A Hematogenous Route for Medulloblastoma Leptomeningeal Metastases.

While the preponderance of morbidity and mortality in medulloblastoma patients are due to metastatic disease, most research focuses on the primary tumor due to a dearth of metastatic tissue samples and model systems. Medulloblastoma metastases are found almost exclusively on the leptomeningeal surface of the brain and spinal cord; dissemination is therefore thought to occur through shedding of primary tumor cells into the cerebrospinal fluid followed by distal re-implantation on the leptomeninges. We present evidence for medulloblastoma circulating tumor cells (CTCs) in therapy-naive patients and demonstrate in vivo, through flank xenografting and parabiosis, that medulloblastoma CTCs can spread through the blood to the leptomeningeal space to form leptomeningeal metastases. Medulloblastoma leptomeningeal metastases express high levels of the chemokine CCL2, and expression of CCL2 in medulloblastoma in vivo is sufficient to drive leptomeningeal dissemination. Hematogenous dissemination of medulloblastoma offers a new opportunity to diagnose and treat lethal disseminated medulloblastoma.

In Silico-Predicted Dynamic Oxlipidomics MS/MS Library: High-Throughput Discovery and Characterization of Unknown Oxidized Lipids.

Nontargeted lipidomics using liquid chromatography-tandem mass spectrometry can detect thousands of molecules in biological samples. However, the annotation of unknown oxidized lipids is limited to the structures present in libraries, restricting the analysis and interpretation of experimental data. Here, we describe Doxlipid, a computational tool for oxidized lipid annotation that predicts a dynamic MS/MS library for every experiment. Doxlipid integrates three key simulation algorithms to predict libraries and covers 32 subclasses of oxidized lipids from the three main classes. In the evaluation, Doxlipid achieves very high prediction and characterization performance and outperforms the current oxidized lipid annotation methods. Doxlipid, combined with a molecular network, further annotates unknown chemical analogs in the same reaction or pathway. We demonstrate the broad utility of Doxlipid by analyzing oxidized lipids in ferroptosis hepatocellular carcinoma, tissue samples, and other biological samples, substantially advancing the discovery of biological pathways at the trace oxidized lipid level.

Carbonaceous Materials-Based Photothermal Process in Water Treatment: From Originals to Frontier Applications.

The photothermal process has attracted considerable attention in water treatment due to its advantages of low energy consumption and high efficiency. In this respect, photothermal materials play a crucial role in the photothermal process. Particularly, carbonaceous materials have emerged as promising candidates for this process because of exceptional photothermal performance. While previous research on carbonaceous materials has primarily focused on photothermal evaporation and sterilization, there is now a growing interest in exploring the potential of photothermal effect-assisted advanced oxidation processes (AOPs). However, the underlying mechanism of the photothermal effect assisted by carbonaceous materials remains unclear. This review aims to provide a comprehensive review of the photothermal process of carbonaceous materials in water treatment. It begins by introducing the photothermal properties of carbonaceous materials, followed by a discussion on strategies for enhancing these properties. Then, the application of carbonaceous materials-based photothermal process for water treatment is summarized. This includes both direct photothermal processes such as photothermal evaporation and sterilization, as well as indirect photothermal processes that assisted AOPs. Meanwhile, various mechanisms assisted by the photothermal effect are summarized. Finally, the challenges and opportunities of using carbonaceous materials-based photothermal processes for water treatment are proposed.

Dual-Salts Localized High-Concentration Electrolyte for Li- and Mn-Rich High-Voltage Cathodes in Lithium Metal Batteries.

