Mechanical quenching phenomenon in diamond.

The structure of dislocation cores, the fundamental knowledge on crystal plasticity, remains largely unexplored in covalent crystals. Here, we conducted atomically resolved characterizations of dislocation core structures in a plastically deformed diamond anvil cell tip that was unloaded from an exceptionally high pressure of 360 GPa. Our observations unveiled a series of nonequilibrium dislocation cores that deviate from the commonly accepted "five-seven-membered ring" dislocation core model found in FCC-structured covalent crystals. The nonequilibrium dislocation cores were generated through a process known as "mechanical quenching," analogous to the quenching process where a high-energy state is rapidly frozen. The density functional theory-based molecular dynamic simulations reveal that the phenomenon of mechanical quenching in diamond arises from the challenging relaxation of the nonequilibrium configuration, necessitating a large critical strain of 25% that is difficult to maintain. Further electronic-scale analysis suggested that such large critical strain is spent on the excitation of valance electrons for bond breaking and rebonding during relaxation. These findings establish a foundation for the plasticity theory of covalent materials and provide insights into the design of electrical and luminescent properties in diamond, which are intimately linked to the dislocation core structure.

LUX ARRHYTHMO links CBF pathway and jasmonic acid metabolism to regulate cold tolerance of tea plants.

Cold stress declines the quality and yield of tea, yet the molecular basis underlying cold tolerance of tea plants (Camellia sinensis) remains largely unknown. Here, we identified a circadian rhythm component LUX ARRHYTHMO (LUX) that potentially regulates cold tolerance of tea plants through a genome-wide association study and transcriptomic analysis. The expression of CsLUX phased with sunrise and sunset and was strongly induced by cold stress. Genetic assays indicated that CsLUX is a positive regulator of freezing tolerance in tea plants. CsLUX was directly activated by CsCBF1 and repressed the expression level of CsLOX2, which regulates the cold tolerance of tea plants through dynamically modulating jasmonic acid content. Furthermore, we showed that the CsLUX-CsJAZ1 complex attenuated the physical interaction of CsJAZ1 with CsICE1, liberating CsICE1 with transcriptional activities to withstand cold stress. Notably, a single-nucleotide variation of C-to-A in the coding region of CsLUX was functionally validated as the potential elite haplotype for cold response, which provided valuable molecular markers for future cold resistance breeding in tea plants.

CsMYBL2 homologs modulate the light and temperature stress-regulated anthocyanin and catechins biosynthesis in tea plants (Camellia sinensis).

Anthocyanin and catechin production in tea (Camellia sinensis) leaves can positively affect tea quality; however, their regulatory mechanisms are not fully understood. Here we report that, while the CsMYB75- or CsMYB86-directed MYB-bHLH-WD40 (MBW) complexes differentially activate anthocyanin or catechin biosynthesis in tea leaves, respectively, CsMYBL2a and CsMYBL2b homologs negatively modified the light- and temperature-induced anthocyanin and catechin production in both Arabidopsis and tea plants. The MBW complexes activated both anthocyanin synthesis genes and the downstream repressor genes CsMYBL2a and CsMYBL2b. Overexpression of CsMYBL2b, but not CsMYBL2a, repressed Arabidopsis leaf anthocyanin accumulation and seed coat proanthocyanin production. CsMYBL2b strongly and CsMYBL2a weakly repressed the activating effects of CsMYB75/CsMYB86 on CsDFR and CsANS, due to their different EAR and TLLLFR domains and interactions with CsTT8/CsGL3, interfering with the functions of activating MBW complexes. CsMYBL2b and CsMYBL2a in tea leaves play different roles in fine-tuning CsMYB75/CsMYB86-MBW activation of biosynthesis of anthocyanins and catechins, respectively. The CsbZIP1-CsmiR858a-CsMYBL2 module mediated the UV-B- or cold-activated CsMYB75/CsMYB86 regulation of anthocyanin/catechin biosynthesis by repressing CsMYBL2a and CsMYBL2b. Similarly, the CsCOP1-CsbZIP1-CsPIF3 module, and BR signaling as well, mediated the high temperature repression of anthocyanin and catechin biosynthesis through differentially upregulating CsMYBL2b and CsMYBL2a, respectively. The present study provides new insights into the complex regulatory networks in environmental stress-modified flavonoid production in tea plant leaves.

