Microbial interactions facilitating efficient methane driven denitrification via in-situ utilization of short chain fatty acids.

High nitrate pollution in agriculture and industry poses a challenge to emerging methane oxidation coupled denitrification. In this study, an efficient nitrate removal efficiency of 100 % was achieved at an influent loading rate of 400 mg-N/L·d, accompanied by the production of short chain fatty acids (SCFAs) with a maximum value of 80.9 mg/L. Batch tests confirmed that methane was initially converted to acetate, which then served as a carbon source for denitrification. Microbial community characterization revealed the dominance of heterotrophic denitrifiers, including Simplicispira (22.8 %), Stappia (4.9 %), and the high­nitrogen-tolerant heterotrophic denitrifier Diaphorobacter (19.0 %), at the nitrate removal rate of 400 mg-N/L·d. Notably, the low abundance of methanotrophs ranging from 0.24 % to 3.75 % across all operational stages does not fully align with the abundance of pmoA genes, suggesting the presence of other functional microorganisms capable of methane oxidation and SCFAs production. These findings could facilitate highly efficient denitrification driven by methane and contributed to the development of denitrification using methane as an electron donor.

ß-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer's disease.

Introduction: The study of the pathophysiology study of Alzheimer's disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular -amyloid (A) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration. Methods: The humanized APPNL-G-F knock-in mouse line was crossed to the PS19 MAPTP301S, over-expression mouse line to create the dual APPNL-G-F/PS19 MAPTP301S line. The resulting pathologies were characterized by immunochemical methods and PCR. Results: We now report on a double transgenic APPNL-G-F/PS19 MAPTP301S mouse that at 6 months of age exhibits robust A plaque accumulation, intense MAPT pathology, strong inflammation and extensive neurodegeneration. The presence of A pathology potentiated the other major pathologies, including MAPT pathology, inflammation and neurodegeneration. MAPT pathology neither changed levels of amyloid precursor protein nor potentiated A accumulation. Interestingly, study of immunofluorescence in cleared brains indicates that microglial inflammation was generally stronger in the hippocampus, dentate gyrus and entorhinal cortex, which are regions with predominant MAPT pathology. The APPNL-G-F/MAPTP301S mouse model also showed strong accumulation of N6-methyladenosine (m6A), which was recently shown to be elevated in the AD brain. m6A primarily accumulated in neuronal soma, but also co-localized with a subset of astrocytes and microglia. The accumulation of m6A corresponded with increases in METTL3 and decreases in ALKBH5, which are enzymes that add or remove m6A from mRNA, respectively. Discussion: Our understanding of the pathophysiology of Alzheimer's disease (AD) has been hampered by lack animal models that recapitulate the major AD pathologies, including extracellular -amyloid (A) deposition, intracellular aggregation of microtubule associated protein tau (MAPT), inflammation and neurodegeneration. The APPNL-G-F/MAPTP301S mouse recapitulates many features of AD pathology beginning at 6 months of aging, and thus represents a useful new mouse model for the field.

Hydrophobic carbon quantum dots with red fluorescence: An optical dual-mode and smartphone imaging sensor for identifying Chinese Baijiu quality.

Chinese Baijiu (Liquor) is a popular alcoholic beverage, and the ethanol content in Baijiu is closely related to its quality; therefore, it is of great significance to explore a facile, sensitive, and rapid method to detect ethanol content in Baijiu. Hydrophobic carbon quantum dots (H-CQDs) with bright red fluorescence (24.14 %) were fabricated by hydrothermal method using o-phenylenediamine, p-aminobenzoic acid, manganese chloride, and hydrochloric acid as reaction precursors. After the introduction of ultrapure water into the ethanol solution dissolved with H-CQDs, the aggregated H-CQDs resulted in significant changes in fluorescence intensity and absorbance. On this basis, a sensor for detecting ethanol by optical dual-mode and smartphone imaging was constructed. More importantly, the sensor can be used for detecting ethanol content in Chinese Baijiu with satisfactory results. This sensing platform has great potential for quality identification in Chinese Baijiu, broadening the application scope of CQDs in food safety detection.

