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Three previously undescribed coumarins ( 1 - 3 ) were obtained from the roots of Notopterygium incisum . Their chemical structures were elucidated using a variety of spectroscopic techniques and chemical calculations. The inhibitory effects of these new compounds on NO production and pro-inflammatory factors ( IL-1β , IL-6 , and TNF-α ) in LPS-stimulated RAW 264.7 cells were investigated. Further studies revealed that compound 1 suppressed the expression of COX-2 and iNOS while also reduced ROS accumulation. Western blot analysis demonstrated that compound 1 could inhibit the PI3K/AKT pathway by decreasing the levels of p-PI3K and p-AKT. Collectively, these findings suggest that compounds 1 - 3 exhibit promising anti-inflammatory properties.

Kendomycin B is distinguished from other ansamycins by its unique, fully carbogenic ansa scaffold. We show here that FAD-dependent monooxygenase Kmy13 is solely responsible for installing the rare ansa structural framework; in vivo gene disruption/complementation experiments and in vitro enzymatic assays are described in detail. Moreover, the compound with a β-keto ester, kendolactone A ( 2 ), was confirmed as the natural substrate of Kmy13 and a bona fide biosynthetic intermediate en route to kendomycin B. Further structural prediction and biochemical assays have provided significant insights into the catalytic mechanism of Kmy13.

The incidence of Mycobacterium marinum infection is on the rise; however, the existing drug treatment cycle is lengthy and often requires multi-drug combination. Therefore, there is a need to develop new and effective anti- M. marinum drugs. Cochliomycin A, a 14-membered resorcylic acid lactone with an acetonide group at C-5' and C-6', exhibits a wide range of antimicrobial, antimalarial, and antifouling activities. To further explore the effect of this structural change at C-5' and C-6' on this compound's activity, we synthesized a series of compounds with a structure similar to that of cochliomycin A, bearing ketal groups at C-5' and C-6'. The R / S configuration of the diastereoisomer at C-13' was further determined through an NOE correlation analysis of CH 3 or CH 2 at the derivative C-13' position and the H-5' and H-6' by means of a 1D NOE experiment. Further comparative 1 H NMR analysis of diastereoisomers showed the difference in the chemical shift ( δ ) value of the diastereoisomers. The synthetic compounds were screened for their anti-microbial activities in vitro. Compounds 15 - 24 and 28 - 35 demonstrated promising activity against M. marinum , with MIC 90 values ranging from 70 to 90 μM, closely approaching the MIC 90 of isoniazid. The preliminary structure-activity relationships showed that the ketal groups with aromatic rings at C-5' and C-6' could enhance the inhibition of M. marinum . Further study demonstrated that compounds 23 , 24 , 29 , and 30 had significant inhibitory effects on M. marinum and addictive effects with isoniazid and rifampicin. Its effective properties make it an important clue for future drug development toward combatting M. marinum resistance.

Deep-sea derived fungi are considered as significant resources to discovery structurally diverse and biologically active natural compounds. In this study, four new sulfurated butyrolactones, penijanthiones A-D (1-4), together with four known analogues (5-8), were isolated from a Mariana Trench-derived fungus Penicillium janthinellum SH0301. Compounds 1-4 were the undescribed examples for natural butyrolactones coupling with a mercaptolactate moiety. Their structures including the absolute configurations of these new compounds were elucidated by comprehensive spectroscopic data, and calculated electronic circular dichroism (ECD). The plausible biosynthetic pathway of sulfur-incorporation of 1-4 was proposed. All of these isolated compounds were evaluated their cytotoxic, antimicrobial and antiviral activities., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Surface-enhanced Raman spectroscopy (SERS) is widely utilized in bacterial analyses, with the dominant SERS peaks attributed to purine metabolites released during sample preparation. Although adenosine triphosphate (ATP) and nucleic acids are potential molecular origins of these metabolites, research on their exact contributions remains limited. This study explored purine metabolite release from E. coli and RNA integrity following various sample preparation methods. Standard water washing generated dominant SERS signals within 10 s, a duration shorter than the anticipated RNA half-lives under starvation. Evaluating RNA integrity indicated that the most abundant ribosomal RNA species remained intact for hours post-washing, whereas messenger RNA and transfer RNA species degraded gradually. This suggests that bacterial SERS signatures observed after the typical washing step could originate from only a small fraction of endogenous purine-containing molecules. In contrast, acid depurination led to degradation of most RNA species, releasing about 40 times more purine derivatives than water washing. Mild heating also instigated the RNA degradation and released more purine derivatives than water washing. Notably, differences were also evident in the dominant SERS signals following these treatments. This work provides insights into SERS-based studies of purine metabolites released by bacteria and future development of methodologies., (© 2024. The Author(s).)

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future., (© 2024 Wiley Periodicals LLC.)

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Within pharmaceutical research, ensuring the enantiomeric purity of chiral compounds is critical. Specifically, chiral amines are a crucial category of compounds, due to their extensive therapeutic uses. However, the enantiomeric analysis of these compounds, particularly those with significant steric hindrance, remains a challenge. To address this issue, our research introduces a novel chiral 19 F-tagged NNO palladium pincer probe, strategically engineered with an open binding site to accommodate bulky amines. This probe facilitates the enantiodifferentiation of such amines, as evidenced by the distinct 19 F NMR signals generated by the enantiomers. Moreover, our findings highlight the probe's applicability in the chiral discrimination of various psychoactive substances, underscoring its potential for the identification of illegal stimulant use and contributing to forensic investigations.

