Enzyme-catalysed [6+4] cycloadditions in the biosynthesis of natural products.

Pericyclic reactions are powerful transformations for the construction of carbon-carbon and carbon-heteroatom bonds in organic synthesis. Their role in biosynthesis is increasingly apparent, and mechanisms by which pericyclases can catalyse reactions are of major interest1. [4+2] cycloadditions (Diels-Alder reactions) have been widely used in organic synthesis2 for the formation of six-membered rings and are now well-established in biosynthesis3-6. [6+4] and other 'higher-order' cycloadditions were predicted7 in 1965, and are now increasingly common in the laboratory despite challenges arising from the generation of a highly strained ten-membered ring system8,9. However, although enzyme-catalysed [6+4] cycloadditions have been proposed10-12, they have not been proven to occur. Here we demonstrate a group of enzymes that catalyse a pericyclic [6+4] cycloaddition, which is a crucial step in the biosynthesis of streptoseomycin-type natural products. This type of pericyclase catalyses [6+4] and [4+2] cycloadditions through a single ambimodal transition state, which is consistent with previous proposals11,12. The [6+4] product is transformed to a less stable [4+2] adduct via a facile Cope rearrangement, and the [4+2] adduct is converted into the natural product enzymatically. Crystal structures of three pericyclases, computational simulations of potential energies and molecular dynamics, and site-directed mutagenesis establish the mechanism of this transformation. This work shows how enzymes are able to catalyse concerted pericyclic reactions involving ambimodal transition states.

A universal mechanism on desiccation tolerance of Cronobacter based on intracellular trehalose accumulation regulated by EnvZ/OmpR.

Cronobacter (seven species) can survive in dry powdered infant formula for a long time, but the thorough molecular mechanism of resistance to desiccation remains elusive. Here we examine the regulation mechanism of Cronobacter's tolerance to desiccation by the typical two-component system (TCS) EnvZ/OmpR. When exposed to desiccation conditions, Cronobacter showed higher survival than other pathogens, as well as significantly up-regulated expression of ompR and otsAB genes with markedly decreased survival of their mutants, suggesting their relationship with desiccation tolerance. OmpR directly binds to the promoter of trehalose biosynthesis operon otsBA, significantly enhancing their expression, and boosting the trehalose levels. The ompR-deletion in other six species further confirmed its positive regulation in desiccation tolerance. Our data present a hypothesis that EnvZ/OmpR increases intracellular trehalose levels against damage to the cells, which prompts Cronobacter to survive in desiccation conditions. This study reveals a universal molecular mechanism for desiccation resistance in Cronobacter species.

Correlation of academic emotion and hardiness personality of undergraduate nursing students.

BACKGROUND: Academic emotion is a fundamental emotional concept closely linked to academic achievement. Understanding the connection between academic emotion and the personality trait of hardiness is pivotal in maintaining a stable career orientation throughout one's educational career. Therefore, in pursuit of fostering the robust growth of nursing careers, it is imperative to delve into the academic emotions experienced by undergraduate nursing students. This study endeavors to mitigate the impact of gender differences among nursing students while investigating the intricate relationship between academic emotions and the trait of hardiness in their personalities. METHODS: This study employed a cross-sectional research design. We gathered data from a convenient sample of 292 nursing students enrolled at Shanxi University of Chinese Medicine. Each student provided demographic information and responded to a general academic mood questionnaire, as well as a Hardiness Personality Rating Scale. Subsequently, we used canonical correlation analysis to evaluate the correlation between academic emotion and tenacity personality in 292 undergraduate nursing students. RESULTS: We discovered that academic emotions among nursing students are predominantly characterized by feelings of disappointment and boredom. Furthermore, personality hardiness is primarily influenced by the dimensions of engagement and control. It is important to note that a heightened level of negative, low-arousal academic emotions can diminish the level of engagement. The first typical correlation coefficient corresponding to academic emotion and hardiness were 0.660. The linear combination of standardized variables of the first typical variable corresponding to academic emotion (X1) = -0.444*negative hyperarousal -0.443 * positive hyperarousal + 0.694 * negative hypoarousal -0.260 * positive hypoarousal. The standardized variable equation of the first typical variable corresponding to hardiness personality (η1) = 0.235* hardiness -0.433* control -0.530* investment -0.303* challenge. CONCLUSIONS: Nursing students generally believe that their input is out of proportion to the return, and this unbalanced emotional experience will seriously affect their academic emotions in China. It is suggested that paying attention to cultivating their tenacious personality traits in the teaching process may help to enhance their academic emotions and enhance the sense of belonging and identity of nursing students engaged in the nursing profession.