Phenolic constituents from the branches of Viburnum chinshanense as potential α-amylase and α-glucosidase inhibitory agents.

This paper reports the isolation of two undescribed phenolic glycosides (1 and 2), together with seven known compounds (3-9) from the branches of Viburnum chinshanense. The structures of undescribed compounds were elucidated by comprehensive spectroscopic methods (1D NMR, 2D NMR, and HRESIMS). The sugar units of compounds 1 and 2 were identified by acid hydrolysis and HPLC analysis of the chiral derivatives of the monosaccharides. Furthermore, the α­amylase and α-glucosidase inhibitory activities of all isolates were evaluated and compounds 1, 5, and 8 displayed potential α­amylase and α-glucosidase inhibitory activities. The molecular docking analyses of compounds 1 and 8 with the potent inhibition towards the target enzymes were also performed.

Bioavailability and Metabolism of Bioactive Peptide IRW with Angiotensin-Converting Enzyme 2 (ACE2) Upregulatory Activity in Spontaneously Hypertensive Rats.

Peptide IRW is the first food-derived angiotensin-converting enzyme 2 (ACE2) upregulator. This study aimed to investigate the pharmacokinetic characteristics of IRW and identify the metabolites contributing to its antihypertensive activity in spontaneously hypertensive rats (SHRs). Rats were administered 100 mg of IRW/kg of the body weight via an intragastric or intravenous route. The bioavailability (F %) was determined to be 11.7%, and the half-lives were 7.9 ± 0.5 and 28.5 ± 6.8 min for gavage and injection, respectively. Interestingly, significant blood pressure reduction was not observed until 1.5 h post oral administration, or 2 h post injection, indicating that the peptide's metabolites are likely responsible for the blood pressure-lowering activity. Time-course metabolomics revealed a significant increase in the level of kynurenine, a tryptophan metabolite, in blood after IRW administration. Kynurenine increased the level of ACE2 in cells. Oral administration of tryptophan (W), but not dipeptide IR, lowered the blood pressure and upregulated aortic ACE2 in SHRs. Our study supports the key role of tryptophan and its metabolite, kynurenine, in IRW's blood pressure-lowering effects.

PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint inflammation and bone damage, that not only restricts patient activity but also tends to be accompanied by a series of complications, seriously affecting patient prognosis. Peroxisome proliferator-activated receptor gamma (PPARG), a receptor that controls cellular metabolism, regulates the function of immune cells and stromal cells. Previous studies have shown that PPARG is closely related to the regulation of inflammation. However, the role of PPARG in regulating the pathological processes of RA is poorly understood. MATERIALS AND METHODS: PPARG expression was examined in the synovial tissues and peripheral blood mononuclear cells (PBMCs) from RA patients and the paw of collagen-induced arthritis (CIA) model rats. Molecular biology experiments were designed to examine the effect of PPARG and cannabidiol (CBD) on RAW264.7 cells and CIA rats. RESULTS: The results reveal that PPARG accelerates reactive oxygen species (ROS) clearance by promoting autophagy, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation. Notably, CBD may be a promising candidate for understanding the mechanism by which PPARG regulates autophagy-mediated inflammation. CONCLUSIONS: Taken together, these findings indicate that PPARG may have a role for distinguishing between RA patients and healthy control, and for distinguishing RA activity; moreover, PPARG could be a novel pharmacological target for alleviating RA through the mediation of autophagy. CBD can act as a PPARG agonist that alleviates the inflammatory progression of RA.

Ultra-Low-Dose UV-C Photo-stimulation Promotes Neural Stem Cells Differentiation via Presenilin 1 Mediated Notch and ß-Catenin Activation.