Five new sesquiterpenoids, (4 S , 5 S , 6 S , 7 S , 8  R )-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone ( 1 ), (4 S , 5  R , 6 S , 7 S , 8  R )-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone ( 2 ), 6-O-propionyl-britannilactone ( 3 ), 1 β -hydroxy-3 α -acetoxyeudesma-11(13)-en-12,8 β -olide ( 4 ) and 1 β ,5 β -dihydroxyeudesma-11(13)-en-12,8 β -olide ( 5 ), along with twelve known ones were isolated from the flowers of Pentanema britannicum (L.) D.Gut.Larr. Among them, compounds 1 and 2 were stereoisomers which belong to 1,10-seco-eudesmane sesquiterpenoid with rare double bond between C-10 and C-14. The structures of the isolated compounds were elucidated by various spectroscopic methods, including 1D and 2D NMR experiments.

Heterocyclic trifluoromethylation is efficiently initiated through a photochemical reaction utilizing an electron donor-acceptor (EDA) complex, proceeding smoothly without the use of photocatalysts, transition-metal catalysts, or additional oxidants. This method has been optimized through extensive experimentation, demonstrating its versatility and efficacy across various substrates, including quinoxalinones, coumarins, and indolones. Notably, this approach enables the practical synthesis of trifluoromethylated quinoxalinones on a gram scale. Mechanistic investigations that incorporate radical trapping and ultraviolet/visible spectroscopy, confirmed the formation of the an EDA complex and elucidated the reaction pathways. This study highlights the crucial role of EDA photoactivation in trifluoromethylation, significantly expanding the application scope of EDA complexes in chemical synthesis., (© 2024 Wiley-VCH GmbH.)

One new highly degraded steroid, namely 21-nor-4-ene-chaxine A (1) furnishing a 5/6/5-tricyclic, along with one known related analogue (2), were isolated from the South China Sea sponge Spongia officinalis. Their structures including absolute configurations were established by extensive spectroscopic data analysis, TDDFT-ECD calculation, and comparison with the spectral data previously reported in the literature. Compound 1 represent the new member of incisterols family with a highly degradation in ring B. In vitro bioassays revealed compound 2 exhibited significant anti-microglial inflammatory effect on lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Ergot alkaloids (EAs) are a diverse group of indole alkaloids known for their complex structures, significant pharmacological effects, and toxicity to plants. The biosynthesis of these compounds begins with chanoclavine-I aldehyde (CC aldehyde, 2), an important intermediate produced by the enzyme EasD af or its counterpart FgaDH from chanoclavine-I (CC, 1). However, how CC aldehyde 2 is converted to chanoclavine-I acid (CC acid, 3), first isolated from Ipomoea violacea several decades ago, is still unclear. In this study, we provide in vitro biochemical evidence showing that EasD af not only converts CC 1 to CC aldehyde 2 but also directly transforms CC 1 into CC acid 3 through two sequential oxidations. Molecular docking and site-directed mutagenesis experiments confirmed the crucial role of two amino acids, Y166 and S153, within the active site, which suggests that Y166 acts as a general base for hydride transfer, while S153 facilitates proton transfer, thereby increasing the acidity of the reaction. KEY POINTS: • EAs possess complicated skeletons and are widely used in several clinical diseases • EasD af belongs to the short-chain dehydrogenases/reductases (SDRs) and converted CC or CC aldehyde to CC acid • The catalytic mechanism of EasD af for dehydrogenation was analyzed by molecular docking and site mutations., (© 2024. The Author(s).)

An undescribed trichodenone derivative (1), two new diketopiperazines (3 and 4) along with a bisabolane analog (2) were isolated from Trichoderma hamatum b-3. The structures of the new findings were established through comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR, Marfey's analysis as well as comparisons of ECD. The absolute configuration of 2 was unambiguously confirmed by NMR, ECD calculation and Mo 2 (AcO) 4 induced circular dichroism. Compounds 1-4 were tested for their fungicidal effects against eight crop pathogenic fungi, among which 1 showed 51% inhibition against Sclerotinia sclerotiorum at a concentration of 50 μg/mL., Competing Interests: Declaration of competing interest The authors did not report any potential conflicts of interest., (Copyright © 2024. Published by Elsevier B.V.)

The surge in applications of nitrile compounds across diverse fields, such as pharmaceuticals, agrochemicals, dyes, and functional materials, necessitates the development of rapid and efficient detection and identification methods. In this study, we introduce a chemosensing strategy employing a novel 19 F-labeled probe, facilitating swift and accurate analysis of a broad spectrum of nitrile-containing analytes. This approach leverages the reversible interaction between the 19 F-labeled probe and the analytes to produce chromatogram-like outputs, ensuring the precise identification of various pharmaceuticals and pesticides within complex matrices. Additionally, this dynamic system offers a versatile platform to investigate through-space 19 F- 19 F interactions, showcasing its potential for future applications in mechanistic studies.