Limited electrochemical stability windows of conventional carbonate-based electrolytes pose a challenge to support the Lithium (Li)- and manganese (Mn)-rich (LMR) high-voltage cathodes in rechargeable Li-metal batteries (LMBs). To address this issue, a novel localized high-concentration electrolyte (LHCE) composition incorporating LiPF6 and LiTFSI as dual-salts (D-LHCE), tailored for high-voltage (>4.6 Vvs.Li) operation of LMR cathodes in LMBs is introduced. 7Li nuclear magnetic resonance and Raman spectroscopy revealed the characteristics of the solvation structure of D-LHCE. The addition of LiPF6 provides stable Al-current-collector passivation while the addition of LiTFSI improves the stability of D-LHCE by producing a more robust cathode-electrolyte interphase (CEI) on LMR cathode and solid-electrolyte interphase (SEI) on Li-metal anode. As a result, LMR/Li cell, using the D-LHCE, achieved 72.5% capacity retention after 300 cycles, a significant improvement compared to the conventional electrolyte (21.9% after 100 cycles). The stabilities of LMR CEI and Li-metal SEI are systematically analyzed through combined applications of electrochemical impedance spectroscopy and distribution of relaxation times techniques. The results present that D-LHCE concept represents an effective strategy for designing next-generation electrolytes for high-energy and high-voltage LMB cells.

Strategies for Enhancing the Photocatalytic and Electrocatalytic Efficiency of Covalent Triazine Frameworks for CO2 Reduction.

Converting carbon dioxide (CO2) into fuel and high-value-added chemicals is considered a green and effective way to solve global energy and environmental problems. Covalent triazine frameworks (CTFs) are extensively utilized as an emerging catalyst for photo/electrocatalytic CO2 reduction reaction (CO2RR) recently recognized for their distinctive qualities, including excellent thermal and chemical stability, π-conjugated structure, rich nitrogen content, and a strong affinity for CO2, etc. Nevertheless, single-component CTFs have the problems of accelerated recombination of photoexcited electron-hole pairs and restricted conductivity, which limit their application for photo/electrocatalytic CO2RR. Therefore, emphasis will then summarize the strategies for enhancing the photocatalytic and electrocatalytic efficiency of CTFs for CO2RR in this paper, including atom doping, constructing a heterojunction structure, etc. This review first illustrates the synthesis strategies of CTFs and the advantages of CTFs in the field of photo/electrocatalytic CO2RR. Subsequently, the mechanism of CTF-based materials in photo/electrocatalytic CO2RR is described. Lastly, the challenges and future prospects of CTFs in photo/electrocatalytic CO2RR are addressed, which offers a fresh perspective for the future development of CTFs in photo/electrocatalytic CO2RR.

Functional analysis of OmpA and its contribution to pathogenesis of Edwardsiella tarda.

Outer membrane protein A (OmpA), a major component of outer membrane proteins in gram-negative bacteria, is considered to be an important virulence factor in various pathogenic bacteria, but its underlying mechanisms involved in pathogenic process of Edwardsiella tarda has not yet been fully elucidated. E. tarda is an important facultative intracellular pathogen with a broad host range. This bacterium could survive and replicate in macrophages as an escape mechanism from the host defense. To address the functions of OmpA and its potential roles in the pathogenesis of E. tarda, ΔompA mutant strain and ΔompA-C complementary strain were constructed by the allelic exchange method in this study. Here, we demonstrate that the abilities of motility, biofilm formation and adherence to RAW264.7 cells of ΔompA were significantly impaired, although there was no difference in growth between wild-type (WT) strain and ΔompA. Moreover, inactivation of ompA rendered E. tarda more sensitive to oxidative, heat shock and osmotic stress, which simulate the in vivo conditions that E. tarda encounters within the intramacrophage environment. Consist with this observation, ΔompA was also found to be markedly attenuated for growth within macrophages. In addition, compared with the WT strain, ΔompA activated macrophages to release more inflammatory mediators, including tumor necrosis factor alpha (TNF-α), reactive oxygen species (ROS) and nitric oxide (NO). However, flow cytometry analysis revealed that ΔompA induced less apoptosis of RAW264.7 cells as compared with WT strain, characterized by decreased Annexin V binding and the activation of caspase-3. Overall, our findings suggest an importance of OmpA to E. tarda and provide the first comprehensive insight into its functions and potential roles in the pathogenesis of E. tarda, including its effect on interaction with macrophages.

Intraperitoneal administration of carcinoembryonic antigen-directed chimeric antigen receptor T cells is a robust delivery route for effective treatment of peritoneal carcinomatosis from colorectal cancer in pre-clinical study.