P450-Modified Multicyclic Cyclophane-Containing Ribosomally Synthesized and Post-Translationally Modified Peptides.

Cyclic peptides with cyclophane linkers are an attractive compound type owing to the fine-tuned rigid three-dimensional structures and unusual biophysical features. Cytochrome P450 enzymes are capable of catalyzing not only the C-C and C-O oxidative coupling reactions found in vancomycin and other nonribosomal peptides (NRPs), but they also exhibit novel catalytic activities to generate cyclic ribosomally synthesized and post-translationally modified peptides (RiPPs) through cyclophane linkage. To discover more P450-modified multicyclic RiPPs, we set out to find cryptic and unknown P450-modified RiPP biosynthetic gene clusters (BGCs) through genome mining. Synergized bioinformatic analysis reveals that P450-modified RiPP BGCs are broadly distributed in bacteria and can be classified into 11 classes. Focusing on two classes of P450-modified RiPP BGCs where precursor peptides contain multiple conserved aromatic amino acid residues, we characterized 11 novel P450-modified multicyclic RiPPs with different cyclophane linkers through heterologous expression. Further mutation of the key ring-forming residues and combinatorial biosynthesis study revealed the order of bond formation and the specificity of P450s. This study reveals the functional diversity of P450 enzymes involved in the cyclophane-containing RiPPs and indicates that P450 enzymes are promising tools for rapidly obtaining structurally diverse cyclic peptide derivatives.

P450-Modified Ribosomally Synthesized Peptides with Aromatic Cross-Links.

Cyclization of linear peptides is an effective strategy to convert flexible molecules into rigid compounds, which is of great significance for enhancing the peptide stability and bioactivity. Despite significant advances in the past few decades, Nature and chemists' ability to macrocyclize linear peptides is still quite limited. P450 enzymes have been reported to catalyze macrocyclization of peptides through cross-linkers between aromatic amino acids with only three examples. Herein, we developed an efficient workflow for the identification of P450-modified RiPPs in bacterial genomes, resulting in the discovery of a large number of P450-modified RiPP gene clusters. Combined with subsequent expression and structural characterization of the products, we have identified 11 novel P450-modified RiPPs with different cross-linking patterns from four distinct classes. Our results greatly expand the structural diversity of P450-modified RiPPs and provide new insights and enzymatic tools for the production of cyclic peptides.

Carbonized Polymer Dots with Controllable N, O Functional Groups as Electrolyte Additives to Achieve Stable Li Metal Batteries.

Electrolyte additive is an effective strategy to inhibit the uncontrolled growth of Li dendrites for lithium metal batteries (LMBs). However, most of the additives are complex synthesis and prone to decompose in cycling. Herein, in order to guide the homogeneous deposition of Li+ , carbonized polymer dots (CPDs) as electrolyte additives are successfully designed and synthesized by microwave (M-CPDs) and hydrothermal (H-CPDs) approaches. The controllable functional groups containing N or O (especially pyridinic-N, pyrrolic-N, and carboxyl group) enable CPDs to keep stable in electrolytes for at least 3 months. Meanwhile, the clusters formed between CPDs and Li+ through electrostatic interaction effectively guide the uniform Li dispersion and limit the "tip effect" and dendrite formation. Moreover, as lithiophilic groups increase, the strong electrostatic interference for the solvation effect of Li+ in the electrolyte is formed, which induces faster Li+ diffusion/transfer. As expected, H-CPDs achieve the ultra-even Li+ transfer. The corresponding Li//LiFePO4 full cell delivers a high capacity retention rate of 93.8% after 200 cycles, which is much higher than that of the cells without additives (61.2%) and with M-CPDs (83.7%) as additives. The strategy in this work provides a theoretical direction for CPDs as electrolyte additives used in energy storage devices.

Tuning Anomalous Floquet Topological Bands with Ultracold Atoms.

The Floquet engineering opens the way to create new topological states without counterparts in static systems. Here, we report the experimental realization and characterization of new anomalous topological states with high-precision Floquet engineering for ultracold atoms trapped in a shaking optical Raman lattice. The Floquet band topology is manipulated by tuning the driving-induced band crossings referred to as band inversion surfaces (BISs), whose configurations fully characterize the topology of the underlying states. We uncover various exotic anomalous topological states by measuring the configurations of BISs that correspond to the bulk Floquet topology. In particular, we identify an unprecedented anomalous Floquet valley-Hall state that possesses anomalous helical-like edge modes protected by valleys and a chiral state with high Chern number.

