Structure-based characterization and compound identification of the wild-type THF class-II riboswitch.

Riboswitches are conserved regulatory RNA elements participating in various metabolic pathways. Recently, a novel RNA motif known as the folE RNA motif was discovered upstream of folE genes. It specifically senses tetrahydrofolate (THF) and is therefore termed THF-II riboswitch. To unravel the ligand recognition mechanism of this newly discovered riboswitch and decipher the underlying principles governing its tertiary folding, we determined both the free-form and bound-form THF-II riboswitch in the wild-type sequences. Combining structural information and isothermal titration calorimetry (ITC) binding assays on structure-based mutants, we successfully elucidated the significant long-range interactions governing the function of THF-II riboswitch and identified additional compounds, including alternative natural metabolites and potential lead compounds for drug discovery, that interact with THF-II riboswitch. Our structural research on the ligand recognition mechanism of the THF-II riboswitch not only paves the way for identification of compounds targeting riboswitches, but also facilitates the exploration of THF analogs in diverse biological contexts or for therapeutic applications.

A Pyrophosphate Bifunctional Cathode with Inductive Effect for High-Voltage and Self-Charging Zinc Ion Battery.

With the growing demand for new energy storage devices, rechargeable aqueous zinc ion batteries (ZIBs) have attracted widespread attention due to their low cost and high safety. Among the cathode materials for ZIBs, polyanionic-based cathode materials with high voltage, high stability, and low cost have great potential. In this paper, tetragonal Na2VOP2O7 was prepared using a simple sol-gel method. The discharge platform voltage amounted to 1.8 V and had good rate and cycle performance due to the inductive effect of pyrophosphate. Then, a protective layer of Zn-hydroxyapatite (ZnHAP) modification was applied to the cathode surface, which can inhibit the hydrolysis of vanadium ions. The capacity was enhanced by 19 % after modification and the capacity retention after 100 cycles was also higher. Interestingly, the Na2VOP2O7 cathode also possesses a self-charging effect, recovering to 48 % of its initial capacity with an open-circuit voltage (OCV) of 1.1 V within a certain period, and light exposure can reduce the self-charging time by 83 %. These beneficial results indicate that the pyrophosphate bifunctional cathode with inductive effect has a great potential to construct high-voltage and multifunctional zinc ion battery.

Integrated assessment of the pollution and risk of heavy metals in soils near chemical industry parks along the middle Yangtze River.

Industrialization in riparian areas of critical rivers has caused significant environmental and health impacts. Taking eight industrial parks along the middle Yangtze River as examples, this study proposes a multiple-criteria approach to investigate soil heavy metal pollution and associated ecological and health risks posed by industrial activities. Aiming at seven heavy metals, the results show that nickel (Ni), cadmium (Cd), and copper (Cu) exhibited the most significant accumulation above background levels. The comprehensive findings from Pearson correlation analysis, cluster analysis, principal component analysis, and industrial investigation uncover the primary sources of Cd, arsenic (As), mercury (Hg), and lead (Pb) to be chemical processing, while Ni and chromium (Cr) are predominantly derived from mechanical and electrical equipment manufacturing. In contrast, Cu exhibits a broad range of origins across various industrial processes. Soil heavy metals can cause serious ecological and carcinogenic health risks, of which Cd and Hg contribute to >70 % of the total ecological risk, and As contributes over 80 % of the total health risk. This study highlights the importance of employing multiple mathematical and statistical models in determining and evaluating environmental hazards, and may aid in planning the environmental remediation engineering and optimizing the industry standards.

Multilayer Online Sequential Reduced Kernel Extreme Learning Machine-Based Modeling for Time-Varying Distributed Parameter Systems.