Light-based photo-stimulation has demonstrated promising effects on stem cell behavior, particularly in optimizing neurogenesis. However, the precise parameters for achieving optimal results, including the wavelengths, light intensity, radiating energy, and underlying mechanisms, remain incompletely understood. In this study, we focused on utilizing ultraviolet-C (UV-C) at a specific wavelength of 254 nm, with an ultra-low dose at intensity of 330 µW/cm2 and a total energy of 594 mJ/cm2 per day over a period of seven days, to stimulate the proliferation and differentiation of mouse neural stem cells (NSCs). The results revealed that the application of ultra-low-dose UV-C yielded the most significant effect in promoting differentiation when compared to mixed ultraviolet (UV) and ultraviolet-A (UV-A) radiation at equivalent exposure levels. The mechanism exploration elucidated the role of Presenilin 1 in mediating the activation of ß-catenin and Notch 1 by the UV-C treatment, both of which are key factors facilitating NSCs proliferation and differentiation. These findings introduce a novel approach employing ultra-low-dose UV-C for specifically enhancing NSC differentiation, as well as the underlying mechanism. It would contribute valuable insights into brain stimulation and neurogenesis modulation for various diseases, offering potential therapeutic avenues for further exploration.

Precision of liver and pancreas apparent diffusion coefficients using motion-compensated gradient waveforms in DWI.

BACKGROUND: Diffusion weighted imaging (DWI) with optimized motion-compensated gradient waveforms reduces signal dropouts in the liver and pancreas caused by cardiovascular-associated motion, however its precision is unknown. We hypothesized that DWI with motion-compensated DW gradient waveforms would improve apparent diffusion coefficient (ADC)-repeatability and inter-reader reproducibility compared to conventional DWI in these organs. METHODS: In this IRB-approved, prospective, single center study, subjects recruited between October 2019 and March 2020 were scanned twice on a 3 T scanner, with repositioning between test and retest. Each scan included two respiratory-triggered DWI series with comparable acquisition time: 1) conventional (monopolar) 2) motion- compensated diffusion gradients. Three readers measured ADC values. One-way ANOVA, Bland-Altman analysis were used for statistical analysis. RESULTS: Eight healthy participants (4 male/4 female), with a mean age of 29 ± 4 years, underwent the liver and pancreas MRI protocol. Four patients with liver metastases (2 male/2 female) with a mean age of 58 ± 5 years underwent the liver MRI protocol. In healthy participants, motion-compensated DWI outperformed conventional DWI with mean repeatability coefficient of 0.14 × 10-3 (CI:0.12-0.17) vs. 0.31 × 10-3 (CI:0.27-0.37) mm2/s for liver, and 0.11 × 10-3 (CI:0.08-0.15) vs. 0.34 × 10-3 (CI:0.27-0.49) mm2/s for pancreas; and with mean reproducibility coefficient of 0.20 × 10-3 (CI:0.18-0.23) vs. 0.51 × 10-3 (CI:0.46-0.58) mm2/s for liver, and 0.16 × 10-3 (CI:0.13-0.20) vs. 0.42 × 10-3 (CI:0.34-0.52) mm2/s for pancreas. In patients, improved repeatability was observed for motion-compensated DWI in comparison to conventional with repeatability coefficient of 0.51 × 10- 3 mm2/s (CI:0.35-0.89) vs. 0.70 × 10-3 mm2/s (CI:0.49-1.20). CONCLUSION: Motion-compensated DWI enhances the precision of ADC measurements in the liver and pancreas compared to conventional DWI.

One-Dimensional MoS2 Nanoscrolls as Miniaturized Memories.