Ferroelectric Bi2O2Te-Based Plasmonic Biosensor for Ultrasensitive Biomolecular Detection.

Ultrasensitive detection of biomarkers, particularly proteins, and microRNA, is critical for disease early diagnosis. Although surface plasmon resonance biosensors offer label-free, real-time detection, it is challenging to detect biomolecules at low concentrations that only induce a minor mass or refractive index change on the analyte molecules. Here an ultrasensitive plasmonic biosensor strategy is reported by utilizing the ferroelectric properties of Bi2O2Te as a sensitive-layer material. The polarization alteration of ferroelectric Bi2O2Te produces a significant plasmonic biosensing response, enabling the detection of charged biomolecules even at ultralow concentrations. An extraordinary ultralow detection limit of 1 fm is achieved for protein molecules and an unprecedented 0.1 fm for miRNA molecules, demonstrating exceptional specificity. The finding opens a promising avenue for the integration of 2D ferroelectric materials into plasmonic biosensors, with potential applications spanning a wide range.

Scalable integration of hybrid high-κ dielectric materials on two-dimensional semiconductors.

Two-dimensional (2D) semiconductors are promising channel materials for next-generation field-effect transistors (FETs). However, it remains challenging to integrate ultrathin and uniform high-κ dielectrics on 2D semiconductors to fabricate FETs with large gate capacitance. We report a versatile two-step approach to integrating high-quality dielectric film with sub-1 nm equivalent oxide thickness (EOT) on 2D semiconductors. Inorganic molecular crystal Sb2O3 is homogeneously deposited on 2D semiconductors as a buffer layer, which forms a high-quality oxide-to-semiconductor interface and offers a highly hydrophilic surface, enabling the integration of high-κ dielectrics via atomic layer deposition. Using this approach, we can fabricate monolayer molybdenum disulfide-based FETs with the thinnest EOT (0.67 nm). The transistors exhibit an on/off ratio of over 106 using an ultra-low operating voltage of 0.4 V, achieving unprecedently high gating efficiency. Our results may pave the way for the application of 2D materials in low-power ultrascaling electronics.

Glutamatergic melanocortin-4 receptor neurons regulate body weight.

The locus coeruleus (LC), enriched in vesicular glutamate transporter 2 (VGlut2) neurons, is a potential homeostasis-regulating hub. However, the identity of melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus (PVN) of the hypothalamus, PVNVGlut2::MC4R and LCVGlut2::MC4R regulation of body weight, and axonal projections of LCVGlut2 neurons remain unclear. Conditional knockout of MC4R in chimeric mice was used to confirm the effects of VGlut2. Interscapular brown adipose tissue was injected with pseudorabies virus to study the central nervous system projections. We mapped the LCVGlut2 circuitry. Based on the Cre-LoxP recombination system, specific knockdown of MC4R in VGlut2 neurons resulted in weight gain in chimeric mice. Adeno-associated virus-mediated knockdown of MC4R expression in the PVN and LC had potential superimposed effects on weight gain, demonstrating the importance of VGlut2 neurons. Unlike these wide-ranging efferent projections, the PVN, hypothalamic arcuate nucleus, supraoptic nucleus of the lateral olfactory tegmental nuclei, and nucleus tractus solitarius send excitatory projections to LCVGlut2 neurons. The PVN → LC glutamatergic MC4R long-term neural circuit positively affected weight management and could help treat obesity.

Micro(nano)plastics in the Human Body: Sources, Occurrences, Fates, and Health Risks.

