunotherapy response in patients with GBM.

Rational design of transaminases based on comparative analysis of catalytically active and distance-free modes of the high-energy intermediate state.

Bioproduction of chiral amines is limited by low transaminase (TA) activity on nonnatural substrates, leading to the need for protein engineering. To address the challenge of quickly and precisely identifying the engineering targets, a strategy was proposed based on analyzing the mode changes in the high-energy intermediate state (H-state) of the substrate-enzyme complex during catalysis. By substituting the residues with minimal structural changes in catalytically active mode (A-mode) and distance-free mode (F-mode) of the H-state complex with more conserved ones to stabilize it, a TA mutant M5(T295C/L387A/V436A) with 121.9-fold higher activity for synthesizing the (S)-Rivastigmine precursor (S)-1-(3-methoxyphenyl)ethylamine was created. The applicability of this strategy was also validated by engineering another TA for 1.52-fold higher activity and >99% selectivity toward (R)-3-amino-1-butanol biopreparation. The much higher stereoselectivity of the mutant compared with the wild type (28.3%) demonstrated that this strategy is not only advantageous in engineering enzyme activity but also applicable for modulating stereoselectivity.

From NaGa(IO3)3F to NaGa(IO3)2F2 and NaGa(IO3)4: The Effects of Chemical Substitution between F- Anions and IO3- Groups on the Structures and Properties of Gallium Iodates.

Introducing F- anions or substituting F- anions with IO3- groups has been proven to be ideal strategies for designing novel noncentrosymmetric (NCS) and polar materials, yet systematic investigation into the effect of F- anions or the substitution of IO3- for F- anions on structures and properties remains rarely explored. Herein, two new gallium iodates, NaGa(IO3)2F2 (1) and NaGa(IO3)4 (2), were successfully designed and synthesized based on NaGa(IO3)3F by introducing more F- anions and replacing F- anions with IO3 groups, respectively. Structurally, in compound 1, the adjacent [GaF3(IO3)3]3- polyanions are connected in an antiparallel manner, resulting in a complete cancellation of local polarity. While in compound 2, all IO3 groups in 2D [Ga(IO3)4]∞- layers are aligned, leading to large macroscopic polarization. Additionally, chemical substitution also results in a qualitative improvement in the functional properties of compound 2. It possesses strong SHG response (12 × KDP @1064 nm) and broad optical transparency, coupled with large birefringence (0.21 @1064 nm), showcasing its promise as a promising nonlinear optical (NLO) crystal. The effects of chemical substitution between F- anions and IO3- groups on the structures and properties are discussed in detail.

Pb3[O10Pb20](SiO4)4X10 (X = Cl, Br): The First Pb-Containing Halogen Silicates with Mirror-Symmetric Pseudo-Aurivillius Bilayers.

Two new congruently melting Pb-containing halogen silicates, Pb3[O10Pb20](SiO4)4X10 (X = Cl, Br), have been synthesized using a high-temperature solution method. Their crystal structures were determined by single-crystal X-ray diffraction, and both compounds crystallize in the orthorhombic space group Cmca. In both structures, the mirror-symmetric bilayer composed of Pb-O polyhedra is observed for the first time in Pb-containing silicates and belongs to α-PbO derivatives and is related to the Aurivillius phase. Thermal behavior analysis, UV-vis diffuse-reflectance spectroscopy, and IR spectroscopy were also performed. The Pb3[O10Pb20](SiO4)4Cl10 matrix was doped with Eu3+ ions as a dopant, and its potential application in fluorescence was confirmed from the resulting orange-red emission.

Can "Risk-Sharing" Mechanisms Help Clonal Aquatic Plants Mitigate the Stress of Nanoplastics?