A significant number of industrial dynamic processes belong to time-varying distributed parameter systems (DPSs). To develop an accurate approximation model for these systems, it is critical to capture their time-varying behavior and strong nonlinearity. In this article, a multilayer online sequential reduced kernel extreme learning machine (ML-OSRKELM)-based online spatiotemporal modeling approach is developed for such DPSs. First, ML-OSRKELM stacks multiple online sequential reduced kernel extreme learning machine autoencoders (OSRKELM-AEs) to create a deep network, which can translate the spatiotemporal domain into a low-dimensional time domain. Then, an online sequential reduced kernel extreme learning machine (OS-RKELM) is employed to construct a dynamic temporal model. Finally, after obtaining time coefficients from the time domain, OS-RKELM is also used to reconstruct the original spatiotemporal domain. By using the kernel trick and the support vector selection strategy, the proposed method can remove redundant information while maintaining satisfactory nonlinear learning performance. Furthermore, the designed sequential update scheme can update the model parameters with real-time data, which makes it a promising method for capturing time-varying dynamics. Experiments and simulations on a lithium-ion battery's thermal process confirm the excellent performance and validity of the proposed model.

Piezo-photocatalytic properties of BaTiO3/CeO2 nanoparticles with heterogeneous structure synthesized by a gel-assisted hydrothermal method.

BaTiO3/CeO2 nanoparticles with heterogeneous structure were successfully synthesized via a gel-assisted hydrothermal method. The molar ratio of Ti/Ce was set as 1 : 0, 0.925 : 0.075, 0.9 : 0.1; 0.875 : 0.125, and 0.85 : 0.15 in the dried gels. Affected by the values of Ti/Ce, the particle sizes of hydrothermal products decreased obviously, and the surface of nanoparticles became rough and even had small protrusions. XRD, SEM, HRTEM, XPS, DRS, ESR, and PFM were used to characterize the nanoparticle textures. We speculated that the main body and surface of nanoparticles were BaTiO3 and CeO2 protrusions, respectively. The catalytic performance of BaTiO3/CeO2 nanoparticles was characterized by their abilities to degrade RhB in water under different external conditions (light irradiation, ultrasonic oscillation, or both). In all test groups, BaTiO3/CeO2 nanoparticles with a Ti/Ce molar ratio of 0.875 : 0.125 in the initial dried gel exhibited the strongest catalytic ability when light irradiation and ultrasonication were applied simultaneously owing to the appropriate amount of Ce3+ and oxygen vacancies.

Synergy of multiple precipitate/matrix interface structures for a heat resistant high-strength Al alloy.

High strength aluminum alloys are widely used but their strength is reduced as nano-precipitates coarsen rapidly in medium and high temperatures, which greatly limits their application. Single solute segregation layers at precipitate/matrix interfaces are not satisfactory in stabilizing precipitates. Here we obtain multiple interface structures in an Al-Cu-Mg-Ag-Si-Sc alloy including Sc segregation layers, C and L phases as well as a newly discovered χ-AgMg phase, which partially cover the θ' precipitates. By atomic resolution characterizations and ab initio calculations, such interface structures have been confirmed to synergistically retard coarsening of precipitates. Therefore, the designed alloy shows the good combination of heat resistance and strength among all series of Al alloys, with 97% yield strength retained after thermal exposure, which is as high as 400 MPa. This concept of covering precipitates with multiple interface phases and segregation layers provides an effective strategy for designing other heat resistant materials.

Review on Rice Husk Biochar as an Adsorbent for Soil and Water Remediation.

Rice husk biochar (RHB) is a low-cost and renewable resource that has been found to be highly effective for the remediation of water and soil environments. Its yield, structure, composition, and physicochemical properties can be modified by changing the parameters of the preparation process, such as the heating rate, pyrolysis temperature, and carrier gas flow rate. Additionally, its specific surface area and functional groups can be modified through physical, chemical, and biological means. Compared to biochar from other feedstocks, RHB performs poorly in solutions with coexisting metal, but can be modified for improved adsorption. In contaminated soils, RHB has been found to be effective in adsorbing heavy metals and organic matter, as well as reducing pollutant availability and enhancing crop growth by regulating soil properties and releasing beneficial elements. However, its effectiveness in complex environments remains uncertain, and further research is needed to fully understand its mechanisms and effectiveness in environmental remediation.