BACKGROUND AIMS: Peritoneal carcinomatosis (PC) from colorectal cancer (CRC) is a highly challenging disease to treat. Systemic chimeric antigen receptor (CAR) T cells have shown impressive efficacy in hematologic malignancies but have been less effective in solid tumors. We explored whether intraperitoneal (i.p.) administration of CAR T cells could provide an effective and robust route of treatment for PC from CRC. METHODS: We generated second-generation carcinoembryonic antigen (CEA)-specific CAR T cells. Various animal models of PC with i.p. and extraperitoneal metastasis were treated by i.p. or intravenous (i.v.) administration of CEA CAR T cells. RESULTS: Intraperitoneally administered CAR T cells exhibited superior anti-tumor activity compared with systemic i.v. cell infusion in an animal model of PC. In addition, i.p. administration conferred a durable effect and protection against tumor recurrence and exerted strong anti-tumor activity in an animal model of PC with metastasis in i.p. or extraperitoneal organs. Moreover, compared with systemic delivery, i.p. transfer of CAR T cells provided increased anti-tumor activity in extraperitoneal tumors without PC. This phenomenon was further confirmed in an animal model of pancreatic carcinoma after i.p. administration of our newly constructed prostate stem cell antigen-directed CAR T cells. CONCLUSIONS: Taken together, our data suggest that i.p. administration of CAR T cells may be a robust delivery route for effective treatment of cancer.

Supramolecular Control of the Temperature Responsiveness of Fluorescent Macrocyclic Molecular Rotamers.

To fully harness the potential of molecular machines, it is crucial to develop methods by which to exert control over their speed of motion through the application of external stimuli. A conformationally strained macrocyclic fluorescent rotamer, CarROT, displays a reproducible and linear fluorescence decrease towards temperature over the physiological temperature range. Through the external addition of anions, cations or through deprotonation, the compound can access four discreet rotational speeds via supramolecular interactions (very slow, slow, fast and very fast) which in turn stop, reduce or enhance the thermoluminescent properties due to increasing or decreasing non-radiative decay processes, thereby providing a means to externally control the temperature sensitivity of the system. Through comparison with analogues with a higher degree of conformational freedom, the high thermosensitivity of CarROT over the physiological temperature range was determined to be due to conformational strain, which causes a high energy barrier to rotation over this range. Analogues with a higher degree of conformational freedom display lower sensitivities towards temperature over the same temperature range. This study provides an example of an information rich small molecule, in which programable rotational speed states can be observed with facile read-out.

Analysis of the Unusual Chemical Bonds and Dipole Moments of AeF- (Ae=Be-Ba): A Lesson in Covalent Bonding.

Quantum chemical calculations of the anions AeF- (Ae=Be-Ba) have been carried out using ab initio methods at the CCSD(T)/def2-TZVPP level and density functional theory employing BP86 with various basis sets. The detailed bonding analyses using different charge- and energy partitioning methods show that the molecules possess three distinctively different dative bonds in the lighter species with Ae=Be, Mg and four dative bonds when Ae=Ca, Sr, Ba. The occupied 2p atomic orbitals (AOs) and to a lesser degree the occupied 2s AO of F- donate electronic charge into the vacant spx(σ) and p(π) orbitals of Be and Mg which leads to a triple bond Ae F-. The heavier Ae atoms Ca, Sr, Ba use their vacant (n-1)d AOs as acceptor orbitals which enables them to form a second σ donor bond with F- that leads to quadruply bonded Ae F- (Ae=Ca-Ba). The presentation of molecular orbitals or charge distribution using only one isodensity value may give misleading information about the overall nature of the orbital or charge distribution. Better insights are given by contour line diagrams. The ELF calculations provide monosynaptic and disynaptic basins of AeF- which nicely agree with the analysis of the occupied molecular orbitals and with the charge density difference maps. A particular feature of the covalent bonds in AeF- concerns the inductive interaction of F- with the soft valence electrons in the (n)s valence orbitals of Ae. The polarization of the (n)s2 electrons induces a (n)spx hybridized lone-pair orbital at atom Ae, which yields a large dipole moment with the negative end at Ae. The concomitant formation of a vacant (n)spx AO of atom Ae, which overlaps with the occupied 2p(σ) AO of F-, leads to a strong covalent σ bond.