Dimensionality of materials is closely related to their physical properties. For two-dimensional (2D) semiconductors such as monolayer molybdenum disulfide (MoS2), converting them from 2D nanosheets to one-dimensional (1D) nanoscrolls could contribute to remarkable electronic and optoelectronic properties, yet the rolling-up process still lacks sufficient controllability, which limits the development of their device applications. Herein we report a modified solvent evaporation-induced rolling process that halts at intermediate states and achieve MoS2 nanoscrolls with high yield and decent axial uniformity. The accordingly fabricated nanoscroll memories exhibit an on/off ratio of ∼104 and a retention time exceeding 103 s and can realize multilevel storage with pulsed gate voltages. Such open-end, high-curvature, and hollow 1D nanostructures provide new possibilities to manipulate the hysteresis windows and, consequently, the charge storage characteristics of nanoscale field-effect transistors, thereby holding great promise for the development of miniaturized memories.

Synergistic Effects and Kinetic Analysis in Co-Pyrolysis of Peanut Shells and Polypropylene.

The impact of COVID-19 has boosted growth in the takeaway and medical industries but has also generated a large amount of plastic waste. Peanut shells (PS) are produced in large quantities and are challenging to recycle in China. Co-pyrolysis of peanut shells (PS) and polypropylene (PP) is an effective method for processing plastic waste and energy mitigation. Thermogravimetric analysis was conducted on PS, PP, and their blends (PS-PP) at different heating rates (10, 20, 30 °C·min-1). The results illustrated that the co-pyrolysis process of PS-PP was divided into two distinct decomposition stages. The first stage (170-400 °C) was predominantly linked to PS decomposition. The second stage (400-520 °C) resulted from the combinations of PS and PP's thermal degradations, with the most contribution from PP degradation. With the increase in heating rate, thermogravimetric hysteresis appeared. Kinetic analysis indicated that the co-pyrolysis process reduced the individual pyrolysis activation energy, especially in the second stage, with a correlation coefficient (R2) generally maintained above 0.95. The multi-level reaction mechanism function model can effectively reveal the co-pyrolysis process mechanism. PS proved to be high-quality biomass for co-pyrolysis with PP, and all mixtures exhibited synergistic effects at a mixing ratio of 1:1 (PS1-PP1). This study accomplished effective waste utilization and optimized energy consumption. It holds significance in determining the interaction mechanism of mixed samples in the co-pyrolysis process.

Risk factors of Carbapenem-resistant Enterobacterales intestinal colonization for subsequent infections in hematological patients: a retrospective case-control study.

Objective: Infections caused by Carbapenem-resistant Enterobacterales (CRE) have high treatment costs, high mortality and few effective therapeutic agents. This study aimed to determine the risk factors for progression from intestinal colonization to infection in hematological patients and the risk factors for 30-day mortality in infected patients. Methods: A retrospective case-control study was conducted in the Department of Hematology at Shandong Provincial Hospital affiliated to Shandong First Medical University from April 2018 to April 2022. Patients who developed subsequent infections were identified as the case group by electronic medical record query of patients with a positive rectal screen for CRE colonization, and patients who did not develop subsequent infections were identified as the control group by stratified random sampling. Univariate analysis and logistic regression analysis determined risk factors for developing CRE infection and risk factors for mortality in CRE-infected patients. Results: Eleven hematological patients in the study developed subsequent infections. The overall 30-day mortality rate for the 44 hematological patients in the case-control study was 11.4% (5/44). Mortality was higher in the case group than in the control group (36.5 vs. 3.0%, P = 0.0026), and septic shock was an independent risk factor for death (P = 0.024). Univariate analysis showed that risk factors for developing infections were non-steroidal immunosuppressants, serum albumin levels, and days of hospitalization. In multivariable logistic regression analysis, immunosuppressants [odds ratio (OR), 19.132; 95% confidence interval (CI), 1.349-271.420; P = 0.029] and serum albumin levels (OR, 0.817; 95% CI, 0.668-0.999; P = 0.049) were independent risk factors for developing infections. Conclusion: Our findings suggest that septic shock increases mortality in CRE-infected hematological patients. Hematological patients with CRE colonization using immunosuppressive agents and reduced serum albumin are more likely to progress to CRE infection. This study may help clinicians prevent the onset of infection early and take measures to reduce mortality rates.