The increasing global attention on micro(nano)plastics (MNPs) is a result of their ubiquity in the water, air, soil, and biosphere, exposing humans to MNPs on a daily basis and threatening human health. However, crucial data on MNPs in the human body, including the sources, occurrences, behaviors, and health risks, are limited, which greatly impedes any systematic assessment of their impact on the human body. To further understand the effects of MNPs on the human body, we must identify existing knowledge gaps that need to be immediately addressed and provide potential solutions to these issues. Herein, we examined the current literature on the sources, occurrences, and behaviors of MNPs in the human body as well as their potential health risks. Furthermore, we identified key knowledge gaps that must be resolved to comprehensively assess the effects of MNPs on human health. Additionally, we addressed that the complexity of MNPs and the lack of efficient analytical methods are the main barriers impeding current investigations on MNPs in the human body, necessitating the development of a standard and unified analytical method. Finally, we highlighted the need for interdisciplinary studies from environmental, biological, medical, chemical, computer, and material scientists to fill these knowledge gaps and drive further research. Considering the inevitability and daily occurrence of human exposure to MNPs, more studies are urgently required to enhance our understanding of their potential negative effects on human health.

The Hunt for Chemical Dark Matter across a River-to-Ocean Continuum.

Thousands of mass peaks emerge during molecular characterization of natural dissolved organic matter (DOM) using ultrahigh-resolution mass spectrometry. While mass peaks assigned to certain molecular formulas have been extensively studied, the uncharacterized mass peaks that represent a significant fraction of organic matter and convey biogenic elements and energy have been previously ignored. In this study, we introduce the term dark DOM (DDOM) for unassigned mass peaks and have explored its characteristics and environmental behaviors using a data set of 38 DOM extracts covering the Yangtze River-to-ocean continuum. We identified a total of 9141 DDOM molecules, which exhibited higher molecular weight and greater diversity than the DOM subset with assigned DOM formulas. Although DDOM contributed a smaller fraction of relative abundance, it significantly impacted the molecular weight and molecular composition of bulk DOM. A portion of DDOM with higher molecular weight was found to increase molecular abundance across the river-to-ocean continuum. These compounds could contain halogenated organic molecules and might have a high potential to contribute to the refractory organic carbon pool. With this study, we underline the contribution of dark matter to the total DOM pool and emphasize that more DDOM research is needed to understand its contribution to global biogeochemical cycles and carbon sequestration.

Dissecting the chiral recognition of TLR4/MD2 with Neoseptin-3 enantiomers by molecular dynamics simulations.

Toll-like receptor 4 (TLR4) is a pivotal innate immune recognition receptor that regulates intricate signaling pathways within the immune system. Neoseptin-3 (Neo-3), a recently identified small-molecule agonist for mouse TLR4/MD2, exhibits chiral recognition properties. Specifically, the L-enantiomer of Neo-3 (L-Neo-3) effectively activates the TLR4 signaling pathway, while D-Neo-3 fails to induce TLR4 activation. However, the underlying mechanism by which TLR4 enantioselectively recognizes Neo-3 enantiomers remains poorly understood. In this study, in silico simulations were performed to investigate the mechanism of chiral recognition of Neo-3 enantiomers by TLR4/MD2. Two L-Neo-3 molecules stably resided within the cavity of MD2 as a dimer, and the L-Neo-3 binding stabilized the (TLR4/MD2)2 dimerization state. However, the strong electrostatic repulsion between the hydrogen atoms on the chiral carbon of D-Neo-3 molecules caused the relative positions of two D-Neo-3 molecules to continuously shift during the simulation process, thus preventing the formation of D-Neo-3 dimer as well as their stable interactions with the surrounding residues in (TLR4/MD2)2. Considering that L-Neo-3 could not sustain a stable dimeric state in the bulk aqueous environment, it is unlikely that L-Neo-3 entered the cavity of MD2 as a dimeric unit. Umbrella sampling simulations revealed that the second L-Neo-3 molecule entering the cavity of MD2 exhibited a lower binding energy (-25.75 kcal mol-1) than that of the first L-Neo-3 molecule (-14.31 kcal mol-1). These results imply that two L-Neo-3 molecules enter the cavity of MD2 sequentially, with the binding of the first L-Neo-3 molecule facilitating the entry of the second one. This study dissects the binding process of Neo-3 enantiomers, offering a comprehensive understanding of the atomic-level mechanism underlying TLR4's chiral recognition of Neo-3 molecules.

Severe flood modulates the sources and age of dissolved organic carbon in the Yangtze River Estuary.