Most aquatic plants applied to ecological restoration have demonstrated a clonal growth pattern. The risk-spreading strategy plays a crucial role in facilitating clonal plant growth under external environmental stresses via clonal integration. However, the effects of different concentrations of nanoplastics (NPs) on the growth traits of clonal aquatic plants are not well understood. Therefore, this study aimed to investigate the impact of NPs exposure on seedlings of parent plants and connected offspring ramets. A dose response experiment (0.1, 1, and 10 mg L-1) showed that the growth of Eichhornia crassipes (water hyacinth) was affected by 100 nm polystyrene nanoplastics after 28 days of exposure. Tracer analysis revealed that NPs are accumulated by parent plants and transferred to offspring ramets through stolon. Quantification analysis showed that when the parent plant was exposed to 10 mg L-1 NPs alone for 28 days, the offspring ramets contained approximately 13 ± 2 µg/g NPs. In the case of connected offspring ramets, leaf and root biomass decreased by 24%-51% and 32%-51%, respectively, when exposed to NP concentrations ranging from 0.1 to 10 mg L-1. Excessive enrichment of NPs had a detrimental effect on the photosynthetic system, decreasing the chlorophyll content and nonphotochemical quenching. An imbalance in the antioxidant defense systems, which were unable to cope with the oxidative stress caused by NP concentrations, further damaged various organs. The root system can take up NPs and then transfer them to the offspring through the stolon. Interference effects of NPs were observed in terms of root activity, metabolism, biofilm composition, and the plant's ability to purify water. However, the risk-spreading strategy employed by parent plants (interconnected offspring ramets) offered some relief from NP-induced stress, as it increased their relative growth rate by 1 to 1.38 times compared to individual plants. These findings provide substantial evidence of the high NP enrichment capacity of E. crassipes for ecological remediation. Nevertheless, we must also remain aware of the environmental risk associated with the spread of NPs within the clonal system of E. crassipes, and contaminated cloned individuals need to be precisely removed in a timely manner to maintain normal functions.

Assembly of π-Conjugated [B3O6] Units by Mer-Isomer [YO3F3] Octahedra to Design a UV Nonlinear Optical Material, Cs2YB3O6F2.

Achieving the extreme balance of the key performance requirements is the crucial to breakthrough the application bottleneck for nonlinear optical (NLO) materials. Herein, by assembly of the π-conjugated [B3O6] functional species with the aid of structure-directing property of mer-isomer [YO3F3] octahedra, a new ultraviolet (UV) NLO material, Cs2YB3O6F2 with aligned arrangement of coplanar [B3O6] groups has been synthesized. The polar material exhibits the rare coexistence of the largest second harmonic generation response of 5.6×KDP, the largest birefringence of 0.091 at 532 nm, the shortest Type I phase-matching down to 200.5 nm and deep-ultraviolet transparency among reported acentric rare-earth borates with [B3O6] groups. Remarkably, benefiting from the enhanced bonding force among functional units [B3O6], a firm three-dimensional framework is constructed, which facilitates the growth of large crystals. This can be proved by a block shape crystal with dimensional of 6×5×4 mm3, indicating that it was a promising UV NLO crystal. This work provides a powerful strategy to design UV NLO materials with good performances.

Cs3In(In4Se7)(P2Se6): A Multi-Chromophore Chalcogenide with Excellent Nonlinear Optical Property Designed by Group Grafting.

Non-centrosymmetric (NCS) and polar materials capable of exhibiting many important functional properties are indispensable for electro-optical technologies, yet their rational structural design remains a significant challenge. Here, we report a "group grafting" strategy for designing the first multi-chromophore selenophosphate, Cs3In(In4Se7)(P2Se6), that crystallizes in a NCS and polar space group of Cm. The structure features a unique basic building unit (BBU) [In(In4Se10)(P2Se6)], formed through "grafting [In4Se10] supertetrahedra on the root of [In(P2Se6)2] groups". Theoretical calculations confirm that this [In(In4Se10)(P2Se6)] BBU can achieve a "1+1>2" combination of properties from two chromophores, [In4Se10] supertetrahedron and ethane-like [P2Se6] dimer. That makes Cs3In(In4Se7)(P2Se6) exhibit excellent linear and nonlinear optical (NLO) properties, including a strong second harmonic generation (SHG) response (~6×AgGaS2), a large band gap (2.45 eV), broad infrared (IR) transmission (up to 19.5 µm), a significant birefringence (0.26 @1064 nm) as well as the congruently-melting property at ~700 °C. Therefore, Cs3In(In4Se7)(P2Se6) will be a promising NLO crystal, especially in the IR region, and this research also demonstrates that "group grafting" will be an effective strategy for constructing novel polar BBUs with multi-chromophore to design NCS structures and high-performance IR NLO materials.