[Effects of organic fertilizer from traditional Chinese medicine residues on growth and soil microbial community of Salvia miltiorrhiza by metagenomic technique].

Soil microbiome is a key evaluation index of soil health. Previous studies have shown that organic fertilizer from traditional Chinese medicine(TCM)residues can improve the yield and quality of cultivated traditional Chinese medicinal materials. However, there are few reports on the effects of organic fertilizer from TCM residues on soil microbiome. Therefore, on the basis of evaluating the effects of organic fertilizer from TCM residues on the yield and quality of cultivated Salvia miltiorrhiza, the metagenomic sequencing technique was used to study the effects of organic fertilizer from TCM residues on rhizosphere microbiome community and function of cultivated S. miltiorrhiza. The results showed that:(1) the application of organic fertilizer from TCM residues promoted the growth of S. miltiorrhiza and the accumulation of active components, and the above-ground and underground dry weight and fresh weight of S. miltiorrhiza increased by 371.4%, 288.3%, 313.4%, and 151.9%. The increases of rosmarinic acid and salvianolic acid B were 887.0% and 183.0%.(2)The application of organic fertilizer from TCM residues significantly changed the rhizosphere bacterial and fungal community structures, and the microbial community composition was significantly different.(3)The relative abundance of soil-beneficial bacteria, such as Nitrosospira multiformis, Bacillus subtilis, Lysobacter enzymogenes, and Trichoderma was significantly increased by the application of organic fertilizer from TCM residues.(4)KEGG function prediction analysis showed that metabolism-related microorganisms were more easily enriched in the soil environment after organic fertilizer application. The abundance of functional genes related to nitrification and denitrification could also be increased after the application of organic fertilizer from TCM residues. The results of this study provide guidance for the future application of organic fertilizer from TCM residues in the cultivation of traditio-nal Chinese medicinal materials and enrich the content of green cultivation technology of traditional Chinese medicinal materials.

Thromboprophylaxis for outpatients with COVID-19: a Systematic Review and Meta-analysis.

Patients with COVID-19 develop an increased risk of thromboembolism. Thromboprophylaxis is recommended for hospitalized COVID-19 patients, but the role of thromboprophylaxis in outpatients with COVID-19 is less well defined. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of thromboprophylaxis among outpatients with COVID-19. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to August 2023. The outcomes of interest were venous thromboembolic events including deep venous thrombosis and pulmonary embolism, all-cause mortality, cardiovascular events, hospitalization, major bleeding events, and non-major bleeding events. We included 6 trials comprising 3352 patients. Patients who received thromboprophylaxis had an approximately 70% reduction in venous thromboembolism (RR, 0.28 [95% CI, 0.08 to 0.93]) compared to patients who did not receive thromboprophylaxis. The risk of mortality (RR, 0.79 [95% CI, 0.35 to 1.77]), cardiovascular events (RR, 0.91 [95% CI, 0.30 to 2.73]), and hospitalization (RR, 1.09 [95% CI, 0.81 to 1.47]) were similar between the two groups. Patients who received thromboprophylaxis had a higher risk of non-major bleeding (RR, 3.48 [95% CI, 1.72 to 7.05) compared to patients who did not receive thromboprophylaxis. Thromboprophylaxis reduced the risk of venous thromboembolism but not mortality, cardiovascular events, or hospitalization among outpatients with COVID-19.

Performance Enhancement of Silicone Rubber Using Superhydrophobic Silica Aerogel with Robust Nanonetwork Structure and Outstanding Interfacial Effect.