Floods in global large rivers modulate the transport of dissolved organic carbon (DOC) and estuarine hydrological characteristics significantly. This study investigated the impact of a severe flood on the sources and age of DOC in the Yangtze River Estuary (YRE) in 2020. Comparing the flood period in 2020 to the non-flood period in 2017, we found that the flood enhanced the transport of young DOC to the East China Sea (ECS), resulting in significantly enriched Δ14C-DOC values. During the flood period, the proportion of modern terrestrial organic carbon (OC) was significantly higher compared to the non-flood period. Conversely, the proportion of pre-aged sediment OC was significantly lower during the flood period. The high turbidity associated with the flood facilitated rapid transformation and mineralization of sedimentary and fresh terrestrial OC, modifying the sources of DOC. The flux of modern terrestrial OC transported to the ECS during the flood period was 1.58 times higher than that of the non-flood period. These findings suggest that floods can modulate the sources and decrease the age of DOC, potentially leading to increased greenhouse gas emissions. Further research is needed to understand the long-term impacts of floods on DOC dynamics in global estuaries.

M1 macrophage-related gene model for NSCLC immunotherapy response prediction.

Patients diagnosed with non-small cell lung cancer (NSCLC) have a limited lifespan and exhibit poor immunotherapy outcomes. M1 macrophages have been found to be essential for antitumor immunity. This study aims to develop an immunotherapy response evaluation model for NSCLC patients based on transcription. RNA sequencing profiles of 254 advanced-stage NSCLC patients treated with immunotherapy are downloaded from the POPLAR and OAK projects. Immune cell infiltration in NSCLC patients is examined, and thereafter, different coexpressed genes are identified. Next, the impact of M1 macrophage-related genes on the prognosis of NSCLC patients is investigated. Six M1 macrophage coexpressed genes, namely, NKX2-1, CD8A , SFTA3, IL2RB, IDO1, and CXCL9, exhibit a strong association with the prognosis of NSCLC and serve as effective predictors for immunotherapy response. A response model is constructed using a Cox regression model and Lasso Cox regression analysis. The M1 genes are validated in our TD-FOREKNOW NSCLC clinical trial by RT-qPCR. The response model shows excellent immunotherapy response prediction and prognosis evaluation value in advanced-stage NSCLC. This model can effectively predict advanced NSCLC prognosis and aid in identifying patients who could benefit from customized immunotherapy as well as sensitive drugs.

Seeds Priming with Melatonin Improves Root Hydraulic Conductivity of Wheat Varieties under Drought, Salinity, and Combined Stress.

Drought and salinity stress reduce root hydraulic conductivity of plant seedlings, and melatonin application positively mitigates stress-induced damage. However, the underlying effect of melatonin priming on root hydraulic conductivity of seedlings under drought-salinity combined remains greatly unclear. In the current report, we investigated the influence of seeds of three wheat lines' 12 h priming with 100 µM of melatonin on root hydraulic conductivity (Lpr) and relevant physiological indicators of seedlings under PEG, NaCl, and PEG + NaCl combined stress. A previous study found that the combined PEG and NaCl stress remarkably reduced the Lpr of three wheat varieties, and its value could not be detected. Melatonin priming mitigated the adverse effects of combined PEG + NaCl stress on Lpr of H4399, Y1212, and X19 to 0.0071 mL·h-1·MPa-1, 0.2477 mL·h-1·MPa-1, and 0.4444 mL·h-1·MPa-1, respectively, by modulating translation levels of aquaporin genes and contributed root elongation and seedlings growth. The root length of H4399, Y1212, and X19 was increased by 129.07%, 141.64%, and 497.58%, respectively, after seeds pre-treatment with melatonin under PEG + NaCl combined stress. Melatonin -priming appreciably regulated antioxidant enzyme activities, reduced accumulation of osmotic regulators, decreased levels of malondialdehyde (MDA), and increased K+ content in stems and root of H4399, Y1212, and X19 under PEG + NaCl stress. The path investigation displayed that seeds primed with melatonin altered the modification of the path relationship between Lpr and leaf area under stress. The present study suggested that melatonin priming was a strategy as regards the enhancement of root hydraulic conductivity under PEG, NaCl, and PEG + NaCl stress, which efficiently enhanced wheat resistant to drought-salinity stress.