Rapid evolutionary trade-offs between resistance to herbivory and tolerance to abiotic stress in an invasive plant.

Release from enemies can lead to rapid evolution in invasive plants, including reduced metabolic investment in defence. Conversely, reassociation with enemies leads to renewed evolution of defence, but the potential costs of this evolution are poorly documented. We report increased resistance of the invader Ambrosia artemisiifolia after reassociation with a coevolved specialist herbivore, and that this increase corresponds with reduced abiotic stress tolerance. Herbivore resistance was higher, but drought tolerance was lower in plants from populations with a longer reassociation history, and this corresponded with changes in phenylpropanoids involved in insect resistance and abiotic stress tolerance. These changes were corroborated by shifts in the expression of underlying biosynthetic genes and plant anti-oxidants. Together, our findings suggest rapid evolution of plant traits after reassociation with coevolved enemies, resulting in genetically based shifts in investment between abiotic and biotic stress responses, providing insights into co-evolution, plant invasion and biological control.

Cs3[(BOP)2(B3O7)3]: A Deep-Ultraviolet Nonlinear Optical Crystal Designed by Optimizing Matching of Cation and Anion Groups.

Deep-ultraviolet nonlinear optical (DUV NLO) crystals are indispensable for solid-state lasers to produce coherent light with wavelengths shorter than 200 nm, yet their structure design still faces great challenges because two groups of conflicting properties must be satisfied simultaneously, i.e., "large second harmonic generation (SHG) response-large band gap" and "large birefringence-weak growth anisotropy". Clearly, hitherto, no crystal can perfectly satisfy these properties, including KBe2BO3F2. Herein, we design a new mixed-coordinated borophosphate Cs3[(BOP)2(B3O7)3] (CBPO) by optimizing the matching of cation and anion groups, which unprecedentedly achieves a balance for two groups of contradictions concurrently for the first time. In the structure of CBPO, it has the coplanar and π-conjugated B3O7 groups, which can make it possess a large SHG response (3 × KDP) and large birefringence (0.075@532 nm). Then, terminal O atoms of these B3O7 groups are connected by BO4 and PO4 tetrahedra, which eliminates all dangling bonds and blue shifts the UV absorption edge to the DUV region (165 nm). More importantly, owing to the judicious selection of cations, the size of cations and void of anion groups is a perfect match, which makes CBPO possess a very stable three-dimensional anion framework and thus reduces the crystal growth anisotropy. A CBPO single crystal with a size of up to 20 × 17 × 8 mm3 has been successfully grown, through which a DUV coherent light has also been achieved in Be-free DUV NLO crystals for the first time. These indicate CBPO will be the next generation of DUV NLO crystals.

NaRb6(B4O5(OH)4)3(BO2) Featuring Noncentrosymmetry, Chirality, and the Linear Anionic Group BO2.

Noncentrosymmetric (NCS) structures are of particular interest owing to their symmetry-dependent physical properties, e.g., pyroelectricity, ferroelectricity, piezoelectricity, and nonlinear optical (NLO) behavior. Among them, chiral materials exhibit polarization rotation and host topological properties. Borates often contribute to NCS and chiral structures via their triangular [BO3] and tetrahedral [BO4] units and their numerous superstructure motifs. However, no chiral compound with the linear [BO2] unit has been reported to date. Herein, an NCS and chiral mixed-alkali-metal borate, NaRb6(B4O5(OH)4)3(BO2), with a linear BO2- unit in the structure was synthesized and characterized. The structure features a combination of three types of basic building units (BBUs), [BO2], [BO3], and [BO4] with sp-, sp2-, and sp3-hybridization of boron atoms, respectively. It crystallizes in the trigonal space group R32 (No. 155), one of the 65 Sohncke space groups. Two enantiomers of NaRb6(B4O5(OH)4)3(BO2) were found, and their crystallographic relationships are discussed. These results not only expand the small family of NCS structures with the rare linear BO2- unit but also prompt recognition to the fact that NLO materials have generally overlooked the existence of two enantiomers in achiral Sohncke space groups.