Feasibility of achieving two-electron K-O2 batteries.

A deep understanding of the oxygen (O2) reduction and evolution mechanisms is crucial for understanding metal-O2 batteries. It has become evident that the instability of superoxide in the presence of lithium (Li) ions and sodium (Na) ions is the root cause for the poor reversibility and energy efficiency of Li-O2 and Na-O2 batteries. A straightforward yet elegant method is stabilizing superoxide with the larger potassium (K) ions. Superoxide-based K-O2 batteries, invented by our group in 2013, are operated based on one-electron redox of O2/potassium superoxide (KO2) and have high energy efficiencies without any electrocatalysts. Nevertheless, limiting the anionic redox to O2/superoxide affects the capacity output. Therefore, it is attractive to explore the possibility of beyond KO2 in the K-O2 batteries, especially if the use of catalysts can still be avoided. In this research, solid KO2 was used as the condensed O2 source and pre-dissolved in the dimethyl sulfoxide (DMSO)-based electrolyte. It is encouraging to observe two sets of reversible peaks during the three-electrode cyclic voltammetry scan under an argon atmosphere. One pair of peaks is attributed to the KO2/potassium peroxide (K2O2) interconversion. Such redox has superb reversibility and a small overpotential of 239 mV in the absence of explicit electrocatalysts. Notably, it is further revealed that K2O2 reacts with gaseous O2. Therefore, a gas-open system with an O2 supply is unfavorable for realizing the reversible KO2/K2O2 redox, and a closed cell system with a KO2 supply as the starting active material is suggested instead.

Prediction of mass spectrometry ionization efficiency based on COSMO-RS and machine learning algorithms.

Non-targeted analysis of high-resolution mass spectrometry (MS) can identify thousands of compounds, which also gives a huge challenge to their quantification. The aim of this study is to investigate the impact of mass spectrometry ionization efficiency on various compounds in food at different solvent ratios and to develop a predictive model for mass spectrometry ionization efficiency to enable non-targeted quantitative prediction of unknown compounds. This study covered 70 compounds in 14 different mobile phase ratio environments in positive ion mode to analyze the rules of the matrix effect. With the organic phase ratio from low to high, most compounds changed by 1.0 log units in log IE. The addition of formic acid enhanced the signal but also promoted the matrix effect, which often occurred in compounds with strong ionization capacity. It was speculated that the matrix effect was mainly in the form of competitive charge and charged droplet' gasification sites during MS detection. Subsequently, we present a log IE prediction method built using the COSMO-RS software and the artificial neural network (ANN) algorithm to address this difficulty and overcome the shortcomings of previous models, which always ignore the matrix effect. This model was developed following the principles of QSAR modeling recommended by the Organization for Economic Cooperation and Development (OECD). Furthermore, we validated this approach by predicting the log IE of 70 compounds, including those not involved in the log IE model development. The results presented demonstrate that the method we put forward has an excellent prediction accuracy for log IE (R2pred = 0.880), which means that it has the potential to predict the log IE of new compounds without authentic standards.

Application of strain elastography ultrasound to the endometrium of normal women.

BACKGROUND: While there is a scarcity of studies utilizing strain elastography (SE) for the endometrium, commonly used gynecologic ultrasound instruments are equipped with built-in elastography modalities, primarily SE. With the objective of facilitating comprehensive examinations for gynecologic patients on a single ultrasound instrument, we undertook this study. Therefore, our aim was to study the value of SE ultrasonography in the assessment of endometrial elasticity in normal women. METHODS: Three hundred and twenty normal women were recruited at our hospitals from November 2021 to December 2022. Each volunteer underwent a transvaginal two-dimensional (2D) and SE ultrasound during either the endometrial proliferative or secretory phase. The 2D ultrasound indices obtained included endometrial thickness, echo type (type A, B, and C), and blood flow grading (grades 0, 1, 2, and 3). SE indices obtained included endometrial strain values, myometrial strain values, and endometrial strain ratios. Differences in endometrial ultrasound indices between different menstrual cycles and different age groups were compared. RESULTS: Comparison of 2D ultrasound parameters revealed that endometrial thickness in the proliferative phase endometrium group was smaller than that in the secretory phase endometrium group, with a statistically significant difference. Additionally, there was a statistically significant difference in endometrial echo types between the two groups, while the disparity in endometrial blood flow grading was not significant. Regarding SE parameters, the median and mean values of endometrial strain ratio in the proliferative phase endometrium group were smaller than those in the secretory phase endometrium group, showing a statistically significant difference. However, there were no significant differences observed between the two groups in endometrial strain and myometrial strain in the fundus. Furthermore, there were no significant differences in any of the endometrial ultrasound indices among the different age groups. CONCLUSIONS: SE can reflect changes in endometrial stiffness in different menstrual cycles and is an important tool for assessing endometrial softness.