The Effect of Solvents on the Crystal Morphology of Isosorbide Mononitrate and Its Molecular Mechanisms.

In this work, the modified attachment energy model was used to predict the crystal morphology of isosorbide mononitrate (ISMN) in the dichloromethane (CH2Cl2) solvent system and dichloromethane-n-hexane (CH2Cl2-C6H14) mixed solvent system. The solvent effect can significantly affect the crystal morphology, which can profoundly impact both the drug's physicochemical properties and the subsequent technological treatment process. In addition, the interactions between solvent molecules and crystal faces were investigated using molecular dynamics simulation, and radial distribution function (RDF) analysis was performed to determine the types of interactions. The structural parameter S was introduced to characterize the roughness of each crystal surface; the change in the CH2Cl2 diffusion coefficient before and after the addition of C6H14 was analyzed using mean square displacement (MSD). The calculation results of the modified attachment energy from the two solvent systems revealed that C6H14 could accelerate crystal growth, while the crystal morphology was not greatly affected, which is of some significance as a guide for the industrial crystallization process.

Diverse roles of MYB transcription factors in regulating secondary metabolite biosynthesis, shoot development, and stress responses in tea plants (Camellia sinensis).

Tea (Camellia sinensis) is concocted from tea plant shoot tips that produce catechins, caffeine, theanine, and terpenoids, which collectively determine the rich flavors and health benefits of the infusion. However, little is known about the integrated regulation of shoot tip development and characteristic secondary metabolite biosynthesis in tea plants. Here, we demonstrate that MYB transcription factors (TFs) play key and yet diverse roles in regulating leaf and stem development, secondary metabolite biosynthesis, and environmental stress responses in tea plants. By integrating transcriptomic and metabolic profiling data in different tissues at a series of developmental stages or under various stress conditions, alongside biochemical and genetic analyses, we predicted the MYB TFs involved in regulating shoot development (CsMYB2, 98, 107, and 221), epidermal cell initiation (CsMYB184, 41, 139, and 219), stomatal initiation (CsMYB113 and 153), and the biosynthesis of flavonoids (including catechins, anthocyanins, and flavonols; CsMYB8 and 99), caffeine (CsMYB85 and 86), theanine (CsMYB9 and 49), carotenoids (CsMYB110), mono-/sesquiterpenoid volatiles (CsMYB68, 147, 148, and 193), lignin (CsMYB164 and 192), and indolic compounds (CsMYB139, 162, and 198), as well as the MYB TFs that are likely involved in hormone signaling-mediated environmental stress and defense responses. We characterized the functions of some key MYBs in regulating flavonoid and carotenoid biosynthesis for tea quality and flavor. This study provides a cross-family analysis of MYBs in tea alongside new insights into the coordinated regulation of tea plant shoot development and secondary metabolism, paving the way towards understanding of tea quality trait formation and genetic improvement of quality tea plants.

Regulatory effects of silicon nanoparticles on the growth and photosynthesis of cotton seedlings under salt and low-temperature dual stress.