Multishell Copper Oxide Hollow Spheres Incorporated with Fatty Amines for High Light-To-Thermal Conversion.

Composite phase change materials (PCMs) are of great importance for the storage and conversion of energy. In this study, a multishell metal oxide hollow microsphere (CuOHS) was prepared by the hydrothermal method, and a new composite PCM (CuOHS@PCMs) for energy storage and conversion purposes was developed by effectively absorbing fatty amines [namely, tetradecylamine (TDA), hexadecylamine (HDA), and octadecylamine (ODA)] PCMs into the CuOHS via the abundant micropores located on the surface of the microsphere. The incorporation of uncontaminated phase alteration substances with CuOHS yields superior light absorption and leak prevention traits. The three CuOHS@PCMs, specifically CuOHS@TDA, CuOHS@HDA, and CuOHS@ODA, possess considerable latent heats of 198.8, 192.6, and 196.0 J·g-1, respectively, and exhibit desirable thermal properties even after completing 50 and 100 thermal cycles. Moreover, under illumination, the photothermal conversion efficiencies of the three variations of CuOHS@PCMs were 84.0, 81.4, and 78.0%. This CuOHS@PCMs, which are based on CuOHS, have considerable potential in the fields of photothermal conversion, solar energy harvesting, and storage.

Guar Gum-Based Macroporous Hygroscopic Polymer for Efficient Atmospheric Water Harvesting.

Solar-driven atmospheric water harvesting technology has the advantage of not being limited by geography and has great potential in solving the freshwater crisis. Here, we first propose a purely natural and degradable superhydrophilic composite macroporous hygroscopic material by applying guar gum (GG) to atmospheric water harvesting. The material consists of GG-cellulose nanofibers (CNFs) as a porous substrate material, limiting the hygroscopic factor lithium chloride (LiCl) in its three-dimensional (3D) network structure, and carbon nanotubes (CNTs) play a photothermal conversion role. The composite material has a high light absorption rate of more than 95%, and the macroporous structure (20-60 µm) allows for rapid adsorption/desorption kinetics. At 35 °C and 90% relative humidity (RH), the moisture absorption capacity is as high as 1.94 g/g. Under 100 mW/cm2 irradiation, the absorbed water is almost completely desorbed within 3 h, and the water harvesting performance is stable in 10 cycles. Moreover, liquid water was successfully collected in an actual outdoor experiment. This work demonstrates the great potential of biomass materials in the field of atmospheric water collection and provides more opportunities for various energy and sustainable applications in the future.

Safety of pregnancy in acromegaly patients and maternal and infant outcomes after pregnancy: single-center experience from China and review of the literature.

BACKGROUND: Pregnancy in acromegaly is uncommon and still in debate for fear of tumor progression or potential threat to both mother and fetus's health. Besides, the data for pregnancy complications in uncontrolled acromegaly is limited. Thus, the objective of this study was to summarize pregnancy safety and disease courses after pregnancy in acromegalic patients and review their clinical characteristics based on disease activity in the literature. METHODS: An evaluation of eight acromegalic women from Peking Union Medical College Hospital (PUMCH) with 11 pregnancies was conducted. We also summarized a literature review of 82 disease-active pregnancies and 63 disease-controlled pregnancies with acromegaly. A second analysis was conducted to compare pregnancy courses and outcomes in different disease activities. RESULTS: Before pregnancy, all patients had macroadenomas and underwent pituitary surgery. Pregnancy occurred at a median of 6 years (4-10) after the diagnosis of acromegaly. Assisted reproductive therapy was needed in 42.9% of participants. No cases had a premature birth or congenital malformations. Biochemical control was achieved in 50% of females before pregnancy and 75% at the last follow-up after delivery. Data analysis showed no differences in the prevalence of gestational diabetes mellitus (GDM) or pregnancy-induced hypertension (PIH) between acromegaly-active or acromegaly-controlled groups. The GDM prevalence in patients diagnosed during pregnancy (33.3%) was higher than that in patients diagnosed before pregnancy (4.8%) (p = 0.001). CONCLUSION: Pregnancy without biochemical control in acromegaly and receiving medical treatment during pregnancy are not rare and generally safe for the fetus. There could be a higher prevalence of PIH in acromegalic pregnancies. The treatment of acromegaly and related complications can be managed with regular follow-up after pregnancy.