Background: Suspension concentrate (SC) is one of the most widely used formulations for agricultural plant protection. With the rapid development of unmanned aerial vehicle (UAV) plant protection, the problems of spray drift, droplet rebound and poor wettability in the application of SC from UAVs have attracted wide attention. Although some tank-mix adjuvants have been used to enhance dosage delivery for UAV, their effects and mechanisms are not fully clear, and few formulations are specifically designed for UAV., Results: The type and concentration of tank-mix adjuvant affect the dosage delivery of SC. MO501 can significantly reduce DV <100μm , and inhibit droplet rebound on peanut leaves at concentrations ≥0.5%. Silwet 408 can achieve complete wetting and superspreading after adding ≥0.2% concentrations, but only ≥0.5% can inhibit rebound. XL-70 shows excellent regulation ability even at low concentration, and 0.2% concentration can simultaneously suppress impact and promote spreading. Besides, the formulation oil dispersion (OD) can significantly reduce the driftable fine fraction and inhibit rebound at dilution ratios of ≤250-fold, thus enhancing dosage delivery., Conclusion: SC is prone to rebound on hydrophobic leaf surfaces and shows poor wetting and spreading properties. Appropriate types and concentrations of tank-mix adjuvants and formulation improvement are two effective strategies for improving the dosage delivery of pesticides, whereas the addition of inappropriate adjuvants may cause potential risks instead. These findings provide guidance for the rational selection of tank-mix adjuvants and potential applications of OD for UAV plant protection. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Purpose: In response to the growing challenges posed by an aging society, a telemedicine system was developed specifically for older adults postoperative patients, and its effectiveness was thoroughly investigated., Methods: Between May 2020 and May 2022, a total of 88 older adults postoperative patients were enrolled and randomly allocated into an experimental group and a control group. The experimental group received telemedicine services after discharge, while the control group received conventional medical services following the traditional protocol. One month after discharge, various indicators were evaluated for both groups, including number of visits, medical expenditures, postoperative recovery, anxiety, depression and satisfaction., Results: The number of visits and medical expenditures of the experimental group were less than those of the control group [1 (0, 1) vs. 1 (1, 2), Z  = -3.977, p  < 0.001; 25.25 (0.00, 277.40) yuan vs. 174.65 (49.63, 446.10) yuan, Z  = -2.150, p  = 0.032]. In both groups, there were 2 cases of incision infection, respectively. No significant difference was observed between the two groups (Fisher χ 2 , p = 0.259). In both groups, there was no instance of incision bleeding, incision dehiscence, readmission, or reoperation. Additionally, there was no significant difference in physical status between the two groups at discharge and after discharge (66.06 ± 8.92 vs. 65.45 ± 7.39 t = 0.287, p = 0.775; 73.33 ± 9.97 vs. 70.91 ± 7.50, t = 1.202, p = 0.235). And there was no significant difference in the change of physical status between the two groups after discharge [10.00 (0.00, 10.00) vs. 5.00 (0.00, 10.00), Z = -1.077, p = 0.281]. There was no significant difference in body weight change between the two groups after discharge [1.05 (0.38, 1.60) Kg vs. 0.80 (0.50, 1.43) Kg, Z = -0.265, p = 0.791]. There was no significant difference in the levels of anxiety and depression between the two groups at discharge (45.64 ± 8.10 vs. 44.60 ± 8.24, t = 0.520, p = 0.604, 48.33 ± 8.46 vs. 47.50 ± 6.85, t = 0.418, p = 0.677). But the levels of anxiety and depression in the experimental group were lower than those in the control group after discharge (34.92 ± 7.38 vs. 39.03 ± 8.42, t  = -2.183, p  = 0.032, 37.86 ± 7.29 vs. 41.93 ± 7.13, t  = -2.281, p  = 0.025); The change of anxiety level and depression level of the experimental group were more than those of the control group [-10.00 (-11.25, -8.75) vs. -5.00 (-7.81, -3.75), Z = -5.277, p < 0.001; -10.00 (-12.50, -7.50) vs. -5.00 (-7.75, -3.44), Z = -4.596, p < 0.001]. The level of satisfaction regarding medical services, daily care, and psychological comfort was higher in the experimental group compared to the control group [3 (3, 3.25) vs. 2 (1, 2), Z  = -5.931, p  < 0.001; 3 (3, 4) vs. 3 (2, 3), Z  = -2.286, p  = 0.022; 2 (1, 3) vs. 1 (0.75, 2), Z  = -2.081, p  = 0.037]., Conclusion: In the context of an aging society, telemedicine system can offer improved healthcare to older adults postoperative patients. This includes benefits such as reducing number of visits, saving medical expenditures, enhancing psychological comfort and daily care., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Chang, Han, Hu, Lin and Gu.)

Purpose: To explore the cytotoxic effect of a menthol-favored E-liquid on human periodontal ligament stem cells (hPDLSCs), as well as the underlying mechanism of electronic cigarette (E-cig)-induced cell apoptosis., Methods: PDLSCs were isolated and cultured from periodontal ligament tissues of healthy premolars extracted for orthodontic reasons. Cells in passage 3 were used to detect the surface markers of stem cells by flow cytometry. Then the cells were exposed to different doses of menthol-favored E-liquid (at 59 mg/L nicotine concentration) in the culture median (the final nicotine concentrations were 0.1 μg/mL, 1.0 μg/mL, 10 μg/mL, 50 μg/mL, 0.1 mg/mL, 0.2 mg/mL and 0.5 mg/mL, respectively) for different period of times (24, 48 and 72 h). The cell viability was analyzed by CCK-8 assay. Cell apoptosis was evaluated by flow cytometry (7-AAD and Annexin V staining) and TUNEL assay. Reactive oxygen species (ROS) production was detected with fluorescence probe DCFH-DA by confocal microscopy and flow cytometry. The protein expression levels associated with ROS/JNK/caspase 3 axis(p-JNK, JNK, c-Jun, p-c-Jun, Bcl-2, Bax and cleaved-caspase 3) were analyzed by Western blot. Immunocytofluorescense staining was applied to evaluate the expression level of p-JNK. After addition of NAC, a ROS scavenger, and MAPK/JNK specific blocker SP600125, their effects on E-cig-induced cell apoptosis were evaluated. Statistical analysis was performed with Graph Pad 5.0 software package., Results: Human PDLSCs were successfully isolated and cultured and flow cytometry assay showed the mesenchymal stem cell surface biomarkers (CD73, CD90 and CD105) were positively expressed. CCK8 assay indicated cell viability was significantly(P＜0.001) different among all concentration groups at various time points (24, 48 or 72 h), and the difference in apoptosis rate among all concentration groups was also statistically significant (P＜0.001). After exposure to E-liquid with nicotine concentration ≥50 μg/mL, cell viability was significantly reduced, and the proportion of apoptotic cells and the cellular ROS level was significantly increased in a dose-dependent manner as compared with the control group(0.0 mg/mL). Western blot assay showed E-cig exposure could promote MAPK/JNK phosphorylation in a dose-dependent and time-dependent manner. Either NAC or SP600125 could partially rescue the E-cig-induced cell apoptosis via reversing up-regulation of p-JNK and cleaved caspase 3., Conclusions: ROS/JNK/caspase 3 axis is involved in menthol-favored E-liquid-induced apoptosis of hPDLSCs.