BACKGROUND: Silicon nanoparticles (SiO2-NPs) play a crucial role in plants mitigating abiotic stress. However, the regulatory mechanism of SiO2-NPs in response to multiple stress remains unclear. The objectives of this study were to reveal the regulatory mechanism of SiO2-NPs on the growth and photosynthesis in cotton seedlings under salt and low-temperature dual stress. It will provide a theoretical basis for perfecting the mechanism of crop resistance and developing the technology of cotton seedling preservation and stable yield in arid and high salt areas. RESULTS: The results showed that the salt and low-temperature dual stress markedly decreased the plant height, leaf area, and aboveground biomass of cotton seedlings by 9.58%, 15.76%, and 39.80%, respectively. While SiO2-NPs alleviated the damage of the dual stress to cotton seedling growth. In addition to reduced intercellular CO2 concentration, SiO2-NPs significantly improved the photosynthetic rate, stomatal conductance, and transpiration rate of cotton seedling leaves. Additionally, stomatal length, stomatal width, and stomatal density increased with the increase in SiO2-NPs concentration. Notably, SiO2-NPs not only enhanced chlorophyll a, chlorophyll b, and total chlorophyll content, but also slowed the decrease of maximum photochemical efficiency, actual photochemical efficiency, photochemical quenching of variable chlorophyll, and the increase in non-photochemical quenching. Moreover, SiO2-NPs enhanced the activities of ribulose-1,5-bisphosphate carboxylase/oxygenase and phosphoenolpyruvate carboxylase, improved leaf water potential, and decreased abscisic acid and malondialdehyde content. All the parameters obtained the optimal effects at a SiO2-NPs concentration of 100 mg L- 1, and significantly increased the plant height, leaf area, and aboveground biomass by 7.68%, 5.37%, and 43.00%, respectively. Furthermore, significant correlation relationships were observed between photosynthetic rate and stomatal conductance, stomatal length, stomatal width, stomatal density, chlorophyll content, maximum photochemical efficiency, actual photochemical efficiency, photochemical quenching of variable chlorophyll, and Rubisco activity. CONCLUSION: The results suggested that the SiO2-NPs improved the growth and photosynthesis of cotton seedlings might mainly result from regulating the stomatal state, improving the light energy utilization efficiency and electron transport activity of PSII reaction center, and inducing the increase of Rubisco activity to enhance carbon assimilation under the salt and low-temperature dual stress.

Broadband Polarization-Sensitive Photodetection of Magnetic Semiconducting MnTe Nanoribbons.

2D materials with low symmetry are explored in recent years because of their anisotropic advantage in polarization-sensitive photodetection. Herein the controllably grown hexagonal magnetic semiconducting α-MnTe nanoribbons are reported with a highly anisotropic (100) surface and their high sensitivity to polarization in a broadband photodetection, whereas the hexagonal structure is highly symmetric. The outstanding photoresponse of α-MnTe nanoribbons occurs in a broadband range from ultraviolet (UV, 360 nm) to near infrared (NIR, 914 nm) with short response times of 46 ms (rise) and 37 ms (fall), excellent environmental stability, and repeatability. Furthermore, due to highly anisotropic (100) surface, the α-MnTe nanoribbons as photodetector exhibit attractive sensitivity to polarization and high dichroic ratios of up to 2.8 under light illumination of UV-to-NIR wavelengths. These results demonstrate that 2D magnetic semiconducting α-MnTe nanoribbons provide a promising platform to design the next-generation polarization-sensitive photodetectors in a broadband range.

Unraveling the Linkages between Molecular Abundance and Stable Carbon Isotope Ratio in Dissolved Organic Matter Using Machine Learning.

Dissolved organic matter (DOM) is a complex mixture of molecules that constitutes one of the largest reservoirs of organic matter on Earth. While stable carbon isotope values (δ13C) provide valuable insights into DOM transformations from land to ocean, it remains unclear how individual molecules respond to changes in DOM properties such as δ13C. To address this, we employed Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) to characterize the molecular composition of DOM in 510 samples from the China Coastal Environments, with 320 samples having δ13C measurements. Utilizing a machine learning model based on 5199 molecular formulas, we predicted δ13C values with a mean absolute error (MAE) of 0.30‰ on the training data set, surpassing traditional linear regression methods (MAE 0.85‰). Our findings suggest that degradation processes, microbial activities, and primary production regulate DOM from rivers to the ocean continuum. Additionally, the machine learning model accurately predicted δ13C values in samples without known δ13C values and in other published data sets, reflecting the δ13C trend along the land to ocean continuum. This study demonstrates the potential of machine learning to capture the complex relationships between DOM composition and bulk parameters, particularly with larger learning data sets and increasing molecular research in the future.

Exploring the Complexities of Dissolved Organic Matter Photochemistry from the Molecular Level by Using Machine Learning Approaches.