Long Non-coding RNA LINC00342 Promotes the Proliferation, Invasion, and Migration of Primary Hepatocellular Carcinoma Cells by Regulating the Expression of miRNA-19a-3p, miRNA-545-5p, and miRNA-203a-3p.

This study aimed to investigate the role of the long non-coding RNA (lncRNA) LINC00342-207 (LINC00342) in the development and progression of primary hepatocellular carcinoma (HCC). Forty-two surgically resected HCC tissues and corresponding paracancerous tissues were collected from October 2019 to December 2020 and examined for lncRNA LINC00342, microRNA (miR)-19a-3p, miR-545-5p, miR-203a-3p, cell cycle protein D1 (CyclinD1/CCND1), murine double minute 2 (MDM2), and fibroblast growth factor 2 (FGF2) expression. The disease-free survival and overall survival of patients with HCC were followed up. HCC cell lines and the normal hepatocyte cell line HL-7702 were cultured and the expression level of LINC00342 was measured. HepG2 cells were transfected with LINC00342 siRNA, LINC00342 overexpression plasmid, miR-19a-3p mimics and their corresponding suppressors, miR-545-5p mimics and their corresponding suppressors, and miR-203a-3p mimics and their corresponding suppressors. The proliferation, apoptosis, migration, and invasion of HepG2 cells were detected. Stably transfected HepG2 cells were inoculated into the left axilla of male BALB/c nude mice, and the volume and quality of transplanted tumors as well as the expression levels of LINC00342, miR-19a-3p, miR-545-5p, miR-203a-3p, CCND1, MDM2, and FGF2 were examined. LINC00342 played an oncogenic role in HCC and exhibited inhibitory effects on proliferation, migration, and invasion, and promoted the apoptosis of HepG2 cells. Moreover, it inhibited the growth of transplanted tumors in vivo in mice. Mechanistically, the oncogenic effect of LINC00342 was associated with the targeted regulation of the miR-19a-3p/CCND1, miR-545-5p/MDM2, and miR-203a-3p/FGF2 axes.

A High-Performance Flexible Hydroacoustic Transducer Based on 1-3 PZT-5A/Silicone Rubber Composite.

In recent years, hydroacoustic transducers made of PZT/epoxy composites have been extensively employed in underwater detection, communication, and recognition for their high energy conversion efficiency. Despite the ease with which these transducers can be formed into complex shapes, their lack of mechanical flexibility limits their versatility across various sizes of underwater vehicles. This study introduces a novel flexible piezoelectric composite hydroacoustic transducer (FPCHT) based on a 1-3 PZT-5A/silicone rubber composite and an island-bridge flexible electrode, which can break the limitations of existing hydroacoustic transducers that do not have flexibility. The finite element method is used to optimize the structural parameters of high-performance 1-3 FPC. A large-sized (187 mm × 47 mm × 5.12 mm) FPC is fabricated using an improved cutting-filling method and packaged into the FPCHT. Compared with the planar rigid PZT/epoxy composite hydroacoustic transducer (RPCHT) of the same size, the TVR (186.5 db) of the FPCHT has increased by about 7 dB, indicating that it has better acoustic radiation performance and electroacoustic conversion efficiency. Furthermore, its electroacoustic performance exhibits excellent stability under different bending states. Therefore, the FPCHT with high electroacoustic performance is an ideal substitute for the existing RPCHT and promotes the development of hydroacoustic transducers towards flexibility and portability.