The merger of electrochemistry and transition metal catalysis has emerged as a powerful tool to join two electrophiles in an enantioselective manner. However, the development of enantioselective electroreductive cross-couplings of olefins remains a challenge. Inspired by the advantages of the synergistic use of electrochemistry with nickel catalysis, we present here a Ni-catalyzed enantioselective electroreductive cross-coupling of acrylates with aryl halides and alkyl bromides, which affords chiral α-aryl carbonyls in good to excellent enantioselectivity. Additionally, this catalytic reaction can be applied to (hetero)aryl chlorides, which is difficult to achieve by other methods. The combination of cyclic voltammetry analysis with electrode potential studies suggests that the Ni I species activates aryl halides by oxidative addition and alkyl bromides by single-electron transfer.

We report new Gaussian boson sampling experiments with pseudo-photon-number-resolving detection, which register up to 255 photon-click events. We consider partial photon distinguishability and develop a more complete model for the characterization of the noisy Gaussian boson sampling. In the quantum computational advantage regime, we use Bayesian tests and correlation function analysis to validate the samples against all current classical spoofing mockups. Estimating with the best classical algorithms to date, generating a single ideal sample from the same distribution on the supercomputer Frontier would take ∼600  yr using exact methods, whereas our quantum computer, Jiǔzhāng 3.0, takes only 1.27  μs to produce a sample. Generating the hardest sample from the experiment using an exact algorithm would take Frontier∼3.1×10^{10}  yr.

Metal-catalyzed asymmetric electro-reductive couplings have emerged as a powerful tool for organic synthesis, wherein a sacrificial anode is typically required. Herein, a parallel paired electrolysis (PPE)-enabled asymmetric catalysis has been developed, and the alcohols and ketones could be simultaneously converted to the corresponding aldehydes and chiral tertiary alcohols with high yields and enantioselectivity in an undivided cell. Additionally, this Ni-catalyzed asymmetric reductive coupling can well match the anodic oxidative C-H bond bromination of (hetero)arenes. This protocol opens an alternative avenue for organic synthesis., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the influencing factors of lung function in pneumoconiosis patients, and to provide reference for clinical treatment. Methods: From July 2020 to December 2020, a questionnaire survey was conducted on pneumoconiosis patients in the jurisdiction by using the "Guangdong Province Occupational Disease Prevention and Control Institute" questionnaire, and the relevant items of patients were examined. The rate of counting data is expressed, and the measurement data is expressed by mean and standard deviation. Chi-square test was used for comparison between groups, trend chi-square test was used for trend analysis of ordered classified data. Multivariate analysis was carried out with binary logistic regression model. Results: A total of 1409 pneumoconiosis patients were enrolled. The abnormal rate of lung function in pneumoconiosis patients was 68.77%. The results of trend Chi-square test showed that the abnormal rate of lung function increased with the age of exposure to dust in different age groups (Chi Sqnare Trend=64.12、8.49、24.20, P <0.05) . In univariate analysis, there were statistical significance in different dust exposure age, working age, pneumoconiosis stage, complications and occupational pneumoconiosis diseases ( P <0.05) . Multiple logistic regression results showed that age of exposure to dust, years of service, stage of pneumoconiosis and complications were the main influencing factors of lung function in pneumoconiosis patients ( P <0.05) . Compared with patients aged 0-30 years, patients aged 50-70 years and older had a higher rate of abnormal lung function ( OR =2.16, 95% CI : 1.12~4.16; OR =4.82, 95% CI : 2.05~11.35, all P <0.05) ; Compared with patients with 0~20 years of service, patients with 20~30 years of service and more than 30 years of service had a higher rate of abnormal lung function ( OR =1.58, 95% CI : 1.10~2.25; OR =1.63, 95% CI : 1.28~2.40, P <0.05) ; Compared with stage Ⅰ patients, Stage Ⅱ and Stage Ⅲ patients had a higher rate of abnormal lung function ( OR =1.62, 95% CI : 1.20~2.17; OR =2.23, 95% CI : 1.40~3.55, all P <0.05) ; Compared with patients without comorbidities, patients with comorbidities had a higher rate of abnormal lung function ( OR =1.68, 95% CI : 1.20~2.38, P <0.05) . Conclusion: The factors such as age of exposure to dust, working age, stage of pneumoconiosis and complications may be the influencing factors of lung function in pneumoconiosis patients.