Dissolved organic matter (DOM) sustains a substantial part of the organic matter transported seaward, where photochemical reactions significantly affect its transformation and fate. The irradiation experiments can provide valuable information on the photochemical reactivity (photolabile, photoresistant, and photoproduct) of molecules. However, the inconsistency of the fate of irradiated molecules among different experiments curtailed our understanding of the roles the photochemical reactions have played, which cannot be properly addressed by traditional approaches. Here, we conducted irradiation experiments for samples from two large estuaries in China. Molecules that occurred in irradiation experiments were characterized by the Fourier transform ion cyclotron resonance mass spectrometry and assigned probabilistic labels to define their photochemical reactivity. These molecules with probabilistic labels were used to construct a learning database for establishing a suitable machine learning (ML) model. We further applied our well-trained ML model to "un-matched" (i.e., not detected in our irradiation experiments) molecules from five estuaries worldwide, to predict their photochemical reactivity. Results showed that numerous molecules with strong photolability can be captured solely by the ML model. Moreover, comparing DOM photochemical reactivity in five estuaries revealed that the riverine DOM chemistry largely determines their subsequent photochemical transformation. We offer an expandable and renewable approach based on ML to compatibly integrate existing irradiation experiments and shed insight into DOM transformation and degradation processes.

HPLC-CAD as a supplementary method for the quantification of related structure impurities for the purity assessment of organic CRMs.

In organic purity assessment, chromatography separation with a suitable detector is required. Diode array detection (DAD) has been a widely used technique for high-performance liquid chromatography (HPLC) analyses, but its application is limited to compounds with sufficient UV chromophores. Charged aerosol detector (CAD), as a mass-dependent detector, is advantageous for providing a nearly uniform response for analytes, regardless of their structures. In this study, 11 non-volatile compounds with/without UV chromophores were analyzed by CAD using continuous direct injection mode. The RSDs of CAD responses were within 17%. For saccharides and bisphenols, especially, the RSDs were lower (2.12% and 8.14%, respectively). Since bisphenols exist in UV chromophores, their HPLC-DAD responses were studied and compared with CAD responses, with CAD showing a more uniform response. Besides, the key parameters of HPLC-CAD were optimized and the developed method was verified using a Certified Reference Material (CRM, dulcitol, GBW06144). The area normalization result of dulcitol measured by HPLC-CAD was 99.89% ± 0.02% (n = 6), consistent with the certified value of 99.8% ± 0.2% (k = 2). The result of this work indicated that the HPLC-CAD method could be a good complementary tool to traditional techniques for the purity assessment of organic compounds, especially for compounds lacking UV chromophores.

Dissecting the species-specific recognition of Neoseptin 3 by TLR4/MD2 via molecular dynamics simulations.

Toll-like receptor 4 (TLR4) is crucial in the innate immune response with species-specific recognition. As a novel small-molecule agonist for mouse TLR4/MD2, Neoseptin 3 fails to activate human TLR4/MD2, while the underlying mechanism is unclear. Herein, molecular dynamics simulations were performed to investigate the species-specific molecular recognition of Neoseptin 3. Lipid A, a classic TLR4 agonist showing no apparent species-specific sensing by TLR4/MD2, was also investigated for comparison. Neoseptin 3 and lipid A showed similar binding patterns with mouse TLR4/MD2. Although the binding free energies of Neoseptin 3 interacting with TLR4/MD2 from mouse and human species were similar, protein-ligand interactions and the details of the dimerization interface were substantially different between Neoseptin 3-bound mouse and human heterotetramers at the atomic level. Neoseptin 3 binding made human (TLR4/MD2)2 more flexible than human (TLR4/MD2/Lipid A)2, especially at the TLR4 C-terminus and MD2, which drives human (TLR4/MD2)2 fluctuating away from the active conformation. In contrast to mouse (TLR4/MD2/2*Neoseptin 3)2 and mouse/human (TLR4/MD2/Lipid A)2 systems, Neoseptin 3 binding to human TLR4/MD2 led to the separating trend of the C-terminus of TLR4. Furthermore, the protein-protein interactions at the dimerization interface between TLR4 and the neighboring MD2 in the human (TLR4/MD2/2*Neoseptin 3)2 system were much weaker than those of the lipid A-bound human TLR4/MD2 heterotetramer. These results explained the inability of Neoseptin 3 to activate human TLR4 signaling and accounted for the species-specific activation of TLR4/MD2, which provides insight for transforming Neoseptin 3 as a human TLR4 agonist.