Structure-based insights into recognition and regulation of SAM-sensing riboswitches.

Riboswitches are highly conserved RNA elements that located in the 5'-UTR of mRNAs, which undergo real-time structure conformational change to achieve the regulation of downstream gene expression by sensing their cognate ligands. S-adenosylmethionine (SAM) is a ubiquitous methyl donor for transmethylation reactions in all living organisms. SAM riboswitch is one of the most abundant riboswitches that bind to SAM with high affinity and selectivity, serving as regulatory modules in multiple metabolic pathways. To date, seven SAM-specific riboswitch classes that belong to four families, one SAM/SAH riboswitch and one SAH riboswitch have been identified. Each SAM riboswitch family has a well-organized tertiary core scaffold to support their unique ligand-specific binding pocket. In this review, we summarize the current research progress on the distribution, structure, ligand recognition and gene regulation mechanism of these SAM-related riboswitch families, and further discuss their evolutionary prospects and potential applications.

Solid-Liquid Equilibrium Behavior and Solvent Effect of Gliclazide in Mono- and Binary Solvents.

The solubility data of gliclazide in 10 mono-solvents (1,2-dichloroethane, 1,4-dioxane, 2-methoxyethanol, n-propyl acetate, isopropyl acetate, n-butyl acetate, pentyl acetate, dimethyl sulfoxide (DMSO), N,N-dimethylacetamide (DMA), and 2-butanone) and one kind of binary solvent (DMA + water) were measured between 278.15 and 323.15 K under atmospheric pressure by the gravimetric method. The Hansen solubility parameters and the KAT-LSER equation were used to investigate the solubility order and the influence of solvent effects on solubility. The experimental data were correlated by six thermodynamic models (the λh model, the Yaws model, the Apelblat model, the Jouyban model, the modified Jouyban-Acree model, and the Sun model). The results show that all of these models can correlate the experimental data well. Among them, the Apelblat model is the most suitable for correlating the solubility data of gliclazide in mono-solvents and binary solvents.

Identification of PKS-NRPS Hybrid Metabolites in Marine-Derived Penicillium oxalicum.

Filamentous fungi are abundant resources of bioactive natural products. Here, 151 marine-derived fungi were collected from the north Yellow Sea and identified by an internal transcribed spacer (ITS) sequence. The crude extracts of all strains were evaluated for their antimicrobial activities and analyzed by HPLC fingerprint. Based on these, strain Penicillium oxalicum MEFC104 was selected for further investigation. Two new polyketide-amino acid hybrid compounds with feature structures of tetramic acid, oxopyrrolidine A and B, were isolated. Their planner structures were assigned by HRESIMS and 1D/2D NMR experiments. The absolute configurations were determined by modified Mosher's method, J-based configuration analysis, and ECD calculations. Furthermore, the biosynthetic pathway was identified by bioinformatic analysis and gene-deletion experiments. This study established a link between oxopyrrolidines and the corresponding biosynthesis genes in P. oxalicum.

ER/AR Multi-Conformational Docking Server: A Tool for Discovering and Studying Estrogen and Androgen Receptor Modulators.

The prediction of the estrogen receptor (ER) and androgen receptor (AR) activity of a compound is quite important to avoid the environmental exposures of endocrine-disrupting chemicals. The Estrogen and Androgen Receptor Database (EARDB, http://eardb.schanglab.org.cn/) provides a unique collection of reported ERα, ERß, or AR protein structures and known small molecule modulators. With the user-uploaded query molecules, molecular docking based on multi-conformations of a single target will be performed. Moreover, the 2D similarity search against known modulators is also provided. Molecules predicted with a low binding energy or high similarity to known ERα, ERß, or AR modulators may be potential endocrine-disrupting chemicals or new modulators. The server provides a tool to predict the endocrine activity for compounds of interests, benefiting for the ER and AR drug design and endocrine-disrupting chemical identification.