Pyridoxal-5'-phosphate-dependent bifunctional enzyme catalyzed biosynthesis of indolizidine alkaloids in fungi.

Indolizidine alkaloids such as anticancer drugs vinblastine and vincristine are exceptionally attractive due to their widespread occurrence, prominent bioactivity, complex structure, and sophisticated involvement in the chemical defense for the producing organisms. However, the versatility of the indolizidine alkaloid biosynthesis remains incompletely addressed since the knowledge about such biosynthetic machineries is only limited to several representatives. Herein, we describe the biosynthetic gene cluster (BGC) for the biosynthesis of curvulamine, a skeletally unprecedented antibacterial indolizidine alkaloid from Curvularia sp. IFB-Z10. The molecular architecture of curvulamine results from the functional collaboration of a highly reducing polyketide synthase (CuaA), a pyridoxal-5'-phosphate (PLP)-dependent aminotransferase (CuaB), an NADPH-dependent dehydrogenase (CuaC), and a FAD-dependent monooxygenase (CuaD), with its transportation and abundance regulated by a major facilitator superfamily permease (CuaE) and a Zn(II)Cys6 transcription factor (CuaF), respectively. In contrast to expectations, CuaB is bifunctional and capable of catalyzing the Claisen condensation to form a new C-C bond and the α-hydroxylation of the alanine moiety in exposure to dioxygen. Inspired and guided by the distinct function of CuaB, our genome mining effort discovers bipolamines A-I (bipolamine G is more antibacterial than curvulamine), which represent a collection of previously undescribed polyketide alkaloids from a silent BGC in Bipolaris maydis ATCC48331. The work provides insight into nature's arsenal for the indolizidine-coined skeletal formation and adds evidence in support of the functional versatility of PLP-dependent enzymes in fungi.

Cholesterol-Lowering Activity of Vitisin A Is Mediated by Inhibiting Cholesterol Biosynthesis and Enhancing LDL Uptake in HepG2 Cells.

Pyranoanthocyanins have been reported to possess better chemical stability and bioactivities than monomeric anthocyanins in some aspects. The hypocholesterolemic activity of pyranoanthocyanins is unclear. In view of this, this study was conducted to compare the cholesterol-lowering activities of Vitisin A with the anthocyanin counterpart Cyanidin-3-O-glucoside(C3G) in HepG2 cells and to investigate the interaction of Vitisin A with the expression of genes and proteins associated with cholesterol metabolism. HepG2 cells were incubated with 40 µM cholesterol and 4 µM 25-hydroxycholeterol with various concentrations of Vitisin A or C3G for 24 h. It was found that Vitisin A decreased the cholesterol levels at the concentrations of 100 µM and 200 µM with a dose-response relationship, while C3G exhibited no significant effect on cellular cholesterol. Furthermore, Vitisin A could down-regulate 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR) to inhibit cholesterol biosynthesis through a sterol regulatory element-binding protein 2 (SREBP2)-dependent mechanism, and up-regulate low-density lipoprotein receptor (LDLR) and blunt the secretion of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein to promote intracellular LDL uptake without LDLR degradation. In conclusion, Vitisin A demonstrated hypocholesterolemic activity, by inhibiting cholesterol biosynthesis and enhancing LDL uptake in HepG2 cells.

The mediating role of coping styles between nurses' workplace bullying and professional quality of life.

AIMS: This study aimed to explore the relationship between workplace bullying among nurses and their professional quality of life, as well as the mediating role of coping styles between the two factors. BACKGROUND: In China, the overall status of nurses' professional quality of life is not optimistic, and the problems of low compassion satisfaction and high compassion fatigue persist. Workplace bullying, which is a serious global issue, can negatively impact the mental health and professional quality of nurses. However, it has still not attracted enough attention from managers. METHODS: The study used a cross-sectional research design and surveyed 297 clinical nurses from two tertiary grade A hospitals in Wuhan, China. Data were collected through an online questionnaire survey from March to May 2022. The data were analyzed using descriptive statistical methods, including Pearson correlation analysis and structural equation modeling. RESULTS: The score for nurses' workplace bullying was 38.72 ± 12.30. The scores for the three dimensions of professional quality of life were 27.56 ± 4.79 for compassion satisfaction, 30.51 ± 4.33 for burnout, and 28.47 ± 4.65 for secondary trauma stress. The scores for positive coping style and negative coping style were 34.59 ± 5.72 and 20.34 ± 5.08 points, respectively. Workplace bullying had a direct negative effect on compassion satisfaction, as well as positive direct effects on burnout and secondary traumatic stress. Coping styles played a mediating effect between workplace bullying and the pairwise relationships of compassion satisfaction, burnout, and secondary trauma stress. CONCLUSION: Workplace bullying hurts nurses' professional quality of life while coping styles plays an mediating role between workplace bullying and professional quality of life. Nursing managers can improve nurses' professional quality of life by reducing workplace bullying and enhancing positive coping style. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing managers can employ management wisdom and techniques to mitigate the presence and detrimental effects of workplace bullying. This, in turn, promotes a positive work environment and enhances the professional quality of life for nurses.