Electronic cigarettes have rapidly gained acceptance recently. Nicotine-containing electronic cigarette liquids (e-liquids) are prohibited in some countries, but are permitted and simply available online in others. A rapid detection method is therefore required for on-site inspection or screening of a large amount of samples. Our previous study demonstrated a surface-enhanced Raman scattering (SERS)-based approach to identify nicotine-containing e-liquids; without any pre-treatment, e-liquid can be directly tested on our solid-phase SERS substrates, made of silver nanoparticle arrays embedded in anodic aluminium oxide nanochannels (Ag/AAO). However, this approach required manual determination of spectral signatures and negative samples should be validated in the second round detection. Here, after examining 406 commercial e-liquids, we refined this approach by developing artificial intelligence (AI)-assisted spectrum interpretations. We also found that nicotine and benzoic acid can be simultaneously detected in our platform. This increased test sensitivity because benzoic acid is usually used in nicotine salts. Around 64% of nicotine-positive samples in this study showed both signatures. Using either cutoffs of nicotine and benzoic acid peak intensities or a machine learning model based on the CatBoost algorithm, over 90% of tested samples can be correctly discriminated with only one round of SERS measurement. False negative and false positive rates were 2.5-4.4% and 4.4-8.9%, respectively, depending on the interpretation method and thresholds applied. The new approach takes only 1 microliter of sample and can be performed in 1-2 min, suitable for on-site inspection with portable Raman detectors. It could also be a complementary platform to reduce samples that need to be analyzed in the central labs and has the potential to identify other prohibited additives., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Carbamoyl fluorides, fluoroformates, and their analogues are a class of important compounds and have been evidenced as versatile building blocks for the preparation of useful molecules in organic chemistry. While major achievements were made in the synthesis of carbamoyl fluorides, fluoroformates, and their analogues in the last half of 20 th century, an increasing number of reports have focused on using O/S/Se=CF 2 species or their equivalents as the fluorocarbonylation reagents for the direct construction of these compounds from the parent heteroatom-nucleophiles in recent years. This review mainly summarizes the advances in the synthesis and typical application of carbamoyl fluorides, fluoroformates, and their analogues by the halide exchanges and fluorocarbonylation reactions since 1980., (© 2023 The Chemical Society of Japan & Wiley-VCH GmbH.)

Among the large series of marine natural products (MNPs), sulfur-containing MNPs have emerged as potential therapeutic agents for the treatment of a range of diseases. Herein, we reviewed 95 new sulfur-containing MNPs isolated during the period between 2021 and March 2023. In addition, we discuss that the widely used strategies and the emerging technologies including natural product-based antibody drug conjugates (ADCs), small-molecule-based proteolysis targeting chimeras (PROTACs), nanotechnology-based drug carriers, artificial intelligence (AI)-driven drug discovery have been used for improving the efficiency and success rate of NP-based drug development. We also provide perspectives regarding the challenges and opportunities in sulfur-containing MNPs based drug discovery and development and future research directions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Visible-light-induced decarboxylative trifluoromethylselenolation of (hetero)aromatic carboxylic acids with [Me 4 N][SeCF 3 ], oxidant, and catalysts afforded a variety of (hetero)aryl trifluoromethyl selenoethers in good yields. The reaction might involve a radical process, which generated (hetero)aryl radicals from the stable (hetero)aromatic carboxylic acids via oxidative decarboxylation with NFSI as the oxidant, [di- t Bu-Mes-Acr-Ph][BF 4 ] as the photocatalyst, and 1,1'-biphenyl as the cocatalyst. Both catalysts had a decisive influence on the reaction. The trifluoromethylselenolation was further promoted by the copper salts probably via Cu-mediated cross-coupling of the sensitive SeCF 3 species with the in situ formed (hetero)aryl radicals. Advantages of the method include visible light irradiation, mild reaction conditions at ambient temperature, good functional group tolerance, no pre-functionalization/activation of the starting carboxylic acids, and applicability to drug molecules. This protocol is promising and synthetically useful, which overcame the limitations of the known trifluoromethylselenolation methods and represented the first decarboxylative trifluoromethylselenolation of (hetero)aromatic carboxylic acids.

Two new cembranoids, namely sarcoboettgerols D and E, together with four known related ones, have been isolated from the soft coral Sarcophyton boettgeri collected from Weizhou Island in the South China Sea. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance methods, time-dependent density functional theory-electronic circular dichroism calculations, as well as comparison with the reported data in the literature. A plausible biogenetic relationship of four cembranoids was proposed. In bioassays, sarcomililatin B exhibited cytotoxic activity against H1299 cell (IC 50 =35.0 μM), whereas sarcomililatin B and sarcomililatin A displayed moderate antibacterial activities (MIC 17.4-34.8 μg/mL)., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Instruction: Hypericum bellum Li is rich in xanthones with various bioactivities, especially in anti-breast cancer. While the scarcity of mass spectral data of xanthones in Global Natural Products Social Molecular Networking (GNPS) libraries have challenged the rapid recognition of xanthones with similar structures., Objective: This study is aimed to enhance the molecular networking (MN)-based dereplication and visualisation ability of potential anti-breast cancer xanthones from H. bellum to overcome the scarcity of xanthones mass spectral data in GNPS libraries. Separating and purifying the MN-screening bioactive xanthones to verify the practicality and accuracy of this rapid recognition strategy., Methodology: A combined strategy of "seed" mass spectra-based MN, in silico annotation tools, substructure identification tools, reverse molecular docking, ADMET screening, molecular dynamics (MDs) simulation experiments, and an MN-oriented separation procedure was first introduced to facilitate the rapid recognition and targeted isolation of potential anti-breast cancer xanthones in H. bellum., Results: A total of 41 xanthones could only be tentatively identified. Among them, eight xanthones were screened to have potential anti-breast cancer activities, and six xanthones that were initially reported in H. bellum were obtained and verified to have good binding abilities with their paired targets., Conclusion: This is a successful case study that validated the application of "seed" mass spectral data could overcome the drawbacks of GNPS libraries with limited mass spectra and enhance the accuracy and visualisation of natural products (NPs) dereplication, and this rapid recognition and targeted isolation strategy can be also applicable for other types of NPs., (© 2023 John Wiley & Sons Ltd.)

Fifteen new diterpenoids, namely xishaklyanes A-O ( 1 - 15 ), along with three known related ones ( 16 - 18 ), were isolated from the soft coral Klyxum molle collected from Xisha Islands, South China Sea. The stereochemistry of the new compounds was elucidated by a combination of detailed spectroscopic analyses, chemical derivatization, quantum chemical calculations, and comparison with the reported data. The absolute configuration of compound 18 was established by the modified Mosher's method for the first time. In bioassay, some of these compounds exhibited considerable antibacterial activities on fish pathogenic bacteria, and compound 4 showed the most effective activity with MIC of 0.225 μg/mL against Lactococcus garvieae .