The application of high-performance rubber nanocomposites has attracted wide attention, but its development is limited by the imbalance of interface and network effects caused by fillers. Herein, an ultrastrong polymer nanocomposite is successfully designed by introducing a superhydrophobic and mesoporous silica aerogel (HSA) as the filler to poly(methyl vinyl phenyl) siloxane (PVMQ), which increased the PVMQ elongation at break (∼690.1%) by ∼9.3 times and the strength at break (∼6.6 MPa) by ∼24.3 times. Furthermore, HSA/PVMQ with a high dynamic storage modulus (G'0) of ∼12.2 MPa and high Payne effect (ΔG') of ∼9.4 MPa is simultaneously achieved, which is equivalent to 2-3 times that of commercial fumed silica reinforced PVMQ. The superior performance is attributed to the filler-rubber interfacial interaction and the robust filler-rubber entanglement network which is observed by scanning electron microscopy. When the HSA-PVMQ entanglement network is subjected to external stress, both the HSA and bound-PVMQ chains are synergistically involved in resisting structural evolution, resulting in the maximized energy dissipation and deformation resistance through the desorption of the polymer chain and the slip/interpenetrating of the exchange hydrogen bond pairs. Hence, highly aggregated nanoporous silica aerogels may soon be widely used in the application of reinforced silicone rubber or other polymers shortly.

Engineering of single atomic Fe-N4 sites on hollow carbon cages to achieve highly reversible MoS2 anodes for Li-ion batteries.

Although the single atom electrocatalysts have been demonstrated as efficient catalysts for promoting Li2S/Na2S formation and decomposition in Li-S/Na-S batteries, the functional morphological and structural engineering capable of exposing more active sites is regarded as an essential factor to further enhance the catalytic activity. Here, we have synthesized a single atomically dispersed Fe sites embedded within hollow nitrogen doped carbon cages (Fe-N-HCN) using Fe3O4 spheres as an oxidant and sacrificial template, which is used as a high-efficiency catalyst for boosting the reversible capacity of MoS2 anode in lithium-ion batteries (LIBs). As expected, the electrochemical reaction of MoS2/Fe-N-HCN anode exhibits higher reversibility than pure MoS2 electrodes. Moreover, density functional theory is also employed to reveal that Fe-N-HCN can be effectively adsorbed and catalyze the rapid decomposition of Li2S. The hollow carbon cage structure can facilitate the exposure of the active Fe-N4 sites and favor the mass transfer during the electrochemical reactions, thus the synergistic effect of the Fe-N4 site and the hollow carbon cage structure together improve the catalytic activity for the conversion reaction of MoS2 anode.

Co-existing inorganic anions influenced the Norrish I and Norrish II type photoaging mechanism of biodegradable microplastics.

The degradation of biodegradable plastics (BPs) in natural environments is constrained, and the mechanisms underlying their photoaging in aquatic settings remain inadequately understood. In view of this, this study systematically investigated the photoaging process of biodegradable Poly (butyleneadipate-co-terephthalate) microplastics (PBAT-MPs), which are more widely used. The investigation was carried out in the presence of common inorganic anions (Br-, Cl- and NO3-). The results of EPR, FTIR and FESEM tests, along with pseudo-first-order kinetics analyses, showed that the presence of NO3- promoted the photoaging of PBAT-MPs, while the presence of Br- and Cl- inhibited the photoaging of PBAT-MPs. In addition, the results of the Two-Dimensional Correlation Spectroscopy (2D-COS) analysis determined the order of the changes in the functional groups, revealing that the Norrish I and Norrish II reaction mechanisms are presented by PBAT-MPs during the aging process, and the process is closely related to the ion concentration and UV irradiation time. This study provides valuable insights for understanding the phototransformation process of BPs in natural aqueous environments.

Dual quantum spin Hall insulator by density-tuned correlations in TaIrTe4.