Total Biosynthesis of Mutaxanthene Unveils a Flavoprotein Monooxygenase Catalyzing Xanthene Ring Formation.

Flavoprotein monooxygenases (FPMOs) play important roles in generating structural complexity and diversity in natural products biosynthesized by type II polyketide synthases (PKSs). In this study, we used genome mining to discover novel mutaxanthene analogues and investigated the biosynthesis of these aromatic polyketides and their unusual xanthene framework. We determined the complete biosynthetic pathway of mutaxathene through in vivo gene deletion and in vitro biochemical experiments. We show that a multifunctional FPMO, MtxO4, catalyzes ring rearrangement and generates the required xanthene ring through a multistep transformation. In addition, we successfully obtained all necessary enzymes for in vitro reconstitution and completed the total biosynthesis of mutaxanthene in a stepwise manner. Our results revealed the formation of a rare xanthene ring in type II polyketide biosynthesis, and demonstrate the potential of using total biosynthesis for the discovery of natural products synthesized by type II PKSs.

Cytochrome†P450 Catalyzes Benzene Ring Formation in the Biosynthesis of Trialkyl-Substituted Aromatic Polyketides.

Lorneic acid and related natural products are characterized by a trialkyl-substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis. Using this P450 as a beacon for genome mining, we obtained 12 homologous type I polyketide synthase (PKS) gene clusters, among which two gene clusters are activated and able to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to elucidate the plausible mechanism for P450-catalyzed benzene ring formation. Our work expands our knowledge of the catalytic diversity of cytochrome P450.

In Vitro Reconstitution of Cinnamoyl Moiety Reveals Two Distinct Cyclases for Benzene Ring Formation.

Cinnamoyl-containing natural products (CCNPs) are a small class of bacterial metabolites with notable bioactivities. The biosynthesis of cinnamoyl moiety has been proposed to be assembled by an unusual highly reducing (HR) type II polyketide synthases (PKS). However, the biosynthetic route, especially the cyclization step for the benzene ring formation, remains unclear. In this work, we successfully reconstituted the pathway of cinnamoyl moiety in kitacinnamycin biosynthesis through a step-wise approach in vitro and demonstrated that a three-protein complex, Kcn17-Kcn18-Kcn19, can catalyze 6π-electrocyclization followed by dehydrogenation to form the benzene ring. We found that the three-protein homologues were widely distributed among 207 HR type II PKS biosynthetic gene clusters including five known CCNPs. In contrast, in the biosynthesis of youssoufene, a cinnamoyl-containing polyene, we identified that the benzene ring formation was accomplished by a distinct orphan protein. Thus, our work resolved the long-standing mystery in cinnamoyl biosynthesis and revealed two distinct enzymes that can synthesize benzene rings via polyene precursors.

Interpretable Graph Transformer Network for Predicting Adsorption Isotherms of Metal-Organic Frameworks.

Predicting interactions between metal-organic frameworks (MOFs) and their adsorbates based on structures is critical to design high-performance porous materials. Many gas uptake prediction models have been proposed, but adsorption isotherm prediction is still challenging for most existing models. Here, we report a deep learning approach (MOFNet) that can predict adsorption isotherms for MOFs based on hierarchical representation and pressure adaptive mechanism. We elaborately design a hierarchical representation to encode the MOF structures. We adopt a graph transformer network to capture atomic-level information, which can help learn chemical features required under low-pressure conditions. A pressure adaptive mechanism is employed to interpolate and extrapolate the given limited data points by transfer learning, which can predict adsorption isotherms on a wider pressure range by only one model. We demonstrate that our predictor outperformed other traditional machine learning as well as graph neural network models on the challenging benchmarks and also achieves high performance on the real-world experimental observed adsorption isotherms. Finally, we interpret the models to discover and present potential structure-property relationships using the self-attention mechanism in the network. The proof-of-concept applications, such as disordered MOF predictions and missing data imputation of gas adsorption isotherms, showcase the generality and usability of our model to improve MOF material design.