Background: To obtain new environmentally friendly fungicides, we used the natural product pimprinine as the lead compound, and designed and synthesized two series of ring-opening derivatives of pimprinine containing amide/thioamide. We then studied their antifungal activity against six common plant pathogenic fungi in vitro., Results: Most of the target compounds have good antifungal activity against six important plant pathogenic fungi in vitro. At a concentration of 50 μg ml -1 , compound 3o showed prominent antifungal effects on Alternaria solani and Rhioctornia solani, with inhibition rates of 91.8% and 97.4%, and a 50% effective concentration (EC 50 ) of 6.2255 and 0.6969 μg ml -1 respectively. The EC 50 of compound 3o against Alternaria solani was significantly lower than that of boscalid (13.0380 μg ml -1 ) and flutriafol (11.9057 μg ml -1 ). In addition, compound 3o had good antifungal activity against Sclerotinia sclerotiorum, cucumber powdery mildew, cucumber Botrytis cinerea and Phytophthora capsici in vivo; the antifungal activity of compound 3o against cucumber Botrytis cinerea is 91.7%. At the same time, docking results for highly active compound 3o with the presumed target succinate dehydrogenase and the molecular docking prediction scores of all compounds further indicate its possible antifungal activity mechanism., Conclusion: The designed and optimized derivative 3o of ring-opening pimprinine has good antifungal activity and can be used as a new antifungal drug for further research. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Gaussian boson sampling (GBS) is not only a feasible protocol for demonstrating quantum computational advantage, but also mathematically associated with certain graph-related and quantum chemistry problems. In particular, it is proposed that the generated samples from the GBS could be harnessed to enhance the classical stochastic algorithms in searching some graph features. Here, we use Jiǔzhāng, a noisy intermediate-scale quantum computer, to solve graph problems. The samples are generated from a 144-mode fully connected photonic processor, with photon click up to 80 in the quantum computational advantage regime. We investigate the open question of whether the GBS enhancement over the classical stochastic algorithms persists-and how it scales-with an increasing system size on noisy quantum devices in the computationally interesting regime. We experimentally observe the presence of GBS enhancement with a large photon-click number and a robustness of the enhancement under certain noise. Our work is a step toward testing real-world problems using the existing noisy intermediate-scale quantum computers and hopes to stimulate the development of more efficient classical and quantum-inspired algorithms.

Nanolobatone A, featuring an unprecedented tricyclo[10.3.0.0 1,2 ]pentadecane carbon skeleton, along with four new polyoxygenated and four unusual endoperoxide-bridged casbane-type diterpenoids were isolated from the Hainan soft coral Sinularia nanolobata. The structures of the new compounds were established by extensive spectroscopic analysis, X-ray diffraction analysis, and time-dependent density functional theory/electronic circular dichroism calculations. A plausible biosynthetic pathway of new isolates was proposed. Bioassays revealed that nanolobatone A showed weak antibacterial activity against the Gram-positive bacteria Streptococcus pyogenes., (© 2023 Wiley-VCH GmbH.)

Polo like kinase 1 (PLK1) is a serine/threonine kinase that is widely distributed in eukaryotic cells and plays an important role in multiple phases of the cell cycle. Its importance in tumorigenesis has been increasingly recognized in recent years. Herein, we describe the optimization of a series of novel dihydropteridone derivatives (13a-13v and 21g-21l) possessing oxadiazoles moiety as potent inhibitors of PLK1. Compound 21g exhibited improved PLK1 inhibitory capability with an IC 50 value of 0.45 nM and significant anti-proliferative activities against four tumor-derived cell lines (MCF-7 IC 50  = 8.64 nM, HCT-116 IC 50  = 26.0 nM, MDA-MB-231 IC 50  = 14.8 nM and MV4-11 IC 50  = 47.4 nM) with better pharmacokinetic characteristics than BI2536 in mice (AUC 0-t  = 11 227 ng h mL -1 vs 556 ng h mL -1 ). Moreover, 21g exhibited moderate liver microsomal stability and excellent pharmacokinetic profile (AUC 0-t  = 11227 ng h mL -1 , oral bioavailability of 77.4%) in Balb/c mice, acceptable PPB, improved PLK1 inhibitory selectivity, and no apparent toxicity was observed in the acute toxicity assay (20 mg/kg). Further investigation showed that 21 g could arrest HCT-116 cells in G2 phase and induce apoptosis in a dose-dependent manner. These results indicate that 21g is a promising PLK1 inhibitor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Masson SAS.)