The convergence of topology and correlations represents a highly coveted realm in the pursuit of new quantum states of matter1. Introducing electron correlations to a quantum spin Hall (QSH) insulator can lead to the emergence of a fractional topological insulator and other exotic time-reversal-symmetric topological order2-8, not possible in quantum Hall and Chern insulator systems. Here we report a new dual QSH insulator within the intrinsic monolayer crystal of TaIrTe4, arising from the interplay of its single-particle topology and density-tuned electron correlations. At charge neutrality, monolayer TaIrTe4 demonstrates the QSH insulator, manifesting enhanced nonlocal transport and quantized helical edge conductance. After introducing electrons from charge neutrality, TaIrTe4 shows metallic behaviour in only a small range of charge densities but quickly goes into a new insulating state, entirely unexpected on the basis of the single-particle band structure of TaIrTe4. This insulating state could arise from a strong electronic instability near the van Hove singularities, probably leading to a charge density wave (CDW). Remarkably, within this correlated insulating gap, we observe a resurgence of the QSH state. The observation of helical edge conduction in a CDW gap could bridge spin physics and charge orders. The discovery of a dual QSH insulator introduces a new method for creating topological flat minibands through CDW superlattices, which offer a promising platform for exploring time-reversal-symmetric fractional phases and electromagnetism2-4,9,10.

Molecular mechanism of the metal-independent production of hydroxyl radicals by thiourea dioxide and H2O2.

It is well-known that highly reactive hydroxyl radicals (HO•) can be produced by the classic Fenton system and our recently discovered haloquinone/H2O2 system, but rarely from thiol-derivatives. Here, we found, unexpectedly, that HO• can be generated from H2O2 and thiourea dioxide (TUO2), a widely used and environmentally friendly bleaching agent. A carbon-centered radical and sulfite were detected and identified as the transient intermediates, and urea and sulfate as the final products, with the complementary application of electron spin-trapping, oxygen-18 isotope labeling coupled with HPLC/MS analysis. Density functional theory calculations were conducted to further elucidate the detailed pathways for HO• production. Taken together, we proposed that the molecular mechanism for HO• generation by TUO2/H2O2: TUO2 tautomerizes from sulfinic acid into ketone isomer (TUO2-K) through proton transfer, then a nucleophilic addition of H2O2 on the S atom of TUO2-K, forming a S-hydroperoxide intermediate TUO2-OOH, which dissociates homolytically to produce HO•. Our findings represent the first experimental and computational study on an unprecedented new molecular mechanism of HO• production from simple thiol-derived sulfinic acids, which may have broad chemical, environmental, and biomedical significance for future research on the application of the well-known bleaching agent and its analogs.

Advancing Natural Product Discovery: A Structure-Oriented Fractions Screening Platform for Compound Annotation and Isolation.

Natural product discovery is hindered by the lack of tools that integrate untargeted nuclear magnetic resonance and mass spectrometry data on a library scale. This article describes the first application of the innovative NMR/MS-based machine learning tool, the "Structure-Oriented Fractions Screening Platform (SFSP)", enabling functional-group-guided fractionation and accelerating the discovery and characterization of undescribed natural products. The concept was applied to the extract of a marine fungus known to be a prolific producer of diverse natural products. With the assistance of SFSP, we isolated 24 flavipidin derivatives and five phenalenone analogues from Aspergillus sp. GE2-6, revealing 27 undescribed compounds. Compounds 7-22 were proposed as isomeric derivatives featuring a 5/6-ring fusion, formed by the dimerization of flavipidin E (5). Compounds 23 and 24 were envisaged as isomeric derivatives with a 6/5/6-ring fusion, generated through the degradation of two flavipidin E molecules. Furthermore, flavipidin A (1) and asperphenalenone E (28) exhibited potent anti-influenza (PR8) activities, with IC50 values of 21.9 ± 0.2 and 12.9 ± 0.1 µM, respectively. Meanwhile, asperphenalenone (26) and asperphenalenone P (27) treatments exhibited significant inhibition of HIV pseudovirus infection in 293FT cells, boasting IC50 values of 6.1 ± 0.9 and 4.6 ± 1.1 µM, respectively. Overall, SFSP streamlines natural product isolation through NMR and MS data integration, as showcased by the discovery of numerous undescribed flavipidins and phenalenones based on NMR olefinic signals and low-field hydroxy signals.