Association between P-Selectin Autoantibody Positive and Response to Steroid Treatment in Newly Diagnosed Immune Thrombocytopenia Patients.

OBJECTIVE: This study aimed to detect the association between P-selectin autoantibody positive and response to steroid treatment in newly diagnosed immune thrombocytopenia (ITP) patients. METHODS: The data from 105 newly diagnosed adult ITP patients administered with first-line of steroid treatment from October 2016 to May 2021 were retrospectively analyzed. Treatment responses were evaluated within 3 months after the onset of treatment. RESULTS: Among the 105 patients, 80.00% (84/105) of patients presented with platelet glycoprotein-specific antibody positive; 44.76% (47/105) patients were anti-P-selectin positive, while 35.24% (37/105) were anti-P-selectin negative. No significant difference in overall response was observed between patients who were anti-P-selectin positive and those who were anti-P-selectin negative (74.47% vs. 89.19, χ2 = 2.910, p = 0.088). But patients who were anti-P-selectin negative had significantly higher complete response rate, compared to those who were anti-P-selectin positive (72.97% vs. 48.94%, χ2 = 4,965, p = 0.026). Logistic regression analysis revealed that anti-GP IIb/IIIa positive (OR = 3.114, p = 0.010, 95% CI: 1.313-7.388) and anti-P-selectin positive (OR = 0.309, p = 0.036, 95% CI: 0.127-0.753) were two factors that could affect patients' response. CONCLUSIONS: Our study found that ITP patients with anti-GP IIb/IIIa may have a higher response to steroid treatment, but anti-P-selectin-mediated-ITP might be less responsive to steroid treatment. In adults with ITP, the presence of anti-P-selectin autoantibodies is a predictive factor for poor response to steroid treatment.

Highly crosslinking core-shell magnetic nanocomposites based catalyst and heat free polymerization for isolation of glycoprotein.

New approaches for the engineering of well-defined, pore modality, and multi-chemical functionality nanocomposites are crucial to generate the next generation of functional materials with recoverable and easy preparation properties. Here, a catalyst and heat free polymerization reaction is exploited and fabricated zwitterionic system around magnetic nanoparticles. N-aminoethyl piperazine propane sulfonate (AEPPS) and dopamine (DA) are introduced as the zwitterionic system, which provided abundant zwitterionic groups (NH2, SO3-, N+) and strong adhesion and various oxidation state properties. And that, the zwitterionic engineering will assemble between AEPPS and DA whereby Schiff base formation or Michael type addition. Whereafter, a series of sophisticated array of microscopic, spectroscopic, and structure techniques verify the formation of highly crosslinking internal zwitterionic architectures, well-defined core-shell structure, and better porosity. The zwitterionic structure-function relationships and striking porous structure are explored in a multi-interaction adsorption assay. The adsorption capacity of the magnetic nanocomposites was 1065.8 mg/g. And that, the system exhibited with hydrophilic-hydrophobic activity towards glycoprotein and better performance to bioactive protein (Ig-G) isolation form human whole blood sample. The synergistic enhancement interaction in hydrophilic target enrichment, easy preparation, and soft substrate properties of the AEPPS-DA zwitterionic materials make them intriguing candidates for sustainable biomedical loading and chromatographic separation.

Spirocitromycetin, a Fungal Polyketide with an Antiosteoporotic Pharmacophore.

Spirocitromycetin, an antiosteoporotic polyketide bearing a unique spirocycle, was characterized from a human mucus sputum-derived Penicillium velutinum. Its structure and absolute configuration were elucidated spectrally, with its biosynthetic pathway likely mediated via polivione, a reported heptaketide. Spirocitromycetin was shown to be antiosteoporotic at 0.1 µM in the prednisolone-induced osteoporotic zebrafish model. A combination of spirocitromycetin variant synthesis and bioassay has identified 5'-methyl-3'H-spiro[chromane-3,2'-furan]-3',4-dione as an unreported antiosteroporotic pharmacophore. Collectively, this work offers new starting (sub)structures that may be of significance for antiosteoporotic drug discovery.