Dual inhibitors of JAK2 and FLT3 can synergistically control the development of acute myeloid leukemia (AML), and overcome secondary drug resistance of AML that is associated with FLT3 inhibition. We therefore designed and synthesized a series of 4-piperazinyl-2-aminopyrimidines as dual inhibitors of JAK2 and FLT3, and improved their selectivity for JAK2. Screening cascades revealed that compound 11r exhibited inhibitory activity with IC 50 values of 2.01, 0.51, and 104.40 nM against JAK2, FLT3, and JAK3, respectively. Compound 11r achieved a high selectivity for JAK2 at a ratio of 51.94, and also showed potent antiproliferative activity in HEL (IC 50  = 1.10 μM) and MV4-11 (IC 50  = 9.43 nM) cell lines. In an in vitro metabolism assay, 11r exhibited moderate stability in human liver microsomes (HLMs), with a half-life time of 44.4 min, and in rat liver microsomes (RLMs), with a half-life of 143 min. In pharmacokinetic studies, compound 11r showed moderate absorption (Tmax = 5.33 h), with a peak concentration of 38.7 ng/mL and an AUC of 522 ng h/mL in rats, and an oral bioavailability of 25.2%. In addition, 11r induced MV4-11 cell apoptosis in a dose-dependent manner. These results indicate that 11r is a promising selective JAK2/FLT3 dual inhibitor., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Carbon-heteroatom bond formation under transition-metal free conditions provides a powerful synthetic alternative for the efficient synthesis of valuable molecules. In particular, C-N and C-O bonds are two important types of carbon-heteroatom bonds. Thus, continuous efforts have been deployed to develop novel C-N/C-O bond formation methodologies involving various catalysts or promoters under TM-free conditions, which enables the synthesis of various functional molecules comprising C-N/C-O bonds in a facile and sustainable manner. Considering the significance of C-N/C-O bond construction in organic synthesis and materials science, this review aims to comprehensively present selected examples on the construction of C-N (including amination and amidation) and C-O (including etherification and hydroxylation) bonds without transition metals. Besides, the involved promoters/catalysts, substrate scope, potential application and possible reaction mechanisms are also systematically discussed., (© 2023 The Chemical Society of Japan & Wiley-VCH GmbH.)

Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator. It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity, type 2 diabetes and NASH. In this study, we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator, candidusin A ( CHNQD-0803 ). Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a K D value of 4.728 × 10 -8  M and activates AMPK at both molecular and intracellular levels. We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition, LPS-stimulated inflammation, TGF-β-induced fibrosis cell models and the MCD-induced mouse model of NASH. The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition, negatively regulated the NF-κB-TNFα inflammatory axis to suppress inflammation, and ameliorated liver injury and fibrosis. These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00168-z., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2023.)

Streptochlorin is a kind of indole alkaloid derived from marine microorganisms. It is a promising lead compound due to its potent bioactivity in preventing many phytopathogens, as shown in our previous study. To explore the potential applications of this natural product, a series of novel benzoxaborole-containing streptochlorin derivatives were designed and synthesized through a one-step and catalyst-free reaction in water at room temperature. All target compounds were first screened for their antifungal profiles in vitro against six common phytopathogenic fungi. The results of bioassay revealed that most of the designed compounds exhibited more significant antifungal activities against Botrytis cinrea , Gibberella zeae , Rhizoctorzia solani , Colletotrichum lagenarium, and alternaria leaf spot under the concentration of 50 μg/mL, and this is highlighted by compounds 4i and 5f , which demonstrated impressive antifungal effects against G. zeae and R. solani , with their corresponding EC 50 values 0.2983 and 0.2657 μg/mL, which are obviously better than positive control flutriafol and boscalid (5.2606 and 1.2048 μg/mL, respectively). Scanning electron microscopy on the hyphae morphology showed that compound 5b might cause mycelial abnormalities of G. zeae . 3D-QSAR studies of CoMFA and CoMSIA were carried out on 29 target compounds with antifungal activity against B. cinrea . The analysis results indicated that introducing appropriate electronegative groups at the 5-position of benzoxaborole and the 4,5-positions of the indole ring could effectively improve the anti- B. cinrea activity. Moreover, compound 5b showed good antifungal activities in vivo against Phytophthora capsici . Molecular docking was further explored to ascertain the practical value of the active compound as a potential inhibitor of LeuRS. The abovementioned results indicate that the designed benzoxaborole-containing streptochlorin derivatives could be further studied as template molecules of novel antifungal agents.

Here, we report an asymmetric electrochemical organonickel-catalyzed reductive cross-coupling of aryl aziridines with aryl iodides in an undivided cell, affording β-phenethylamines in good to excellent enantioselectivity with broad functional group tolerance. The combination of cyclic voltammetry analysis of the catalyst reduction potential as well as an electrode potential study provides a convenient route for reaction optimization. Overall, the high efficiency of this method is credited to the electroreduction-mediated turnover of the nickel catalyst instead of a metal reductant-mediated turnover. Mechanistic studies suggest a radical pathway is involved in the ring opening of aziridines. The statistical analysis serves to compare the different design requirements for photochemically and electrochemically mediated reactions under this type of mechanistic manifold., (© 2023. The Author(s).)

The Panxi area in Sichuan Province is the main area for the production of truffles in China, and several species of truffle are known to exist in this region. Nevertheless, it is unclear what the differences in chemical composition between the truffles are. Using an ultra-high-performance liquid chromatography quadrupole/orbitrap high-resolution mass spectrometry coupled with Compound Discoverer 3.0, we identified chemical components in three mainly known truffles from the Panxi region. Further analysis of chemical composition differences was conducted using principal component analysis, and orthogonal partial least squares discriminant analysis. Note that, 78.9% of the variance was uncovered by the principal component analysis model. As a result of the orthogonal partial least squares discriminant analysis model, the three species of truffles (Tuber pesudohimalayense, Tuber indicum, and Tuber sinense) from Panxi were better discriminated, with R 2 X, R 2 Y, and Q 2 being 0.821, 0.993, and 0.947, respectively. In this study, 87 components were identified. T. pesudohimalayense contained significantly higher levels of nine different compounds than the other two species. Hence, it was possible to identify similarities and differences between three species of truffles from Panxi in terms of chemical composition. This can be used as a basis for quality control., (© 2023 Wiley-VCH GmbH.)

Quinolizidomycins A ( 1 ) and B ( 2 ), two unprecedented quinolizidine alkaloids featuring a tricyclic 6/6/5 ring system, were isolated from Streptomyces sp. KIB-1714. Their structures were assigned by detailed spectroscopic data analyses and X-ray diffraction. Stable isotope labeling experiments suggested that compounds 1 and 2 are derived from lysine, ribose 5-phosphate, and acetate units, which indicates an unprecedented manner of assembly of the quinolizidine (1-azabicyclo[4.4.0]decane) scaffold in quinolizidomycin biosynthesis. Quinolizidomycin A ( 1 ) was active in an acetylcholinesterase inhibitory assay.