Genome-Guided Discovery of Antifungal Filipins from a Deep-Sea-Derived Streptomyces antibioticus.

Nine new (1-3, 5-8, 11, and 12; named filipins VI-XIV) and three known (4, 9, and 10) filipin-type polyene macrolides were isolated from the deep-sea-derived Streptomyces antibioticus OUCT16-23 using a genome-guided strategy coupled with bioassay. Their structures were elucidated based on the extensive MS and NMR spectroscopic analyses together with ECD calculations. In an antifungal assay, compounds 4, 5, and 7-10 showed different degrees of growth inhibition against Candida albicans with minimum inhibitory concentrations (MICs) of 1.56-12.5 µg/mL, by which the alkyl side-chain substitution affecting the activity was preliminarily studied. A biosynthetic pathway to 1-12 in S. antibioticus OUCT16-23 is also proposed.

Adaptive Notch Filter for Piezo-Actuated Nanopositioning System via Position and Online Estimate Dual-Mode.

Due to the excellent advantages of high speed, high precision, and driving force, piezoelectric actuators nanopositioning systems have been widely used in various micro/nanomachining fields. However, the inherent resonance dynamic of the nanopositioning system generated by the flexure-hinge greatly deteriorates the positioning performance and limits the closed-loop bandwidth. Even worse, the notch filter for eliminating the effect of resonance does not work due to the varying resonant frequency resulting from the external disturbance or mass load. To this end, an adaptive notch filter for piezo-actuated nanopositioning system via position and online estimate dual-mode (POEDM) has been proposed in this paper, which can estimate the varying resonant frequency in real-time and suppress the resonance to improve the closed-loop bandwidth. First, a novel variable forgetting factor recursive least squares (VFF-RLS) algorithm for estimating resonant frequency online is presented, which is robust to the noise and provides the performances of both fast tracking and stability. Then, a POEDM method is proposed to achieve the online identification of the resonant frequency in the presence of noise and disturbance. Finally, a series of validation simulations are carried out, and the results indicate that, the frequency of input signal and the bandwidth have been achieved up to 12.5% and 87.5% of the first resonant frequency, respectively.

Proteomic approaches for the profiling of ubiquitylation events and their applications in drug discovery.

Protein ubiquitylation regulates almost all aspects of the biological processes including gene expression, DNA repair, cell proliferation and apoptosis in eukaryotic cells. Dysregulation of protein ubiquitylation caused by abnormal expression of enzymes in the ubiquitin system results in the onset of many diseases including cancer, neurodegenerative diseases, and metabolic syndromes. Therefore, targeting the ubiquitin system becomes a promising research area in drug discovery. Identification of protein ubiquitylation sites is critical for revealing the key ubiquitylation events associated with diseases and specific signaling pathways and for elucidating the biological functions of the specific ubiquitylation events. Many approaches that enrich for the ubiquitylated proteins and ubiquitylated peptides at the protein and peptide levels have been developed to facilitate their identification by MS. In this paper, we will review the proteomic approaches available for the identification of ubiquitylation events at the proteome scale and discuss their advantages and limitations. We will also brief the application of the profiling of ubiquitylation events in drug target discovery and in target validation for proteolysis-targeting chimera (PROTAC). Possible future research directions in this field will also be discussed. SIGNIFICANCE: Ubiquitylation plays critical roles in regulating many biological processes in eukaryotic cells. Identification of ubiquitylation sites can provide the essential information for the functional study of the specific modified substrates. Since ubiquitylated proteins have much lower abundance than non-ubiquitylated proteins, enrichment of ubiquitylated proteins or peptides is critical for their identification by MS. This review focuses on different enrichment approaches that facilitate their isolation and identification by MS and discusses the advantages and drawbacks of these approaches. The application of the profiling of ubiquitylation events in drug target discovery and future research directions will be beneficial to the research community.