Peripheral sensory neurons and non-neuronal cells express functional Piezo1 channels.

Here, we present evidence showing Piezo1 protein expression in the primary sensory neurons (PSNs) and non-neuronal cells of rat peripheral nervous system. Using a knockdown/knockout validated antibody, we detected Piezo1 immunoreactivity (IR) in ∼60% of PSNs of rat dorsal root ganglia (DRG) with higher IR density in the small- and medium-sized neurons. Piezo1-IR was clearly identified in DRG perineuronal glia, including satellite glial cells (SGCs) and Schwann cells; in sciatic nerve Schwann cells surrounding the axons and cutaneous afferent endings; and in skin epidermal Merkel cells and melanocytes. Neuronal and non-neuronal Piezo1 channels were functional since various cells (dissociated PSNs and SGCs from DRGs, isolated Schwann cells, and primary human melanocytes) exhibited a robust response to Piezo1 agonist Yoda1 by an increase of intracellular Ca2+ concentration ([Ca2+]i). These responses were abolished by non-specific Piezo1 antagonist GsMTx4. Immunoblots showed elevated Piezo1 protein in DRG proximal to peripheral nerve injury-induced painful neuropathy, while PSNs and SGCs from rats with neuropathic pain showed greater Yoda1-evoked elevation of [Ca2+]i and an increased frequency of cells responding to Yoda1, compared to controls. Sciatic nerve application of GsMTx4 alleviated mechanical hypersensitivity induced by Yoda1. Overall, our data show that Piezo1 is widely expressed by the neuronal and non-neuronal cells in the peripheral sensory pathways and that painful nerve injury appeared associated with activation of Piezo1 in PSNs and peripheral glial cells.

[Ba4 (S2 )][ZnGa4 S10 ]: Design of an Unprecedented Infrared Nonlinear Salt-Inclusion Chalcogenide with Disulfide-Bonds.

Salt-inclusion chalcogenides (SICs) have been receiving widespread attention due to their large second harmonic generation (SHG) responses and wide bandgaps, however most of them suffer from small birefringence limiting their technical application. Herein, by introducing the π-conjugated (S2 )2- units in the ionic guest of salt-inclusion structure, the first disulfide-bond-containing SIC, [Ba4 (S2 )][ZnGa4 S10 ] has been synthesized. It exhibits the widest bandgap up to 3.39 eV among polychalcogenides and strong SHG response as large as that of AgGaS2 (AGS). Importantly, its birefringence reaches a max value of 0.053@1064 nm among AGS-like SICs, indicating it is a promising IR nonlinear optical (NLO) material. Theoretical calculations reveal that the π-conjugated (S2 )2- units and covalent GaS layers favor the enhanced birefringence and large SHG response. This work provides not only a new type of SIC for the first time, but also new lights on the design of IR NLO materials.

Effective Faraday rotator based on the TbYO3 crystal with a high Verdet constant and a high thermal conductivity.

Facing the demand of high-power laser development, a high-quality magneto-optical crystal with a high Verdet constant and a high thermal conductivity is needed. Herein, an effective Faraday rotation based on a TbYO3 single crystal with a strong magneto-optical effect, grown by the laser floating zone method, is demonstrated for the first time, to the best of our knowledge. The TbYO3 crystal has the Verdet constant which is 2.16 times (106 rad·m-1 T-1) higher than that of the TGG crystal (49 rad·m-1 T-1) at 880 nm. Additionally, the TbYO3 crystal also has a thermal conductivity of 11.8 W·m-1·K-1 and a laser-induced damage threshold of 1.59 GW·cm-2. These advantages can allow the TbYO3 crystal to be an attractive magneto-optical material.