Inflammation is connected with a variety of diseases and there is still a need to develop more effective and safer anti-inflammatory drugs. Herein, we synthesized, resolved, and characterized eight enantiopure isomers of yaequinolone J1 (1), yaequinolone J2 (2), 4'-desmethoxyyaequinolone J1 (3), and 4'-desmethoxyyaequinolone J2 (4). The key synthetic steps were extended and 34 racemic analogues modified at the 4-aryl, the N-position, and the pyran ring were designed and synthesized. All the synthesized compounds were evaluated for their anti-inflammatory activities in RAW 264.7 cells of which 13 compounds showed significant inhibition of nitric oxide (NO) production at a concentration of 0.1 μM, which was more potent than that of indomethacin. Furthermore, compounds (-)-3, (-)-4, 5h, and 6g reduced the production of IL-6 in LPS-stimulated RAW 264.7 cells at a concentration of 50 nM. A preliminary SAR indicated that 3'-Br (5h), 4'-NO 2 (6g) on 4-phenyl and 3-bromobenzyl (7f) on the N-position were the most effective substituents. This is the first report of the anti-inflammatory yaequinolone alkaloids and the present study provided evidence for exploiting this series of highly efficacious derivatives for new anti-inflammatory agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the normal process of tooth development of C57BL/6 mouse strain by using micro-CT for better understanding about the tooth development of the human being and other species. Methods: A total of 54 C57BL/6 mice were used at postnatal day 1 (P1), P3, P7, P10, P14, P21, P28, P42 and P56 ( n= 6 for each age group). After euthanasia, the skulls and alveolar bones (with molars) were isolated and scanned by micro-CT scanner. After three dimensional reconstruction, the developmental status of the crown and root(s) for each tooth type was examined in different views. Results: The tooth development of mice from birth to mature (P56) could be divided into three stages. The first stage was from P1 to P14, in which the crowns of all the first, second and third molars had formed, while the roots had not fully developed yet. The second stage was from ablactation (P21) to P28, in which all the roots of the molars had reached their normal length, and the apical foramens had closed. Due to the mastication and occlusal abrasion, the incisors exhibited sharp cutting edges at the buccal enamel layer, and the corresponding molars formed a pit-to-fossa articulated relationship. The third stage was from P42 to P56, in which the root canal differentiation occurred, and 1-2 canal configuration was formed in several flat roots. The development of molar roots had completed and the apexes were enlarged due to the deposition of cementum around. Conclusions: In the process of mouse tooth development, the mineralization of the cusps, followed by crown formation and roots elongation, was precisely regulated in a spatial-temporal pattern. The incisors and the molars exhibited different modes of development.

Based on the structures of natural products streptochlorin and pimprinine derived from marine or soil microorganisms, a series of streptochlorin derivatives containing the nitrile group were designed and synthesized through acylation and oxidative annulation. Evaluation for antifungal activity showed that compound 3a could be regarded as the most promising candidate-it demonstrated over 85% growth inhibition against Botrytis cinerea, Gibberella zeae, and Colletotrichum lagenarium , as well as a broad antifungal spectrum in primary screening at the concentration of 50 μg/mL. The SAR study revealed that non-substituent or alkyl substituent at the 2-position of oxazole ring were favorable for antifungal activity, while aryl and monosubstituted aryl were detrimental to activity. Molecular docking models indicated that 3a formed hydrogen bonds and hydrophobic interactions with Leucyl-tRNA Synthetase, offering a perspective for the possible mechanism of action for antifungal activity of the target compounds.

Six new azoxy-aromatic compounds ( o -alkylazoxymycins A-F, 1 - 6 ) and two new nitrogen-bearing phenylvaleric/phenylheptanoic acid derivatives ( o -alkylphemycins A and B, 7 and 8 ) were isolated from Streptomyces sp. Py50. Their structures were elucidated based on HRESIMS, NMR, UV spectroscopic analyses, and X-ray crystallographic data. O -Alkylazoxymycins A-F ( 1 - 6 ) are the first natural examples of azoxy compounds with the azoxy bond attached to the ortho -position of the phenylheptanoic acid or phenylvaleric acid moiety. Compounds 1 , 5 , and 6 were active against Epidermophyton floccosum with MIC 50 values ranging from 10.1 to 51.2 μM. A plausible biosynthetic pathway of 2 and 3 was proposed.

Further insights on the secondary metabolites of a soft coral-derived fungus Aspergillus versicolor under the guidance of MS/MS-based molecular networking led to the isolation of seven known cycloheptapeptides, namely, asperversiamides A-C ( 1 - 3 ) and asperheptatides A-D ( 4 - 7 ) and an unusual pyrroloindoline-containing new cycloheptapeptide, asperpyrroindotide A ( 8 ). The structure of 8 was elucidated by comprehensive spectroscopic data analysis, and its absolute configuration was determined by advanced Marfey's method. The semisynthetic transformation of 1 into 8 was successfully achieved and the reaction conditions were optimized. Additionally, a series of new derivatives ( 10 - 19 ) of asperversiamide A ( 1 ) was semi-synthesized and their anti-tubercular activities were evaluated against Mycobacterium tuberculosis H37Ra. The preliminary structure-activity relationships revealed that the serine hydroxy groups and the tryptophan residue are important to the activity., Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-022-00157-8., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest. Author Chang-Lun Shao, Chang-Yun Wang are the Editorial Board Members of the journal, but was not involved in the journal's review of, or decision related to this manuscript., (© The Author(s) 2023.)