Inflammation plays a critical role in damage to the bronchiolar epithelium induced by Trueperella pyogenes in vitro and in vivo.

Trueperella pyogenes can cause severe pulmonary disease in swine, but the mechanism of pathogenesis is not well defined. T. pyogenes-induced damage to porcine bronchial epithelial cells (PBECs), porcine precision-cut lung slices (PCLS), and respiratory epithelium of mice remains unknown. In this study, we used T. pyogenes 20121 to infect PBECs in air-liquid interface conditions and porcine PCLS. T. pyogenes could adhere to, colonize, and induce cytotoxic effect on PBECs and the luminal surface of bronchi in PCLS, which damaged the bronchiolar epithelium. Moreover, bronchiolar epithelial cells showed extensive degeneration in the lungs of infected mice. Furthermore, western blot showed that the NOD-like receptor (NLR)/C-terminal caspase recruitment domain (ASC)/caspase-1 axis and nuclear factor-kappa B pathway were involved in inflammation in PCLS and lungs of mice, which also confirms that porcine PCLS provide a platform to analyze the pulmonary immune response. Meanwhile, the levels of p-c-Jun N-terminal kinase, p-extracellular signal-regulated kinase, and p-protein kinase B (AKT) were increased significantly, which indicated the mitogen-activated protein kinase and Akt pathways were also involved in inflammation in T. pyogenes-infected mice. In addition, we used T. pyogenes 20121 to infect tumor necrosis factor-alpha (tnf-α-/-) mice, and the results indicated that apoptosis and injury in respiratory epithelium of infected tnf-α-/- mice were alleviated. Thus, the pro-inflammatory cytokine TNF-α played a role in apoptosis and the respiratory epithelium injury in mouse lungs. Collectively, our study provides insight into the inflammatory injury induced by T. pyogenes and suggests that blocking NLR may be a potential therapeutic strategy against T. pyogenes infection.

Bivalirudin plus a high-dose infusion versus heparin monotherapy in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a randomised trial.

BACKGROUND: Previous randomised trials of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have reported conflicting results, in part because of treatment with different pharmacological regimens. We designed a large-scale trial examining bivalirudin with a post-PCI high-dose infusion compared with heparin alone, the regimens that previous studies have shown to have the best balance of safety and efficacy. METHODS: BRIGHT-4 was an investigator-initiated, open-label, randomised controlled trial conducted at 87 clinical centres in 63 cities in China. Patients with STEMI undergoing primary PCI with radial artery access within 48 h of symptom onset who had not received previous fibrinolytic therapy, anticoagulants, or glycoprotein IIb/IIIa inhibitors were randomly assigned (1:1) to receive bivalirudin with a post-PCI high-dose infusion for 2-4 h or unfractionated heparin monotherapy. There was no masking. Glycoprotein IIb/IIIa inhibitor use was reserved for procedural thrombotic complications in both groups. The primary endpoint was a composite of all-cause mortality or Bleeding Academic Research Consortium (BARC) types 3-5 bleeding at 30 days. This trial is registered with ClinicalTrials.gov (NCT03822975), and is ongoing. FINDINGS: Between Feb 14, 2019, and April 7, 2022, a total of 6016 patients with STEMI undergoing primary PCI were randomly assigned to receive either bivalirudin plus a high-dose infusion after PCI (n=3009) or unfractionated heparin monotherapy (n=3007). Radial artery access was used in 5593 (93·1%) of 6008 patients. Compared with heparin monotherapy, bivalirudin reduced the 30-day rate of the primary endpoint (132 events [4·39%] in the heparin group vs 92 events [3·06%] in the bivalirudin group; difference, 1·33%, 95% CI 0·38-2·29%; hazard ratio [HR] 0·69, 95% CI 0·53-0·91; p=0·0070). All-cause mortality within 30 days occurred in 118 (3·92%) heparin-assigned patients and in 89 (2·96%) bivalirudin-assigned patients (HR 0·75; 95% CI 0·57-0·99; p=0·0420), and BARC types 3-5 bleeding occurred in 24 (0·80%) heparin-assigned patients and five (0·17%) bivalirudin-assigned patients (HR 0·21; 95% CI 0·08-0·54; p=0·0014). There were no significant differences in the 30-day rates of reinfarction, stroke, or ischaemia-driven target vessel revascularisation between the groups. Within 30 days, stent thrombosis occurred in 11 (0·37%) of bivalirudin-assigned patients and 33 (1·10%) of heparin-assigned patients (p=0·0015). INTERPRETATION: In patients with STEMI undergoing primary PCI predominantly with radial artery access, anticoagulation with bivalirudin plus a post-PCI high-dose infusion for 2-4 h significantly reduced the 30-day composite rate of all-cause mortality or BARC types 3-5 major bleeding compared with heparin monotherapy. FUNDING: Chinese Society of Cardiology Foundation (CSCF2019A01), and a research grant from Jiangsu Hengrui Pharmaceuticals.