Inhibition of invadopodia formation by diosgenin in tumor cells.

Diosgenin is a type of steroid extracted from the rhizome of Dioscorea plants. In traditional Chinese medicine, Dioscorea has the effect of 'eliminating phlegm, promoting digestion, relaxing tendons, promoting blood circulation and inhibiting malaria'. Recent studies have confirmed that diosgenin exhibits a number of pharmacological effects, including antitumor activities. Through its antitumor effect, diosgenin is able to block tumor progression and increase the survival rate of patients with cancer; ultimately improving their quality of life. However, the mechanism underlying its pharmacological action remains unclear. Once tumor cells reach a metastatic phase, it can be fatal. Increased migration and invasiveness are the hallmarks of metastatic tumor cells. Invadopodia formation is key to maintaining the high migration and invasive ability of tumor cells. Invadopodia are a type of membrane structure process rich in filamentous-actin and are common in highly invasive tumor cells. In addition to actin, numerous actin regulators, including cortical actin-binding protein (Cortactin), accumulate in invadopodia. Cortactin is a microfilament actin-binding protein with special repetitive domains that are directly involved in the formation of the cortical microfilament actin cell skeleton. Cortactin is also one of the main substrates of intracellular Src-type tyrosine protein kinases and represents a highly conserved family of intracellular cortical signaling proteins. In recent years, great progress has been made in understanding the role of Cortactin and its molecular mechanism in cell motility. However, the diosgenin-Cortactin-invadopodia mechanism is still under investigation. Therefore, the present review focused on the current research on the regulation of invadopodia by diosgenin via Cortactin.

Circularly Polarized Thermally Activated Delayed Fluorescence Emitters in Through-Space Charge Transfer on Asymmetric Spiro Skeletons.

This work describes a strategy to produce circularly polarized thermally activated delayed fluorescence (CP-TADF). A set of two structurally similar organic emitters SFST and SFOT are constructed, whose spiro architectures containing asymmetric donors result in chirality. Upon grafting within the spiro frameworks, the donor and acceptor are fixed proximally in a face-to-face manner. This orientation allows intramolecular through-space charge transfer (TSCT) to occur in both emitters, leading to TADF properties. The donor units in SFST and SFOT have a sulfur and oxygen atom, respectively; such a subtle difference has great impacts on their photophysical, chiroptical, and electroluminescence (EL) properties. SFOT exhibits greatly enhanced EL performance in doped organic light-emitting diodes, with external quantum efficiency (EQE) up to 23.1%, owing to the concurrent manipulation of highly photoluminescent quantum efficiency (PLQY, ∼90%) and high exciton utilization. As a comparison, the relatively larger sulfur atom in SFST introduces heavy atom effects and leads to distortion of the molecular backbone that lengthens the donor-acceptor distance. SFST thus has lower PLQY and faster nonradiative decay rate. The collective consequence is that the EQE value of SFST, i.e., 12.5%, is much lower than that of SFOT. The chirality of these two spiro emitters results in circularly polarized luminescence. Because SFST has a more distorted molecular architecture than SFOT, the luminescence dissymmetry factor (|glum|) of circularly polarized luminescence of one enantiomer of the former, namely, either (S)-SFST or (R)-SFST, is almost twice that of (S)-SFOT/(R)-SFOT. Moreover, the CP organic light-emitting diodes (CP-OLEDs) show obvious circularly polarized electroluminescence (CPEL) signals with gEL of 1.30 × 10-3 and 1.0 × 10-3 for (S)-SFST and (S)-SFOT, respectively.

Highly Efficient Thermally Activated Delayed Fluorescence via an Unconjugated Donor-Acceptor System Realizing EQE of Over 30.