Oxychalcogenides: A Promising Class of Materials for Nonlinear Optical Crystals with Mixed-Anion Groups.

Infrared nonlinear optical (IR NLO) materials are of great significance in the development of IR laser technology. But rationally designing high-performance IR NLO materials remains a huge challenge due to the conflict between the necessary properties required for NLO materials. Notably, oxychalcogenides with mixed-anion groups have drawn extensive interest as a family of important IR NLO candidates because they integrate the property advantages of oxides and chalcogenides by chemical substitution engineering. In this review, we provide a survey of reported oxychalcogenides and aim to present the development of NLO oxychalcogenides from the perspective of rational design of their structural chemistry. Furthermore, we focus on the relationships between partial substitution and structural symmetry as well as optical properties. These provide some helpful guidance for the further exploration and design of novel oxychalcogenide materials with excellent NLO performance in the future.

A platform for qualitative and quantitative characterization of α-Gal and NeuGc at the oligosaccharide level.

Glycosylation modification serves as a pivotal quality attribute in glycoprotein-based therapeutics, emphasizing its role in drug safety and efficacy. Prior studies have underscored the potential immunogenic risks posed by the presence of galactose-α-1,3-galactose (α-Gal) and N-glycolylneuraminic acid (NeuGc) in glycoprotein formulations. This accentuates the imperative for developing robust qualitative and quantitative analytical methods to monitor these immunogenic epitopes, thereby ensuring drug safety. In the present investigation, α-Gal and NeuGc were accurately quantified using UPLC-FLR-MS/MS at the oligosaccharide level. Remarkably, α-Gal could be identified when the ion intensity ratio or the mass-to-charge ratio (m/z) of 528.19 to 366.14 exceeded 1. Concurrently, NeuGc and N-acetylneuraminic acid (NeuAc) could be unambiguously identified through their respective fragment ions at m/z 673.23 and m/z 657.23. Furthermore, relative quantification of α-Gal and NeuGc was achieved using fluorescence signals. This study introduces a sensitive and reliable analytical approach for the qualitative and quantitative assessment of α-Gal and NeuGc in glycoprotein pharmaceuticals. The methodology offers significant potential for application in process control and optimization of glycoprotein production, aimed at minimizing immunogenicity and enhancing product quality.

Peritumoral and Intratumoral Texture Features Based on Multiparametric MRI and Multiple Machine Learning Methods to Preoperatively Evaluate the Pathological Outcomes of Pancreatic Cancer.

BACKGROUND: Radiomics-based preoperative evaluation of lymph node metastasis (LNM) and histological grade (HG) might facilitate the decision-making for pancreatic cancer and further efforts are needed to develop effective models. PURPOSE: To develop multiparametric MRI (MP-MRI)-based radiomics models to evaluate LNM and HG. STUDY TYPE: Retrospective. POPULATION: The pancreatic cancer patients from the main center (n = 126) were assigned to the training and validation sets at a 4:1 ratio. The patients from the other center (n = 40) served as external test sets. FIELD STRENGTH/SEQUENCE: A 3.0 T and 1.5 T/T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast enhancement T1-weighted imaging. ASSESSMENT: A total of 10,686 peritumoral and intratumoral radiomics features were extracted which contained first-order, shape-based, and texture features. The following three-step method was applied to reduce the feature dimensionality: SelectKBest (a function from scikit-learn package), least absolute shrinkage and selection operator (LASSO), and recursive feature elimination based on random forest (RFE-RF). Six classifiers (random forest, logistic regression, support vector machine, K-nearest neighbor, decision tree, and XGBOOST) were trained and selected based on their performance to construct the clinical, radiomics, and combination models. STATISTICAL TESTS: Delong's test was used to compare the models' performance. P value less than 0.05 was considered significant. RESULTS: Twelve significant features for LNM and 11 features for HG were obtained. Random forest and logistic regression performed better than the other classifiers in evaluating LNM and HG, respectively, according to the surgical pathological results. The best performance was obtained with the models that combined peritumoral and intratumoral features with area under curve (AUC) values of 0.944 and 0.892 in the validation and external test sets for HG and 0.924 and 0.875 for LNM. DATA CONCLUSION: Radiomics holds the potential to evaluate LNM and HG of pancreatic cancer. The combination of peritumoral and intratumoral features will make models more accurate. EVIDENCE LEVEL: 4. TECHNICAL EFFICACY: Stage 2.