Oriented Self-assembly of Flexible MOFs Nanocrystals into Anisotropic Superstructures with Homogeneous Hydrogels Behaviors.

Building of metal-organic frameworks (MOFs) homogeneous hydrogels made by spontaneous crystallization remains a significant challenge. Inspired by anisotropically structured materials in nature, an oriented super-assembly strategy to construct micro-scale MOFs superstructure is reported, in which the strong intermolecular interactions between zirconium-oxygen (Zr─O) cluster and glutamic acid are utilized to drive the self-assembly of flexible nanoribbons into pumpkin-like microspheres. The confined effect between water-flexible building blocks and crosslinked hydrogen networks of superstructures achieved a mismatch transformation of MOFs powders into homogeneous hydrogels. Importantly, the elastic and rigid properties of hydrogels can be simply controlled by precise modulation of coordination and self-assembly for anisotropic superstructure. Experimental results and theoretical calculations demonstrates that MOFs anisotropic superstructure exhibits dynamic double networks with a superior water harvesting capacity (119.73 g g-1 ) accompanied with heavy metal removal (1331.67 mg g-1 ) and strong mechanical strength (Young's modulus of 0.3 GPa). The study highlights the unique possibility of tailoring MOFs superstructure with homogeneous hydrogel behavior for application in diverse fields.

De novo biosynthesis of anticarcinogenic icariin in engineered yeast.

Icariin (ICA) has wide applications in nutraceuticals and medicine with strong anticancer activities. However, the structural complexity and low abundance in plants of ICA lead to the unsustainable and high-cost supply from chemical synthesis and plant extraction. Here, the whole biosynthesis pathway of ICA was elucidated, then was constructed in Saccharomyces cerevisiae, including a 13-step heterologous ICA pathway from eleven kinds of plants as well as deletions or overexpression of ten yeast endogenous genes. Spatial regulation of 8-C-prenyltransferase to mitochondria and three-stage sequential control of 4'-O-methyltransferase, 3-OH rhamnosyltransferase, and 7-OH glycosyltransferase expression successfully achieved the de novo synthesis of ICA with a titer of 130 µg/L under shake-flask culture. The ICA synthesis from glucose represents the longest reconstructed pathway of flavonoid in microbe so far. This study provides a potential choice for the sustainable microbial production of number of complex flavonoids.

Characterization of regulatory modules controlling leaf angle in maize.

Leaf angle is an important agronomic trait determining maize (Zea mays) planting density and light penetration into the canopy and contributes to the yield gain in modern maize hybrids. However, little is known about the molecular mechanisms underlying leaf angle beyond the ZmLG1 (liguleless1) and ZmLG2 (Liguleless2) genes. In this study, we found that the transcription factor (TF) ZmBEH1 (BZR1/BES1 homolog gene 1) is targeted by ZmLG2 and regulates leaf angle formation by influencing sclerenchyma cell layers on the adaxial side. ZmBEH1 interacted with the TF ZmBZR1 (Brassinazole Resistant 1), whose gene expression was also directly activated by ZmLG2. Both ZmBEH1 and ZmBZR1 are bound to the promoter of ZmSCL28 (SCARECROW-LIKE 28), a third TF that influences leaf angle. Our study demonstrates regulatory modules controlling leaf angle and provides gene editing targets for creating optimal maize architecture suitable for dense planting.