In this work, two novel thermally activated delayed fluorescence (TADF) emitters, 2tDMG and 3tDMG, are synthesized for high-efficiency organic light-emitting diodes (OLEDs), The two emitters have a tilted face-to-face alignment of donor (D)/acceptor (A) units presenting intramolecular noncovalent interactions. The two TADF materials are deposited either by an evaporation-process or by a solution-process, both of them leading to high OLED performance. 2tDMG used as the emitter in evaporation-processed OLEDs achieves a high external quantum efficiency (EQE) of 30.8% with a very flat efficiency roll-off of 7% at 1000 cd m-2 . The solution-processed OLEDs also display an interesting EQE of 16.2%. 3tDMG shows improved solubility and solution processability as compared to 2tDMG, and thus a high EQE of 20.2% in solution-processed OLEDs is recorded. The corresponding evaporation-processed OLEDs also reach a reasonably high EQE of 26.3%. Encouragingly, this work provides a novel strategy to address the imperious demands for OLEDs with high EQE and low roll-off.

Sky-Blue Thermally Activated Delayed Fluorescence with Intramolecular Spatial Charge Transfer Based on a Dibenzothiophene Sulfone Emitter.

Intramolecular spatial charge transfer (ISCT) plays a critical role in determining the optical and charge transport properties of thermally activated delayed fluorescence (TADF) materials. Herein, a new donor/acceptor-type TADF compound based on rigid dibenzothiophene sulfone (DBTS) moiety, STF-DBTS, was designed and synthesized. Fluorene unit was used as a rigid linker to position the rigid acceptor and donor subunit in close vicinity with control over their spacing and molecular structure and to achieve high photoluminescence quantum yield (∼53%) and TADF property. For comparison purposes, we constructed the more flexible STF-DPS with a less rotationally constrained diphenylsulphone (DPS) acceptor instead of the rigid DBTS units, and STF-DPS showed no TADF properties and lower PLQY (16.0%). Organic light-emitting diodes (OLEDs) based on STF-DBTS achieve an external quantum efficiency (EQE) of 10.3% at 488 nm, which is a fivefold improvement in EQE with respect to STF-DPS.

Highly efficient luminescence from space-confined charge-transfer emitters.

Charge-transfer (CT) complexes, formed by electron transfer from a donor to an acceptor, play a crucial role in organic semiconductors. Excited-state CT complexes, termed exciplexes, harness both singlet and triplet excitons for light emission, and are thus useful for organic light-emitting diodes (OLEDs). However, present exciplex emitters often suffer from low photoluminescence quantum efficiencies (PLQEs), due to limited control over the relative orientation, electronic coupling and non-radiative recombination channels of the donor and acceptor subunits. Here, we use a rigid linker to control the spacing and relative orientation of the donor and acceptor subunits, as demonstrated with a series of intramolecular exciplex emitters based on 10-phenyl-9,10-dihydroacridine and 2,4,6-triphenyl-1,3,5-triazine. Sky-blue OLEDs employing one of these emitters achieve an external quantum efficiency (EQE) of 27.4% at 67 cd m-2 with only minor efficiency roll-off (EQE = 24.4%) at a higher luminous intensity of 1,000 cd m-2. As a control experiment, devices using chemically and structurally related but less rigid emitters reach substantially lower EQEs. These design rules are transferrable to other donor/acceptor combinations, which will allow further tuning of emission colour and other key optoelectronic properties.

Discovery and Characterization of a PKS-NRPS Hybrid in Aspergillus terreus by Genome Mining.

Fungal polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) hybrids have been characterized to produce polyketide-amino acid compounds with striking structural features and biological activities. In this study, a PKS-NRPS hybrid enzyme was found in Aspergillus terreus by genome mining. By activating the cluster-specific transcriptional regulator, this cryptic PKS-NRPS gene cluster was successfully activated and ten products (1-10) were identified as pyranterreones. Using functional genetics, bioinformatics, and isotope-labeling feeding analysis, the biosynthetic pathway was revealed. This is the second PKS-NRPS hybrid identified in A. terreus.