Hierarchical dynamic regulation of Saccharomyces cerevisiae for enhanced lutein biosynthesis.

Lutein, as a carotenoid with strong antioxidant capacity and an important component of macular pigment in the retina, has wide applications in pharmaceutical, food, feed, and cosmetics industries. Besides extraction from plant and algae, microbial fermentation using engineered cell factories to produce lutein has emerged as a promising route. However, intra-pathway competition between the lycopene cyclases and the conflict between cell growth and production are two major challenges. In our previous study, de novo synthesis of lutein had been achieved in Saccharomyces cerevisiae by dividing the pathway into two stages (δ-carotene formation and conversion) using temperature as the input signal to realize sequential cyclation of lycopene. However, lutein production was limited to microgram level, which is still too low to meet industrial demand. In this study, a dual-signal hierarchical dynamic regulation system was developed and applied to divide lutein biosynthesis into three stages in response to glucose concentration and culture temperature. By placing the genes involved in δ-carotene formation under the glucose-responsive ADH2 promoter and genes involved in the conversion of δ-carotene to lutein under temperature-responsive GAL promoters, the growth-production conflict and intra-pathway competition were simultaneously resolved. Meanwhile, the rate-limiting lycopene ε-cyclation and carotene hydroxylation reactions were improved by screening for lycopene ε-cyclase with higher activity and fine tuning of the P450 enzymes and their redox partners. Finally, a lutein titer of 19.92 mg/L (4.53 mg/g DCW) was obtained in shake-flask cultures using the engineered yeast strain YLutein-3S-6, which is the highest lutein titer ever reported in heterologous production systems.

Detection of serum Aspergillus-specific IgM and IgG antibody levels for the diagnosis of chronic pulmonary aspergillosis developed in patients with tuberculosis.

Chronic pulmonary aspergillosis (CPA) is common among individuals with underlying lung diseases. The clinical manifestations of CPA include systemic symptoms (e.g., weight loss, fatigue, fever), chronic productive cough, chest discomfort, and occasional haemoptysis, which are similar to the manifestations of pulmonary tuberculosis (PTB) and are often misdiagnosed as PTB. Considering the striking similarities between CPA and PTB in clinical manifestations and imaging features, more specific microbiological and serological detections are needed for a definitive diagnosis. This study aimed to explore the clinical characteristics of CPA in TB as well as the diagnostic significance of Aspergillus-specific IgG and Aspergillus-specific IgM.A total of 140 patients diagnosed with TB by culture between December 2017 and February 2019 were included. Enrolled patients were categorized into two groups (CPA group and non-CPA group) according to CPA diagnostic criteria. All collected specimens were subjected to Aspergillus-specific IgG and IgM detection testing.The median concentration of Aspergillus-specific IgG in the CPA group (211.04 AU/ml) was significantly higher than that in the non-CPA group (77.88 AU/ml) (Z value - 6.397, P < 0.001). The sensitivity and specificity of Aspergillus-specific IgG for CPA diagnosis were 81.82% and 72.97%, respectively. In the chronic cavitary pulmonary aspergillosis (CCPA) group, the IgG positivity rate (≥ 120 AU/ml) was 96.2%, which was 21.4% in the non-CCPA patients (P < 0.001).The detection of Aspergillus-specific IgG serological changes is feasible and facilitates reliable differentiation between Aspergillus and Mycobacterium tuberculosis infection. However, Aspergillus-specific IgM has limited diagnostic value, with unsatisfactory sensitivity results.